What are the diagnostic steps and treatment options for thrombocytopenia (low platelet count)?

Diagnostic Approach to Thrombocytopenia

The diagnosis of thrombocytopenia requires a systematic approach starting with confirmation of true thrombocytopenia through peripheral blood smear examination, followed by targeted history, physical examination, and laboratory testing to determine the underlying cause. 1

Initial Evaluation

• Confirm true thrombocytopenia by examining the peripheral blood smear to exclude pseudothrombocytopenia due to platelet clumping in EDTA tubes (occurs in about 0.1% of adults) 2
• If pseudothrombocytopenia is suspected, collect blood in a tube containing heparin or sodium citrate and repeat the platelet count 3
• Review previous platelet counts to distinguish between acute and chronic thrombocytopenia 3
• Perform a complete blood count with differential to assess for other cytopenias that may suggest specific diagnoses 1

Key History Elements

• Bleeding symptoms (type, severity, duration) 2
• Medication history, particularly focusing on heparin, quinidine/quinine, sulfonamides, and alcohol 2
• Recent vaccinations (to assess for vaccine-induced immune thrombocytopenia and thrombosis) 2
• Transfusion history 2
• Family history of thrombocytopenia 2
• Risk factors for HIV infection 2
• Comorbid conditions that may increase bleeding risk 2
• Recent trauma or surgeries and hemostasis with prior procedures 2

Physical Examination Focus

• Assess for bleeding signs (petechiae, purpura, ecchymosis, retinal hemorrhages) 2
• Evaluate for hepatosplenomegaly (splenomegaly argues against ITP) 2
• Check for lymphadenopathy (may suggest lymphoproliferative disorders) 2
• Look for signs of infection, particularly bacteremia or HIV 2
• Evaluate for evidence of autoimmune disease (arthritis, goiter, nephritis, cutaneous vasculitis) 2
• Assess for thrombosis (may indicate heparin-induced thrombocytopenia or antiphospholipid syndrome) 2

Laboratory Testing

First-line Tests

• Complete blood count with differential and peripheral blood smear 1
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) 1
• D-dimer measurement and fibrinogen assay (to assess for DIC) 1
• Liver function tests 1
• Chemistry profile to assess renal function 1

Second-line Tests (Based on Clinical Suspicion)

• HIV testing for patients with risk factors 2
• Bone marrow examination for patients with:
  • Persistent thrombocytopenia (>6-12 months) 2
  • Abnormal cells on peripheral smear 1
  • No obvious cause identified from initial testing 1
• Anti-PF4 antibody testing if heparin-induced thrombocytopenia is suspected 2
• Imaging studies (abdominal ultrasound or CT) if splenomegaly is suspected 2

Diagnostic Algorithms for Specific Scenarios

For Suspected Heparin-Induced Thrombocytopenia (HIT)

1. Apply the 4T score based on: 2

   • Thrombocytopenia severity (platelet count typically 30-70 × 10⁹/L)
   • Timing of onset (typically 5-10 days after starting heparin)
   • Thrombosis or other clinical sequelae
   • Other potential causes of thrombocytopenia

2. If 4T score indicates intermediate or high probability:

   • Order anti-PF4 antibody testing 2
   • Consider alternative anticoagulation 2

For Suspected Immune Thrombocytopenia (ITP)

1. Confirm isolated thrombocytopenia without other cytopenias 2
2. Exclude other causes through history, physical exam, and basic labs 2
3. Consider bone marrow examination for:
   • Patients with persistent thrombocytopenia (>6-12 months) 2
   • Patients unresponsive to initial therapy 2
   • Atypical features (e.g., abnormal cells on peripheral smear) 2

For Suspected Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT)

1. Assess vaccination history 2
2. Perform initial tests (full blood count) 2
3. If thrombocytopenia is present:
   • Measure D-dimer 2
   • Perform coagulation screen including Clauss fibrinogen assay 2
   • Consider anti-PF4 antibody testing 2
   • Perform appropriate imaging based on symptoms 2

Treatment Considerations

• For platelet counts <10 × 10⁹/L or active bleeding, platelet transfusion is recommended 3
• For ITP:
  • First-line therapy typically includes corticosteroids, IVIG, or anti-Rh(D) 4
  • For insufficient response, romiplostim may be indicated (starting dose 1 mcg/kg weekly) 4
  • Splenectomy may be considered for persistent ITP unresponsive to medical therapy 2
• For VITT:
  • Administer 1 g/kg intravenous immunoglobulin 2
  • Use non-heparin based anticoagulants for confirmed thrombosis 2
• For HIT:
  • Discontinue all heparin products 2
  • Use alternative anticoagulants (direct oral anticoagulants, fondaparinux, or danaparoid sodium) 2

Common Pitfalls to Avoid

• Failing to confirm true thrombocytopenia by examining the peripheral blood smear 2
• Assuming thrombocytopenia is always due to a single cause when multiple pathologies may coexist 1
• Delaying bone marrow examination when clinically indicated, especially with high suspicion for malignancy 1
• Overlooking drug-induced causes, particularly heparin, quinidine, and sulfonamides 2
• Assuming bleeding risk based solely on platelet count without considering other factors 3
• Failing to recognize thrombotic conditions that can present with thrombocytopenia (HIT, antiphospholipid syndrome, TTP) 3