Do patients with sickle cell disease require anticoagulants?

Anticoagulation in Sickle Cell Disease Patients

Sickle cell disease patients do not require routine anticoagulation unless they have specific indications such as venous thromboembolism (VTE) or pulmonary hypertension with VTE. 1

Risk of Thrombosis in Sickle Cell Disease

• Patients with sickle cell disease (SCD) have an increased risk of both large and small vessel pulmonary embolism as well as an increased risk for intracerebral hemorrhage 1
• The incidence of VTE in adults with SCD ranges from 11.2% in all adults with SCD to 17.1% in those with more severe disease 1
• Risk factors for VTE in SCD include female sex, more severe disease, severe sickle cell genotype, and hospitalization ≥3 times per year 1
• The 5-year recurrence rate of VTE is high among SCD patients, and VTE is associated with higher overall mortality 2
• Children with SCD have a VTE incidence of 1.7-2.9%, with risk factors including central venous catheters, chronic renal disease, stroke history, and ICU utilization 1

Anticoagulation Recommendations for Specific Scenarios

For SCD Patients with VTE:

• Short-term anticoagulant therapy is widely accepted for most patients with acute VTE 1
• For patients with a first unprovoked VTE or recurrent provoked VTE, indefinite anticoagulation is suggested due to the high recurrence risk 1
• For patients with a first surgically or non-surgically provoked VTE, defined periods of anticoagulation (rather than indefinite therapy) are recommended 1
• For patients with right heart catheterization-confirmed pulmonary hypertension plus VTE and no additional bleeding risk factors, indefinite anticoagulation is suggested 1

For SCD Patients with Ischemic Stroke/TIA:

• For adults with SCD and ischemic stroke or TIA, antiplatelet therapy (rather than anticoagulation) is recommended unless other indications for anticoagulation exist 1
• Additional therapies that may be considered include regular blood transfusions to reduce hemoglobin S to <30-50% of total hemoglobin, hydroxyurea, or bypass surgery in cases of advanced occlusive disease 1

Safety Considerations

• The cumulative incidence of bleeding in SCD patients on anticoagulation is 4.9% at 6 months and 7.9% at 1 year 2
• In a retrospective study of SCD patients receiving VTE prophylaxis, anticoagulation was discontinued for hemorrhage in 4.3% of patients 1
• When comparing anticoagulant options, direct oral anticoagulants (DOACs) may have a lower bleeding risk compared to vitamin K antagonists (VKAs) or low-molecular-weight heparin (LMWH) in SCD patients 3
• In a small retrospective cohort study, 14% of patients receiving DOACs developed non-major bleeding versus 7% major bleeding and 13% non-major bleeding with warfarin 4

Anticoagulant Selection

• Anticoagulant selection should account for comorbidities such as renal impairment that may affect drug clearance 1
• For SCD patients with creatinine clearance >95 mL/min, alternatives to edoxaban should be considered due to potentially decreased efficacy 1
• DOACs may be an alternative treatment for VTE in patients with SCD, except when there is associated antiphospholipid syndrome 5
• For mechanical heart valves in SCD patients, bioprosthetic valves are recommended over mechanical valves to avoid lifelong anticoagulation 6

Special Considerations

• The balance between VTE risk and bleeding risk must be carefully evaluated in each patient 1
• Maintaining adequate hydration is crucial for SCD patients on anticoagulation to prevent sickling crises that could increase thrombotic risk 6, 7
• SCD patients frequently require interruption of anticoagulation for painful crises, procedures, or surgeries, which can complicate management 6
• Perioperative management should include thromboprophylaxis for all peri- and post-pubertal patients, maintenance of normothermia, and early mobilization 7