Role of the coagulation system in the pathogenesis of sickle cell disease
Open Access
- 22 October 2019
- journal article
- review article
- Published by American Society of Hematology in Blood Advances
- Vol. 3 (20), 3170-3180
- https://doi.org/10.1182/bloodadvances.2019000193
Abstract
Sickle cell disease (SCD) is an inherited monogenic red blood cell disorder affecting millions worldwide. SCD causes vascular occlusions, chronic hemolytic anemia, and cumulative organ damage such as nephropathy, pulmonary hypertension, pathologic heart remodeling, and liver necrosis. Coagulation system activation, a conspicuous feature of SCD that causes chronic inflammation, is an important component of SCD pathophysiology. The key coagulation factor, thrombin (factor IIa [FIIa]), is both a central protease in hemostasis and thrombosis and a key modifier of inflammation. Pharmacologic or genetic reduction of circulating prothrombin in Berkeley sickle mice significantly improves survival, ameliorates vascular inflammation, and results in markedly reduced end-organ damage. Accordingly, factors both upstream and downstream of thrombin, such as the tissue factor–FX complex, fibrinogen, platelets, von Willebrand factor, FXII, high-molecular-weight kininogen, etc, also play important roles in SCD pathogenesis. In this review, we discuss the various aspects of coagulation system activation and their roles in the pathophysiology of SCD.This publication has 140 references indexed in Scilit:
- Platelets induce neutrophil extracellular traps in transfusion-related acute lung injuryJCI Insight, 2012
- P-Selectin–Mediated Platelet-Neutrophil Aggregate Formation Activates Neutrophils in Mouse and Human Sickle Cell DiseaseArteriosclerosis, Thrombosis, and Vascular Biology, 2010
- Extracellular DNA traps promote thrombosisProceedings of the National Academy of Sciences of the United States of America, 2010
- Cellular sources of tissue factor in endotoxemia and sepsisThrombosis Research, 2010
- Netting neutrophils in autoimmune small-vessel vasculitisNature Medicine, 2009
- Increased von Willebrand factor antigen and high molecular weight multimers in sickle cell disease associated with nocturnal hypoxemiaThrombosis Research, 2008
- Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin αMβ2 binding motifJCI Insight, 2007
- Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobinBlood, 2007
- Sickle cell disease: old discoveries, new concepts, and future promiseJCI Insight, 2007
- Neutrophil Extracellular Traps Kill BacteriaScience, 2004