A life-threatening condition characterized by widespread activation of the coagulation cascade leading to diffuse microvascular thrombi formation with simultaneous consumption of clotting factors and platelets, resulting in paradoxical thrombosis and hemorrhage.

Exam domain	One-glance essentials
Definition / diagnosis	Acquired systemic activation of coagulation causes diffuse fibrin-rich microthrombi while consuming platelets and clotting factors → simultaneous thrombosis + bleeding ^[1]^[2] DIC is always secondary to an underlying disorder; it is a clinicopathological syndrome, not a standalone diagnosis
Epidemiology / risks	Major triggers: sepsis, major trauma/burns, obstetric catastrophe, malignancy—especially acute promyelocytic leukaemia (APL)—and severe transfusion reactions ^[1]^[2] Rapid, severe triggers favour acute bleeding DIC; malignancy or vascular lesions may produce chronic thrombotic DIC
Core mechanism	Tissue-factor/thrombin excess → systemic fibrin deposition → microvascular ischaemia and organ dysfunction ^[1] Consumption of platelets/factors plus secondary fibrinolysis → bleeding; shearing through fibrin strands produces schistocytes
Clinical picture	Oozing from venepuncture/wounds, ecchymoses, mucosal or internal bleeding plus shock or organ ischaemia ^[1]^[2] Look for the trigger: fever/sepsis, obstetric emergency, trauma, cancer or APL
Investigations	*Prolonged PT and APTT + low platelets + low fibrinogen + red-cell fragmentation is the classic in-house pattern* ^[3] D-dimer/FDP ↑, blood film may show schistocytes; trend results and apply the ISTH DIC score in the clinical context ^[1]^[2] Send cultures and targeted tests for the underlying cause; do not delay treatment while awaiting a complete panel
Management	*Reverse the underlying cause and replenish consumed factors when clinically required* ^[3] Active bleeding/procedure: platelets for thrombocytopenia, FFP for factor depletion, cryoprecipitate/fibrinogen concentrate for marked hypofibrinogenaemia ^[1]^[2] Suspected APL: urgent haematology input and start ATRA immediately; reserve heparin for selected predominantly thrombotic/chronic DIC
Complications	Major haemorrhage, digital/limb ischaemia, venous or arterial thrombosis ^[1]^[2] Microvascular thrombosis → AKI, hepatic injury, respiratory failure, neurological injury and multiorgan failure
Prevention / follow-up	Early source control/antimicrobials for sepsis and prompt definitive treatment of obstetric, traumatic or malignant triggers In high-risk patients, trend platelets, PT/APTT, fibrinogen and D-dimer; minimise unnecessary invasive procedures
Exam traps	Do not treat abnormal numbers alone: blood products are guided mainly by bleeding/procedural risk ^[1]^[2] Normal fibrinogen does not exclude early/septic DIC—it is an acute-phase reactant; serial change matters TTP/HUS usually has normal PT/APTT; severe liver disease can mimic DIC but requires the full clinical context

References

^[1] Senior notes: Ryan Ho Haemtology.pdf — DIC section, pp.136–138 ^[2] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — DIC overview and treatment, p.1335 ^[3] Lecture slides: GC 027. Abnormal bleeding after tooth extraction.pdf, p.27 (classic laboratory pattern and management priorities)

Disseminated Intravascular Coagulation (DIC)

Disseminated intravascular coagulation (DIC) is a systemic thrombohemorrhagic disorder that is always secondary to an underlying condition. Let's break the name down:

Disseminated = widespread, throughout the body
Intravascular = within the blood vessels
Coagulation = clotting

So DIC literally means "widespread clotting happening inside blood vessels throughout the body." The paradox of DIC is that this uncontrolled activation of coagulation leads to both thrombosis AND bleeding — you clot so much that you run out of clotting factors and platelets, and then you bleed.

"DIC is a systemic process with potential for causing thrombosis and hemorrhage. The processes of coagulation and fibrinolysis become abnormally and massively activated within the vasculature leading to ongoing coagulation and fibrinolysis." ^[1]^[2]

Core Concept — The DIC Paradox

DIC is not a disease itself — it is always a secondary phenomenon triggered by an underlying condition. The key paradox: excessive clotting → consumption of clotting factors and platelets → bleeding. You must always find and treat the underlying cause.

2. Epidemiology and Risk Factors

DIC occurs in approximately 1% of all hospitalized patients but is far more common in critically ill ICU populations (up to 30–50% of severe sepsis patients develop some degree of DIC)
Mortality is high: 40–80% depending on severity and underlying cause, largely driven by the precipitating condition and degree of organ dysfunction
In Hong Kong, the most clinically relevant triggers include:
- Sepsis (most common cause overall, including gram-negative bacteraemia which remains prevalent in HK hospital settings)
- Obstetric emergencies (amniotic fluid embolism, placental abruption, eclampsia/HELLP — relevant given HK's obstetric tertiary centres)
- Acute promyelocytic leukaemia (APL / AML-M3) — a haematological emergency where DIC is the presenting feature; HK has a relatively higher incidence of leukaemia compared with some Western populations
- Malignancy — particularly mucinous adenocarcinomas (pancreas, stomach, ovary) which are common in the East Asian population
- Trauma / major surgery / burns

Severe sepsis / septic shock (especially gram-negative organisms releasing endotoxin)
Major trauma, extensive burns, crush injuries
Obstetric complications
Haematological malignancies (especially APL)
Solid organ malignancies (especially mucinous tumours)
Massive transfusion / ABO-incompatible transfusion
Snake envenomation (relevant in rural HK and Southeast Asia — pit viper bites)
Vascular abnormalities (giant haemangiomas — Kasabach-Merritt phenomenon)
Liver failure (impaired clearance of activated clotting factors)

3. Relevant Anatomy and Physiology — Normal Haemostasis

To understand DIC, you must first understand normal haemostasis. Think of it as a carefully balanced system with three main components:

Vascular injury → exposure of subendothelial collagen
Platelet adhesion: Platelets bind to exposed collagen via von Willebrand factor (vWF) acting as a bridge between platelet GPIb receptors and collagen
Platelet activation: Platelets change shape, release granule contents (ADP, thromboxane A2, serotonin) → recruit more platelets
Platelet aggregation: Activated platelets cross-link via fibrinogen binding to GPIIb/IIIa receptors → forms a platelet plug

The coagulation cascade amplifies and stabilizes the platelet plug by generating fibrin.

Extrinsic pathway (measured by PT/INR):
- Triggered by tissue factor (TF, Factor III) released from damaged cells → activates Factor VII → forms TF-VIIa complex → activates Factor X
- Factor VII has the shortest half-life (~6 hours) of all coagulation factors — this is why PT rises first in DIC ^[3]
Intrinsic pathway (measured by aPTT):
- Contact activation: Factor XII → XI → IX → (with Factor VIII as cofactor) → activates Factor X
- In early DIC, Factor VIII (an acute phase reactant) is initially elevated, which buffers the intrinsic pathway, allowing aPTT to remain relatively preserved initially ^[3]
Common pathway: Factor Xa + Factor Va (prothrombinase complex) → converts prothrombin (II) → thrombin (IIa) → converts fibrinogen (I) → fibrin (Ia) → stabilized by Factor XIIIa (cross-linking)

Plasminogen → converted to plasmin by tissue plasminogen activator (tPA)
Plasmin breaks down fibrin → produces fibrin degradation products (FDPs), including D-dimer (specific for cross-linked fibrin degradation)
FDPs themselves are anticoagulant — they interfere with fibrin polymerization and platelet function, worsening the bleeding tendency

Antithrombin (AT): inactivates thrombin and Factor Xa (enhanced 1000× by heparin)
Protein C / Protein S system: activated protein C (with cofactor protein S) inactivates Factors Va and VIIIa
Tissue factor pathway inhibitor (TFPI): inhibits TF-VIIa complex

Why This Matters for DIC

In DIC, there is overwhelming activation of coagulation that exhausts the natural anticoagulant mechanisms (AT, protein C/S are consumed). The system spirals out of control — like a fire burning through all the fire extinguishers.

4. Aetiology (with Focus on Hong Kong)

Aetiology mnemonic "OMIT HSR": Obstetrics, Malignancy, Infections, Trauma, Haemolytic transfusion reaction / Snake bite / Hypersensitivity reactions ^[4]

Category	Mechanism	Examples
O — Obstetric	Release of placental/amniotic materials into maternal circulation → potent procoagulant effect	Amniotic fluid embolism, placental abruption, eclampsia/HELLP syndrome, septic abortion ^[5]
M — Malignancy	Release of procoagulant factors (e.g., tissue factor) from tumour cells ^[5]	APL (AML-M3), mucinous tumours (CA pancreas, stomach, ovaries), brain tumours ^[5]
I — Infections	Microbial toxins → endothelial damage and release of procoagulant factors ^[5]	Septicaemia of any cause (especially gram-negative), severe viral infections (e.g., dengue), meningococcaemia ^[5]
T — Trauma	Widespread endothelial damage ^[5]	Extensive trauma/burns, crush injury, severe head injury, fat embolism ^[5]
H — Haemolytic / Hypersensitivity	Immune activation → activation of coagulation cascade ^[5]	Intravascular haemolysis (severe malaria, ABO haemolytic transfusion reaction, PNH), acute solid organ transplant rejection ^[5]
S — Snake bite	Venom contains procoagulant enzymes	Snake/viper venoms ^[5]
R — Rare/Others	Various	Kasabach-Merritt phenomenon (giant haemangioma), AAA, catastrophic antiphospholipid syndrome, fulminant hepatic failure ^[5]

Sepsis remains the most common trigger in HK ICU settings — gram-negative bacteraemia (E. coli, Klebsiella) particularly common
Hepatitis B-related hepatocellular carcinoma — HK has a high HBV carrier rate (~7–8% of population); HCC can cause DIC through tissue factor release
Nasopharyngeal carcinoma (NPC) — endemic in Southern China/HK; advanced NPC can rarely trigger DIC
APL — recognized haematological emergency; HKU Queen Mary Hospital is a major treatment centre
Dengue fever — increasingly reported in HK with imported and locally acquired cases; severe dengue can trigger DIC
Pit viper bites — reported in rural New Territories areas; venom-induced consumptive coagulopathy

In APL, bleeding symptoms are "out of proportion to the platelet amounts" — this is because APL cells release tissue factor (Factor III, the initiator of the extrinsic pathway), directly triggering the extrinsic pathway and causing DIC ^[3]^[6]

APL is characterized by t(15;17)(q22;q21) resulting in PML-RARA fusion protein ^[6]
APL typically presents with pancytopenia rather than high WBC ^[6]
Investigations for suspected APL-associated DIC: Platelet count, PT, aPTT, D-dimer, Fibrinogen ^[6]
Gold standard for APL diagnosis: Cytogenetics ^[6]

5. Pathophysiology

This is the crux of understanding DIC. Think of it as a chain of dominoes:

Excessive activation of coagulation cascade, leading to three processes that characterize DIC:

"Too much thrombin → too much formation of fibrin → these fibrin clots block blood vessels" → organ ischaemia

"Excessive consumption of coagulation factors → no more coagulation factors → bleeding tendency"

"Excess fibrin clots in circulation will trap and over-consume platelets → thrombocytopenia"

"These fibrin clots line the blood vessels and will shear RBCs that are passing through → microangiopathic haemolytic anaemia (MAHA)" ^[3]

This is a commonly tested concept:

The trigger (e.g., tissue factor from APL cells or damaged endothelium) initiates the extrinsic pathway first
Factor VII has the shortest half-life of all coagulation factors (~6 hours) → it is consumed/depleted first → PT rises first ^[3]
Factor VIII is an acute phase reactant → in the acute phase, Factor VIII levels are actually increased → this buffers the intrinsic pathway → aPTT stays relatively preserved initially ^[3]
If left untreated over a longer period, all clotting factors will eventually be used up, causing a rise in aPTT as well ^[3]

Fibrinogen (Factor I) is consumed in two ways:
1. Converted to fibrin by excess thrombin (consumed in clot formation)
2. Degraded by plasmin during secondary fibrinolysis
However, fibrinogen is also an acute phase reactant — in chronic/early DIC, the liver may increase production enough to keep levels normal or even elevated

Antithrombin is consumed by binding excess thrombin → AT levels fall → less ability to control thrombin → vicious cycle
Protein C and S are consumed → loss of physiological anticoagulant → further thrombosis
Severe protein C depletion → purpura fulminans (extensive skin necrosis due to microvascular thrombosis in dermal vessels) — this is the same mechanism as warfarin-induced skin necrosis ^[4]

DIC involves predominantly coagulation cascade activation (fibrin-rich thrombi with RBCs), while TMA (e.g., TTP, HUS) involves predominantly platelet-rich thrombi with vWF. However, both cause MAHA and can overlap clinically. ^[5]

Feature	DIC	TTP/HUS (TMA)
Primary defect	Coagulation cascade activation	Platelet/vWF-mediated microthrombi
Thrombus composition	Fibrin + RBCs	Platelets + vWF
PT/aPTT	Prolonged	Usually normal
Fibrinogen	Low	Usually normal
D-dimer	Markedly elevated	Mildly elevated
ADAMTS13	Normal	Severely deficient in TTP

6. Classification

These represent two ends of the same spectrum:

Feature	Acute (Decompensated) DIC	Chronic (Compensated) DIC
Pathology	Predominant coagulation factor/platelet consumption with disruption of normal clotting due to fibrin degradation products	Predominant activation of coagulation cascade as production of procoagulant factors keeps pace with ongoing thrombosis
Setting	Recent Hx of trauma, sepsis, malignancy (APL), or ABO-incompatible blood transfusion	Malignancy esp. CA pancreas, stomach, ovaries, brain
Clinical features	Predominated by BLEEDING: Bleeding (64%, esp. from sites of trauma, catheter, drains), Renal dysfunction (25%), Hepatic dysfunction (19%), Respiratory dysfunction (16%), Shock (14%)	Predominated by unprovoked arteriovenous thromboembolism: Unprovoked VTE, Unprovoked arterial thrombosis
Platelet count	Reduced	Variable (normal or mildly reduced)
Clotting times	↑PT, ↑aPTT, ↑TT	Normal PT/aPTT, normal to slightly prolonged TT
Plasma fibrinogen	Reduced	Normal or elevated
D-dimer	Elevated	Elevated (often markedly)

Why the Difference?

