The biconcave disc shape and remarkable deformability of a normal RBC depend entirely on the integrity of these cytoskeletal-membrane interactions. Any defect in these proteins weakens the connection between the skeleton and the lipid bilayer → the unsupported lipid bilayer buds off as tiny vesicles (microvesiculation) → progressive loss of membrane surface area → the cell becomes a sphere.

• Autosomal dominant (AD) inheritance in ~75% of cases ^[1][2]
  • This means a single mutant allele is sufficient to cause disease
  • Affected parent → 50% chance of passing to each child
  • Equal male and female affected
• ~25% are sporadic (de novo mutations or autosomal recessive inheritance) ^[1][2]
  • Autosomal recessive HS tends to be more severe (homozygous or compound heterozygous mutations → more severe protein deficiency)
  • ↑ severity if compound heterozygosity ^[1][2]

The proteins mutated in HS include ^[1][2]:

Unlike thalassaemia and G6PD deficiency (which confer malaria resistance and are thus prevalent in tropical/subtropical regions), HS mutations do not appear to confer any selective advantage against malaria. Their prevalence in Northern Europe likely reflects founder effects and genetic drift in European populations rather than positive natural selection.

↓ cytoskeleton-membrane interaction → ↓ membrane stability ^[1][2]

• Whichever protein is mutated (ankyrin, spectrin, band 3, protein 4.2), the result is the same: the lipid bilayer is inadequately tethered to the spectrin skeleton underneath.
• Think of it as the tent canvas not being properly pegged down to its frame — the canvas flaps loose.

Primary loss of membrane due to microvesiculation → progressive spherocytosis ^[1][2]

• The unsupported regions of lipid bilayer bud off as microvesicles (tiny lipid-containing vesicles that pinch off from the cell surface).
• Each microvesicle carries away a small piece of membrane but the cytoplasmic contents (haemoglobin) stay behind inside the cell.
• Result: the cell progressively loses surface area without losing volume.
• As surface area decreases relative to volume, the cell has no choice but to assume the shape with the lowest surface-area-to-volume ratio: a sphere.

• A normal biconcave disc can fold and squeeze through the tiny (1–3 μm) inter-endothelial slits of the splenic sinusoids in the red pulp.
• A spherocyte cannot deform to pass through these slits.

Spherocytosis → ↓ deformability → inability to pass through splenic microcirculation → confers liability to haemolysis ^[1][2]

• Spherocytes get trapped in the red pulp of the spleen.
• Once trapped, they are exposed to the hostile splenic environment:
  • Low pH
  • Low glucose
  • High concentration of splenic macrophages
• The macrophages phagocytose and destroy the trapped spherocytes → extravascular haemolysis
• This is why splenectomy is effective: remove the site of destruction, and the cells survive longer (even though they remain spherocytic).

An important additional detail: even spherocytes that manage to pass through the spleen on one transit get further "conditioned" — the spleen nibbles off more membrane with each pass. So with each transit through the spleen, the cell loses more membrane and becomes an even more perfect sphere. This is a vicious cycle that accelerates their destruction.

Because spherocytes are selectively trapped in the splenic red pulp (they can't squeeze through the sinusoidal slits). The spleen becomes engorged with trapped RBCs and its macrophages undergo work hypertrophy from constantly phagocytosing these cells → organ enlarges.

Removing the spleen removes the site of destruction. The spherocytes still exist (the genetic defect persists), but without the spleen to trap and destroy them, they survive longer in the circulation. Post-splenectomy, Hb usually normalises, though spherocytes persist on blood film.

Chronic haemolysis → chronic ↑ unconjugated bilirubin → liver conjugates as much as it can → ↑ conjugated bilirubin excreted in bile → supersaturation of bile with calcium bilirubinate → black pigment gallstones. This process starts in childhood, so gallstones can present in teenagers — much earlier than the typical cholesterol gallstones of middle-aged women.

Chronic haemolysis → compensatory ↑ erythropoiesis → ↑ cell division in marrow → ↑ folate demand (folate is essential for DNA synthesis). If dietary intake doesn't keep up, folate deficiency develops → megaloblastic crisis.

