What is thrombocytopenia?

Thrombocytopenia: Definition, Diagnosis, and Management

Thrombocytopenia is defined as a platelet count less than 150,000/μL (150 × 10³/μL) and can result from decreased platelet production, increased destruction, splenic sequestration, or dilution. 1 The severity of thrombocytopenia is classified according to platelet count as mild (50-150 × 10³/μL), moderate (20-50 × 10³/μL), severe (<20 × 10³/μL), or very severe (<10 × 10³/μL). 2

Clinical Presentation

The clinical manifestations of thrombocytopenia correlate with the severity of the platelet count reduction:

• >50,000/μL: Generally asymptomatic
• 20,000-50,000/μL: Mild skin manifestations such as petechiae, purpura, or ecchymosis
• <10,000/μL: High risk of serious bleeding 1

Etiology

Thrombocytopenia can result from various mechanisms:

1. Decreased platelet production:

   • Bone marrow disorders
   • Megaloblastic anemia
   • Viral infections affecting bone marrow

2. Increased platelet destruction:

   • Immune thrombocytopenia (ITP)
   • Drug-induced thrombocytopenia
   • Heparin-induced thrombocytopenia (HIT)

3. Splenic sequestration:

   • Liver disease
   • Portal hypertension

4. Dilution:

   • Massive transfusion

5. Other causes:

   • Pregnancy-related (gestational thrombocytopenia, preeclampsia)
   • Infections (HIV, hepatitis C)
   • Autoimmune disorders 3, 2

Diagnostic Approach

When thrombocytopenia is identified, follow these steps:

1. Rule out pseudothrombocytopenia by collecting blood in a tube containing heparin or sodium citrate and repeating the platelet count

2. Determine if acute or chronic by reviewing previous platelet counts

3. Assess for emergency conditions requiring immediate hospitalization:

   • Heparin-induced thrombocytopenia
   • Thrombotic microangiopathies
   • HELLP syndrome (hemolysis, elevated liver enzymes, low platelets)

4. Laboratory evaluation:

   • Complete blood count with differential
   • Peripheral blood smear examination
   • Reticulocyte count
   • Vitamin B12 and folate levels
   • Thyroid function tests
   • HIV testing and hepatitis screening
   • Iron studies
   • Autoimmune serology (ANA, antiphospholipid antibodies)
   • Bone marrow aspiration and biopsy for unexplained cases 2, 1

Special Considerations

Immune Thrombocytopenia (ITP)

ITP is an acquired autoimmune disorder characterized by platelet destruction and impaired platelet production. It remains a diagnosis of exclusion after ruling out other causes of thrombocytopenia. 3

• Primary ITP is not associated with other conditions
• Secondary ITP occurs with additional autoimmune cytopenias, primary immunodeficiency, or underlying autoimmune conditions/infections 3

Heparin-Induced Thrombocytopenia (HIT)

HIT is an immune-mediated disorder characterized by antibodies against the heparin-platelet factor 4 complex. Unlike typical thrombocytopenia, HIT paradoxically increases thrombosis risk. 2

• Women have twice the risk of developing HIT compared to men
• Typical onset is 5-10 days after heparin initiation
• Can occur rapidly within 24 hours in patients with recent heparin exposure 2

Pregnancy-Related Thrombocytopenia

Gestational thrombocytopenia is the most common cause of thrombocytopenia during pregnancy, accounting for about 75% of cases. It's characterized by:

• Mild thrombocytopenia (typically >70,000/μL)
• Occurs during late gestation
• No past history of thrombocytopenia (except possibly during previous pregnancy)
• Not associated with fetal thrombocytopenia
• Resolves spontaneously after delivery 3

Management

Management depends on the underlying cause and severity of thrombocytopenia:

1. Severe thrombocytopenia (<10,000/μL) or active bleeding:

   • Urgent management including transfusion support
   • Specific therapy directed at underlying cause 2, 1

2. Moderate thrombocytopenia:

   • Activity restrictions to avoid trauma-associated bleeding
   • Treatment of underlying cause 1

3. Platelet transfusion indications:

   • Active hemorrhage
   • Platelet count <10,000/μL
   • Before invasive procedures when platelet count is inadequate 1

4. Specific treatments based on etiology:

   • ITP: Corticosteroids, intravenous immunoglobulin, thrombopoietin receptor agonists, rituximab 3, 4
   • HIT: Discontinue heparin, use direct thrombin inhibitors or other alternative anticoagulants 2
   • Drug-induced thrombocytopenia: Discontinue offending medication 5

Prognosis

The prognosis varies based on the underlying cause:

• ITP in children: Often self-limiting with high remission rates (62-74% at 1 year) 3
• ITP in adults: Less predictable with 20-45% achieving complete remission by 6 months 3
• Mortality risk: Adults with ITP have a 1.3-2.2-fold higher mortality than the general population due to cardiovascular disease, infection, and bleeding 3

Understanding the specific cause of thrombocytopenia is crucial for appropriate management and improving outcomes.