In acute DIC, the trigger is sudden and overwhelming — the liver and bone marrow cannot produce clotting factors and platelets fast enough to replace what is consumed → decompensation → bleeding predominates.

In chronic DIC, the stimulus is low-grade and ongoing (e.g., a slow-growing tumour continuously releasing small amounts of tissue factor). The liver can compensate by increasing factor production, and the bone marrow can ramp up platelet production → clotting factors keep pace → thrombosis predominates because the procoagulant state is maintained without running out of substrate.

Overt DIC: Clinically evident bleeding and/or thrombosis with clear laboratory derangement — corresponds roughly to acute/decompensated DIC
Non-overt DIC: Subclinical activation of coagulation without overt clinical manifestations — requires serial monitoring; may progress to overt DIC if the underlying cause is not addressed

7. Clinical Features

Symptom	Pathophysiological Basis
Bleeding from multiple sites simultaneously (wounds, venipuncture sites, catheter sites, drains)	Consumption of clotting factors + platelets + anticoagulant effect of FDPs → loss of haemostatic capacity → oozing from any site of vascular disruption
Mucosal bleeding (epistaxis, gingival bleeding, GI bleeding, haematuria)	Platelet consumption (thrombocytopenia) → failure of primary haemostasis at mucosal surfaces which are naturally high-flow and prone to minor trauma
Bruising / petechiae / purpura appearing spontaneously	Thrombocytopenia + capillary fragility from microvascular damage → spontaneous extravasation of blood into skin
Haematuria	Renal microvascular thrombosis + consumption coagulopathy → bleeding into urinary tract
Dyspnoea / respiratory distress	Pulmonary microvascular thrombosis → V/Q mismatch + potential ARDS; also pulmonary haemorrhage from coagulopathy
Confusion / altered mental status	Cerebral microvascular thrombosis → ischaemia of brain parenchyma; also potential intracranial haemorrhage
Oliguria / anuria	Renal microvascular thrombosis → ischaemic acute tubular necrosis (ATN) → acute kidney injury ^[7]
Abdominal pain	Mesenteric/hepatic microvascular thrombosis → ischaemia of abdominal organs
Jaundice	Hepatic microvascular thrombosis + haemolysis (MAHA) → increased bilirubin production + impaired hepatic clearance
Symptoms of the underlying cause	e.g., fever/rigors (sepsis), obstetric pain (abruption), bone pain (malignancy)

Sign	Pathophysiological Basis
Petechiae (pinpoint, non-blanching)	Thrombocytopenia → capillary bleeding; < 2mm by definition
Purpura (larger non-blanching patches)	More severe thrombocytopenia + vascular damage
Purpura fulminans	Severe protein C depletion → extensive microvascular thrombosis in dermal vessels → large areas of haemorrhagic skin necrosis, typically on extremities and buttocks ^[4] — characteristically starts as painful red areas that rapidly become purplish-black
Ecchymoses (bruises) at sites of venipuncture, IV lines, surgical wounds	Consumption coagulopathy → inability to form stable clots at sites of iatrogenic trauma
Oozing from wounds, drain sites, catheter sites	Bleeding (64%), especially from sites of trauma, catheter, drains — classic presentation of acute DIC ^[4]^[5]
Acral cyanosis / gangrene (fingers, toes, ears, nose)	Microvascular thrombosis in end-arteries → digital ischaemia → necrosis
Hepatomegaly / jaundice	Hepatic microvascular thrombosis + haemolysis → hepatic congestion and dysfunction
Signs of shock (tachycardia, hypotension, cold peripheries)	Hypovolaemia from bleeding + vasodilation from sepsis/systemic inflammation → circulatory failure
Signs of multi-organ dysfunction	Microvascular thrombosis → ischaemia of kidneys (oliguria), lungs (ARDS/crackles), brain (confusion/coma), liver (jaundice/coagulopathy worsening)
Schistocytes on peripheral blood smear	Fibrin strands deposited in the microvasculature physically shear RBCs as they pass through → fragmented RBCs (schistocytes) = hallmark of MAHA ^[3]^[5]
Signs of underlying cause	e.g., fever/septic foci (sepsis), tense/tender uterus (placental abruption), lymphadenopathy/splenomegaly (malignancy)

DIC produces a mixed pattern because both platelets and coagulation factors are consumed:

"Coagulation defects generally cause deeper-seated bleeding — but remember that both platelet and coagulation disorders can cause intracranial haemorrhages, so you cannot say one is more deadly than the other." ^[8]

Feature	Platelet-Type Bleeding	Coagulation-Type Bleeding
Onset after injury	Immediate	Delayed (hours)
Type	Petechiae, purpura, mucosal (epistaxis, gingival, GI, GU)	Deep tissue (haemarthrosis, muscle haematoma, retroperitoneal)
Severity	Often superficial	Often deep-seated, potentially life-threatening

In DIC, you typically see both patterns simultaneously — this clinical finding of concurrent superficial mucosal bleeding AND deep tissue bleeding/organ dysfunction should immediately raise the suspicion of DIC.

The organ dysfunction is caused by microvascular thrombosis leading to ischaemia:

Organ	Manifestation	Frequency in Acute DIC
Kidneys	Acute kidney injury (oliguria, rising creatinine) — ischaemic ATN from microvascular thrombosis ^[7]	~25% ^[4]
Liver	Hepatic dysfunction (rising transaminases, jaundice, worsening synthetic function)	~19% ^[4]
Lungs	ARDS, pulmonary haemorrhage, respiratory failure	~16% ^[4]
Brain	Confusion, seizures, focal neurological deficits, coma	Variable
Skin	Purpura fulminans, acral ischaemia/gangrene	Variable
Adrenal glands	Adrenal haemorrhage → acute adrenal crisis (Waterhouse-Friderichsen syndrome — classically in meningococcal sepsis)	Rare but devastating

The laboratory picture in DIC is so characteristic that it essentially forms part of the clinical presentation:

"Features of DIC: classically 'full house' clotting parameters, but seldom all present" ^[4]^[5]:

Thrombocytopenia: typically mild/moderate reduction, seldom < 20 × 10⁹/L

Features of MAHA: anaemia, features of intravascular haemolysis, schistocytes on PBS

Evidence of consumed coagulation factors: ↑PT, ↑aPTT, ↑TT, ↓fibrinogen

↑Fibrin degradation products: ↑D-dimer

Clinical situation four: Prolonged PT & APTT → Repeat and confirm → Measure fibrinogen concentration → Measure platelet concentration → "disseminated intravascular coagulopathy" → ↑PT, ↑APTT, ↓fibrinogen, ↓platelets, Red blood cell fragmentation ^[9]

High Yield — GC Lecture Point

"DIC with all these components [↑PT, ↑APTT, ↓fibrinogen, ↓platelets, RBC fragmentation] is a very uncommon clinical situation" — meaning the full-house picture with every single parameter deranged simultaneously is uncommon; partial presentations are more typical. "Treatment of DIC is to replenish the consumed coagulation factors" and "Reverse the underlying causative factor." ^[9]

This is directly from the GC 027 lecture slide — expect this exact framing in the in-house exam.

In chronic (compensated) DIC, the clinical picture is dominated by thrombosis rather than bleeding:

Unprovoked venous thromboembolism (DVT, PE) ^[4]^[5]
Unprovoked arterial thrombosis (stroke, limb ischaemia) ^[4]^[5]
Trousseau syndrome (migratory superficial thrombophlebitis — classically associated with pancreatic cancer)
Non-bacterial thrombotic endocarditis (Libman-Sacks-like vegetations → embolic events)
Laboratory findings may be subtle: D-dimer elevated but platelet count and clotting times may be normal or only mildly deranged

Pathophysiology	→	Clinical Feature
Thrombin generation → fibrin deposition in microvasculature	→	Organ ischaemia, multi-organ failure
Fibrin strands shearing RBCs	→	MAHA with schistocytes, anaemia
Consumption of clotting factors	→	↑PT, ↑aPTT, bleeding tendency
Consumption of platelets	→	Thrombocytopenia, petechiae, mucosal bleeding
Secondary fibrinolysis (plasmin activation)	→	↑D-dimer, ↑FDPs (which further inhibit clotting)
Consumption of fibrinogen	→	↓Fibrinogen, impaired fibrin formation
Depletion of natural anticoagulants (AT, Protein C/S)	→	Purpura fulminans, worsening thrombosis
FDPs interfering with platelet function + fibrin polymerization	→	Worsened bleeding tendency beyond what platelet count alone would predict

High Yield Summary

DIC — Key Points for Exam:

Definition: Always secondary. Systemic activation of coagulation → simultaneous thrombosis AND bleeding
Causes — OMIT HSR: Obstetric, Malignancy (APL, mucinous tumours), Infections (sepsis), Trauma, Haemolytic transfusion/Snake bite/Hypersensitivity
Pathophysiology triad: (i) Microvascular thrombosis → organ failure, (ii) Consumption of clotting factors/platelets → bleeding, (iii) Secondary fibrinolysis → ↑FDPs/D-dimer which worsen bleeding
Why PT rises before aPTT: Factor VII (extrinsic pathway) has shortest half-life + Factor VIII (intrinsic pathway) is an acute phase reactant that is initially elevated
Full-house labs: ↓Platelets, ↑PT, ↑aPTT, ↓Fibrinogen, ↑D-dimer, Schistocytes on PBS — but seldom ALL present simultaneously
Acute DIC = bleeding predominates (consumption > production); Chronic DIC = thrombosis predominates (production keeps pace)
MAHA mechanism: Fibrin strands in microvasculature physically shear RBCs → schistocytes
Purpura fulminans: Due to severe protein C depletion → microvascular thrombosis in skin
Treatment cornerstone: Treat the underlying cause + replenish consumed components
APL-DIC: APL cells release tissue factor → extrinsic pathway activation; bleeding out of proportion to platelet count; confirm with cytogenetics showing t(15;17)

Active Recall - Disseminated Intravascular Coagulation (DIC)

^[1] MBBS Final MB (Surgery) (Felix PY Lai).pdf — Disseminated intravascular coagulopathy section, p.43 ^[2] MBBS Final MB (Medicine) (Felix PY Lai).pdf — Disseminated intravascular coagulopathy section, p.1335 ^[3] Senior notes: Block A - Introduction to Haematological investigations (CBP, Clotting).pdf, p.19 ^[4] Senior notes: Maksim Medicine Notes.pdf — Haematology section, p.165 ^[5] Senior notes: Ryan Ho Haemtology.pdf — DIC section, pp.136–138 ^[6] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf, p.19 ^[7] Senior notes: Block A - Nephrotology Teaching Clinic RTD.pdf — ATN section, p.7 ^[8] Senior notes: Block A - Abnormal bleeding after tooth extraction_ bleeding tendency; thrombocytopenia.pdf, p.8 ^[9] Lecture slides: GC 027. Abnormal bleeding after tooth extraction.pdf, p.27

Differential Diagnosis of Disseminated Intravascular Coagulation (DIC)

DIC never exists in isolation — it is always secondary to something. But equally important, the clinical picture of DIC (bleeding + thrombocytopenia + deranged clotting + MAHA) overlaps with several other serious conditions. Getting the differential wrong can be fatal: treating presumed DIC when the patient actually has TTP (and needs plasma exchange, not FFP replacement) is a classic lethal error.

The differential diagnosis operates on two levels:

Conditions that mimic or overlap with DIC — i.e., "the patient looks like they have DIC, but could it be something else?"
Underlying causes of DIC — i.e., "we've confirmed DIC, now what triggered it?" (covered in Part 1 under aetiology; briefly cross-referenced here)

9.1 Conditions That Mimic or Overlap with DIC

The unifying clinical thread in all these differentials is some combination of thrombocytopenia, MAHA (schistocytes), bleeding, organ dysfunction, and/or deranged coagulation studies. The challenge is distinguishing which of these is primarily driving the picture.

MAHA: non-immune haemolysis due to intravascular RBC fragmentation. Causes: TMA (due to microvascular thrombosis), prosthetic heart valve, LVAD, DIC ^[5]

Thrombotic microangiopathy (TMA): pathological diagnosis of abnormalities in vessel wall of arterioles/capillaries leading to microvascular thrombosis. Primary TMA: TTP, HUS, drug-induced TMA, complement-mediated TMA. Secondary TMA: HELLP syndrome, malignant HTN, SLE, scleroderma, antiphospholipid syndrome ^[5]

DIC: intravascular activation of coagulation with loss of localization due to systemic cause — usually associated with MAHA and microvascular thrombosis predominantly RBCs/fibrin instead of platelets and vWF in TMA (predominantly coagulation cascade activation over platelet activation) ^[5]

This is the crucial conceptual distinction: DIC = primarily coagulation cascade activation (fibrin-rich thrombi), while TMA (TTP/HUS) = primarily platelet/vWF-mediated (platelet-rich thrombi). This difference explains the laboratory divergence.