Parvovirus B19 has tropism for erythroid precursors (binds P antigen on proerythroblasts). It causes a transient red cell aplasia lasting ~7–14 days. In a normal person with RBC lifespan of 120 days, losing 7–14 days of production causes a negligible Hb drop. But in HS, where RBC lifespan may be only 10–20 days, losing even a week of production means nearly all circulating RBCs will have been destroyed without replacement → catastrophic anaemia.

HS is an important cause of pathological NNJ ^[2][6]. The differential in this setting:

Gallstones in a teenager or young adult should trigger the thought of chronic haemolysis. DDx:

• Hereditary spherocytosis → pigmented gallstones (50% adults) ^[2][6]
• Sickle cell disease
• Thalassaemia intermedia
• Hereditary elliptocytosis
• G6PD deficiency (if chronic variant)
• Gilbert syndrome (can co-exist and worsen jaundice but doesn't cause gallstones by itself — actually, the combination of Gilbert + mild haemolysis dramatically increases gallstone risk)

The key DDx here is not "what caused the haemolysis" but "why did the patient suddenly decompensate?"

A diagnosis of HS can be established when all of the following are present:

In patients with a classic presentation (positive family history in first-degree relative + typical clinical features + spherocytes on PBS + elevated MCHC + negative DAT + evidence of haemolysis), the BSH guidelines state that further confirmatory testing (EMA, osmotic fragility) is not mandatory — the diagnosis is clinically secure. Confirmatory tests become essential when:

• Family history is negative (sporadic cases — 25%)
• The clinical picture is ambiguous
• The PBS findings are subtle (mild HS with few spherocytes)
• You need to distinguish from other causes of DAT-negative spherocytosis (e.g., hereditary stomatocytosis — important because splenectomy is contraindicated in stomatocytosis)

What: Automated analysis of blood providing Hb, MCV, MCH, MCHC, RDW, WBC, platelet count.

Findings in HS ^[6][2]:

Why MCHC matters so much: MCHC = Hb / Haematocrit. It tells you the average haemoglobin concentration within the red cell. Normally, this is tightly regulated at 33–36 g/dL. In spherocytosis, the cell has lost membrane (and with it some water) but kept its haemoglobin → same Hb crammed into a smaller, denser cell → MCHC rises above 36. This is one of the most useful automated screening clues — many haematologists use MCHC > 35.5–36 g/dL combined with elevated RDW as a screening trigger for further HS testing.

What: Measures the proportion of immature red cells (reticulocytes) in peripheral blood, reflecting bone marrow erythropoietic output.

Findings in HS ^[6][2]:

• Reticulocyte count > 6% (can range from 3–15% depending on severity)
• Absolute reticulocyte count also elevated

Interpretation: A high reticulocyte count confirms the marrow is responding appropriately to the haemolysis — the "factory is working well" ^[4]. This is compensatory erythropoiesis.

Critical exception: In aplastic crisis (parvovirus B19), the reticulocyte count drops precipitously ^[6][2] — this is the hallmark distinguishing aplastic crisis from haemolytic crisis. An inappropriately low reticulocyte count in a known HS patient with worsening anaemia = parvovirus B19 until proven otherwise.

What: Manual microscopic examination of a Wright-Giemsa stained thin blood film.

Blood film is extremely valuable as it provides clues to aetiology ^[2][4][14].

Findings in HS ^{[1][6][10][14]}:

What: A set of blood tests that together confirm haemolysis is occurring.

Laboratory features of haemolytic anaemia ^[1][10]:

What about direct (conjugated) bilirubin? — Should be normal or minimally elevated. If direct bilirubin is disproportionately high, think of concurrent hepatic or post-hepatic pathology (e.g., gallstone obstructing the CBD — a real complication of HS).

What: Detects antibodies (IgG) or complement (C3) already bound to the surface of the patient's RBCs.

Principle: Patient's washed RBCs are incubated with anti-human globulin (Coombs' reagent). If IgG or C3 is bound to the RBC surface, the reagent causes agglutination → positive test.

