When sickle cell trait is not just trait: risk of VTE.

The pathophysiology of venous thromboembolism (VTE) is complex. While perturbations in the coagulation system have generally been considered the primary driver of VTE risk, there is increasing recognition that additional whole-blood components also play a crucial role in clot formation. The erythrocyte is a particularly important-and often overlooked-contributor to venous thrombi ("red clots"). Sickle cell trait (SCT), the most common hemoglobin variant worldwide, has been consistently shown to confer a modestly increased risk of VTE, and pathophysiologic studies indicate that subclinical erythrocyte changes in SCT interact both with the coagulation system and with clot composition. In this review, we characterize SCT ("HbAS" or "heterozygous HbS") as a low-risk inherited thrombophilia and compare it to the most well-known thrombophilias: heterozygous factor V Leiden and prothrombin 20210A mutation.