Condition	Core Mechanism	PT/aPTT	Fibrinogen	D-dimer	Platelet Count	Schistocytes	Distinguishing Feature
DIC (acute)	Coagulation cascade activation → fibrin-rich microthrombi → consumption	↑PT, ↑aPTT	↓↓	↑↑↑	↓	Yes	Full-house clotting derangement + identifiable trigger ^[5]^[9]
TTP	ADAMTS13 deficiency → unprocessed ultra-large vWF multimers → platelet-rich microthrombi	Normal	Normal	Mildly ↑	↓↓↓ (often < 30)	Yes	Clotting profile should be NORMAL except in severe organ ischaemia causing DIC ^[10]; ADAMTS13 activity < 10%; classic pentad: fever, MAHA, thrombocytopenia, renal impairment, neurological features
HUS (typical)	Shiga toxin → endothelial damage → platelet-rich microthrombi, predominantly renal	Normal	Normal	Mildly ↑	↓	Yes	Diarrhoea prodrome (bloody); renal failure predominant; usually children; stool culture for STEC
aHUS (atypical)	Complement dysregulation → uncontrolled complement activation on endothelium	Normal	Normal	Mildly ↑	↓	Yes	No diarrhoea prodrome; complement pathway abnormalities; may have family history
HELLP syndrome	Endothelial dysfunction in pregnancy → secondary TMA	Variable (may be mildly ↑)	Variable	↑	↓	Yes	Pregnant patient (usually 3rd trimester); haemolysis, elevated liver enzymes, low platelets; may overlap with DIC
Severe liver disease	Impaired synthesis of clotting factors + impaired clearance of FDPs + portal hypertension → splenic sequestration of platelets	↑PT, ↑aPTT	↓ (impaired synthesis)	↑ (impaired clearance)	↓ (mild, due to hypersplenism)	Usually absent	Clinical signs of chronic liver disease; Factor VIII is normal or elevated (since VIII is synthesized by endothelium, not hepatocytes) — this distinguishes liver failure from DIC where Factor VIII is consumed
Heparin-induced thrombocytopenia (HIT)	Anti-PF4/heparin antibodies → platelet activation → thrombosis	Usually normal	Normal	↑	↓ (typically 50% drop from baseline)	Usually absent	Timing: 5–14 days after heparin exposure; thrombosis predominates; 4T score
ITP	Anti-platelet antibodies → peripheral platelet destruction	Normal	Normal	Normal	↓↓↓	Absent	Isolated thrombocytopenia; no coagulation derangement; no MAHA ^[10]^[11]
Antiphospholipid syndrome (APS)	Autoantibodies against phospholipid-binding proteins → thrombosis + pregnancy morbidity	aPTT may be ↑ (lupus anticoagulant)	Normal	↑ if acute thrombosis	↓ (mild)	Usually absent (unless catastrophic APS)	Recurrent arterial and venous thrombosis, livedo reticularis, recurrent fetal loss, thrombocytopenia; positive aCL, anti-β2GPI, or lupus anticoagulant on 2 occasions ≥ 12 weeks apart ^[12]
Vitamin K deficiency / Warfarin	Impaired synthesis of Factors II, VII, IX, X	↑PT (predominantly)	Normal	Normal	Normal	Absent	Warfarin causes ↑PT → extrinsic pathway factors II, VII, IX, X are vitamin K-dependent; Factor VII has shortest half-life so PT rises first ^[13]
Catastrophic APS	Acute, massive multi-organ thrombosis from antiphospholipid antibodies	May be ↑	May be ↓	↑↑	↓	May be present	Overlaps significantly with DIC; differentiate by positive aPL antibodies + biopsy showing small vessel thrombosis without vasculitis

Critical Distinction — DIC vs TTP

The single most important differential to get right is DIC vs TTP, because the management is diametrically opposite:

DIC: Treat the underlying cause + replace consumed factors (FFP, cryoprecipitate, platelets)
TTP: Urgent plasma exchange (PEX) — platelet transfusion is contraindicated in TTP as it fuels the microvascular thrombosis and can be fatal

The key laboratory discriminator: in TTP, PT and aPTT are normal and fibrinogen is normal (because the coagulation cascade is not primarily activated; it's a platelet/vWF problem). In DIC, you see the full-house derangement: ↑PT, ↑aPTT, ↓fibrinogen, ↓platelets, ↑D-dimer, schistocytes ^[5]^[9].

When DIC presents primarily with thrombocytopenia, the differential includes all causes of low platelets:

All causes of increased platelet consumption: Hypersplenism, Disseminated intravascular coagulation (DIC), Thrombotic thrombocytopenic purpura (TTP) ^[10]

All causes of bone marrow failure: Acute leukemia, Aplastic anemia, Myelodysplastic syndrome (MDS), Bone marrow infiltration by neoplastic disease ^[10]

Structured as a framework ^[11]:

A. Decreased Production (Bone Marrow Failure)

Acute leukaemia (especially APL — look for circulating promyelocytes) ^[14]
Aplastic anaemia
Myelodysplastic syndrome (MDS)
Bone marrow infiltration (metastatic carcinoma, lymphoma, myelofibrosis)
Chemotherapy/radiotherapy
B12/folate deficiency (megaloblastic anaemia)

B. Increased Destruction — Immune

Immune thrombocytopenia (ITP) ^[10]^[11]
Systemic lupus erythematosus (SLE) ^[11]
Drug-induced thrombocytopenia (ibuprofen, ampicillin, heparin → HIT) ^[11]

C. Increased Destruction — Non-Immune

Thrombotic thrombocytopenic purpura (TTP) ^[11]
Haemolytic uraemic syndrome (HUS) ^[11]
Disseminated intravascular coagulopathy (DIC) ^[11]
Hypersplenism ^[10]^[11]

D. Qualitative Platelet Disorders (Bleeding with Normal Platelet Count)

Liver disease, Uraemia, Drug-induced (aspirin/COX inhibitors, clopidogrel/ADP antagonists, GPIIb/IIIa inhibitors) ^[11]
Essential thrombocythaemia with acquired von Willebrand disease (paradoxical bleeding from extremely high platelets consuming vWF) ^[15]

When DIC presents primarily with deranged clotting, the differential for simultaneous prolongation of both PT and aPTT is:

Approach to prolonged PT + aPTT: Repeat and confirm → Consider DIC → take fibrinogen, D-dimer, platelet + look for underlying cause ^[13]

Prolonged PT and aPTT: Disseminated intravascular coagulopathy (DIC), Factor X and fibrinogen deficiency (rare) ^[13]

Cause of Both ↑PT + ↑aPTT	Mechanism	Key Distinguishing Features
DIC	Consumption of all factors	↓Fibrinogen, ↓Platelets, ↑D-dimer, schistocytes, identifiable trigger ^[9]^[13]
Severe liver disease	Impaired factor synthesis by hepatocytes	Signs of chronic liver disease; Factor VIII preserved/elevated (VIII is made by endothelium); mild thrombocytopenia from hypersplenism
Massive transfusion / dilutional coagulopathy	Dilution of clotting factors by large volume resuscitation	Clinical context: massive haemorrhage/surgery with > 1 blood volume replaced in 24h
Vitamin K deficiency (severe)	Loss of Factors II, VII, IX, X + Protein C/S	↑PT first (VII shortest half-life); malabsorption, obstructive jaundice, prolonged antibiotics
Supratherapeutic anticoagulation	Warfarin (↑PT > aPTT) or Heparin (↑aPTT > PT); DOACs can affect both	Drug history; mixing study corrects for factor deficiency but not for inhibitors
Combined factor deficiency (rare)	Inherited deficiency of Factor X, Factor V, or fibrinogen	Family history; rare; isolated lab finding without MAHA

GC Lecture High Yield — Clinical Situation Four

"Clinical situation four: Prolonged PT & APTT → 1. Repeat and confirm → 2. Measure fibrinogen concentration → 3. Measure platelet concentration → 4. 'disseminated intravascular coagulopathy' → ↑PT, ↑APTT, ↓fibrinogen, ↓platelets, Red blood cell fragmentation → 5. DIC with all these components is a very uncommon clinical situation → 6. Treatment of DIC is to replenish the consumed coagulation factors → 7. Reverse the underlying causative factor" ^[9]

This is exactly how DIC should be approached when you encounter both PT and aPTT prolonged on a clotting profile. The GC lecture explicitly tells you to check fibrinogen and platelets next, and that the "full-house" picture is uncommon.

Schistocytes on peripheral blood smear mean mechanical RBC fragmentation is occurring. The causes include ^[5]:

Category	Condition	Why Schistocytes?
DIC	Fibrin strands in microvasculature shear RBCs	Fibrin-rich thrombi
TMA	TTP, HUS, aHUS	Platelet/vWF-rich thrombi in arterioles/capillaries
Secondary TMA	HELLP, malignant HTN, SLE, scleroderma, APS	Endothelial damage → microthrombi
Mechanical	Prosthetic heart valve, LVAD ^[5]	Turbulent flow across prosthesis physically fragments RBCs
March haemoglobinuria	Repetitive physical trauma (e.g., long-distance running)	Mechanical destruction in foot capillaries — very rare

This comes up frequently in exams because liver disease can produce a laboratory picture that superficially resembles DIC (↑PT, ↑aPTT, ↓fibrinogen, ↓platelets, ↑D-dimer). The distinction:

Feature	DIC	Severe Liver Disease
Factor VIII level	↓↓ (consumed in widespread coagulation)	Normal or ↑ (Factor VIII is synthesized by sinusoidal endothelial cells, not hepatocytes — so liver failure doesn't impair its production; it's also an acute phase reactant)
Schistocytes	Present (MAHA)	Usually absent
D-dimer	Markedly ↑ (active fibrinolysis)	Mildly ↑ (impaired hepatic clearance of FDPs)
Thrombocytopenia mechanism	Consumption by microvascular thrombi	Splenic sequestration (portal hypertension → splenomegaly → hypersplenism)
Clinical context	Acute trigger (sepsis, trauma, obstetric emergency)	Chronic liver disease stigmata (spider naevi, palmar erythema, ascites, caput medusae)

High Yield Distinction

Factor VIII is the key discriminator: it is low in DIC (consumed) but normal/high in liver disease (made by endothelium, not hepatocytes, and is an acute phase reactant). If you remember only one distinguishing test, remember Factor VIII.

When chronic (compensated) DIC presents with thrombosis rather than bleeding, the differential includes:

Antiphospholipid syndrome (APS): Recurrent arterial and venous thrombosis, livedo reticularis, recurrent fetal loss, thrombocytopenia ^[12] — distinguished by positive aPL antibodies on two occasions ≥ 12 weeks apart
Myeloproliferative neoplasm (MPN)-associated thrombosis: JAK2 mutation positive → particularly polycythaemia vera and essential thrombocythaemia; can cause thrombosis in unusual sites (e.g., mesenteric vein) ^[15] — screen with JAK2 mutation, CBC showing erythrocytosis/thrombocytosis
Inherited thrombophilias: Factor V Leiden, prothrombin G20210A, protein C/S deficiency, antithrombin deficiency — thrombophilia screening indicated in young patients with idiopathic VTE, unusual site thrombosis, recurrent VTE, warfarin-induced skin necrosis ^[4]
Occult malignancy (Trousseau syndrome): Migratory superficial thrombophlebitis, unprovoked VTE in older patients — screen with CT, tumour markers as appropriate
Heparin-induced thrombocytopenia (HIT): Temporal relationship with heparin exposure; 4T score

"What are the useful investigations for the purpose of exclusion of disseminated intravascular coagulation (DIC)? → Peripheral blood film: Fragmented red cell → Clotting profile: ↑PT and APTT, ↑D-dimer, ↓Fibrinogen level" ^[10]

When a patient presents with bleeding and thrombocytopenia (e.g., suspected ITP), you must exclude DIC before concluding ITP. The investigations to rule out DIC are:

PBS — look for schistocytes (absent in ITP)
PT and aPTT — normal in ITP; prolonged in DIC
D-dimer — normal in ITP; elevated in DIC
Fibrinogen — normal in ITP; low in DIC

If all four are normal, DIC is effectively excluded and you can proceed with the ITP diagnostic pathway.

Ask three sequential questions:

Is this truly DIC? → Check for the full-house picture (↑PT, ↑aPTT, ↓fibrinogen, ↓platelets, ↑D-dimer, schistocytes). If coagulation is normal, think TTP/HUS/ITP instead.
If it's DIC, what triggered it? → Use the OMIT HSR mnemonic to systematically search for the underlying cause. The cause is usually clinically apparent.
If it's not DIC, what else could cause this clinical picture? → Use the framework above: TTP (check ADAMTS13), HUS (diarrhoea prodrome + renal failure), HELLP (pregnancy + liver enzymes), liver disease (Factor VIII normal, chronic liver stigmata), APS (antibody testing), drug effect.

High Yield Summary — DDx of DIC

DIC vs TTP: The most critical distinction. Normal PT/aPTT and fibrinogen in TTP vs deranged in DIC. ADAMTS13 < 10% confirms TTP. Platelet transfusion contraindicated in TTP.
DIC vs Liver Disease: Factor VIII is the key — low in DIC (consumed), normal/high in liver disease (made by endothelium). Schistocytes present in DIC, absent in liver disease.
Full-house DIC picture (↑PT, ↑aPTT, ↓fibrinogen, ↓platelets, ↑D-dimer, schistocytes) is uncommon — partial presentations are more typical.
To exclude DIC when evaluating thrombocytopenia: check PBS for schistocytes, PT, aPTT, D-dimer, fibrinogen.
Both PT+aPTT prolonged: Think DIC first, then liver disease, massive transfusion, vitamin K deficiency, or anticoagulant effect.
Chronic DIC (thrombosis-predominant): DDx includes APS, MPN-associated thrombosis, inherited thrombophilia, HIT, occult malignancy.