Finding in HS: Negative ^[1][6][10]

Finding in immune haemolytic anaemia: Positive ^[1][10][11]

Why this test is critical: It is the single most important test to separate immune from non-immune causes of spherocytosis. In clinical practice and exams, your first reflex upon seeing spherocytes should be to order a DAT.

What: A flow cytometric assay that quantifies the binding of the fluorescent dye eosin-5-maleimide (EMA) to Band 3 protein and other cytoskeletal proteins (Rh-related proteins, glycophorin A, CD47) on the RBC surface.

Principle from first principles:

• EMA = "eosin" (a fluorescent dye) + "5-maleimide" (a chemical group that covalently binds to sulphydryl groups on proteins)
• Band 3 is the major integral membrane protein of the RBC
• In HS, membrane protein content is reduced (due to microvesiculation and primary protein deficiency) → fewer binding sites for EMA → decreased fluorescence on flow cytometry

Finding in HS: ↓ EMA binding (decreased fluorescence compared to normal control) ^{[1][6][11][12]}

Performance:

• Sensitivity: ~90–93%
• Specificity: ~95–99%
• This is superior to the osmotic fragility test in both sensitivity and specificity ^[6]

Advantages over osmotic fragility test:

• Requires only a small blood volume (can test neonates)
• Rapid (results in hours, not 24 hours)
• Not affected by recent transfusion (can test within 2–3 days of transfusion if using patient's own cells with gating)
• More objective (flow cytometric readout vs. visual assessment of haemolysis)

Limitations:

• EMA binding can also be reduced in hereditary pyropoikilocytosis (HPP), Southeast Asian ovalocytosis (SAO), congenital dyserythropoietic anaemia type II (CDA II), and cryohydrocytosis — so it is not 100% specific for HS alone, but these are rare
• Requires access to a flow cytometer (available in most haematology labs in Hong Kong)

High Yield: Flow cytometric analysis showing ↓ eosin-5-maleimide (EMA) binding on red cell skeletal proteins is the preferred first-line confirmatory test for HS ^[1][6][12].

What: A functional test that assesses how susceptible RBCs are to lysis when placed in hypotonic solutions of decreasing NaCl concentration.

Principle from first principles:

• When you place an RBC in a hypotonic solution (lower NaCl concentration than plasma), water enters the cell by osmosis.
• A normal biconcave disc has "excess" membrane — it can swell considerably before reaching its maximum volume and lysing.
• A spherocyte has already lost excess membrane — it is already at near-maximum volume. It has very little capacity to swell before the membrane ruptures → it lyses at a higher NaCl concentration (i.e., in a less hypotonic solution) than a normal RBC.

Finding in HS: ↑ osmotic fragility compared to normal RBCs when exposed to hypotonic solutions of decreasing tonicities ^[6][12]

Graphical interpretation:

• The osmotic fragility curve plots % haemolysis (y-axis) against NaCl concentration (x-axis, decreasing from left to right).
• In HS, the curve shifts to the RIGHT, meaning that at all levels of NaCl, the degree of lysis is higher than that of normal RBCs ^[12]. In other words, HS RBCs begin lysing at a higher NaCl concentration (more "fragile" in hypotonic solutions).

Pre-incubation at 37°C for 24 hours: Increases diagnostic yield ^[6]. Why? Pre-incubation at 37°C in sterile conditions allows the RBCs to metabolise glucose and slowly lose membrane in vitro (mimicking what happens in vivo). Normal cells tolerate this well, but HS spherocytes — already compromised — become even more spherocytic after 24 hours, exaggerating the fragility difference.

Performance ^[6]:

• Low sensitivity and specificity compared to flow cytometry (EMA binding)
• False negatives: mild HS (especially HS trait), iron deficiency (which makes cells more resistant to osmotic lysis because microcytes have higher SA:V ratio)
• False positives: warm AIHA (spherocytes from any cause will increase fragility), recent transfusion
• For these reasons, EMA binding has largely replaced OFT as the first-line confirmatory test. OFT is used when EMA binding is not available ^[6]

Finding: Erythroid hyperplasia ^[6]

Interpretation: The marrow is responding to chronic haemolysis by increasing red cell precursor production. You see a shift in the myeloid:erythroid (M:E) ratio from the normal ~3:1 to < 2:1 or even 1:1.

