What is the initial workup and treatment for a patient with thrombocytopenia (low platelet count)?

Initial Workup and Treatment for Thrombocytopenia

The initial workup for thrombocytopenia should include confirmation of the low platelet count, determination of chronicity, assessment of bleeding risk, and identification of the underlying cause, followed by appropriate treatment based on severity and etiology.

Confirming Thrombocytopenia

1. Rule out pseudothrombocytopenia

   • Collect blood in a tube containing heparin or sodium citrate and repeat the platelet count 1
   • Examine peripheral blood smear for platelet clumping

2. Determine chronicity

   • Review previous platelet counts to distinguish acute from chronic thrombocytopenia 1
   • Acute thrombocytopenia with rapid decline may require emergency management

Initial Assessment

1. Clinical evaluation

   • Assess for bleeding manifestations:
     • Platelet count >50 × 10³/μL: Generally asymptomatic
     • Platelet count 20-50 × 10³/μL: Mild skin manifestations (petechiae, purpura, ecchymosis)
     • Platelet count <10 × 10³/μL: High risk of serious bleeding 1

2. Laboratory workup

   • Complete blood count with peripheral smear
   • Coagulation studies (PT, aPTT, fibrinogen)
   • Liver function tests
   • Renal function tests
   • Additional tests based on suspected etiology

Identifying Underlying Causes

1. Decreased production

   • Bone marrow disorders (leukemia, myelodysplastic syndrome)
   • Vitamin deficiencies (B12, folate)
   • Viral infections (HIV, hepatitis C)

2. Increased destruction

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

3. Splenic sequestration

   • Portal hypertension
   • Hepatic disease

4. Dilutional

   • Massive transfusion
   • Large volume crystalloid infusion 2

Emergency Causes Requiring Hospitalization

• Heparin-induced thrombocytopenia (HIT)
• Thrombotic microangiopathies
• HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) 1

Treatment Approach

For Severe Thrombocytopenia (Platelet Count <10 × 10³/μL) or Active Bleeding

1. Platelet transfusion

   • Recommended for active hemorrhage or platelet counts <10 × 10³/μL 1
   • For patients requiring invasive procedures, maintain adequate platelet counts to reduce bleeding risk

2. Activity restrictions

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

For Specific Etiologies

Heparin-Induced Thrombocytopenia (HIT)

1. Immediate discontinuation of all heparin products 3, 4
2. Alternative anticoagulation
   • For patients with normal renal function: argatroban, lepirudin, or danaparoid 3
   • For patients with renal insufficiency: argatroban 3
3. Avoid vitamin K antagonists until platelet count recovers to >150 × 10⁹/L 3
4. Monitor for thrombotic complications 4

Immune Thrombocytopenia (ITP)

1. First-line therapy:

   • Corticosteroids
   • Intravenous immunoglobulin
   • Anti-D immunoglobulin (in Rh-positive patients)

2. Second-line therapy:

   • Splenectomy 3
   • TPO receptor agonists (e.g., romiplostim) for patients with insufficient response to corticosteroids, immunoglobulins, or splenectomy 5

3. For refractory ITP:

   • Combination chemotherapy
   • Rituximab
   • Other immunosuppressive agents 3

Cancer-Associated Thrombocytopenia (CAT)

1. For platelet count ≥50 × 10⁹/L:

   • Full therapeutic anticoagulation without platelet transfusion 3

2. For severe thrombocytopenia (<50 × 10⁹/L) with high thrombosis risk:

   • Full-dose anticoagulation with platelet transfusion support to maintain platelet count ≥40-50 × 10⁹/L 3

3. For severe thrombocytopenia with lower thrombosis risk:

   • Platelet count 25-50 × 10⁹/L: Reduce LMWH to 50% of therapeutic dose or use prophylactic dose
   • Platelet count <25 × 10⁹/L: Temporarily discontinue anticoagulation 3

Drug-Induced Thrombocytopenia

1. Identify and discontinue the offending medication 2

   • Common culprits: glycoprotein IIb/IIIa inhibitors, vancomycin, linezolid, beta-lactam antibiotics, quinine, antiepileptic drugs

2. Monitor platelet count for recovery

   • Usually resolves after discontinuation of the offending drug 2

Important Caveats

1. Some thrombocytopenic conditions can present with both bleeding AND thrombosis:

   • Antiphospholipid syndrome
   • Heparin-induced thrombocytopenia
   • Thrombotic microangiopathies 1

2. For HIT, avoid platelet transfusions unless there is life-threatening bleeding 3

3. For patients on TPO receptor agonists (e.g., romiplostim):

   • Use the lowest dose to achieve and maintain platelet count ≥50 × 10⁹/L
   • Monitor complete blood counts weekly during dose adjustment
   • Discontinue if no response after 4 weeks at maximum dose 5

4. Patients with thrombocytopenia who have received rituximab may not respond to vaccinations for at least 6 months 3