Active Recall - Differential Diagnosis of DIC

References

^[4] Senior notes: Maksim Medicine Notes.pdf — Haematology section, p.165 ^[5] Senior notes: Ryan Ho Haemtology.pdf — DIC section, pp.136–138 ^[9] Lecture slides: GC 027. Abnormal bleeding after tooth extraction.pdf, p.27 ^[10] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — Case study, p.613; TTP diagnosis, p.618 ^[11] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — Differential diagnosis of purpura, p.699 ^[12] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf — Antiphospholipid syndrome, p.14 ^[13] Senior notes: Adrian Lui Pediatrics Notes.pdf — Causes of abnormal clotting profile, p.389 ^[14] Senior notes: Learning_Points_All_Lectures.txt — APL as haematological emergency ^[15] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf — MPN-associated thrombosis, p.18; Block A - Splenomegaly_ common causes of splenomegaly; myeloproliferative diseases.pdf — Essential thrombocythaemia, p.29

Diagnostic Criteria, Algorithm and Investigations for DIC

There is no single "gold standard" test for DIC. You cannot biopsy for it, you cannot image it, and no individual laboratory parameter is pathognomonic. Instead, DIC is diagnosed by integrating the clinical picture (a patient with a known precipitating condition showing signs of bleeding and/or thrombosis and/or organ dysfunction) with a constellation of laboratory abnormalities.

"DIC is a clinical + laboratory diagnosis" ^[5]^[16]

"Features of DIC: classically 'full house' clotting parameters, but seldom all present" ^[5]^[16]

This point cannot be overemphasised: the textbook "full-house" derangement (every single parameter abnormal simultaneously) is the exception, not the rule. Partial or evolving laboratory pictures are far more common, which is why a scoring system is used.

10.2 ISTH DIC Scoring System (Overt DIC)

The International Society on Thrombosis and Haemostasis (ISTH) scoring system for overt DIC is the most widely used diagnostic tool. It requires a two-step process:

Does the patient have an underlying condition known to be associated with DIC?
If YES → proceed to Step 2
If NO → do not use this scoring system (the score is only validated when a precipitating cause is present)

This makes sense from first principles: DIC is always secondary, so if there is no identifiable trigger, the diagnosis should be questioned and mimics (TTP, HUS, liver disease) considered more seriously.

Parameter	Score 0	Score 1	Score 2	Score 3
Platelet count (× 10⁹/L)	> 100	50–100	< 50	—
D-dimer / FDPs	No increase	Moderate increase	Strong increase	—
Prolongation of PT (seconds above upper limit of normal)	< 3s	3–6s	> 6s	—
Fibrinogen level (g/L)	> 1.0	—	≤ 1.0	—

Interpretation:

Score ≥ 5: Compatible with overt DIC → repeat scoring daily to monitor trajectory
Score < 5: Suggestive but not affirmative for non-overt (early/compensated) DIC → repeat in 1–2 days; serial monitoring is key

Why These Specific Parameters?

Each parameter reflects a different aspect of the DIC pathophysiology:

Platelet count → reflects consumption by microvascular thrombi
D-dimer → reflects fibrinolysis (breaking down the excessive fibrin being formed)
PT prolongation → reflects consumption of coagulation factors (especially Factor VII with the shortest half-life)
Fibrinogen → reflects consumption of the fibrin precursor (but is an acute phase reactant, so it may be deceptively normal early on — hence it is scored last and contributes less to the total)

The scoring system is designed to be serial and dynamic — a single snapshot may be inconclusive, but the trend over time is highly informative. A patient whose score rises from 3 to 6 over 24 hours is clearly developing overt DIC even if the initial score was below threshold.

Exam Pitfall — Fibrinogen as an Acute Phase Reactant

In sepsis (the most common trigger for DIC), fibrinogen levels may be paradoxically normal or even elevated because fibrinogen is an acute phase reactant — the liver ramps up production in response to inflammation. A "normal" fibrinogen in a septic patient does NOT exclude DIC. This is why fibrinogen only contributes 1 point to the ISTH score and only when it is very low (≤ 1.0 g/L). Serial measurement showing a falling trend is more useful than a single value.

10.4 Investigation Modalities — Detailed Breakdown

10.4.1 First-Line ("Core") Investigations

These are the investigations you order immediately when DIC is suspected. Think of them as answering four questions: Are platelets consumed? Are clotting factors consumed? Is fibrinolysis happening? Are RBCs being sheared?

Finding	Interpretation	Why?
Thrombocytopenia	Typically mild/moderate reduction, seldom < 20 × 10⁹/L ^[5]^[16]	Platelets trapped and consumed by microvascular fibrin thrombi. If platelet count is normal but falling rapidly on serial measurements, this is equally concerning.
Anaemia	Haemoglobin falling without obvious external bleeding	MAHA (intravascular haemolysis) + blood loss from coagulopathic bleeding. In critical care, serial Hb is more important than a single value ^[17].
WBC	Variable — may be high (sepsis/APL with leukocytosis) or low (APL with pancytopenia)	Reflects the underlying trigger rather than DIC itself. APL typically presents with pancytopenia rather than high WBC ^[6].

"Peripheral blood film: Fragmented red cell" — listed as a key investigation for DIC exclusion ^[10]^[18]

Finding	Interpretation	Why?
Schistocytes (fragmented RBCs)	Hallmark of MAHA — confirms mechanical RBC fragmentation	"These fibrin clots line the blood vessels and will shear RBCs that are passing through → microangiopathic haemolytic anaemia (MAHA)" ^[3]
Polychromasia	Reticulocytosis — bone marrow compensatory response to haemolysis	Reticulocytes are larger and stain blue-grey with Wright stain; their presence indicates marrow is attempting to replace destroyed RBCs
Nucleated RBCs	Severe marrow stress response	Very high demand for RBC production → immature nucleated forms released prematurely
Circulating promyelocytes / blasts	Suggestive of APL or acute leukaemia as the underlying cause	In APL, bleeding symptoms are out of proportion to the platelet amounts ^[6] — the PBS may show the diagnostic abnormal promyelocytes with Auer rods

The PBS is Non-Negotiable

Never diagnose DIC without examining the PBS. Schistocytes confirm the microangiopathic component and help distinguish DIC from simple liver disease or vitamin K deficiency (neither of which produce schistocytes). A PBS also helps identify the underlying cause (e.g., APL promyelocytes, malarial parasites, severe sepsis with toxic granulation/Dohle bodies in neutrophils).

"Clotting profile generally will have 4 main parameters: PT, APTT, Fibrinogen, D-dimer" ^[3]

Test	Expected Finding in Acute DIC	Expected Finding in Chronic DIC	Interpretation
Prothrombin Time (PT)	↑ (prolonged)	Normal or mildly ↑	PT reflects the extrinsic pathway (Factor VII). "PT reflecting extrinsic pathway, solely by Factor 7, which has the shortest half-life of all factors → Factor 7 will be the quickest to be consumed" ^[3]. This is why PT rises first.
Activated Partial Thromboplastin Time (aPTT)	↑ (prolonged), may be delayed	Normal or mildly ↑	aPTT reflects the intrinsic pathway (Factors VIII, IX, XI, XII). "In the acute phase, the acute phase reactant Factor 8 is in high supply → this allows for buffering on the intrinsic pathway, allowing for aPTT to stay relatively preserved" ^[3].
Thrombin Time (TT)	↑ (prolonged)	Normal or mildly ↑	TT measures conversion of fibrinogen → fibrin by thrombin. Prolonged due to: (1) low fibrinogen substrate, (2) FDPs interfering with fibrin polymerization, (3) presence of heparin (if administered).
Fibrinogen	↓ (low)	Normal or ↑ (acute phase reactant)	Consumed by excessive thrombin converting it to fibrin, AND degraded by plasmin. But fibrinogen is an acute phase reactant — in sepsis, the liver increases production, so an apparently "normal" fibrinogen may actually represent a significant fall from an elevated baseline. A falling trend is more informative than a single value.
D-dimer	↑↑↑ (markedly elevated)	↑↑ (elevated)	D-dimer is a specific breakdown product of cross-linked fibrin by plasmin. Elevated D-dimer = active fibrinolysis is occurring = fibrin was formed and is being lysed. Highly sensitive but not specific (also elevated in VTE, sepsis, trauma, post-surgical, pregnancy, malignancy, inflammation).

"Clinical situation four: Prolonged PT & APTT → 1. Repeat and confirm → 2. Measure fibrinogen concentration → 3. Measure platelet concentration → 4. 'disseminated intravascular coagulopathy' → ↑PT, ↑APTT, ↓fibrinogen, ↓platelets, Red blood cell fragmentation" ^[9]

GC027 High Yield — Approach to Prolonged PT and aPTT

The GC lecture explicitly teaches this stepwise approach: when you encounter BOTH PT and aPTT prolonged → first repeat and confirm → then measure fibrinogen and platelet → if both are deranged with RBC fragmentation on PBS, this is DIC. "DIC with all these components is a very uncommon clinical situation" — meaning partial presentations are more typical, but this full-house pattern is the classic exam answer. ^[9]

Test	Expected Finding	Why?
LDH (lactate dehydrogenase)	↑↑	Released from lysed RBCs (LDH-1 and LDH-2 isoforms) and from ischaemic/damaged tissue. "If high indicates high turnover, hemolysis" ^[19]. In DIC, LDH is elevated from both haemolysis AND tissue ischaemia from microvascular thrombosis.
Haptoglobin	↓↓ (often undetectable)	Haptoglobin is a scavenger protein that binds free haemoglobin from lysed RBCs. The haptoglobin-Hb complex is cleared by the liver → haptoglobin is consumed and falls. Very sensitive marker of intravascular haemolysis.
Unconjugated (indirect) bilirubin	↑	Haemoglobin from lysed RBCs is metabolised to unconjugated bilirubin. This is pre-hepatic jaundice — you expect jaundice without dark urine (unless there is also hepatic dysfunction from organ ischaemia).
Reticulocyte count	↑	Bone marrow compensatory response — increasing RBC production to replace those being destroyed. However, if the marrow is infiltrated (e.g., APL) or suppressed (sepsis), the reticulocyte response may be blunted.
Direct antiglobulin test (DAT/Coombs)	Negative	This is crucial for distinguishing DIC (non-immune, mechanical haemolysis) from autoimmune haemolytic anaemia (immune-mediated). DIC is Coombs-negative because the haemolysis is mechanical (shearing by fibrin strands), not antibody-mediated.

DIC is always secondary — once you've established the diagnosis, you must identify and treat the trigger. The investigations depend on the clinical context:

Suspected Trigger	Key Investigations
Sepsis	Blood cultures (at least 2 sets from different sites before antibiotics), urine culture, sputum culture, wound swab, CXR, procalcitonin, lactate, CRP
APL / Haematological malignancy	PBS (look for promyelocytes/blasts), bone marrow aspirate and trephine biopsy, cytogenetics — gold standard for APL showing t(15;17)(q22;q21) ^[6], flow cytometry, FISH for PML-RARA
Obstetric emergency	Urgent obstetric assessment, CTG (cardiotocography), pelvic USS, Kleihauer-Betke test (feto-maternal haemorrhage)
Trauma	CT imaging as clinically indicated, lactate (tissue hypoperfusion), FAST scan (focused assessment with sonography in trauma)
Transfusion reaction	Direct antiglobulin test, repeat blood group and crossmatch, free haemoglobin (plasma and urine), visual inspection of post-transfusion plasma (pink = haemolysis) ^[20]
Malignancy (solid organ)	CT chest/abdomen/pelvis, tumour markers as appropriate (CEA, CA19-9, CA-125), tissue biopsy
Snake bite	Clinical history (species identification if possible), venom detection kit

Bone Marrow Examination — Special Considerations in DIC

"C/I: severe bleeding disorders (severe haemophilia, DIC) as only absolute C/I excluding thrombocytopaenia of any severity → just top up to > 20 × 10⁹/L prior" ^[21]

This is important: bone marrow biopsy is an invasive procedure involving puncture of bone, and in active DIC with severe coagulopathy, there is a risk of uncontrollable bleeding from the biopsy site. DIC is listed as one of the absolute contraindications to marrow examination. If marrow is essential for diagnosis (e.g., suspected APL), you must correct the coagulopathy first (give FFP, cryoprecipitate, platelets) before proceeding.

Test	When to Use	Interpretation
Factor VIII level	When distinguishing DIC from liver disease	Factor VIII is LOW in DIC (consumed) but NORMAL/HIGH in liver disease (made by endothelium, not hepatocytes, and is an acute phase reactant) — the single best discriminator
Antithrombin (AT) level	Monitoring severity; guiding heparin therapy	AT is consumed in DIC. Very low AT levels (< 50%) indicate severe DIC and also explain why heparin may be ineffective (heparin works by potentiating AT — if AT is depleted, heparin cannot work).
Protein C / Protein S levels	Assessing severity; explaining purpura fulminans	Severely depleted Protein C → purpura fulminans (skin necrosis from uncontrolled microvascular thrombosis).
Fibrin monomers	Early DIC detection	Soluble fibrin monomers are generated when thrombin cleaves fibrinogen but before cross-linking by Factor XIIa. Elevated fibrin monomers may indicate early/non-overt DIC before the full-house picture develops. More sensitive than D-dimer for early DIC but less widely available.
ADAMTS13 activity	Excluding TTP	If ADAMTS13 < 10%, this is TTP, not DIC. In DIC, ADAMTS13 activity is usually normal or only mildly reduced (30–50%).
Mixing study	Distinguishing factor deficiency from inhibitor	In DIC, the prolonged PT/aPTT corrects with mixing (because the problem is factor depletion, not an inhibitor). In lupus anticoagulant or acquired haemophilia, the mixing study does not correct.
Thromboelastography (TEG) / ROTEM	Point-of-care assessment in theatre/ICU	Viscoelastic tests provide a global assessment of clot formation, clot strength, and fibrinolysis in real time. In DIC, you see prolonged clot formation time (r-time / CT), reduced clot amplitude (MA / MCF reflecting low fibrinogen and platelets), and evidence of hyperfibrinolysis (LY30 / ML elevated). Useful for guiding targeted blood product replacement.

