Sickle Cell Disease and Thromboembolism: New Insights on the Pathophysiology, Diagnosis, and Treatment

Sickle cell disease (SCD) is a genetic hemoglobinopathy caused by the abnormal hemoglobin S (HbS) in red blood cells. As a result of its deoxygenation and polymerization, the properties and formation of red blood cells become altered, which ultimately leads to the development of SCD. Chronic inflammatory processes produced by hemolytic and vaso-occlusive episodes, define SCD clearly. These processes result in various effects, including organ damage and increased mortality in people suffering from the disease. Thromboembolism, a potentially fatal disease, is common in patients with sickle cell disease. Despite the known association between hypercoagulability and SCD, thromboembolism is often overlooked as a major complication of SCD. However, thromboembolism affects nearly one-quarter of adult patients and appears to be a risk factor for death in SCD. It has been well documented that in SCD, hemostatic alterations and thrombotic events are associated with endothelium and leukocyte activation. In SCD, inflammatory pathways play an important role in the activation of coagulation and the generation of platelet activation. Although among other mechanisms, it also involves the activation of tissue factors, the expression of adhesion molecules, and the stimulation of innate immune responses. So, mouse model studies may provide novel mechanistic pathways. These studies on mice models are yet to be applied to humans which will lead to the development of clinical lab treatments and therapeutic drugs. Additionally, SCD is a condition that responds favorably to biological treatments like gene therapy. SCD patients now have more potentially curative alternatives with recent developments in hematopoietic stem cell (HSC) transplantation and gene therapy platforms, including Lentiglobin vectors. In the present review, a discussion of the pathophysiology and thromboinflammation of sickle cell disease, along with its global burden in terms of both diagnosis and treatment, is presented.