What is thrombocytopenia?

Thrombocytopenia: Definition, Diagnosis, and Management

Thrombocytopenia is defined as a platelet count less than 150,000/μL (150 × 10^9/L) and represents an important clinical condition that can range from an incidental finding to a life-threatening emergency depending on severity. 1

Definition and Classification

Thrombocytopenia can be categorized based on:

• Severity:

  • Mild: 100,000-150,000/μL
  • Moderate: 50,000-100,000/μL
  • Severe: 20,000-50,000/μL
  • Very severe: <20,000/μL

• Duration:

  • Newly diagnosed
  • Persistent (3-12 months)
  • Chronic (≥12 months) 2

• Etiology:

  • Primary (immune thrombocytopenia)
  • Secondary (associated with other conditions)

Pathophysiology

Thrombocytopenia results from one or more of these mechanisms:

1. Decreased platelet production in the bone marrow
2. Increased platelet destruction (often immune-mediated)
3. Splenic sequestration of platelets
4. Dilution (as in massive transfusions)
5. Platelet clumping (pseudothrombocytopenia) 1, 2

Clinical Presentation

The clinical manifestations correlate with the severity of thrombocytopenia:

• >50,000/μL: Generally asymptomatic
• 20,000-50,000/μL: Mild skin manifestations (petechiae, purpura, ecchymosis)
• 10,000-20,000/μL: Increased risk of bleeding
• <10,000/μL: High risk of serious bleeding, including gastrointestinal and intracranial hemorrhage 1, 2

Diagnostic Approach

Essential Diagnostic Steps:

1. Confirm true thrombocytopenia by:

   • Examining peripheral blood smear to exclude pseudothrombocytopenia
   • Collecting blood in tubes containing heparin or sodium citrate if pseudothrombocytopenia is suspected 2, 1

2. Assess bleeding severity:

   • Type and extent of bleeding (mucosal, cutaneous, internal)
   • Severity of bleeding 2

3. Evaluate medical history:

   • Medications (heparin, quinidine/quinine, sulfonamides)
   • Alcohol use
   • Recent infections
   • Pregnancy status
   • Family history of thrombocytopenia
   • Comorbid conditions 2

4. Physical examination:

   • Bleeding signs
   • Splenomegaly (suggests against ITP if present)
   • Lymphadenopathy
   • Signs of liver disease
   • Neurological function 2

Laboratory Evaluation:

• Complete blood count with peripheral smear
• Reticulocyte count
• Basic coagulation studies
• Tests for secondary causes as indicated 2

Common Causes of Thrombocytopenia

1. Immune Thrombocytopenia (ITP):

   • Primary autoimmune disorder
   • Diagnosis of exclusion

2. Drug-induced thrombocytopenia:

   • Common culprits: heparin, quinidine, sulfonamides, sulfonylureas 2

3. Infection-associated:

   • Viral (HIV, HCV)
   • Bacterial (sepsis)

4. Bone marrow disorders:

   • Leukemia
   • Myelodysplastic syndromes

5. Thrombotic microangiopathies:

   • Thrombotic thrombocytopenic purpura (TTP)
   • Hemolytic uremic syndrome (HUS)

6. Heparin-induced thrombocytopenia (HIT):

   • Paradoxical thrombosis risk

7. Liver disease and hypersplenism

8. Pregnancy-related:

   • HELLP syndrome
   • Gestational thrombocytopenia 2, 1

Management Principles

General Approach:

• Treatment depends on platelet count, bleeding risk, and underlying cause
• Address the underlying cause when possible

Specific Management:

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

   • Platelet transfusion is indicated 2
   • Consider fibrinogen supplementation with fresh frozen plasma or cryoprecipitate if bleeding is severe 2

2. For immune thrombocytopenia (ITP):

   • First-line: Corticosteroids, IVIG, or anti-D immunoglobulin
   • Second-line: Thrombopoietin receptor agonists (romiplostim, eltrombopag) for insufficient response to first-line therapy 3, 4
   • Splenectomy for refractory cases 2

3. For drug-induced thrombocytopenia:

   • Discontinue the offending medication 2

4. For heparin-induced thrombocytopenia (HIT):

   • Immediate discontinuation of all heparin products
   • Switch to direct thrombin inhibitors if anticoagulation needed 2

Platelet Count Thresholds for Intervention:

• <10,000/μL: Platelet transfusion recommended even without bleeding
• <20,000/μL: Treatment indicated regardless of symptoms 2
• <50,000/μL with significant mucous membrane bleeding: Treatment indicated 2
• <50,000/μL: Activity restrictions to avoid trauma-associated bleeding 1

Special Considerations

1. Pseudothrombocytopenia:

   • Occurs in about 0.1% of adults
   • Due to platelet clumping in EDTA-anticoagulated blood
   • Always confirm thrombocytopenia with peripheral blood smear 2

2. Splenomegaly:

   • Present in <3% of ITP patients
   • If present, suggests alternative diagnosis 2

3. Lifestyle considerations:

   • A sedentary individual may tolerate lower platelet counts than someone with high-risk activities 2

4. Monitoring:

   • Regular platelet count monitoring during treatment
   • Weekly during dose adjustment of medications
   • Monthly after stabilization 3

Thrombocytopenia management requires careful assessment of the underlying cause and bleeding risk, with treatment tailored to the specific etiology and severity of the condition.