approach to thrombocytopaenia

Platelets <150 × 10⁹/L. The first step is always rule out pseudothrombocytopaenia (EDTA clumping — repeat in citrate tube). Then classify by mechanism: decreased production, increased destruction, or sequestration. A blood film is mandatory — it distinguishes TTP, DIC, and marrow pathology from benign causes.

do not miss

TTP — thrombocytopaenia + MAHA (schistocytes on film) + neurological symptoms → plasma exchange within hours; send ADAMTS13 but do not wait for the result. Platelet transfusion can worsen thrombosis.
HIT — platelet drop >50% starting 5–10 days after heparin exposure → stop all heparin (including flushes), start a non-heparin anticoagulant. Thrombosis, not bleeding, is the danger.
DIC — thrombocytopaenia + ↑ INR + ↑ fibrin degradation products + ↓ fibrinogen → treat the underlying cause (sepsis, malignancy, obstetric catastrophe)

classification

decreased production (marrow failure)

Marrow infiltration: leukaemia, lymphoma, metastatic cancer, myelofibrosis
Marrow suppression: chemotherapy, radiation, alcohol, B12/folate deficiency, aplastic anaemia
Myelodysplastic syndromes
Congenital: rare in adults (Wiskott-Aldrich, Bernard-Soulier, MYH9-related)

increased destruction

immune	non-immune
ITP (diagnosis of exclusion)	TMA: TTP (ADAMTS13 <10%), HUS (typical — Shiga toxin; atypical — complement-mediated)
HIT (heparin-induced)	DIC
drug-induced (vancomycin, linezolid, quinine, GP IIb/IIIa inhibitors)	mechanical (ECMO, IABP, prosthetic valve)
post-transfusion purpura	HELLP syndrome
antiphospholipid syndrome

sequestration / dilutional

Splenic sequestration — up to 90% of platelets can be trapped in a massively enlarged spleen (cirrhosis, myeloproliferative neoplasms, storage diseases)
Dilutional — massive transfusion, large-volume resuscitation

workup

always

Repeat CBC in citrate tube → exclude pseudothrombocytopaenia (EDTA artefact — 0.1% of specimens)
Blood film — schistocytes (TMA/DIC), blasts (leukaemia), giant platelets (MYH9 disorders, ITP), platelet clumps (pseudo)
CBC with differential, reticulocyte count
LDH, haptoglobin, unconjugated bilirubin (haemolysis screen)
Coagulation: INR, aPTT, fibrinogen, D-dimer
Liver function (cirrhosis/sequestration)
HIV, HCV, HBV (immune-mediated thrombocytopaenia)

directed by clinical context

suspected	send
TTP	ADAMTS13 activity (before plasma exchange if possible)
HIT	4T score → if intermediate/high, send PF4/heparin ELISA → SRA if ELISA positive
DIC	fibrinogen, fibrin degradation products, D-dimer, INR (trending)
ITP	diagnosis of exclusion — no confirmatory test; consider bone marrow biopsy if age >60, atypical features, or pre-splenectomy
drug-induced	temporal association + recovery after withdrawal

the 4T score for HIT

Pretest probability tool: Thrombocytopaenia (timing and severity), Timing of platelet drop, Thrombosis, oTher causes. Score ≤3 → low probability (HIT essentially excluded). Score 4–5 → intermediate (send immunoassay). Score 6–8 → high (start non-heparin anticoagulant empirically while awaiting results).

management principles

ITP

Observation if platelets >30 × 10⁹/L and no bleeding — most adults do not need treatment above this threshold
First-line: corticosteroids — dexamethasone 40 mg/day × 4 days (preferred for faster response) or prednisone 1 mg/kg/day with taper
IVIG 1 g/kg × 1–2 days — when rapid platelet rise needed (active bleeding, pre-procedure)
Second-line: TPO receptor agonists (eltrombopag, romiplostim), rituximab, splenectomy

HIT

Stop all heparin immediately (including line flushes)
Start non-heparin anticoagulant: argatroban (hepatic metabolism — preferred in renal failure) or fondaparinux (renal clearance)
Do not give warfarin until platelets >150 × 10⁹/L (risk of warfarin-induced venous limb gangrene in acute HIT)
Image for thrombosis — bilateral lower extremity US even if asymptomatic (50% have occult DVT)

TTP

Plasma exchange urgently — mortality drops from ~90% to ~10–20%
Corticosteroids (methylprednisolone 1 g/day × 3 days then taper)
Caplacizumab (anti-von Willebrand factor) — accelerates platelet recovery
Do not transfuse platelets unless life-threatening haemorrhage — theoretical risk of fuelling microvascular thrombosis

transfusion thresholds for thrombocytopaenia

<10 × 10⁹/L → prophylactic transfusion (absent consumption — futile in TTP/ITP)
<50 × 10⁹/L → transfuse for active bleeding or pre-procedure
<100 × 10⁹/L → neurosurgery, ocular surgery

traps

Pseudothrombocytopaenia is common — always confirm with a citrate tube and a blood film before working up a low platelet count. EDTA-dependent agglutinins affect ~0.1% of specimens.
“ITP” in an older adult — consider MDS and marrow infiltration before diagnosing ITP in patients >60. A bone marrow biopsy is warranted.
Thrombocytopaenia + thrombosis ≠ paradox — HIT, TTP, DIC, APS, and PNH all cause both. Thrombocytopaenia does not protect against clotting in consumptive disorders.
Platelet transfusion in TTP — historically taught as contraindicated. The absolute prohibition has softened (transfuse for life-threatening bleeding), but reflexive platelet transfusion without a diagnosis remains dangerous.
Missing HIT window — the classic 5–10 day window after heparin initiation. But prior heparin exposure within 100 days can cause rapid-onset HIT within hours. Always ask about recent heparin history.

thrombocytopaenia