Table 3.

Risk Factors for Venous Thromboembolism in Sickle Cell Disease

Traditional VTE Risk Factors	SCD-Related VTE Risk Factors
•Frequent hospitalizations leading to immobilization86	• Coagulation factors: a. Decreased protein C, protein S, and anti-thrombin III levels b. Decreased factor V, IX, and XII levels87
•Use of central venous catheters for venous access and red cell exchange/transfusion therapy88	•Elevated circulating anti-phospholipid antibodies89
•Genotype (HbSC and HbS-β-thalassemia+, increased risk of non-catheter-related VTE compared with HbSS)	•Elevated plasma levels of thrombin-antithrombin complexes, prothrombin fragment 1+2 (a marker of thrombin and fibrin generation and platelet activation)90
• Surgery: a. Orthopedic surgery (avascular necrosis of hip, shoulder) b. Cholecystectomy	• During VOEs: a. Abnormal externalization of phosphatidylserine in erythrocytes and adherence to the vascular endothelium b. Increased tissue factor expression c. Increased circulating fibrinogen, vWF, and clotting factors VII and VIII
•Increased pregnancy-related VTE	•Impaired fibrinolysis
•Splenectomy: Functional asplenia and postsurgical splenectomy	•Up-regulation of cellular adhesion molecules

SCD = sickle cell disease; VOE = vaso-occlusive event; vWF = von Willebrand factor.