Hypercoagulability in Sickle Cell Disease: A Thrombo-Inflammatory Mechanism.

Abstract

Sickle cell disease (SCD) is a group of inherited disorders characterized by the presence of abnormal hemoglobin S. Patients with SCD suffer from frequent episodes of anemia, chronic hemolysis, pain crisis, and vaso-occlusion. Additionally, SCD is associated with diverse and serious clinical complications, including thrombosis, which can lead to organ failure, increased morbidity, and eventually, mortality. SCD is known to be a hypercoagulable condition, and the cause of hypercoagulability is multifactorial, with the molecular basis of hemoglobin S being the main driver. The presence of hemoglobin S induces sickling of the RBCs and their subsequent hemolysis, as well as oxidative stress. Both of these processes can alter the hemostatic system, through the activation of platelets, coagulation system, and fibrinolysis, as well as depletion of coagulation inhibitors. These changes can also induce the formation of microvesicles and expression of tissue factor, leading to activation of WBCs, endothelial cell damage, and inflammatory response. Understanding the various factors that drive hypercoagulability as a thrombo-inflammatory mechanism in SCD can help provide explanations for the pathogenesis and other complications of the disease.