What investigations are recommended for a patient with a decreasing platelet (thrombocytopenia) count?

Diagnostic Approach to Decreasing Platelet Count (Thrombocytopenia)

The initial workup for a decreasing platelet count should include confirmation of true thrombocytopenia through peripheral blood smear examination, followed by a systematic evaluation including complete blood count with differential, coagulation studies, and specific testing based on clinical presentation.

Initial Evaluation

• Confirm true thrombocytopenia by examining peripheral blood smear to rule out pseudothrombocytopenia (platelet clumping in EDTA) 1
• Perform complete blood count with differential to evaluate other cell lines and assess severity of thrombocytopenia 1
• Conduct coagulation studies including prothrombin time (PT) and activated partial thromboplastin time (aPTT) to identify potential coagulopathies 2, 1
• Measure D-dimer levels, which may help stratify patients who need closer monitoring, especially in conditions like COVID-19 2

Essential Laboratory Tests

• Test for HIV and HCV infections, as these are common causes of secondary thrombocytopenia 2
• Consider testing for H. pylori infection using urea breath test or stool antigen test in adults with typical ITP presentation 2
• Determine blood group Rh(D) typing if anti-D immunoglobulin therapy is being considered 2
• Monitor fibrinogen levels in patients with severe thrombocytopenia to evaluate for potential disseminated intravascular coagulation 2

Specialized Testing Based on Clinical Suspicion

• For suspected immune thrombocytopenia (ITP):

  • Perform testing for antiphospholipid antibodies and antinuclear antibodies 2
  • Consider thyroid function tests and antithyroid antibodies, as 8-14% of ITP patients may develop clinical thyroid disease 2

• For suspected inherited platelet disorders:

  • Perform light transmission aggregometry (LTA) with a panel of agonists as a first-step test 2
  • Consider flow cytometry screening using antibodies against platelet glycoproteins 2, 3
  • Evaluate ristocetin-induced platelet aggregation (RIPA) to detect abnormal interactions between von Willebrand factor and platelet glycoprotein Ib 3

Bone Marrow Examination

• Consider bone marrow examination in the following situations:

  • Patients older than 60 years 2
  • Presence of systemic symptoms or abnormal signs 2
  • Patients with persistent thrombocytopenia unresponsive to initial therapy 2, 1
  • Patients with atypical features suggesting alternative diagnosis 1
  • Cases where splenectomy is being considered 2

• Both bone marrow aspirate and biopsy should be performed, along with flow cytometry and cytogenetic testing 2

Management Based on Platelet Count

• For severe thrombocytopenia (<20 × 10⁹/L):

  • Consider hospital admission for newly diagnosed patients 1
  • Monitor closely for signs of bleeding 4
  • Consider platelet transfusion for patients with active hemorrhage 4

• For moderate thrombocytopenia (20-50 × 10⁹/L):

  • Outpatient management is generally appropriate in the absence of significant bleeding 1
  • Ensure expedited follow-up with a hematologist within 24-72 hours 1
  • Be aware that mild skin manifestations such as petechiae, purpura, or ecchymosis may occur 4

• For mild thrombocytopenia (>50 × 10⁹/L):

  • Outpatient management with appropriate follow-up is recommended 1
  • Spontaneous serious bleeding is rare (<5% of patients) 1, 4

Common Pitfalls to Avoid

• Failing to confirm true thrombocytopenia through peripheral blood smear examination 1
• Overlooking medication-induced thrombocytopenia, especially from heparin, quinidine, and sulfonamides 1
• Missing conditions where both thrombocytopenia and thrombosis can occur, such as heparin-induced thrombocytopenia, antiphospholipid syndrome, and thrombotic microangiopathies 4, 5
• Performing unnecessary bone marrow examination in patients presenting with typical ITP 2
• Neglecting to consider reticulated platelet count, which can help differentiate between decreased production and increased destruction of platelets (cutoff >11% suggests increased thrombopoietic activity with 93% sensitivity and 85% specificity) 6