Clinical utility: Rarely needed for HS diagnosis. A bone marrow biopsy is NOT routinely indicated. It may be performed if:

• There is diagnostic uncertainty (e.g., aplastic crisis with pancytopenia raising concern for aplastic anaemia or haematological malignancy)
• You suspect a concurrent marrow disorder

Once HS is diagnosed, screen for complications:

Because HS is autosomal dominant in ~75% of cases ^[1][6]:

• Screen first-degree relatives with CBC (looking for ↑ MCHC, anaemia), reticulocyte count, blood film, and DAT
• If screening CBC is suspicious, proceed to EMA binding
• Remember that 60% of HS cases result from a defect in the ankyrin–spectrin complex or vertical interaction ^[1] — identifying the affected family members helps genetic counselling

GC Lecture Slide: Folic acid supplement ^[1]

Block A Notes: Folic acid supplementation → as in all cases of hemolysis ^[12]

Indication: All patients with HS who have ongoing haemolysis (moderate or severe). Some guidelines also recommend it for mild HS.

Dose ^[2][6]:

• 1–2 mg/day for moderate/severe haemolysis
• 5 mg/day if pregnant (increased folate demand during pregnancy)

Rationale (from first principles):

• Chronic haemolysis → compensatory ↑ erythropoiesis → bone marrow is turning over cells much faster than normal
• DNA synthesis requires folate (as tetrahydrofolate, a cofactor for thymidylate synthase) → each new red cell precursor division consumes folate
• Without supplementation, the chronically ↑ demand eventually outstrips dietary intake → folate deficiency → megaloblastic crisis ^[2][6]
• This is preventive treatment: cheap, safe, and avoids a completely preventable crisis

Contraindications: Essentially none. Folic acid is water-soluble and non-toxic at these doses.

GC Lecture Slide: Compensated haemolysis – no specific treatment ^[1]

Block A Notes: If compensated hemolysis → no specific treatment ^[12]

Who: Patients with mild HS where the bone marrow can fully compensate for the haemolysis — Hb remains near-normal (≥ 11 g/dL), reticulocyte count only mildly elevated (3–6%), and the patient is asymptomatic.

What this means in practice:

• Folic acid supplementation (as above)
• Regular monitoring (CBC, reticulocytes, bilirubin every 6–12 months)
• Patient/parent education about warning signs of crises (pallor, jaundice, dark urine, fever)
• Awareness of parvovirus B19 risk (avoid known outbreaks; inform school/workplace)
• USG abdomen periodically to screen for gallstones

Why not splenectomise everyone? Because splenectomy carries lifelong risks (overwhelming post-splenectomy infection, thrombosis) that outweigh the benefits in mild/compensated disease. The risk-benefit calculation only tips toward splenectomy when haemolysis is severe.

Indication: Severe anaemia — particularly during aplastic crisis (parvovirus B19), severe haemolytic crisis, or in neonates with severe NNJ/anaemia.

Specifics:

• Packed red cell transfusion to maintain adequate Hb (target depends on clinical context; generally aim for Hb > 7–8 g/dL, higher if symptomatic)
• In neonates: may need top-up transfusions in the first few months of life, especially if severely affected
• In aplastic crisis: single or repeated transfusion to bridge the 10–14 day period of reticulocytopenia until marrow recovery

Risks of chronic transfusion:

• Iron overload → each unit of packed RBCs contains ~200–250 mg of iron; the body has no active iron excretion mechanism → iron accumulates in heart, liver, endocrine organs ^[17]
• If chronically transfused, consider iron chelation therapy (desferrioxamine, deferiprone, or deferasirox) ^[17]
• Alloimmunisation (development of alloantibodies against donor red cell antigens → makes future crossmatching difficult)

EPO: may be useful in some infants < 9 months to ↓ transfusion requirement ^[2][6]

Rationale: Very young infants (< 9 months) have physiologically lower EPO production and are also the age group where we most want to avoid splenectomy (immune system too immature). Exogenous EPO can stimulate erythropoiesis enough to reduce or avoid transfusions during this critical period.