Since DIC causes microvascular thrombosis → multi-organ ischaemia, you should assess end-organ damage:

Organ	Investigation	Expected Finding in Severe DIC
Kidney	RFT (urea, creatinine), urine output monitoring, urinalysis	Rising creatinine, oliguria/anuria (ischaemic ATN from microvascular thrombosis); haematuria (mucosal bleeding); haemoglobinuria (intravascular haemolysis)
Liver	LFT (ALT, AST, bilirubin, albumin), PT	↑ALT/AST ("shock liver" pattern), ↑bilirubin (both haemolysis and hepatic dysfunction), prolonged PT (further impaired factor synthesis on top of consumption)
Lung	CXR, ABG/VBG, SpO₂	Bilateral infiltrates (ARDS from microvascular injury), hypoxaemia, ↑lactate
Brain	Neurological examination, CT head (if acute neuro deficit)	Confusion, focal deficits, seizures — may show ischaemic or haemorrhagic lesions
Lactate	ABG or VBG	Lactic acidosis reflecting poor tissue perfusion ^[17] — a rising lactate in DIC is an ominous sign of worsening microvascular obstruction and shock

"Early investigations: CBC/D, L/RFT, V/ABG + lactate, Clotting + D-dimer: ↑PT/INR (haemorrhagic shock, septic APR), ↑D-dimer (PE, DIC)" ^[17]

10.5 Interpretation Pearls — Putting It All Together

"↑PT, ↑APTT, ↓fibrinogen, ↓platelets, Red blood cell fragmentation" ^[9]

"Clotting profile: PT high, APTT preserved, with low fibrinogen and high D-dimer → Typical picture of disseminated intravascular coagulation" ^[3]

But remember:

"DIC with all these components is a very uncommon clinical situation" ^[9] — partial panels are more common
The trend (serial measurements) matters more than any single snapshot
Fibrinogen may be deceptively normal in sepsis-triggered DIC (acute phase reactant)
aPTT may be initially preserved (Factor VIII buffering)

This is worth re-emphasising because it has direct diagnostic implications:

"Prothrombin time reflecting extrinsic pathway, solely by Factor 7, which has the shortest half-life of all factors → After APL cells express tissue factor (Factor 3, the initiator of the extrinsic pathway), Factor 7 will be the quickest to be consumed" ^[3]

"In the acute phase of APL, the acute phase reactant Factor 8 is in high supply → this allows for buffering on the intrinsic pathway, allowing for APTT to stay relatively preserved" ^[3]

Clinical implication: In early DIC, you may see isolated PT prolongation with a normal aPTT. Do not dismiss this as simply "vitamin K deficiency" or "liver disease" if the clinical context suggests DIC. Check fibrinogen, D-dimer, platelet count, and PBS — the aPTT will catch up later.

"If left untreated over a longer period of time, all clotting factors will eventually be used up, causing a rise in APTT as well" ^[3]

"What are the useful investigations for the purpose of exclusion of DIC? → Peripheral blood film: Fragmented red cell → Clotting profile: ↑PT and APTT, ↑D-dimer, ↓Fibrinogen level" ^[10]^[18]

This is a commonly tested stem: a patient with thrombocytopenia is being worked up for ITP — how do you exclude DIC? Order these four things. If all are normal, DIC is excluded.

Investigation Category	Specific Tests	Purpose in DIC
Core haemostasis	CBC (platelets), PT, aPTT, TT, Fibrinogen, D-dimer	Confirm consumption coagulopathy; calculate ISTH score
PBS	Schistocytes, polychromasia, promyelocytes/blasts	Confirm MAHA; identify underlying cause
Haemolysis markers	LDH, haptoglobin, unconjugated bilirubin, reticulocytes, DAT	Confirm intravascular haemolysis; exclude immune cause (DAT negative)
Cause-directed	Cultures, imaging, bone marrow, cytogenetics, obstetric assessment	Identify and treat the precipitant
Organ dysfunction	RFT, LFT, ABG/lactate, CXR, CT head	Assess end-organ damage for prognosis and management
Specialised	Factor VIII, AT level, Protein C/S, ADAMTS13, fibrin monomers, TEG/ROTEM, mixing study	Distinguish from mimics; guide targeted therapy

High Yield Summary — Diagnosis of DIC

DIC is a clinical + laboratory diagnosis — no single test is diagnostic; use the ISTH scoring system
ISTH Score ≥ 5 = overt DIC (requires: known underlying condition + platelet count, D-dimer, PT prolongation, fibrinogen)
Serial measurements and trends are more valuable than single snapshots — repeat daily
Core investigations: CBC, PT, aPTT, fibrinogen, D-dimer, PBS for schistocytes
GC027 approach to both PT + aPTT prolonged: Repeat → fibrinogen → platelet → if all deranged with RBC fragmentation → DIC
PT rises before aPTT because Factor VII has the shortest half-life; Factor VIII (acute phase reactant) buffers the intrinsic pathway initially
Fibrinogen can be deceptively normal in sepsis (acute phase reactant) — a falling trend is more informative
To exclude DIC when evaluating thrombocytopenia: PBS (schistocytes), PT, aPTT, D-dimer, fibrinogen
Factor VIII level distinguishes DIC (low) from liver disease (normal/high)
Bone marrow biopsy is contraindicated in active DIC — correct coagulopathy first
DAT is negative in DIC (mechanical, non-immune haemolysis)
ADAMTS13 activity distinguishes TTP (< 10%) from DIC (normal/mildly reduced)

Active Recall - Diagnosis and Investigations of DIC

References

^[3] Senior notes: Block A - Introduction to Haematological investigations (CBP, Clotting).pdf, p.19 ^[4] Senior notes: Maksim Medicine Notes.pdf — Haematology section, p.165 ^[5] Senior notes: Ryan Ho Haemtology.pdf — DIC section, pp.136–138 ^[6] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf, p.19 ^[9] Lecture slides: GC 027. Abnormal bleeding after tooth extraction.pdf, p.27 ^[10] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf — Case study / DIC exclusion, p.613 ^[16] Senior notes: Adrian Lui Pediatrics Notes.pdf — DIC section, pp.398–400 ^[17] Senior notes: Ryan Ho Critical Care.pdf — Shock evaluation, p.17 ^[18] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — DIC exclusion, p.1373 ^[19] Senior notes: Block A - Family history of anaemia_ inherited causes of anaemia; haemolytic anaemia; aplastic anaemia.pdf, p.4 ^[20] Senior notes: Block A - Fever after a blood transfusion_ transfusion and related problems.pdf — ABO incompatible reaction, p.10 ^[21] Senior notes: Ryan Ho Fundamentals.pdf — Marrow examination contraindications, p.391

Management of DIC — Algorithm, Treatment Modalities, Indications and Contraindications

Before diving into specifics, understand the three pillars of DIC management. Every decision flows from these:

1. "Treat underlying cause: most important" ^[5]^[16] 2. "Supportive: haemodynamic support, organ support, ventilation, correct electrolytes" ^[5] 3. "Prevention and treatment of bleeding" — "Principle: to replenish the lost components with view on risk of ↑thrombosis" ^[5]^[16]

And from the GC lecture:

"6. Treatment of DIC is to replenish the consumed coagulation factors. 7. Reverse the underlying causative factor." ^[9]

Think of DIC like a house on fire: you can keep pouring water on the flames (replacing consumed factors), but unless you turn off the gas supply (treat the underlying cause), the fire will never go out. Blood product replacement without cause-directed therapy is futile and may even be harmful.

"Precipitating trigger must be eliminated before treatment of DIC is effective. Control of bleeding with frequent monitoring of coagulation screen is essential." ^[22]

This is the single most important intervention. Without it, DIC will not resolve regardless of how much blood product you transfuse.

Underlying Cause	Specific Treatment	Rationale
Sepsis	Empirical broad-spectrum IV antibiotics (within 1 hour of recognition) + source control (drainage, debridement)	Remove the microbial toxins and endothelial damage that drive coagulation activation. Without antibiotics, ongoing bacteraemia perpetually triggers tissue factor release and endothelial injury.
APL (AML-M3)	All-trans retinoic acid (ATRA) + arsenic trioxide (ATO) — start immediately, even before formal cytogenetic confirmation ^[14]^[23]	"The combination of pancytopenia with circulating promyelocytes, DIC with low fibrinogen, and t(15;17) translocation mandates urgent ATRA therapy even before formal diagnosis to prevent fatal bleeding complications" ^[14]. ATRA forces the leukaemic promyelocytes to differentiate into mature granulocytes, which stops them from releasing tissue factor. This directly switches off the DIC trigger.
Obstetric emergencies	Delivery of the fetus/placenta (C-section or vaginal depending on context), uterine evacuation for retained products, management of eclampsia (magnesium sulphate, antihypertensives)	The placenta/amniotic fluid is the source of procoagulant material. Removing it stops the trigger.
Trauma	Surgical haemostasis, damage control surgery, correction of hypothermia and acidosis ("lethal triad" of trauma)	Tissue damage and exposed collagen/tissue factor from injured tissues are driving the DIC. Control the haemorrhage and minimise ongoing tissue injury.
ABO-incompatible transfusion	Stop the transfusion immediately ^[20] + aggressive IV hydration + supportive care	The incompatible RBCs are the trigger — stopping the transfusion removes the ongoing complement activation → stops the cytokine storm → stops DIC propagation ^[20].
Solid organ malignancy	Chemotherapy / surgery / palliative care as appropriate	Tumour cells releasing tissue factor are the trigger; tumour bulk reduction is the only definitive approach.
Snake bite	Antivenom + supportive care	Neutralises the procoagulant venom enzymes.

APL-DIC — A Time-Critical Emergency

"Management of DIC in APL: Specific treatment → reduce early mortality: All-trans retinoic acid (ATRA), Arsenic trioxide. Supportive treatment → Transfusion with platelet, FFP, cryoprecipitate. If you tide them over the acute period, no ICH, then prognosis is good → so cannot miss." ^[23]

The mortality from APL-related DIC is predominantly from intracranial haemorrhage (ICH) in the first few days. ATRA must be started the moment APL is clinically suspected (even on PBS alone, before cytogenetics return). The overall prognosis of APL is excellent once you survive the initial DIC phase — cure rates exceed 90% with ATRA+ATO.

Intervention	Details	Why?
Haemodynamic resuscitation	IV crystalloids (balanced solutions preferred); vasopressors (noradrenaline first-line) if septic shock	Maintain organ perfusion — DIC-related microvascular thrombosis is worsened by hypoperfusion and stasis. Adequate blood pressure reduces ischaemic organ damage.
Organ support	Mechanical ventilation for ARDS/respiratory failure; renal replacement therapy (CRRT preferred in haemodynamically unstable patients) for AKI	Microvascular thrombosis → organ ischaemia → organ failure. You must support failing organs while the underlying cause is being treated.
Correction of hypothermia	Active warming; warm IV fluids and blood products	Hypothermia impairs coagulation enzyme function (coagulation cascade is a series of enzymatic reactions with temperature-dependent kinetics). Even mild hypothermia (< 35°C) significantly prolongs PT/aPTT and worsens platelet dysfunction.
Correction of acidosis	Treat the cause (e.g., restore perfusion, treat sepsis); consider sodium bicarbonate only if pH < 7.1	Acidosis inhibits coagulation factor activity and promotes fibrinolysis. A pH < 7.2 reduces thrombin generation by > 50%.
Electrolyte correction	Monitor and correct calcium, potassium, magnesium	Ionised calcium is essential for multiple steps in the coagulation cascade (Factor IV). Hypocalcaemia (common after massive transfusion due to citrate in stored blood) further impairs clotting.
Serial monitoring	Repeat CBC, PT, aPTT, fibrinogen, D-dimer every 6–12 hours; calculate serial ISTH DIC scores	Track response to therapy and detect deterioration early. The trend matters more than any single value.

11.5 Pillar 3 — Blood Product Replacement Therapy

This is the core of the "replenish consumed components" principle. The key tension is: you are giving products that may fuel ongoing thrombosis, but if the patient is bleeding to death, you have no choice. The approach depends on the clinical context.

"Principle: to replenish the lost components with view on risk of ↑thrombosis" ^[5]^[16]

Indication	Threshold	Rationale
Prophylactic (fever/sepsis, no active bleeding)	Platelet < 20 × 10⁹/L ^[5]^[16]	At this level, the risk of spontaneous ICH becomes significant. The threshold is lower than for surgical bleeding because you want to minimise unnecessary transfusion (each platelet unit theoretically provides substrate for more microvascular thrombosis).
Active serious bleeding or need for invasive procedure	Platelet < 50 × 10⁹/L ^[5]^[16]	Adequate haemostasis for procedures and to control active haemorrhage requires a higher platelet count. Below 50, surgical oozing becomes uncontrollable.
Liver failure context	Platelet < 50 (if bleeding/procedure) or < 20 (prophylactic) ^[24]	Same thresholds apply; the mechanism of thrombocytopenia in liver failure (hypersplenism) is different, but the haemostatic consequences are the same.

Practical points:

One adult therapeutic dose of pooled platelets (derived from ~4–6 whole blood donations) or one apheresis unit typically raises the platelet count by 20–40 × 10⁹/L
In DIC, the increment is often lower than expected because platelets are continuously consumed — do not be surprised if the post-transfusion count barely rises. This is itself diagnostic evidence of ongoing consumption.
No absolute contraindication to platelet transfusion in DIC — unlike TTP/HUS where platelet transfusion is contraindicated (fuels platelet-rich thrombi)

DIC vs TTP — Platelet Transfusion

In DIC: platelet transfusion is indicated for active bleeding or very low counts. The thrombi are fibrin-rich, so adding platelets does not significantly worsen thrombosis.

In TTP/HUS: platelet transfusion is contraindicated (unless life-threatening bleeding) because the thrombi are platelet/vWF-rich and adding platelets directly fuels the pathological process.

Getting this wrong in an exam or clinically is a high-stakes error.

