What is the pathophysiology of Sickle Cell Disease (SCD) that increases the risk of Deep Vein Thromboses (DVTs) and Pulmonary Embolisms (PEs)?

From the Guidelines

Pathophysiology of Sickle Cell Disease and Risk of Deep Vein Thromboses and Pulmonary Embolisms

Patients with Sickle Cell Disease (SCD) are at increased risk of developing Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) due to a complex pathophysiology involving chronic hemolysis, inflammation, and endothelial dysfunction 1. The sickling of red blood cells leads to activation of the coagulation cascade, increased levels of pro-coagulant factors, and decreased levels of anticoagulant proteins, such as protein C and protein S. Additionally, SCD patients often have elevated levels of factor VIII and von Willebrand factor, which further contribute to a pro-thrombotic state.

Key Factors Contributing to Thrombosis Risk

• Chronic hemolysis: leads to the release of pro-coagulant factors and the consumption of anticoagulant proteins 1
• Inflammation: contributes to endothelial dysfunction and the activation of the coagulation cascade 1
• Endothelial dysfunction: impairs the regulation of blood flow and coagulation, increasing the risk of thrombosis 1
• Elevated factor VIII and von Willebrand factor: contribute to a pro-thrombotic state 1

Management and Prevention of Thrombosis

The use of certain medications, such as hydroxyurea, may help reduce the risk of thrombosis, but the risk remains elevated 1. As a precautionary measure, SCD patients should be considered for thromboprophylaxis with low-molecular-weight heparin, such as enoxaparin 40mg subcutaneously daily, during periods of high risk, such as hospitalization or surgery. The decision to remain on anticoagulation should be made through shared decision-making based on patient values/preferences and be subject to regular reevaluation 1.

From the Research

Pathophysiology of Sickle Cell Disease (SCD) and Risk of Deep Vein Thromboses (DVTs) and Pulmonary Embolisms (PEs)

The pathophysiology of SCD that increases the risk of DVTs and PEs is complex and multifactorial. Some of the key factors include:

• Hypercoagulable state: SCD patients have a baseline hypercoagulable state, which increases their risk of developing VTEs 2
• Increased white blood cell count: High white blood cell count has been associated with an increased risk of VTE in SCD patients 3, 2
• Length of stay: Longer hospital stays have been associated with an increased risk of VTE in SCD patients 3
• Presence of additional risk factors: The presence of additional risk factors, such as older age, HbSS/Sβ0-genotype, and lower hemoglobin F%, can increase the risk of VTE in SCD patients 4, 2
• Genetic risk factors: Certain genetic variants, such as thrombomodulin gene variants, have been associated with an increased risk of thrombosis in SCD patients 2

Incidence of VTE in SCD Patients

The incidence of VTE in SCD patients is significant, with studies reporting:

• 11.2% of SCD patients developing incident VTE 4
• 17.1% of severe SCD patients developing VTE by age 40 4
• 17.4% of SCD patients experiencing thrombotic events, including 64 strokes and 288 VTEs 2

Risk Factors for VTE in SCD Patients

Some of the key risk factors for VTE in SCD patients include:

• Severe SCD: Severe SCD has been associated with an increased risk of VTE 4
• Female sex: Female sex has been associated with an increased risk of VTE in SCD patients 4
• Older age: Older age has been associated with an increased risk of stroke in SCD patients 2
• Lower estimated glomerular filtration rate: Lower estimated glomerular filtration rate has been associated with an increased risk of VTE in SCD patients 2
• Hydroxyurea use: Hydroxyurea use has been associated with an increased risk of VTE in SCD patients 2

Management of VTE in SCD Patients

The management of VTE in SCD patients is crucial to prevent recurrence and reduce mortality. Some of the key strategies include:

• Anticoagulation: Anticoagulation has been shown to be effective in preventing recurrence of VTE in SCD patients 5
• VTE prophylaxis: VTE prophylaxis has been shown to be effective in reducing the risk of VTE in SCD patients undergoing noncardiovascular surgery 6
• Extended anticoagulation: Extended anticoagulation may be indicated in patients with severe SCD and a high risk of recurrent VTE 4