Limited role: This is a temporising measure, not a long-term solution. Most children will not need ongoing EPO once they are old enough for splenectomy (if indicated) or once their baseline haemolysis stabilises.

GC Lecture Slide: Cholecystectomy if symptomatic gall-stone ^[1]

Block A Notes: Cholecystectomy if symptomatic gallstones ^[12]

Indication: Symptomatic pigmented gallstones (biliary colic, cholecystitis, choledocholithiasis, gallstone pancreatitis).

Timing and approach:

• Standard laparoscopic cholecystectomy
• If splenectomy is also indicated, combined laparoscopic splenectomy + cholecystectomy can be performed in a single operation — this is preferred to avoid two separate general anaesthetics
• Asymptomatic gallstones: generally observed rather than prophylactically removed, unless splenectomy is being performed simultaneously (in which case prophylactic cholecystectomy is often added)

Rationale: Pigmented gallstones in HS will continue to form as long as haemolysis continues. After splenectomy, haemolysis is dramatically reduced → new stone formation rate drops significantly. Therefore, if cholecystectomy and splenectomy are both needed, combining them is optimal.

Allogeneic HSCT: NOT used due to unfavourable risk-benefit ratio ^[2][6]

Why not? HSCT is the only potentially curative treatment (replacing the defective haematopoietic stem cells with normal donor cells). However:

• HS is rarely life-threatening — most patients do well with conservative management ± splenectomy
• HSCT carries significant morbidity and mortality (graft-versus-host disease, graft failure, infection, long-term immunosuppression, secondary malignancies)
• The risk-benefit ratio is far too unfavourable for a condition manageable with splenectomy

Contrast with thalassaemia major: HSCT is used for thalassaemia major because without it, patients face lifelong transfusion dependence with inevitable iron overload and early death. The severity justifies the HSCT risk. HS is not in the same category.

GC Lecture Slide: Gall-stone ^[1]

Complications of haemolysis: NNJ, splenomegaly and pigmented gallstones (50% adults) ^[2][6]

Prevalence: ~50% of adults with HS develop pigmented gallstones ^[2][6]. Can present as early as the teenage years — an age that would be highly unusual for typical cholesterol gallstones.

Pathophysiology from first principles:

1. Chronic extravascular haemolysis → chronic ↑ unconjugated bilirubin production
2. Liver conjugates bilirubin (UDP-glucuronyl transferase) and excretes conjugated bilirubin into bile via the canalicular membrane
3. The chronically ↑ bilirubin load means more conjugated bilirubin is excreted into bile than normal
4. In bile, conjugated bilirubin is deconjugated by bacterial β-glucuronidase back to unconjugated bilirubin
5. Unconjugated bilirubin complexes with calcium → calcium bilirubinate → precipitates as black pigment stones
6. These stones are small, hard, irregular, multiple, and radiopaque (visible on plain AXR, unlike cholesterol stones which are usually radiolucent)

Clinical consequences:

• Biliary colic: episodic RUQ/epigastric pain, often postprandial
• Acute cholecystitis: stone impacted in cystic duct → gallbladder inflammation
• Choledocholithiasis: stone migrates into CBD → obstructive jaundice (now conjugated hyperbilirubinaemia on top of the baseline unconjugated hyperbilirubinaemia — a double hit)
• Cholangitis: ascending infection of an obstructed biliary tree → Charcot's triad (fever, jaundice, RUQ pain)
• Gallstone pancreatitis: stone impacts at the ampulla of Vater

Management: Cholecystectomy if symptomatic gallstones ^[1][12]. If splenectomy is also indicated, a combined procedure is preferred.

