What is the pathophysiology of Sickle Cell Trait (SCT) increasing the risk of Deep Vein Thrombosis (DVT)/Pulmonary Embolism (PE)?

From the Guidelines

Pathophysiology of Sickle Cell Trait and Increased Risk of DVT/PE

Individuals with sickle cell trait are at increased risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE) due to several pathophysiological mechanisms, including increased blood viscosity, activation of coagulation pathways, and endothelial dysfunction 1.

• The abnormal sickle hemoglobin can lead to microvascular occlusion, inflammation, and release of pro-coagulant factors, further increasing the risk of thrombosis.
• Endothelial dysfunction and activation of coagulation pathways also play a crucial role in the development of DVT/PE in individuals with sickle cell trait 1.
• Additionally, the sickled red blood cells can cause inflammation and release of pro-coagulant factors, which can further increase the risk of thrombosis.
• It is recommended that individuals with sickle cell trait be screened for other thrombophilic conditions and managed with caution, especially during periods of increased risk such as surgery, immobilization, or pregnancy 1.
• Aspirin and other antiplatelet agents may be considered for primary prevention in high-risk individuals, while anticoagulants such as low molecular weight heparin or warfarin may be used for secondary prevention or treatment of DVT/PE 1.
• However, the use of these medications should be individualized and carefully monitored due to the potential for bleeding complications 1.

From the Research

Pathophysiology of Sickle Cell Trait and Deep Vein Thrombosis/Pulmonary Embolism

The pathophysiology of Sickle Cell Trait (SCT) increasing the risk of Deep Vein Thrombosis (DVT)/Pulmonary Embolism (PE) is complex and involves multiple factors. Some key points include:

• Sickle cell trait may increase the risk of venous thromboembolism, but this is not fully established 2
• Sickle cell trait carries a 2-fold increased risk of pulmonary embolism but does not elevate deep vein thrombosis risk 2
• Patients with sickle-cell trait (SCT) have an increased risk of venous thromboembolism (VTE) 3
• Sickle cell disease (SCD) results in many complications, including an increased risk of developing venous thromboembolic events (VTEs) and an increased risk of mortality as a result 4

Risk Factors for Venous Thromboembolism in Sickle Cell Disease

Some risk factors for venous thromboembolism in sickle cell disease include:

• More severe SCD 5
• Lower extremity DVT as the incident event 5
• Pneumonia/acute chest syndrome 5
• Pregnancy or postpartum status 6

Association between Sickle Cell Trait and Venous Thromboembolism

The association between sickle cell trait and venous thromboembolism is not fully established, but some studies suggest that:

• Sickle cell trait may increase the risk of VTE, but not in pregnant or postpartum women 6
• Sickle cell trait is associated with a higher risk of PE, but not of DVT 6
• The risk of VTE is higher in individuals with SCD compared to those with SCT 6

Clinical Implications

The clinical implications of the association between sickle cell trait and venous thromboembolism include:

• Consideration of the increased pulmonary embolism risk in individuals with sickle cell trait 2
• The need for extended anticoagulation in patients with SCD and VTE, weighed against the risk of bleeding 5
• The need for prospective, randomized studies of anticoagulation in SCD patients with VTE 5