title: Modeling the action of factor VIIa in dilutional coagulopathy.
abstract: Dilutional coagulopathy is observed in patients who have lost blood and had the blood volume replaced with components that do not have plasma procoagulants and anticoagulants. Since both procoagulant and anticoagulant mechanisms contribute to total thrombin generation, it is not clear whether the procoagulant or anticoagulant effects will dominate when both are decreased. Decreasing antithrombin levels leads to increasing thrombin generation in ex vivo models. However, in these same models decreasing prothrombin leads to decreasing thrombin generation. Previous studies can be extrapolated to suggest that the ratio of procoagulants and anticoagulants may be the critical component in determining thrombin generation. Limited clinical data suggest that factor VIIa has been useful in controlling intractable bleeding in some cases of dilutional coagulopathy. Preliminary data suggest that factor VIIa activation of factors X and IX on activated platelets enhances thrombin generation significantly in a model of dilutional coagulopathy. This may suggest a mechanism to account for the efficacy of factor VIIa in reducing blood loss in some settings of dilutional coagulopathy.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7035, USA. dmonroe@med.unc.edu
authors.forename: Dougald M
authors.initials: DM
authors.lastname: Monroe
mesh_terms: D000925:Anticoagulants / Q000378:metabolism; D001778:Blood Coagulation Disorders / Q000517:prevention & control*; D001779:Blood Coagulation Factors / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D005164:Factor IX / Q000378:metabolism; D015942:Factor VIIa / Q000378:metabolism*; D005170:Factor X / Q000378:metabolism; D006438:Hemodilution / Q000379:methods*; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D008954:Models, Biological; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X; D015942:Factor VIIa; D013917:Thrombin