"FFP to replenish consumed coagulation factors in active bleeding" ^[13]

"Fresh frozen plasma: Acellular component of blood. Plasma contains all the coagulation factors. Main indication: Correction of coagulopathies." ^[25]

Indication	When to Give	Dose
Active serious bleeding + prolonged PT/aPTT	FFP/cryoprecipitate if serious bleeding + ↑PT/aPTT or fibrinogen < 50 mg/dL ^[5]^[16]	15–20 mL/kg (typically 4–6 units for an adult). Each unit is ~250 mL ^[25]. Check clotting 30 min post-infusion.
Need for invasive procedure + prolonged PT/aPTT	Before procedures such as OGD, central line insertion, bone marrow biopsy	Same dose. Target: PT/aPTT < 1.5× upper limit of normal.
Prophylactic (no bleeding, no procedure)	Controversial and generally NOT recommended	See caution box below.

Why FFP works: FFP contains ALL coagulation factors (including Factor V, which is not in prothrombin complex concentrate), fibrinogen, antithrombin, and protein C/S. It replaces everything that has been consumed.

Storage: Stored at freezing temperatures (-30°C); must be thawed before use ^[25]. Thawing takes ~20–30 minutes — in a true emergency, this delay matters. Pre-alert the blood bank.

Prophylactic FFP — The Controversy

"Treat underlying cause only if no bleeding (prophylactic FFP may ↑risk of thrombosis)" ^[13]

This is a commonly tested nuance. If the patient is NOT actively bleeding and has no planned procedure, giving FFP prophylactically is controversial because:

You are providing fresh substrate (clotting factors) for the ongoing pathological coagulation → potentially worsening microvascular thrombosis ("adding fuel to the fire")
Volume overload risk (each FFP unit = ~250 mL; 4–6 units = > 1L additional fluid in a patient who may already have ARDS/pulmonary oedema)
Transfusion reactions (TRALI, allergic reactions)

Current guideline (ISTH 2024): FFP should be given when there is active bleeding or a high risk of bleeding, not prophylactically to normalise laboratory values alone.

Cryoprecipitate is the cold-insoluble fraction of FFP — what precipitates when FFP is slowly thawed. It is enriched in:

Fibrinogen (Factor I) — ~250 mg per unit
Factor VIII
Factor XIII (fibrin-stabilising factor)
von Willebrand factor (vWF)
Fibronectin

Indication	When to Give	Dose
Fibrinogen < 1.0–1.5 g/L with active bleeding	When FFP alone is insufficient to raise fibrinogen (FFP has a relatively low concentration of fibrinogen compared to cryoprecipitate)	10 units (pools of 5 units, ~2 pools for an adult). Each unit raises fibrinogen by ~0.5 g/L.
Massive transfusion protocol	As part of a fixed-ratio resuscitation	Often given alongside packed RBCs and FFP in a 1:1:1 ratio strategy

Why cryoprecipitate over FFP for fibrinogen? FFP contains fibrinogen, but at a concentration of only ~2–3 g/L — you would need enormous volumes (> 2L) to significantly raise a critically low fibrinogen. Cryoprecipitate is a concentrated source (~15–20 g/L of fibrinogen), so it raises levels efficiently without volume overload.

Alternative: Fibrinogen concentrate (e.g., RiaSTAP) — a purified, pasteurised product that can be reconstituted rapidly and given without thawing. Increasingly used in some centres but more expensive.

Indication	Threshold	Rationale
Symptomatic anaemia or active haemorrhage	Hb < 70 g/L (restrictive strategy) or Hb < 80 g/L (if cardiovascular disease)	Correct anaemia from MAHA + haemorrhage. Restrictive transfusion strategy (Hb trigger 70) is preferred unless the patient has active coronary disease or haemodynamic instability.

Note: In massive haemorrhage, do not wait for a Hb result — transfuse clinically and activate the massive transfusion protocol if applicable (typically defined as replacement of > 1 blood volume in 24 hours or > 4 units pRBC in 1 hour with ongoing bleeding).

Product	Contains	Indication in DIC	Target
Platelets	Platelet concentrates	PLT < 20 (prophylactic) or < 50 (bleeding/procedure)	PLT > 50 if bleeding
FFP	All coagulation factors, AT, Protein C/S	Active bleeding + ↑PT/aPTT; pre-procedure	PT/aPTT < 1.5× ULN
Cryoprecipitate	Fibrinogen, Factor VIII, XIII, vWF	Fibrinogen < 1.0–1.5 g/L with bleeding	Fibrinogen > 1.5 g/L
pRBCs	Red blood cells	Symptomatic anaemia, Hb < 70	Hb > 70–80
Vitamin K	Cofactor for Factor II, VII, IX, X synthesis	If concurrent vitamin K deficiency suspected (malnutrition, cholestasis, antibiotics)	Not a primary DIC treatment — adjunctive

11.6 Pillar 4 — Anticoagulation Therapy (Prevention and Treatment of Thrombosis)

This is the most controversial and nuanced area of DIC management. The fundamental tension: the patient is both clotting AND bleeding, and anticoagulation could worsen bleeding while potentially reducing organ-threatening thrombosis.

Scenario	Anticoagulation?	Agent	Rationale
Chronic (compensated) DIC with predominant thrombosis	Yes — therapeutic anticoagulation	Low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH)	In chronic DIC, the procoagulant drive is the dominant problem. The patient is forming clots (DVT, PE, arterial thrombosis) and the liver is keeping pace with factor production. Anticoagulation slows the coagulation cascade and reduces thrombotic organ damage.
Acute DIC with purpura fulminans or acral ischaemia	Yes — consider heparin	UFH (easier to titrate and reverse)	Purpura fulminans reflects devastating skin microvascular thrombosis from protein C depletion. Without anticoagulation, tissue necrosis progresses.
Acute DIC with predominant bleeding	Generally NO	—	Adding anticoagulation to a patient who is already bleeding from consumption coagulopathy will worsen haemorrhage.
VTE prophylaxis in hospitalised DIC patients	Individualised	Prophylactic-dose LMWH or UFH if platelet > 50 and not actively bleeding	Standard VTE prophylaxis principles apply when the patient is stable enough.

"Anti-coagulants: Not favourable" ^[22] — This statement from the senior notes reflects the fact that in most presentations of acute DIC (which is bleeding-predominant), anticoagulation is not beneficial and may be harmful. However, this does not mean "never" — in thrombosis-predominant or chronic DIC, anticoagulation is indicated.

Heparin in DIC — Mechanism and Limitations:

UFH works by potentiating antithrombin (AT) — it accelerates AT-mediated inactivation of thrombin and Factor Xa by ~1000×
In DIC, AT levels are often severely depleted (consumed by binding excess thrombin). If AT is very low (< 50%), heparin will not work effectively because there is insufficient AT for it to potentiate
This is why some guidelines recommend measuring AT levels before starting heparin and considering AT concentrate supplementation if AT < 50%

"Anti-thrombin concentrate (natural coagulation inhibitor): Not favourable" ^[22]

The evidence for AT concentrate in DIC is mixed:

Theoretical benefit: AT is consumed in DIC → depleted AT removes a key brake on thrombin → replacing AT should slow the coagulation cascade
Evidence: The KyberSept trial (2001) showed no mortality benefit of AT concentrate in severe sepsis/DIC. Subgroup analysis suggested possible benefit in patients NOT receiving concurrent heparin, but this was hypothesis-generating, not confirmatory
Current ISTH position (2024): AT concentrate is not routinely recommended for DIC. It may be considered in selected cases (e.g., AT levels < 50% with clinical thrombosis not responding to heparin), but this is specialist territory
Exception: In Japan, AT concentrate is used more liberally for sepsis-associated DIC based on Japanese observational data — this reflects regional practice variation

11.7 Special Therapeutic Considerations

Mechanism: Thrombomodulin is a natural endothelial receptor that binds thrombin → the thrombin-thrombomodulin complex activates protein C → activated protein C inactivates Factors Va and VIIIa → slows coagulation. Recombinant thrombomodulin mimics this natural anticoagulant pathway.
Evidence: The SCARLET trial (2019) did not show significant mortality benefit in sepsis-associated DIC, but Japanese trials (where it was developed and is approved) showed improvement in DIC resolution
Status: Approved in Japan; not routinely used elsewhere. Know it exists but unlikely to be tested in depth at HKUMed.

TXA is an antifibrinolytic — it inhibits plasminogen activation → reduces plasmin activity → reduces fibrinolysis
In DIC, secondary fibrinolysis is already inadequate relative to the degree of fibrin formation. Blocking fibrinolysis further can worsen microvascular thrombosis and precipitate organ failure
Generally contraindicated in DIC unless there is clear evidence of hyperfibrinolysis (e.g., on TEG/ROTEM showing LY30 > 3% or maximum lysis > 15%)
Exception: May be considered in specific obstetric DIC with massive haemorrhage (e.g., postpartum haemorrhage) where bleeding is immediately life-threatening and hyperfibrinolysis is documented — but this is a high-risk decision requiring senior haematology input

In purpura fulminans due to severe protein C depletion, protein C concentrate (if available) can be given to restore the natural anticoagulant pathway and halt skin necrosis
Limited availability; mainly used in neonatal purpura fulminans from inherited protein C deficiency
Not routine in standard DIC management

A "bypass" agent that generates thrombin independent of the normal cascade — used as a last resort in life-threatening, refractory bleeding
Theoretically contraindicated in DIC because adding a procoagulant agent to a state of disseminated coagulation could worsen thrombosis
May be considered in extremis (e.g., massive obstetric haemorrhage not responding to standard measures) — specialist decision only

Scenario	Priority Treatment	Blood Products	Anticoagulation	Special Points
Sepsis-associated DIC (acute, bleeding)	Antibiotics + source control	Platelets, FFP, cryo as per thresholds	Generally NOT unless thrombosis predominates	Treat sepsis aggressively; DIC resolves when infection controlled
APL-associated DIC	ATRA + ATO immediately ^[14]^[23]	Platelet, FFP, cryoprecipitate — aggressive replacement to prevent ICH ^[23]	NOT usually	"If you tide them over the acute period, no ICH, then prognosis is good" ^[23]. Target platelet > 30–50, fibrinogen > 1.5 g/L.
Obstetric DIC	Deliver the fetus/placenta	Massive transfusion protocol often needed	NOT usually	Correct coagulopathy before/during delivery; involve obstetric anaesthesia
Trauma-associated DIC	Surgical haemostasis; damage control surgery	Massive transfusion protocol (1:1:1 pRBC:FFP:platelets)	NOT in acute phase	Correct the "lethal triad" (hypothermia, acidosis, coagulopathy)
Chronic DIC (malignancy)	Treat underlying malignancy (chemo/surgery)	Usually not needed (production keeps pace)	Therapeutic anticoagulation (LMWH)	Trousseau syndrome may require long-term LMWH
Purpura fulminans	Source control if septic; protein C concentrate if available	Platelets, FFP, cryo	YES — heparin (UFH) to halt microvascular thrombosis	Consider protein C concentrate; surgical debridement of necrotic tissue may be needed later

Intervention	Contraindication / Pitfall
Prophylactic FFP (without active bleeding)	May ↑risk of thrombosis by providing substrate for ongoing coagulation ^[13]; volume overload; TRALI risk
Platelet transfusion in TTP (misdiagnosed as DIC)	Fuels platelet-rich microthrombi → can be fatal. Always check ADAMTS13 if in doubt.
Tranexamic acid	Generally contraindicated in DIC — blocks already-inadequate fibrinolysis → worsens microvascular thrombosis
Heparin when AT is depleted	Heparin will be ineffective if AT < 50% (no substrate to potentiate). Measure AT level before relying on heparin.
Activated Factor VII (rFVIIa)	Theoretically worsens thrombosis; last resort only
Bone marrow biopsy	Absolute contraindication in active DIC ^[21] — correct coagulopathy first
Delaying ATRA in suspected APL	"Mandates urgent ATRA therapy even before formal diagnosis to prevent fatal bleeding complications" ^[14] — do NOT wait for cytogenetics

High Yield Summary — Management of DIC

"Treat the underlying cause" — THE most important intervention. DIC will not resolve without eliminating the trigger.
"Treatment of DIC is to replenish the consumed coagulation factors" + "Reverse the underlying causative factor" ^[9] — the two GC lecture exam points.
Platelet transfusion: < 20 prophylactic (with sepsis/fever); < 50 if active bleeding or procedure needed.
FFP: Only for active bleeding or pre-procedure with ↑PT/aPTT. Prophylactic FFP is controversial and may worsen thrombosis.
Cryoprecipitate: For fibrinogen < 1.0–1.5 g/L with active bleeding (concentrated fibrinogen source).
Anticoagulation: NOT in acute bleeding-predominant DIC; YES in chronic/thrombosis-predominant DIC or purpura fulminans.
APL-DIC: Start ATRA + ATO immediately (even before cytogenetics); aggressive blood product support to prevent ICH; excellent long-term prognosis if patient survives the initial phase.
Tranexamic acid: Generally contraindicated in DIC (worsens microvascular thrombosis).
Correct hypothermia and acidosis — both impair coagulation enzyme function.
Serial monitoring of CBC, clotting, fibrinogen, D-dimer every 6–12h to track response.

