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Presentation Details
| Thrombotic Complications in Sickle Cell Anemia Bhakti Singh1, Neha Thomas1, Atul Laddu1, Fakiha Siddiqui2, Jawed Fareed2. 1Global Thrombosis Forum, Suwanee, GA, USA.2Loyola University, Chicago, IL, USA |
Abstract
Background Sickle cell anemia (SCA) is an inherited blood disorder caused by a mutation in the HBB gene that produces abnormal hemoglobin S (HbS), which distorts red blood cells into rigid, sickle-shaped forms. These cells block vessels, break down quickly, and trigger chronic anemia, pain crises, and an increased risk of thrombosis. It is well known that SCA is a prothrombotic condition, but the precise mechanisms that create this hypercoagulable state in SCA patients remain unestablished. Endothelial dysfunction, chronic inflammation, and abnormalities in the coagulation cascade and fibrinolytic pathway have been suggested as major contributors, making thrombosis an important yet complex component of SCA. Objectives Our objective was to review the literature to better understand how and why thrombosis develops in SCA patients, identify key biological pathways involved, and highlight treatment options targeting platelet-driven thromboinflammation to guide the development of more effective therapies. Methods We reviewed findings from peer-reviewed, population-based studies to elucidate the mechanisms of thrombosis associated with SCA. Cellular and molecular mediators of thrombosis, including platelet activation, natural anticoagulants, and microparticle release, were examined. Epidemiological data on bleeding and thrombosis were included to connect molecular mechanisms with clinical outcomes in the real world. Results SCA produces a chronic hypercoagulable state driven by hemolysis. Free hemoglobin and heme released during hemolysis consume nitric oxide, promoting oxidative stress that impairs endothelial function. Endothelial cells, monocytes, and microparticles express high levels of clotting markers, including prothrombin fragment 1.2 and TAT complexes, leading to continuous thrombin production. Thrombosis in SCA represents a complex pathological process contributing to the disease’s morbidity and mortality. SCA is characterized by acute chest syndrome, avascular necrosis, and stroke. It is crucial to understand the complex mechanisms underlying thrombotic complications in SCA to develop optimal treatment regimens. Patients have slow circulation due to slowed blood flow caused by sickle cells, allowing clotting factors and platelets to accumulate. Platelets are chronically activated, showing increased levels of P-selectin and adhesion. Sickled RBCs expose phosphatidylserine, creating a surface that promotes clotting. Even in steady-state patients, children with SCA have significantly lower levels of natural anticoagulants, such as protein C and antithrombin III, showing evidence of chronic hypercoagulability. Epidemiological studies indicate high incidence rates of thrombotic and bleeding events, specifically gastrointestinal (GI) bleeding, intracranial haemorrhage (ICH), and hematuria. GI bleeding has an incidence of 751.5 per 100,000, and ICH has an incidence of 178.9 per 100,000. Key risk factors include chronic hemolysis, low fetal hemoglobin, renal dysfunction, and recent venous thromboembolism. Conclusion Thrombosis in SCA results from the combined effects of hemolysis, chronic inflammation, and endothelial dysfunction. Understanding these mechanisms is crucial for improving patient care. Management strategies, such as antiplatelet therapy and anticoagulation, may help reduce the risk of thrombosis, and treatment regimens such as hydroxyurea, blood transfusions, and crizanlizumab show promising results. We have reviewed the complex mechanisms that promote thrombotic complications in SCA, discussing their pathophysiology, complications, and advances in targeted therapies to reduce them and improve patient outcomes.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.