GC Lecture Slide: Splenomegaly ^[1]

Pathophysiology:

• Spherocytes are selectively trapped in the splenic red pulp → chronic engorgement of the red pulp sinusoids with trapped cells
• Splenic macrophages undergo work hypertrophy from constantly phagocytosing spherocytes
• Result: progressive splenomegaly, usually mild to moderate (1–2 cm below costal margin) ^[19]

Consequences of splenomegaly:

Hypersplenism occurs because the enlarged spleen has proportionally more red pulp → more blood pools in the spleen → more cells are retained → the peripheral blood counts fall. This can exacerbate the already-existing anaemia and may contribute to bruising (thrombocytopenia) or ↑ infection risk (leukopenia).

Two features that may appear alarming on CBC but are just consequences of splenectomy ^[19]: spurious leukocytosis after splenectomy and increase in platelet counts. Also Howell-Jolly bodies and nucleated RBCs on PBS post-splenectomy.

GC Lecture Slide: Jaundice — indirect hyperbilirubinaemia ^[1]

Complications of haemolysis: NNJ ^[2][6]

Pathophysiology:

• Neonatal hepatic glucuronyl transferase activity is physiologically immature (~1% of adult levels at birth, reaching adult levels by ~2 weeks)
• This already-limited conjugation capacity is overwhelmed by the ↑ unconjugated bilirubin load from HS haemolysis
• Result: severe unconjugated hyperbilirubinaemia in the first 24–48 hours of life
• Risk of kernicterus (bilirubin encephalopathy) if bilirubin exceeds the brain-protective albumin binding capacity → free unconjugated bilirubin crosses the blood-brain barrier → deposits in the basal ganglia, hippocampus, and brainstem nuclei → irreversible neurological damage

Clinical significance:

• HS is one of the causes of pathological NNJ (jaundice within the first 24 hours, or total bilirubin rising faster than 5 mg/dL/day)
• May be the first presentation of HS — a neonate with severe jaundice and a positive family history of anaemia or splenectomy
• Management: phototherapy, exchange transfusion if bilirubin reaches dangerous thresholds

Who is affected: Patients with severe, transfusion-dependent HS (a minority, but important).

Pathophysiology:

• Each unit of packed RBCs contains ~200–250 mg of iron
• The body has no active mechanism for iron excretion — iron can only be lost through desquamation of skin/gut cells, menstruation, or bleeding
• With repeated transfusions, iron accumulates in tissues: heart (cardiomyopathy, arrhythmias), liver (fibrosis, cirrhosis), endocrine organs (diabetes mellitus, hypogonadism, hypothyroidism, growth failure)

Monitoring: Serum ferritin (though an acute phase reactant, so imperfect), transferrin saturation, MRI T2* (cardiac and hepatic iron quantification)

Management: Iron chelation therapy — desferrioxamine (DFO, SC/IV infusion), deferiprone (oral), or deferasirox (oral). Choice depends on iron burden, patient compliance, and side effect profile.

Note: Iron overload is mainly a problem for transfusion-dependent HS patients. In most HS patients (mild/moderate), chronic haemolysis actually causes some degree of iron loading via increased gastrointestinal iron absorption (driven by suppressed hepcidin from expanded erythropoiesis), but this is usually modest and does not require chelation unless significant.

Prevalence: Rare in HS; more commonly seen in sickle cell disease and other severe haemolytic anaemias.

Pathophysiology: Rigid spherocytes impair microcirculation in dependent areas (ankles, lower legs) → tissue ischaemia → ulceration. Usually occurs only in severe, uncorrected HS. Typically resolves after splenectomy.

Prevalence: Very rare; only in severe, untreated HS.

Pathophysiology: When the bone marrow is maximally expanded and still cannot compensate for haemolysis, haematopoietic tissue proliferates outside the marrow — in the liver, spleen, and occasionally paraspinal regions (forming paravertebral masses). This is the same phenomenon seen in thalassaemia major, though much milder in HS.

Pathophysiology: Chronic anaemia → compensatory bone marrow expansion → marrow cavity expands at the expense of cortical bone → cortical thinning, osteopenia. In severe cases, maxillary hypertrophy and frontal bossing (similar to, but much milder than, the "chipmunk facies" of thalassaemia major). Chronic anaemia also impairs growth velocity.