Active Recall - Management of DIC

References

^[3] Senior notes: Block A - Introduction to Haematological investigations (CBP, Clotting).pdf, p.19 ^[5] Senior notes: Ryan Ho Haemtology.pdf — DIC management section, pp.138 ^[9] Lecture slides: GC 027. Abnormal bleeding after tooth extraction.pdf, p.27 ^[13] Senior notes: Adrian Lui Pediatrics Notes.pdf — Approach to prolonged PT+aPTT / DIC management, pp.389, 400 ^[14] Senior notes: Learning_Points_All_Lectures.txt — APL as haematological emergency ^[16] Senior notes: Adrian Lui Pediatrics Notes.pdf — DIC section, pp.398–400 ^[20] Senior notes: Block A - Fever after a blood transfusion_ transfusion and related problems.pdf — ABO incompatible reaction, p.10 ^[21] Senior notes: Ryan Ho Fundamentals.pdf — Marrow examination contraindications, p.391 ^[22] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — DIC treatment, p.1335 ^[23] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf — APL-DIC management, pp.9, 20 ^[24] Senior notes: Block A - A jaundiced and incoherent patient_ liver failure.pdf — Coagulopathy in liver failure, p.23 ^[25] Senior notes: Block A - Fever after a blood transfusion_ transfusion and related problems.pdf — FFP, p.5

Complications of DIC

DIC is not just a laboratory derangement — it is a catastrophic systemic process that damages virtually every organ through two simultaneous mechanisms:

Microvascular thrombosis → ischaemic injury to organs (kidneys, liver, lungs, brain, skin, adrenals)
Consumption coagulopathy + secondary fibrinolysis → haemorrhage (intracranial, mucosal, wound sites, GI tract)

The complications of DIC essentially represent the downstream organ damage from these two processes, compounded by the complications of the underlying trigger (sepsis, trauma, malignancy) and the complications of treatment itself (transfusion reactions, volume overload). The high mortality of DIC (40–80%) is driven by multi-organ failure and uncontrolled haemorrhage, not by the coagulopathy in isolation.

Widespread activation of coagulation → intravascular formation of fibrin → thrombotic occlusion of small vessels → leads to multiple organ failure. Depletion of platelets and clotting factors → widespread intravascular coagulation and secondary fibrinolysis → consumption of clotting factors, inhibitors of coagulation and platelets → leads to severe bleeding. ^[1]^[2]^[5]

12.2 Haemorrhagic Complications

Bleeding is the most immediately visible and often the most life-threatening complication of acute DIC. It results from the triple hit of: (i) platelet consumption → thrombocytopenia; (ii) coagulation factor consumption → prolonged PT/aPTT; (iii) FDPs interfering with fibrin polymerisation and platelet function.

The most feared bleeding complication and the leading cause of early death in DIC, particularly in APL-associated DIC
"If you tide them over the acute period, no ICH, then prognosis is good → so cannot miss" ^[23] — this underscores that ICH is the critical early hurdle
Why ICH occurs: Cerebral vessels are end-arteries with limited collateral supply. The combination of thrombocytopenia + depleted clotting factors + FDP-mediated platelet dysfunction means that even minor vascular insults in the brain (which occur naturally from microvascular thrombosis-induced ischaemia) can lead to catastrophic bleeding into brain parenchyma
Clinical features: Sudden headache, vomiting, rapid decline in consciousness, focal neurological deficits, seizures, coma
Significance: Once ICH occurs in the context of DIC, mortality approaches 70–90%. This is why aggressive platelet and fibrinogen replacement is critical in APL-DIC (target platelets > 30–50 × 10⁹/L, fibrinogen > 1.5 g/L)

Bleeding, e.g. intracranial bleeding, petechiae, haematuria, mucosal bleeding (e.g. epistaxis) ^[4]

Mucosal surfaces of the GI tract are highly vascularised and prone to minor trauma from peristalsis and gastric acid
In DIC, the combination of mucosal ischaemia (from microvascular thrombosis in mesenteric vessels) and impaired haemostasis leads to diffuse mucosal bleeding
Presents as haematemesis, melaena, or fresh PR bleeding
Can be massive and difficult to control because the bleeding is diffuse rather than focal (unlike a peptic ulcer)

Bleeding (64%), esp from sites of trauma, catheter, drains ^[5]^[16]
Epistaxis, gingival bleeding, haematuria, vaginal bleeding
Oozing from venipuncture sites, central line insertion sites, surgical wound sites, drain sites — this is the classic "won't stop oozing" presentation that alerts the clinician to DIC
Petechiae, purpura, ecchymoses — reflect thrombocytopenia and microvascular damage

Deep muscle haematomas (particularly iliopsoas, retroperitoneal) can compress nerves and vessels
Retroperitoneal haemorrhage is particularly dangerous because it is clinically occult until the patient becomes haemodynamically unstable

12.3 Thrombotic Complications

While bleeding is the dominant clinical feature of acute DIC, microvascular thrombosis is the dominant pathological process and drives organ damage.

This is the most devastating systemic complication and the primary mechanism by which DIC kills.

Thrombosis due to thrombin generation → widespread intravascular coagulation → fibrin deposition → microvascular thrombosis → organ ischaemia with multi-organ failure ^[5]

Fibrin strands deposit in the arterioles and capillaries of every organ, obstructing blood flow and causing ischaemic injury. The organs most vulnerable are those with high blood flow relative to their size and those with end-artery circulations.

Renal dysfunction (25%) ^[5]^[16] — one of the most common organ complications
Mechanism: Two pathways converge:
1. Microvascular thrombosis in glomerular and peritubular capillaries → ischaemic acute tubular necrosis (ATN)
2. Hypovolaemia/shock (from bleeding and vasodilation) → pre-renal AKI → if sustained, progresses to ATN

ATN caused by thrombosis: TTP, HUS, Disseminated intravascular coagulation (DIC) ^[7] — DIC is explicitly listed as a cause of ischaemic ATN

Clinical course of ATN: Oliguric phase (oliguria < 500 mL/day, ↓GFR, ↑urea, metabolic acidosis, hyperkalaemia) → Diuretic phase (gradual normalisation of GFR, markedly ↑urine output up to 3 L/day) → Recovery ^[7]
May require renal replacement therapy (CRRT preferred in haemodynamically unstable DIC patients) if severe
AKI also worsens the bleeding tendency because uraemia impairs platelet function (uraemic toxins interfere with platelet adhesion and aggregation)

Hepatic dysfunction (19%) ^[5]^[16]
Mechanism: Microvascular thrombosis in hepatic sinusoids → hepatocellular ischaemia → "shock liver" pattern (markedly ↑ALT/AST, ↑bilirubin)
Hepatic ischaemia further impairs synthesis of clotting factors and natural anticoagulants (protein C, protein S, antithrombin) → creates a vicious cycle where the liver's failure to produce these proteins worsens both the bleeding and thrombotic components of DIC
Also impairs clearance of FDPs and activated clotting factors → perpetuates the coagulopathy

Respiratory dysfunction (16%) ^[5]^[16]
Mechanism: Microvascular thrombosis in pulmonary capillaries → endothelial damage → increased pulmonary capillary permeability → non-cardiogenic pulmonary oedema (ARDS). Additionally, fibrin deposition in alveolar capillaries causes V/Q mismatch.
Pulmonary haemorrhage can also occur (coagulopathy + damaged alveolar-capillary membrane → bleeding into alveolar space)
Presents as progressive dyspnoea, hypoxaemia, bilateral infiltrates on CXR
May require intubation and mechanical ventilation with lung-protective strategy

Ischaemic stroke: Microvascular thrombosis in cerebral vessels → focal neurological deficits
Haemorrhagic stroke: Consumption coagulopathy → intracerebral haemorrhage (as above)
Diffuse encephalopathy: Widespread microvascular ischaemia → confusion, altered consciousness without focal signs
Both ischaemic and haemorrhagic events can occur simultaneously in the same patient, making neuroimaging interpretation challenging

Thrombosis, e.g. ischaemic stroke, MAHA, VTE ^[4]

Particularly prominent in chronic (compensated) DIC where thrombosis predominates
Unprovoked VTE, unprovoked arterial thrombosis ^[4]^[5]
Deep vein thrombosis (DVT) → pulmonary embolism (PE)
Can occur in unusual sites (mesenteric vein, portal vein, cerebral venous sinuses)

12.4 Skin Complications

Purpura fulminans: due to protein C deficiency ^[4]
Mechanism: Severe depletion of protein C (consumed in DIC) → complete loss of the natural anticoagulant brake on Factors Va and VIIIa → uncontrolled microvascular thrombosis in dermal vessels → extensive haemorrhagic skin necrosis
This is the same mechanism as warfarin-induced skin necrosis (warfarin inhibits protein C, which has a shorter half-life than most procoagulant factors, creating a transient prothrombotic state)
Clinical appearance: Begins as painful, red, well-demarcated patches → rapidly progresses to purplish-black necrotic lesions, typically on extremities, buttocks, genitalia, and areas with high subcutaneous fat
Management: Heparin anticoagulation (to halt ongoing thrombosis), protein C concentrate if available, aggressive blood product support, and eventually surgical debridement of necrotic tissue
Classically seen in meningococcaemia (Neisseria meningitidis sepsis → DIC → protein C depletion → purpura fulminans)

Microvascular thrombosis in end-arteries of fingers, toes, ears, nose
Progresses from cyanosis → ischaemia → dry gangrene if not reversed
May eventually require amputation

Mechanism: Bilateral adrenal haemorrhagic infarction due to DIC-related microvascular thrombosis + haemorrhage in adrenal glands → acute adrenal insufficiency
Classically associated with meningococcal sepsis (Neisseria meningitidis)
The adrenal glands are particularly vulnerable because they have a very rich arterial supply (three adrenal arteries) draining into a single central vein — this "vascular bottle-neck" anatomy predisposes to haemorrhagic necrosis when microvascular thrombosis occurs
Clinical features: Sudden cardiovascular collapse (refractory hypotension despite fluids and vasopressors), hypoglycaemia, hyperkalaemia, hyponatraemia
Management: Emergency IV hydrocortisone (100 mg bolus then 50 mg Q8H) + aggressive resuscitation. If you don't recognise and treat this, the patient dies of refractory shock

"These fibrin clots line the blood vessels and will shear RBCs that are passing through → microangiopathic haemolytic anaemia (MAHA)" ^[3]

While MAHA is part of the primary pathophysiology of DIC, it also creates its own complications:

Severe anaemia: Haemolysis + ongoing bleeding can drop Hb to critically low levels, worsening tissue hypoxia (already impaired by microvascular thrombosis)
Free haemoglobin toxicity: Massive intravascular haemolysis releases free haemoglobin, which:
- Scavenges nitric oxide (NO) → vasoconstriction → worsens organ ischaemia, particularly renal
- Is directly nephrotoxic (free haemoglobin precipitates in renal tubules → pigment nephropathy/ATN)
- Causes oxidative stress to endothelium → perpetuates endothelial damage → worsens DIC
Hyperbilirubinaemia: Massive haemolysis → increased unconjugated bilirubin production → jaundice (pre-hepatic component, compounding any hepatic dysfunction)

DIC management itself carries risks:

Treatment Complication	Mechanism	Clinical Significance
Transfusion-associated circulatory overload (TACO)	Large volumes of FFP (each unit ~250 mL), platelets, cryoprecipitate, pRBCs → fluid overload	Pulmonary oedema, worsening respiratory failure. Particularly dangerous in patients who already have DIC-related ARDS.
Transfusion-related acute lung injury (TRALI)	Donor antibodies in plasma-containing products → neutrophil activation in pulmonary vasculature → non-cardiogenic pulmonary oedema	Acute hypoxia and bilateral infiltrates within 6 hours of transfusion. Can be fatal. Distinguished from TACO by low BNP and normal CVP.
Febrile non-haemolytic transfusion reaction	Cytokines accumulated in stored blood products	Fever, rigors during/after transfusion. Usually benign but must rule out haemolytic reaction and bacterial contamination.
Citrate toxicity / Hypocalcaemia	Citrate anticoagulant in stored blood binds ionised calcium	Hypocalcaemia → perioral tingling, muscle cramps, prolonged QT, tetany. Worsens coagulopathy (calcium is Factor IV). Give IV calcium gluconate prophylactically during massive transfusion.
Hyperkalaemia	Potassium leaks from stored RBCs into supernatant during storage	Risk of cardiac arrhythmia, especially with concurrent AKI. Use fresher blood products when possible; monitor potassium closely.
Hypothermia	Rapid transfusion of cold/room-temperature blood products	Impairs coagulation enzyme kinetics, worsens coagulopathy, promotes arrhythmia. Use blood warmers for massive transfusion.
Heparin-induced thrombocytopenia (HIT)	If heparin is used for DIC-related thrombosis, PF4-heparin antibodies may develop → paradoxical thrombosis with thrombocytopenia	New or worsening thrombocytopenia 5–14 days after heparin exposure; arterial or venous thrombosis. Use 4T score. Switch to argatroban or fondaparinux if confirmed.
Worsening microvascular thrombosis from FFP	Prophylactic FFP provides substrate for ongoing coagulation	This is why prophylactic FFP without active bleeding is controversial — it may "add fuel to the fire" of the DIC process.

"Abdominal paracentesis should be avoided in patient with disseminated intravascular coagulation and hyperfibrinolysis." ^[26] — an example of how DIC restricts the ability to perform even routine diagnostic/therapeutic procedures safely.

The complications of DIC compound the complications of whatever triggered it:

Underlying Cause	Compounding Complications
Sepsis	DIC worsens septic shock (hypovolaemia from bleeding + microvascular obstruction → tissue hypoperfusion). Sepsis-related organ dysfunction + DIC-related organ dysfunction = dramatically higher mortality.
APL	DIC in APL is due to the release of procoagulants from the leukaemic blasts ^[23]. If ICH is avoided and ATRA started promptly, long-term prognosis is excellent (> 90% cure). If ATRA is delayed and ICH occurs, mortality is very high.
Obstetric	Postpartum haemorrhage worsened by DIC creates massive blood loss → haemorrhagic shock → Sheehan syndrome (pituitary infarction from hypovolaemia). DIC in pregnancy also threatens fetal survival.
Trauma	"Lethal triad" of hypothermia + acidosis + coagulopathy (DIC) in trauma creates a self-perpetuating cycle → haemorrhagic shock → death. Damage control surgery is critical.

