What is thrombocytopenia?

Thrombocytopenia: Definition, Diagnosis, and Management

Thrombocytopenia is defined as a platelet count less than 150 × 10³ per μL, characterized by decreased platelets in peripheral blood that can result from decreased production, increased destruction, splenic sequestration, or dilution. 1

Clinical Presentation and Significance

The severity of thrombocytopenia correlates with bleeding risk:

• >50 × 10³/μL: Generally asymptomatic 1
• 20-50 × 10³/μL: Risk of mild bleeding with skin manifestations (petechiae, purpura, ecchymosis) 1
• 10-20 × 10³/μL: Increased bleeding risk
• <10 × 10³/μL: High risk of serious bleeding, including gastrointestinal hemorrhage, extensive skin/mucosal bleeding, or intracranial hemorrhage 2, 1

Etiology

Thrombocytopenia can result from four primary mechanisms:

1. Decreased platelet production:

   • Bone marrow disorders
   • Nutritional deficiencies (B12, folate)
   • Medications/chemotherapy
   • Viral infections

2. Increased platelet destruction:

   • Immune thrombocytopenia (ITP)
   • Drug-induced immune thrombocytopenia
   • Heparin-induced thrombocytopenia (HIT)
   • Thrombotic microangiopathies

3. Splenic sequestration:

   • Liver disease with portal hypertension
   • Hypersplenism

4. Dilutional or artifactual:

   • Massive transfusion
   • Pseudothrombocytopenia (EDTA-induced platelet clumping) 2

Diagnostic Approach

When thrombocytopenia is detected:

1. Confirm true thrombocytopenia:

   • Rule out pseudothrombocytopenia by collecting blood in a tube containing heparin or sodium citrate and repeating the platelet count 1
   • Examine peripheral blood smear to assess platelet size, morphology, and clumping 3

2. Determine if acute or chronic:

   • Review previous platelet counts 1
   • Acute severe thrombocytopenia may require emergency hospitalization

3. Essential laboratory evaluation:

   • Complete blood count with differential
   • Peripheral blood smear examination
   • Consider additional tests based on clinical suspicion:
     • Bone marrow examination (if persistent or associated with other abnormalities)
     • HIV and HCV testing
     • Vitamin B12 and folate levels
     • Iron studies
     • Liver function tests
     • Lactate dehydrogenase (LDH)
     • Autoimmune markers (ANA, antiphospholipid antibodies)
     • Flow cytometry for suspected hematologic malignancies 3

Management Considerations

Management depends on the underlying cause, severity of thrombocytopenia, and presence of bleeding:

1. Observation:

   • Appropriate for asymptomatic patients with platelet counts >50 × 10³/μL 1

2. Treat underlying cause:

   • Discontinue suspected causative medications
   • Treat infections
   • Address nutritional deficiencies
   • Manage liver disease 3

3. Specific treatments for immune thrombocytopenia:

   • First-line: Glucocorticoids
   • Acute management of severe thrombocytopenia: Intravenous immunoglobulin (IVIG)
   • Refractory cases: Rituximab, thrombopoietic agents, fostamatinib, splenectomy 3, 4

4. Platelet transfusions:

   • Recommended for:
     • Active hemorrhage
     • Platelet counts <10 × 10³/μL
     • Before invasive procedures (target count depends on procedure)
   • Note: Platelet transfusions may be contraindicated in certain conditions like HIT or thrombotic thrombocytopenic purpura 1

5. Activity restrictions:

   • Patients with platelet counts <50 × 10³/μL should avoid trauma-associated activities 1

Special Considerations

1. Thrombocytopenia with thrombosis risk:

   • Conditions like antiphospholipid syndrome, HIT, and thrombotic microangiopathies can present with both bleeding and thrombosis 1
   • For suspected HIT, use the 4T score for clinical probability assessment:
     • Thrombocytopenia (0-2 points)
     • Timing of onset (0-2 points)
     • Thrombosis or other sequelae (0-2 points)
     • Other causes of thrombocytopenia (0-2 points) 3
   • When HIT is confirmed, alternative anticoagulation should be initiated with direct thrombin inhibitors or factor Xa inhibitors 3

2. Pregnancy-associated thrombocytopenia:

   • Consider gestational thrombocytopenia, preeclampsia, HELLP syndrome
   • HELLP syndrome requires emergency hospitalization 1

Thrombocytopenia is a common hematologic finding that requires systematic evaluation to determine its cause and appropriate management. The severity of thrombocytopenia and presence of bleeding symptoms guide the urgency and intensity of intervention.