Science · 1987 · 705 citations · 54 references
MedicineHematologyHemostasisInflammationPediatric HematologyCoagulation DisordersCoagulation PhysiologyThrombin GenerationThrombosisThrombosis PreventionThrombotic DisordersAnticoagulant MechanismsCoagulationEndothelium-dependent Coagulation RegulationNatural Anticoagulant DeficiencyNatural Anticoagulant PathwaysNatural Anticoagulant ProteinsProtein C Pathway ImpairmentProtein C System
Vascular endothelium prevents clotting by expressing thrombomodulin, which converts thrombin into activated protein C that inactivates factors Va and VIIIa, linking coagulation to inflammation. Homozygous protein C deficiency in infants causes severe thrombotic complications, confirming the physiological importance of the protein C anticoagulant pathway.
Vascular endothelium plays an active role in preventing blood clot formation in vivo. One mechanism by which prevention is achieved involves a cell surface thrombin-binding protein, thrombomodulin, which converts thrombin into a protein C activator. Activated protein C then functions as an anticoagulant by inactivating two regulatory proteins of the coagulation system, factors Va and VIIIa. The physiological relevance of the protein C anticoagulant pathway is demonstrated by the identification of homozygous protein C-deficient infants with severe thrombotic complications. Recent studies suggest that this pathway provides a link between inflammation and coagulation.
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Deficiency of protein C in congenital thrombotic disease.
John H. Griffin, B. L. Evatt, T S Zimmerman et al. · Journal of Clinical Investigation · 1981 · 1.3K citations · Full text
Medicine, Genetics, Hematology +14
M P Bevilacqua, Jordan S. Pober, M E Wheeler et al. · Journal of Clinical Investigation · 1985 · 1.1K citations · Full text