Thrombocytopaenia

Causes

• Decreased Production

  • Chronic liver disease (reduced thrombopoietin)

  • Bone marrow infiltration or suppression (leukaemia, lymphoma, myelodysplasia, SLE, HIV, EBV)

  • Nutritional deficiencies (severe B12 or folate deficiency)

  • Drug-induced marrow suppression (chemotherapy, certain antipsychotics)

  • Aplastic anaemia, congenital disorders (Fanconi anaemia)

• Increased Destruction

  • Immune Thrombocytopaenic Purpura (ITP): Often post-viral, can be acute in children, chronic in adults

  • Drug-Induced: Heparin (HIT), antibiotics (e.g. trimethoprim-sulfamethoxazole, doxycycline), antiepileptics

  • Microangiopathic Processes: TTP (ADAMTS13 deficiency), HUS (Shiga toxin-producing E. coli), DIC (uncontrolled coagulation activation)

  • Splenomegaly/Hypersplenism: Increased sequestration, often in portal hypertension or myelofibrosis

• Other

  • Lab error (platelet clumping or pseudothrombocytopaenia), always confirm with a repeat FBC and peripheral smear

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Clinical Features

• General

  • Easy bruising, petechiae, purpura

  • Mucosal bleeding (epistaxis, gingival bleeds, menorrhagia)

• Severe Presentations

  • TTP: Confusion, neurological symptoms, fever, microangiopathic haemolysis

  • HUS: Haematuria, acute kidney injury, bloody diarrhoea (often in children after E. coli O157:H7 infection)

  • DIC: Widespread bleeding, multi-organ dysfunction

  • Profound thrombocytopaenia (<10 × 10^9/L) raises concern for spontaneous intracranial haemorrhage or major haemorrhage

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Investigations

• Initial Labs

  • FBC + blood film: Assess platelet morphology and RBC fragments (schistocytes suggest TTP/HUS)

  • Reticulocyte count, LDH, bilirubin, haptoglobin for haemolysis screen

  • Coagulation profile (PT, aPTT, fibrinogen) to exclude DIC

  • UEC: Check for AKI (HUS)

  • LFTs for chronic liver disease, low thrombopoietin

  • B12/folate levels

• Specific Tests

  • HIV/Hepatitis serologies

  • ADAMTS13 assay if TTP suspected

  • Anti-PF4 antibodies for suspected heparin-induced thrombocytopaenia (HIT)

  • Stool culture if HUS or GI infection suspected

• Clinical History

  • Onset: acute vs gradual bruising/bleeding

  • Risk factors: alcohol misuse, poor diet, recent viral illness, IV drug use, medication history

  • Family history of bleeding disorders

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Examination

• Mucosal bleeding (gums, nose), petechiae, widespread purpura

• TTP: confusion, neurological deficits, fever, renal impairment

• Signs of chronic liver disease (jaundice, spider naevi, ascites), splenomegaly

• Lymphadenopathy or bone tenderness (possible haematological malignancy)

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When to Refer

• Platelet counts

  • <50 × 10^9/L: Urgent review, especially if bleeding or other cytopenias

  • 50–100 × 10^9/L: Non-urgent referral if persistent or symptomatic

• Presence of

  • Blasts, significant dysplasia on blood smear

  • Suspected TTP/HUS (neurological or renal involvement)

  • Features of malignant infiltration or severe bleeding

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Management

• General Measures

  • Treat underlying cause (reduce alcohol, correct nutritional deficiency, withdraw offending medication)

  • Avoid NSAIDs, vigorous contact sports, or other bleeding risks

• ITP

  • First-line: Corticosteroids (prednisolone 1 mg/kg) if platelets <30 × 10^9/L or bleeding

  • IVIg for severe thrombocytopaenia or active bleeding

  • Splenectomy or rituximab for refractory cases

  • Thrombopoietin receptor agonists (eltrombopag, romiplostim) in chronic unresponsive ITP

• TTP/HUS

  • Urgent plasma exchange ± steroids (TTP)

  • Dialysis for renal failure in HUS

  • Manage fluid balance, correct electrolytes, treat infection if relevant

• Heparin-Induced Thrombocytopaenia (HIT)

  • Stop heparin immediately

  • Commence alternative anticoagulant (e.g. argatroban, fondaparinux)

• DIC

  • Identify and treat underlying cause (sepsis, malignancy, obstetric complications)

  • Supportive care with platelets, FFP, cryoprecipitate if significant bleeding or very low fibrinogen

• Chronic Liver Disease

  • Address portal hypertension, consider beta-blockers for variceal prophylaxis

  • Platelet transfusion or TPO agonists (e.g. eltrombopag) pre-procedure if very low platelet counts

• Platelet Transfusion

  • Indicated if platelets <10 × 10^9/L (prophylaxis) or <50 × 10^9/L with active bleeding or invasive procedure

  • Avoid routine prophylaxis in TTP/HUS unless life-threatening bleeding

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Notes:

• TTP: Microangiopathic haemolytic anaemia + thrombocytopaenia + neurological symptoms ± fever ± renal dysfunction

• HUS: Similar to TTP but predominantly renal involvement, often diarrhoea-related

• Check for Lab Error: Pseudothrombocytopaenia (platelet clumping in EDTA tubes)

• Post-Splenectomy Vaccinations: Pneumococcal, meningococcal, Haemophilus influenzae type b to reduce sepsis risk

• Always confirm thrombocytopaenia with a repeat FBC ± citrate tube if platelet clumping is suspected

• Evaluate for medication causes (heparin, antibiotics, antiplatelet agents)

• Identify urgent conditions: TTP/HUS present with MAHA (schistocytes), neurological or renal signs → immediate referral

• Manage mild ITP in primary care if stable, but refer if platelets <30 × 10^9/L or bleeding

• Chronic or recurrent thrombocytopaenia warrants haematology input for possible bone marrow assessment, immunotherapy, or splenectomy