How to manage thrombocytosis in patients with Sickle Cell Disease (SCD) to reduce the risk of thrombosis?

Management of Thrombocytosis in Sickle Cell Disease to Reduce Thrombosis Risk

For patients with sickle cell disease (SCD) and thrombocytosis, hydroxyurea is the recommended first-line therapy to reduce the risk of thrombosis, with anticoagulation reserved for specific scenarios of confirmed venous thromboembolism (VTE). 1

Understanding Thrombotic Risk in SCD

SCD is inherently a prothrombotic condition with patients experiencing:

• 4 to 100-fold increased risk for thrombosis compared to the general population 2
• High 5-year recurrence rate of VTE 1
• Higher overall mortality associated with VTE 1

Risk factors for thrombotic events in SCD include:

• HbSS/Sβ0-genotype
• Lower estimated glomerular filtration rate
• Higher white blood cell counts 2
• Female sex (for VTE during pregnancy) 1

Assessment of Thrombocytosis in SCD

When evaluating thrombocytosis in SCD patients:

1. Determine platelet count range and trend

   • Platelet counts in SCD can vary widely (19-838 × 10^9/L) 3
   • Both thrombocytopenia and thrombocytosis can occur in SCD patients 3

2. Assess for other risk factors

   • Presence of central venous catheter
   • History of stroke
   • Renal disease 1
   • Recent hospitalization or ICU stay 2

Management Algorithm

First-Line Therapy:

1. Hydroxyurea
   • Strong recommendation with moderate-quality evidence 1
   • Mechanism: Reduces platelet count, decreases white blood cell count, increases fetal hemoglobin
   • Dosing: Individualize based on response and monitoring blood counts
   • Monitor: Complete blood counts at baseline and throughout treatment 4
   • Caution: Reduce dose by 50% in patients with creatinine clearance less than 60 mL/min 4

Second-Line Therapy (if unresponsive to or not a candidate for hydroxyurea):

1. Chronic transfusion therapy
   • Weak recommendation with low-quality evidence 1
   • Goal: Reduce HbS percentage and improve blood rheology
   • Monitor: Iron overload and alloimmunization risk

For Confirmed VTE:

1. Anticoagulation therapy
   • For first provoked VTE: 3-6 months of anticoagulation 1
   • For first unprovoked VTE: Consider indefinite anticoagulation 1
   • For recurrent provoked VTE: Indefinite anticoagulation 1
   • Monitoring: Assess bleeding risk, especially with concomitant use of NSAIDs 1

Important Considerations

• Do not use antiplatelet agents as primary prevention

  • No compelling data exist to recommend aspirin, dipyridamole, or ticlopidine for prevention of vasoocclusive and thrombotic complications in SCD 5
  • SCD should not be used as an independent indication for antiplatelet therapy 5

• Avoid targeted pulmonary arterial hypertension (PAH) therapy

  • Strong recommendation against PAH-targeted therapy for SCD patients with elevated TRV or NT-pro-BNP alone 1
  • Phosphodiesterase-5 inhibitors should not be used as first-line agents 1

• Blood pressure management

  • Target blood pressure ≤130/80 mm Hg in adults with SCD 1
  • Strong recommendation with moderate certainty of evidence

Special Situations

• Pregnancy: Higher risk of VTE in pregnant women with SCD, especially with complications like pneumonia, vaso-occlusive crisis, and acute chest syndrome 1

• Post-allogeneic hematopoietic cell transplantation:

  • Significant reduction in thrombotic events after transplantation 6
  • 32% absolute reduction in VTE events post-transplant 6
  • Consider this curative option for patients with severe SCD and recurrent thrombotic events

Monitoring Recommendations

1. Regular assessment of complete blood counts
2. Evaluation of renal function
3. Monitoring for signs of thrombosis
4. Assessment of hydroxyurea response and adherence

Pitfalls to Avoid

1. Do not use antiplatelet agents alone for thrombosis prevention in SCD with thrombocytosis
2. Do not exceed hemoglobin threshold of 10 g/dL (hematocrit of 30%) when using erythropoiesis-stimulating agents to reduce risk of vaso-occlusion, stroke, and VTE 1
3. Do not continue anticoagulation indefinitely for first provoked VTE such as central venous line-associated thrombosis 1
4. Do not ignore bleeding risk when prescribing anticoagulation; consider concomitant medications and comorbidities

By following these evidence-based recommendations, clinicians can effectively manage thrombocytosis in SCD patients and reduce the risk of thrombotic complications.