Thrombocytopenia

Definition and bleeding risk. Platelet count below 150 × 109/L. Spontaneous bleeding is unusual above 50, purpura and mucosal bleeding appear below 30, and the risk of spontaneous serious or intracranial bleeding rises below 10–20 × 109/L. Always exclude pseudothrombocytopenia from EDTA-induced platelet clumping by repeating the count in a citrate tube and examining the film.

Classification by mechanism. Decreased production — marrow failure or infiltration (leukaemia, myeloma, metastases, myelofibrosis), myelodysplasia, aplastic anaemia, B /folate deficiency, alcohol, chemotherapy and 12 radiation. Increased destruction — immune (ITP, drug-induced, HIT, post-transfusion purpura, secondary to CLL, SLE, HIV, hepatitis C) or non-immune (DIC, TTP/HUS, mechanical valves, sepsis). Sequestration — hypersplenism from portal hypertension. Dilutional — massive transfusion.

Drug-induced thrombocytopenia (high yield in the elderly). Heparin (HIT), quinine and quinidine, sulphonamides and co-trimoxazole, vancomycin, linezolid, rifampicin, valproate, carbamazepine, phenytoin, thiazides, glycoprotein IIb/IIIa inhibitors and chemotherapy. Onset is typically 1–2 weeks after starting a new drug, and recovery follows within 5–7 days of withdrawal.

Immune thrombocytopenia (ITP) in older adults. A diagnosis of exclusion — isolated thrombocytopenia with a normal blood film and no other cause. In the elderly it is more often secondary (to CLL, lymphoma, myelodysplasia, HIV, hepatitis C, H. pylori, SLE or drugs) and carries a higher bleeding risk, so a bone marrow examination should be performed in most patients over 60 to exclude myelodysplasia. Antiplatelet antibody testing is not required.

Emergency causes that must not be missed. Heparin-induced thrombocytopenia — a fall of >50% at 5–10 days with thrombosis, not bleeding; assess with the 4Ts score, stop all heparin (including flushes) and start a non-heparin anticoagulant (argatroban, fondaparinux); never give platelet transfusions or warfarin alone. TTP — microangiopathic haemolytic anaemia with fragmented red cells, fever, renal impairment and neurological signs from ADAMTS13 deficiency, requiring urgent plasma exchange. Also DIC and sepsis.

Management. Treat the cause and stop the offending drug. In ITP, treat only if the platelet count is below 20– 30 × 109/L or there is bleeding: first-line is corticosteroids (prednisolone 1 mg/kg, or dexamethasone 40 mg for 4 days — preferred in the elderly for shorter steroid exposure) with IVIG 1 g/kg for urgent rises. Second-line: thrombopoietin receptor agonists (eltrombopag, romiplostim, avatrombopag), rituximab, or splenectomy (less favoured in the elderly). Platelet transfusion only for active bleeding or before invasive procedures — it is contraindicated in HIT and TTP. Prophylactic transfusion threshold is 10 × 109/L in stable patients.

Newer targeted therapy in ITP. The ADVANCE trials of efgartigimod (a neonatal Fc receptor blocker that accelerates IgG degradation, Lancet 2023) and the Bruton tyrosine kinase inhibitor rilzabrutinib have both demonstrated durable platelet responses in chronic ITP, offering steroid-sparing options that are particularly valuable in older patients, in whom prolonged corticosteroids cause diabetes, osteoporosis, delirium and infection. Current practice increasingly moves to a TPO receptor agonist as early second-line therapy rather than prolonged steroids.