Are patients with sickle cell disease at higher risk for developing deep vein thromboses (DVTs)?

Patients with Sickle Cell Disease Are at Significantly Higher Risk for Developing DVTs

Yes, patients with sickle cell disease (SCD) have a substantially higher risk of developing deep vein thromboses (DVTs) compared to the general population, with incidence rates ranging from 11.2% to 17.1% in adults with SCD. 1

Epidemiology and Risk Factors

The increased risk of venous thromboembolism (VTE) in SCD patients is well-documented:

• Incidence rates:

  • 11.2% in all adults with SCD
  • Up to 17.1% in adults with more severe disease (hospitalized ≥3 times per year) 1
  • 1.7% to 2.9% in children with SCD 1

• Key risk factors for VTE in SCD patients:

  • Female sex
  • More severe disease phenotype
  • Severe sickle cell genotype (though sickle variant genotypes actually confer higher risk than SS/Sβ0 genotypes) 2
  • Central venous catheter use (present in 78% of UEDVT cases) 3
  • Chronic renal disease
  • History of stroke
  • Longer hospitalizations
  • ICU utilization
  • Older age 1
  • Elevated tricuspid regurgitant jet velocity ≥2.5 m/s 2

Pathophysiology

SCD creates a hypercoagulable state through multiple mechanisms:

• Mutant hemoglobin S polymerization leading to sickling
• Vascular occlusion
• Hemolytic anemia
• Chronic inflammation
• Persistent activation of the coagulation cascade 4

Clinical Significance

The high risk of VTE in SCD patients has significant clinical implications:

• Recurrence rates:

  • 13.2% at 1 year
  • 24.1% at 5 years 5

• Mortality impact:

  • VTE is independently associated with increased mortality in both adults and children with SCD 1, 2
  • Non-catheter-related VTE is independently correlated with death (RR 3.63; 95% CI, 1.66-7.92) 2

• Special populations:

  • Pregnant women with SCD have higher VTE incidence than the general pregnant population 1
  • Higher risk during pregnancy is associated with pneumonia, vaso-occlusive crisis, and acute chest syndrome 1

Management Considerations

Given the high risk of VTE in SCD patients, several management considerations are important:

• Thromboprophylaxis:

  • Patients with SCD and central venous access devices who receive thromboprophylaxis have significantly lower VTE rates (RR = 4.0 for those without prophylaxis) 6
  • Hydroxyurea use is associated with lower VTE rates 6

• Anticoagulation safety:

  • Bleeding risk with anticoagulation in SCD patients:
    • 4.9% at 6 months
    • 7.9% at 1 year 1, 5
  • More severe SCD is associated with higher bleeding risk (HR = 1.61; CI: 1.11-2.35) 5

• Anticoagulation duration:

  • The American Society of Hematology suggests indefinite anticoagulation may be appropriate for first unprovoked or recurrent provoked VTE in SCD patients 1
  • For first surgically or non-surgically provoked VTE, defined periods of anticoagulation are recommended 1

Clinical Pitfalls and Caveats

• Quality of anticoagulation control may be suboptimal in SCD patients:

  • Only 36% of INR values were therapeutic in one study 3
  • SCD patients had lower proportion of therapeutic INRs (25% vs 38%) 3
  • Higher rates of loss to follow-up (67% vs 46%) 3

• CVAD selection matters:

  • PICC lines and certain implantable devices (Vortex and Xcela Power) are associated with higher VTE rates compared to Port-a-Cath 6

• Evidence gaps:

  • Despite the established increased risk, there is a lack of specific guidelines for thromboprophylaxis in SCD patients 4
  • Prospective, randomized studies of anticoagulation in SCD patients with VTE are needed 5

In conclusion, the evidence clearly demonstrates that SCD patients are at significantly higher risk for developing DVTs compared to the general population. This increased risk, combined with the high recurrence rates and mortality impact, suggests that clinicians should maintain a high index of suspicion for VTE in SCD patients and consider appropriate thromboprophylaxis in high-risk situations.