What investigations should be done in a patient with thrombocytopenia (decreased platelet count)?

Diagnostic Approach for Thrombocytopenia

For patients with decreased platelet count, a systematic diagnostic workup should begin with first-step tests including complete blood count with peripheral blood smear examination, coagulation studies, and assessment of clinical features, followed by targeted second-line testing based on clinical suspicion. 1, 2

Initial Assessment

Clinical Evaluation

• Bleeding history assessment:

  • Type and severity of bleeding (petechiae, purpura, ecchymosis, mucosal bleeding)
  • Duration of bleeding episodes
  • Hemostasis with prior surgeries or pregnancies 1

• Risk factors and medical history:

  • Medication review (heparin, quinidine/quinine, sulfonamides, alcohol)
  • Recent infections or systemic symptoms
  • HIV risk factors
  • Pregnancy status
  • Transfusion history
  • Family history of thrombocytopenia 1, 2

• Physical examination:

  • Assess bleeding manifestations
  • Check for hepatosplenomegaly and lymphadenopathy
  • Look for signs of infection or autoimmune disorders
  • Evaluate for thrombosis 1

First-Step Laboratory Tests

1. Complete blood count with peripheral blood smear examination

   • Rule out pseudothrombocytopenia (platelet clumping with EDTA)
   • Assess platelet size and morphology
   • Evaluate RBC and WBC morphology 1, 2

2. Basic coagulation studies

   • Prothrombin time (PT)
   • Activated partial thromboplastin time (aPTT)
   • Fibrinogen 1, 2

3. Basic biochemical profile

   • Liver function tests
   • Renal function tests 2

Diagnostic Algorithm Based on Clinical Presentation

For Isolated Thrombocytopenia (Normal RBC and WBC)

• Consider:
  • Immune thrombocytopenia (ITP)
  • Drug-induced thrombocytopenia
  • Early-stage heparin-induced thrombocytopenia (if on heparin) 1, 3

For Thrombocytopenia with Thrombosis

• Consider:
  • Heparin-induced thrombocytopenia (HIT) - apply 4T score 1
  • Antiphospholipid syndrome
  • Thrombotic thrombocytopenic purpura (TTP)
  • Disseminated intravascular coagulation (DIC) 1

For Thrombocytopenia with Anemia and/or Abnormal WBC

• Consider:
  • Bone marrow disorders
  • Myelodysplastic syndromes
  • Leukemia
  • Aplastic anemia 1, 4

Second-Step Tests Based on Clinical Suspicion

For Suspected ITP

• Anti-nuclear antibody (ANA)
• Direct antiglobulin test
• HIV testing
• Hepatitis C testing
• Consider bone marrow examination in patients >60 years or with atypical features 1, 2

For Suspected HIT

• 4T score assessment:
  • Thrombocytopenia (degree of platelet count drop)
  • Timing (typically 5-10 days after heparin initiation)
  • Thrombosis or other clinical sequelae
  • Other potential causes of thrombocytopenia 1
• HIT antibody testing if 4T score is intermediate or high 1

For Suspected Inherited Platelet Function Disorders

• Light transmission aggregometry (LTA)
• Assessment of platelet granule release
• Flow cytometry for platelet surface glycoproteins 1

For Suspected TTP

• ADAMTS13 activity level and inhibitor titer
• Lactate dehydrogenase (LDH)
• Haptoglobin
• Reticulocyte count
• Bilirubin 2

Important Considerations

• Platelet count thresholds associated with bleeding risk:

  • <50 × 10³/μL: Activity restrictions recommended
  • <20 × 10³/μL: Increased risk of any bleeding
  • <10 × 10³/μL: High risk of serious bleeding 3, 5

• Risk factors that increase bleeding risk:

  • Female sex
  • Exposure to anticoagulants or NSAIDs
  • Very low platelet counts (<10 × 10³/μL) 5

• Bone marrow examination is not routinely needed but indicated in:

  • Patients >60 years
  • Presence of systemic symptoms
  • Abnormal signs on physical examination
  • Atypical features on blood smear 2

By following this systematic approach, clinicians can efficiently diagnose the cause of thrombocytopenia and implement appropriate management strategies to reduce morbidity and mortality associated with this condition.