What is the initial approach to evaluating and treating thrombocytopenia (low platelet count)?

Initial Approach to Evaluating and Treating Thrombocytopenia

The initial approach to thrombocytopenia should include confirmation of true thrombocytopenia through peripheral blood smear examination, followed by a focused history and physical examination to distinguish between primary and secondary causes, with treatment guided by bleeding severity and underlying etiology. 1

Confirming True Thrombocytopenia

• First, distinguish between true thrombocytopenia and pseudothrombocytopenia (occurs in ~0.1% of adults) 2
• Examine peripheral blood smear to confirm thrombocytopenia and check for platelet clumping 2
• If pseudothrombocytopenia is suspected, collect blood in a tube containing heparin or sodium citrate and repeat the platelet count 3

Key History and Physical Examination Elements

History

• Bleeding symptoms (type, severity, duration)
• Hemostasis with prior surgeries or pregnancies
• Systemic symptoms (weight loss, fever, arthralgias, skin rash)
• Medication history (heparin, alcohol, quinidine/quinine, sulfonamides)
• Risk factors for HIV, hepatitis C
• Family history of thrombocytopenia 2

Physical Examination

• Bleeding signs (severity, type, including retinal hemorrhages)
• Presence of splenomegaly (suggests against primary ITP)
• Liver examination and stigmata of liver disease
• Evidence of infection or autoimmune disorders
• Evidence of thrombosis 2, 1

Initial Laboratory Evaluation

1. Complete blood count with peripheral smear
2. Basic metabolic panel and liver function tests
3. Coagulation studies (PT, PTT)
4. Consider testing for:
   • HIV, hepatitis C
   • H. pylori infection
   • Antinuclear antibodies (if autoimmune disease suspected)
   • Bone marrow examination (if abnormal cells on peripheral smear or atypical features) 2, 1

Treatment Algorithm Based on Platelet Count and Bleeding

Asymptomatic Patients

• Platelet count >30 × 10^9/L: Observation only 2
• Platelet count <30 × 10^9/L: Consider treatment if risk factors for bleeding exist 1

Patients with Mild Bleeding (Skin Manifestations Only)

• Observation alone regardless of platelet count (for pediatric patients) 2
• For adults with platelet count <30 × 10^9/L: Consider short course of corticosteroids 1

Patients with Active Significant Bleeding

1. First-line treatment options:

   • Corticosteroids: Prednisone 1-2 mg/kg/day for up to 14 days with rapid taper (72-88% response within 72 hours) 1
   • IVIg: 0.8-1 g/kg as single dose (>80% response within 1-2 days) - preferred if rapid platelet increase needed 1

2. For life-threatening bleeding:

   • Combination therapy with platelet transfusions, high-dose corticosteroids, and IVIg
   • Consider larger-than-usual platelet transfusion doses (2-3 fold)
   • Adjunct treatment with antifibrinolytic agents may be beneficial 1

Management of Secondary Thrombocytopenia

• HCV-associated ITP: Consider antiviral therapy; monitor platelet count closely due to risk of worsening thrombocytopenia with interferon 2, 1
• HIV-associated ITP: Treat HIV infection with antiretroviral therapy before other treatment options 2
• H. pylori-associated ITP: Eradication therapy for confirmed H. pylori infection 2
• Drug-induced thrombocytopenia: Discontinue suspected medication 3

Second-Line Therapy for Persistent/Chronic ITP

When to transition to second-line therapy:

• Failure to respond to first-line therapy
• Relapse after initial response
• Need for prolonged corticosteroid use 2

Second-line treatment options:

1. Thrombopoietin receptor agonists (TPO-RAs):

   • Recommended for patients who have failed corticosteroid therapy or who relapse after splenectomy 2
   • Romiplostim: Initial dose 1 mcg/kg weekly subcutaneously, adjust to maintain platelet count ≥50 × 10^9/L, maximum 10 mcg/kg 4
   • Aim for lowest dose to achieve platelet count ≥50 × 10^9/L 4

2. Splenectomy:

   • High initial response rate (85%), but up to 30% relapse within 10 years 2
   • Associated with serious short- and long-term risks including infections, thromboembolism, and increased mortality 2
   • Consider for patients who have failed corticosteroid therapy 2

3. Rituximab:

   • Consider for patients with significant ongoing bleeding despite first-line treatment 2, 1
   • May be considered as an alternative to splenectomy 2

Monitoring and Follow-up

• Monitor platelet counts within 24 hours of initiating treatment, then daily until stable 1
• After establishing stable dose of TPO-RA, monitor CBC monthly 4
• If discontinuing TPO-RA, monitor CBC weekly for at least 2 weeks 4
• Educate patients about avoiding activities with high risk of trauma 1

Important Caveats

• TPO-RAs should not be used to normalize platelet counts, only to reduce bleeding risk 4
• Discontinue TPO-RA if no response after 4 weeks at maximum dose 4
• Splenectomy is increasingly deferred in favor of medical therapies due to associated risks 5
• The goal of treatment is to achieve a safe platelet count (≥50 × 10^9/L) rather than normalizing platelet numbers 1