What are the treatment options and referral criteria for thrombocytopenia?

Treatment Options and Referral Criteria for Thrombocytopenia

Treatment for thrombocytopenia should be initiated based on bleeding risk rather than platelet count alone, with specific therapeutic options determined by the underlying cause and patient-specific factors. 1

When to Initiate Treatment

• Treatment is rarely indicated in patients with platelet counts above 50 × 10^9/L unless they have bleeding, trauma, surgery, comorbidities for bleeding, require anticoagulation, or have professions predisposing to trauma 1
• For immune thrombocytopenia (ITP), treatment is recommended for newly diagnosed patients with platelet counts <30 × 10^9/L 2
• Observation alone is appropriate for patients with no bleeding or only mild skin manifestations, regardless of platelet count 1

First-Line Treatment Options for ITP

Corticosteroids

• Prednisone is standard initial therapy at 0.5-2 mg/kg/day until platelet count increases (30-50 × 10^9/L) 2
• To avoid complications, prednisone should be rapidly tapered and stopped in responders, and especially in non-responders after 4 weeks 2
• Dexamethasone (40 mg/day for 4 days) has shown high initial response rates (50-86%) with potentially better sustained responses 2
• Longer courses of corticosteroids are preferred over shorter courses as first-line treatment 2

Emergency/Rapid Response Options

• Intravenous immunoglobulin (IVIg) at 1 g/kg is recommended when rapid platelet increase is required 2
• IVIg should be used with corticosteroids when a more rapid increase in platelet count is needed 2
• Anti-D immunoglobulin can be used in Rh-positive, non-splenectomized patients 2

Second-Line Treatment Options

Thrombopoietin Receptor Agonists (TPO-RAs)

• Recommended for patients at risk of bleeding who relapse after splenectomy or who have contraindications to splenectomy and have failed at least one other therapy 2
• May be considered for patients at risk of bleeding who have failed one line of therapy such as corticosteroids or IVIg without splenectomy 2
• Romiplostim is FDA-approved for adult ITP patients with insufficient response to corticosteroids, immunoglobulins, or splenectomy 3
• Initial dose of romiplostim is 1 mcg/kg weekly subcutaneously, adjusted to maintain platelet count ≥50 × 10^9/L 3

Rituximab

• May be considered for patients at risk of bleeding who have failed one line of therapy such as corticosteroids, IVIg, or splenectomy 2
• Not FDA-approved specifically for ITP but commonly used off-label 1

Splenectomy

• Recommended for patients who have failed corticosteroid therapy 2
• Provides high initial response rate (85%) but up to 30% of responders relapse within 10 years 2
• Associated with serious short and long-term risks including surgical complications, infections, thromboembolism, and increased malignancy risk 2
• Both laparoscopic and open splenectomy offer similar efficacy 2

Treatment of Secondary Thrombocytopenia

HCV-Associated Thrombocytopenia

• Antiviral therapy should be considered if not contraindicated 2
• Initial ITP treatment should be IVIg if required 2

HIV-Associated Thrombocytopenia

• Antiretroviral therapy should be considered before other treatment options unless significant bleeding is present 2
• Initial treatment should consist of corticosteroids, IVIg, or anti-D if ITP treatment is required 2

H. pylori-Associated Thrombocytopenia

• Eradication therapy should be administered in patients who test positive for H. pylori 2
• Screening for H. pylori should be considered in ITP patients 2

Referral Criteria for Thrombocytopenia

• Refer to hematology when:
  • Platelet count <20 × 10^9/L regardless of bleeding 4
  • Significant bleeding with any level of thrombocytopenia 1
  • Failure to respond to first-line therapy 2
  • Diagnosis is uncertain or complex 4
  • Secondary causes requiring specialized management are suspected 2
  • Patient requires second-line therapies such as TPO-RAs, rituximab, or splenectomy 2

Common Pitfalls and Considerations

• Long-term corticosteroid use should be avoided due to significant adverse effects 2
• Pseudothrombocytopenia (platelet clumping due to EDTA) should be ruled out by examining peripheral blood smear 1
• TPO-RAs should not be used to normalize platelet counts but rather to achieve a safe level (≥50 × 10^9/L) 3
• Discontinue TPO-RAs if platelet count doesn't increase sufficiently after 4 weeks at maximum dose 3
• After splenectomy, no further treatment is needed in asymptomatic patients with platelet counts >30 × 10^9/L 2