Late complication: overwhelming post-splenectomy infection (OPSI) ^[7]

Pathophysiology: asplenic patients are unable to mount an immunological response against encapsulated organisms ^[7]

Why the spleen is irreplaceable for fighting encapsulated bacteria:

• Encapsulated bacteria (e.g., S. pneumoniae) have polysaccharide capsules that resist opsonisation by complement and antibodies
• The spleen's marginal zone B cells are uniquely capable of producing T-independent IgM antibodies against polysaccharide antigens — no other lymphoid organ does this as effectively
• The spleen's open circulation (slow transit through the red pulp cords) allows macrophages to phagocytose poorly-opsonised organisms that would escape capture elsewhere
• Without a spleen, encapsulated organisms can proliferate in the bloodstream unchecked → fulminant bacteraemia → septic shock → death within hours

Epidemiology:

• Lifetime risk of OPSI: ~5% in asplenic patients
• Mortality of OPSI: ~50–70% even with treatment
• Risk is highest in the first 2 years post-splenectomy but persists lifelong
• Risk is higher in children (immature immune system) — one reason splenectomy is deferred until > 6–7 years

Causative organisms ^[7]:

Mnemonic: "Some Nasty Killers Have Some Capsule Protection" ^[7]:

• Streptococcus pneumoniae (most common, ~50–70% of OPSI cases)
• Neisseria meningitidis
• Klebsiella pneumoniae
• Haemophilus influenzae
• Salmonella typhi
• Cryptococcus neoformans
• Pseudomonas aeruginosa

Prevention ^[7]:

• Vaccination: PCV13 + PPSV23 (repeat every 5 years), Hib vaccine, meningococcal ACWY vaccine, influenza — given > 2 weeks pre-op if elective, ASAP if urgent
• Antibiotic prophylaxis (oral penicillin V)
• Patient education + MedicAlert bracelet
• Seek immediate medical attention for any fever > 38°C

Early complication: post-op thrombocytosis: prophylactic aspirin if platelet > 1000 ^[7]

Pathophysiology: The spleen normally sequesters ~30% of circulating platelets. After splenectomy, these platelets are released into the circulation, and there is no ongoing sequestration → platelet count rises, often exceeding 1,000 × 10⁹/L in the first 1–2 weeks post-op.

Risks:

• Reactive thrombocytosis can reach 1,000–2,000 × 10⁹/L
• Elevated platelet count increases the risk of venous thromboembolism (DVT, PE) and, rarely, portal vein thrombosis
• Portal vein thrombosis is a particularly feared complication — presents with abdominal pain, ascites, worsening liver function

Management:

• Prophylactic low-dose aspirin if platelet count > 1,000 × 10⁹/L ^[7]
• Consider prophylactic anticoagulation (LMWH) in high-risk patients
• Platelet count usually normalises within 2–4 weeks as the marrow adjusts

Early complication: post-splenectomy septicaemia ^[7]

Risk factors: young, immunocompromised ^[7]

Pathogens: Streptococcus pneumoniae, N. meningitidis, H. influenzae ^[7]

This overlaps with OPSI but refers specifically to early post-operative sepsis (days to weeks after surgery), before the immune system has had time to develop compensatory mechanisms. Management: urgent broad-spectrum antibiotics (e.g., IV ceftriaxone), blood cultures, close monitoring.

Immediate complications ^[7]:

Prevalence: ~10–15% of people have one or more accessory spleens (ectopic splenic tissue, most commonly at the splenic hilum or in the omentum).

Problem: If an accessory spleen is not identified and removed during splenectomy, it can hypertrophy over time → eventually becomes large enough to resume significant extravascular haemolysis → symptoms recur.

Clue: If a patient has persistent or recurrent haemolysis after splenectomy, AND Howell-Jolly bodies are absent from the blood film (they should be present if the patient is truly asplenic), suspect a missed accessory spleen.

Investigation: Tc-99m sulphur colloid or heat-damaged RBC scan (nuclear medicine) → identifies functional splenic tissue.

Management: Surgical removal of the accessory spleen (accessory splenectomy).