Overall mortality: 40–80% depending on the underlying cause and severity
Mortality is primarily determined by:
1. The underlying condition (e.g., septic shock carries higher mortality than obstetric causes)
2. The severity and number of organ failures (each failing organ adds ~15–20% mortality)
3. The degree of coagulopathy (ISTH DIC score correlates with mortality)
4. Speed of treatment of the underlying cause
APL-DIC has the most paradoxical prognosis: devastatingly high early mortality from ICH, but > 90% long-term cure if the patient survives the first week with ATRA

Category	Specific Complications	Mechanism
Haemorrhagic	ICH, GI bleeding, mucosal bleeding, wound oozing, retroperitoneal haemorrhage	Consumption coagulopathy + FDP-mediated platelet/fibrin dysfunction
Thrombotic / Organ failure	AKI, hepatic dysfunction, ARDS, cerebral ischaemia/encephalopathy, VTE	Microvascular fibrin thrombi → organ ischaemia
Skin	Purpura fulminans, acral ischaemia/gangrene	Protein C depletion → uncontrolled dermal microvascular thrombosis
Endocrine	Waterhouse-Friderichsen syndrome (bilateral adrenal haemorrhagic infarction)	Adrenal vascular anatomy predisposes to haemorrhagic necrosis in DIC
Haematological	Severe anaemia (MAHA + bleeding), free Hb toxicity	Fibrin strands shear RBCs; free Hb scavenges NO and is nephrotoxic
Treatment-related	TACO, TRALI, citrate toxicity, hyperkalaemia, hypothermia, HIT	Complications of massive transfusion and anticoagulation therapy
Procedural	Inability to safely perform invasive procedures (paracentesis, bone marrow biopsy)	Severe coagulopathy makes any invasive procedure high-risk

High Yield Summary — Complications of DIC

ICH is the most feared complication and leading cause of early death, especially in APL-DIC. Aggressive platelet and fibrinogen replacement is critical to prevent it.
Multi-organ failure from microvascular thrombosis — kidneys (25%), liver (19%), lungs (16%), brain — is what kills most DIC patients.
AKI in DIC occurs via ischaemic ATN from microvascular thrombosis and hypovolaemia.
Purpura fulminans occurs due to severe protein C depletion → uncontrolled dermal microvascular thrombosis → haemorrhagic skin necrosis. Classic in meningococcal sepsis.
Waterhouse-Friderichsen syndrome = bilateral adrenal haemorrhagic infarction → acute adrenal crisis → refractory shock. Emergency hydrocortisone is life-saving.
MAHA is both a feature and a complication — free haemoglobin from massive haemolysis scavenges NO (worsening vasoconstriction), is nephrotoxic, and perpetuates endothelial damage.
Treatment complications (TACO, TRALI, citrate toxicity, hyperkalaemia, hypothermia) compound the clinical picture during massive transfusion.
DIC is a contraindication to invasive procedures (paracentesis, bone marrow biopsy) unless coagulopathy is corrected first.
Mortality is 40–80%, driven primarily by the underlying cause and the number of organ failures.

Active Recall - Complications of DIC

References

^[1] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf — DIC overview, p.1335 ^[2] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf — DIC overview, p.43 ^[3] Senior notes: Block A - Introduction to Haematological investigations (CBP, Clotting).pdf, p.19 ^[4] Senior notes: Maksim Medicine Notes.pdf — Haematology section (DIC clinical features), p.165 ^[5] Senior notes: Ryan Ho Haemtology.pdf — DIC section, pp.136–138 ^[7] Senior notes: Block A - Nephrotology Teaching Clinic RTD.pdf — ATN section, p.7 ^[9] Lecture slides: GC 027. Abnormal bleeding after tooth extraction.pdf, p.27 ^[14] Senior notes: Learning_Points_All_Lectures.txt — APL as haematological emergency ^[16] Senior notes: Adrian Lui Pediatrics Notes.pdf — DIC section, pp.398–400 ^[23] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf — APL-DIC management, p.20 ^[26] Senior notes: Handbook of Internal Medicine 2024.pdf — Abdominal paracentesis contraindications, p.499

High Yield Summary

DIC — Key Points for Exam:

Definition: Always secondary. Systemic activation of coagulation → simultaneous thrombosis AND bleeding
Causes — OMIT HSR: Obstetric, Malignancy (APL, mucinous tumours), Infections (sepsis), Trauma, Haemolytic transfusion/Snake bite/Hypersensitivity
Pathophysiology triad: (i) Microvascular thrombosis → organ failure, (ii) Consumption of clotting factors/platelets → bleeding, (iii) Secondary fibrinolysis → ↑FDPs/D-dimer which worsen bleeding
Why PT rises before aPTT: Factor VII (extrinsic pathway) has shortest half-life + Factor VIII (intrinsic pathway) is an acute phase reactant that is initially elevated
Full-house labs: ↓Platelets, ↑PT, ↑aPTT, ↓Fibrinogen, ↑D-dimer, Schistocytes on PBS — but seldom ALL present simultaneously
Acute DIC = bleeding predominates (consumption > production); Chronic DIC = thrombosis predominates (production keeps pace)
MAHA mechanism: Fibrin strands in microvasculature physically shear RBCs → schistocytes
Purpura fulminans: Due to severe protein C depletion → microvascular thrombosis in skin
Treatment cornerstone: Treat the underlying cause + replenish consumed components
APL-DIC: APL cells release tissue factor → extrinsic pathway activation; bleeding out of proportion to platelet count; confirm with cytogenetics showing t(15;17)

High Yield Summary — DDx of DIC

DIC vs TTP: The most critical distinction. Normal PT/aPTT and fibrinogen in TTP vs deranged in DIC. ADAMTS13 < 10% confirms TTP. Platelet transfusion contraindicated in TTP.
DIC vs Liver Disease: Factor VIII is the key — low in DIC (consumed), normal/high in liver disease (made by endothelium). Schistocytes present in DIC, absent in liver disease.
Full-house DIC picture (↑PT, ↑aPTT, ↓fibrinogen, ↓platelets, ↑D-dimer, schistocytes) is uncommon — partial presentations are more typical.
To exclude DIC when evaluating thrombocytopenia: check PBS for schistocytes, PT, aPTT, D-dimer, fibrinogen.
Both PT+aPTT prolonged: Think DIC first, then liver disease, massive transfusion, vitamin K deficiency, or anticoagulant effect.
Chronic DIC (thrombosis-predominant): DDx includes APS, MPN-associated thrombosis, inherited thrombophilia, HIT, occult malignancy.

High Yield Summary — Diagnosis of DIC

DIC is a clinical + laboratory diagnosis — no single test is diagnostic; use the ISTH scoring system
ISTH Score ≥ 5 = overt DIC (requires: known underlying condition + platelet count, D-dimer, PT prolongation, fibrinogen)
Serial measurements and trends are more valuable than single snapshots — repeat daily
Core investigations: CBC, PT, aPTT, fibrinogen, D-dimer, PBS for schistocytes
GC027 approach to both PT + aPTT prolonged: Repeat → fibrinogen → platelet → if all deranged with RBC fragmentation → DIC
PT rises before aPTT because Factor VII has the shortest half-life; Factor VIII (acute phase reactant) buffers the intrinsic pathway initially
Fibrinogen can be deceptively normal in sepsis (acute phase reactant) — a falling trend is more informative
To exclude DIC when evaluating thrombocytopenia: PBS (schistocytes), PT, aPTT, D-dimer, fibrinogen
Factor VIII level distinguishes DIC (low) from liver disease (normal/high)
Bone marrow biopsy is contraindicated in active DIC — correct coagulopathy first
DAT is negative in DIC (mechanical, non-immune haemolysis)
ADAMTS13 activity distinguishes TTP (< 10%) from DIC (normal/mildly reduced)

High Yield Summary — Management of DIC

"Treat the underlying cause" — THE most important intervention. DIC will not resolve without eliminating the trigger.
"Treatment of DIC is to replenish the consumed coagulation factors" + "Reverse the underlying causative factor" ^[9] — the two GC lecture exam points.
Platelet transfusion: < 20 prophylactic (with sepsis/fever); < 50 if active bleeding or procedure needed.
FFP: Only for active bleeding or pre-procedure with ↑PT/aPTT. Prophylactic FFP is controversial and may worsen thrombosis.
Cryoprecipitate: For fibrinogen < 1.0–1.5 g/L with active bleeding (concentrated fibrinogen source).
Anticoagulation: NOT in acute bleeding-predominant DIC; YES in chronic/thrombosis-predominant DIC or purpura fulminans.
APL-DIC: Start ATRA + ATO immediately (even before cytogenetics); aggressive blood product support to prevent ICH; excellent long-term prognosis if patient survives the initial phase.
Tranexamic acid: Generally contraindicated in DIC (worsens microvascular thrombosis).
Correct hypothermia and acidosis — both impair coagulation enzyme function.
Serial monitoring of CBC, clotting, fibrinogen, D-dimer every 6–12h to track response.

High Yield Summary — Complications of DIC

ICH is the most feared complication and leading cause of early death, especially in APL-DIC. Aggressive platelet and fibrinogen replacement is critical to prevent it.
Multi-organ failure from microvascular thrombosis — kidneys (25%), liver (19%), lungs (16%), brain — is what kills most DIC patients.
AKI in DIC occurs via ischaemic ATN from microvascular thrombosis and hypovolaemia.
Purpura fulminans occurs due to severe protein C depletion → uncontrolled dermal microvascular thrombosis → haemorrhagic skin necrosis. Classic in meningococcal sepsis.
Waterhouse-Friderichsen syndrome = bilateral adrenal haemorrhagic infarction → acute adrenal crisis → refractory shock. Emergency hydrocortisone is life-saving.
MAHA is both a feature and a complication — free haemoglobin from massive haemolysis scavenges NO (worsening vasoconstriction), is nephrotoxic, and perpetuates endothelial damage.
Treatment complications (TACO, TRALI, citrate toxicity, hyperkalaemia, hypothermia) compound the clinical picture during massive transfusion.
DIC is a contraindication to invasive procedures (paracentesis, bone marrow biopsy) unless coagulopathy is corrected first.
Mortality is 40–80%, driven primarily by the underlying cause and the number of organ failures.

Disseminated Intravascular Coagulation (DIC)

1. Definition

2. Epidemiology and Risk Factors

Epidemiology

Risk Factors

3. Relevant Anatomy and Physiology — Normal Haemostasis

3.1 Primary Haemostasis (Platelet Plug Formation)

3.2 Secondary Haemostasis (Coagulation Cascade)

3.3 Fibrinolysis (Clot Breakdown)

3.4 Natural Anticoagulants

4. Aetiology (with Focus on Hong Kong)

4.1 Major Causes — Mnemonic: OMIT HSR [4]

4.2 Hong Kong-Specific Considerations

4.3 APL and DIC — A Special Relationship

5. Pathophysiology

5.1 Step-by-Step Pathophysiology

5.2 Three Key Pathological Processes in DIC [3]

5.3 Why Does PT Rise Before aPTT in Acute DIC?

5.4 Why Does Fibrinogen Drop?

5.5 Natural Anticoagulant Depletion

5.6 DIC vs TMA — Understanding the Overlap

6. Classification

6.1 Acute (Decompensated) DIC vs Chronic (Compensated) DIC [4][5]

6.2 Overt vs Non-Overt DIC (ISTH Classification)

7. Clinical Features

7.1 Symptoms

7.2 Signs

7.3 Pattern of Bleeding — Platelet-Type vs Coagulation-Type

7.4 Organ Dysfunction in DIC

7.5 Laboratory Features as "Clinical Features"

7.6 Chronic DIC — Clinical Features

8. Summary of Key Pathophysiology-to-Clinical Feature Connections

Active Recall - Disseminated Intravascular Coagulation (DIC)

References

Why Differential Diagnosis Matters in DIC

9.1 Conditions That Mimic or Overlap with DIC

9.1.1 The MAHA-Thrombocytopenia Overlap — A Framework

9.1.2 Key Differentials — Detailed Comparison

9.1.3 Differentials for Thrombocytopenia Specifically

9.1.4 Differentials for Prolonged PT and aPTT

9.1.5 Differentials for Schistocytes on PBS (MAHA)

9.2 Differentiating DIC from its Closest Mimics — Diagnostic Decision Algorithm

9.3 Liver Disease vs DIC — A Commonly Tested Distinction

9.4 Distinguishing Chronic DIC from Other Causes of Unprovoked Thrombosis

9.5 The Special Case — Useful Investigations to Exclude DIC

9.6 Summary — How to Approach the DDx

Active Recall - Differential Diagnosis of DIC

10.1 Why DIC is a Clinical-Laboratory Diagnosis

10.2 ISTH DIC Scoring System (Overt DIC)

Step 1: Risk Assessment

Step 2: Score the Laboratory Parameters

10.3 Diagnostic Algorithm

10.4 Investigation Modalities — Detailed Breakdown

10.4.1 First-Line ("Core") Investigations

A. Complete Blood Count with Differential (CBC/D)

B. Peripheral Blood Smear (PBS)

C. Coagulation Profile

D. Haemolysis Markers (Supporting Evidence for MAHA)

10.4.2 Investigations to Identify the Underlying Cause

10.4.3 Additional / Specialised Investigations

10.4.4 Investigations for Organ Dysfunction Assessment

10.5 Interpretation Pearls — Putting It All Together

The "Classic" Acute DIC Laboratory Panel

Why PT Rises First — Revisited in Diagnostic Context

Key Investigation Results for DIC Exclusion (from ITP workup)

10.6 Summary Table — Investigations at a Glance

Active Recall - Diagnosis and Investigations of DIC

11.1 Overarching Principles

11.2 Management Algorithm

11.3 Pillar 1 — Treat the Underlying Cause

11.4 Pillar 2 — General Supportive Care

11.5 Pillar 3 — Blood Product Replacement Therapy

11.5.1 Platelet Transfusion

11.5.2 Fresh Frozen Plasma (FFP)

11.5.3 Cryoprecipitate

11.5.4 Packed Red Blood Cells (pRBCs)

11.5.5 Summary Table — Blood Products in DIC

11.6 Pillar 4 — Anticoagulation Therapy (Prevention and Treatment of Thrombosis)

11.6.1 When to Consider Anticoagulation

11.6.2 Antithrombin (AT) Concentrate