Computational Analysis of Intersubject Variability and Thrombin Generation in Dilutional Coagulopathy
ARMY MEDICAL RESEARCH AND MATERIEL COMMAND FORT DETRICK MD
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BACKGROUND Blood dilution is a frequent complication of massive transfusion during trauma and surgery. This article investigates the quantitative effects of blood plasma dilution on thrombin generation in the context of intersubject variability. STUDY DESIGN AND METHODS A thoroughly validated computational model was used to simulate thrombin generation curves for 472 healthy subjects in the Leiden Thrombophilia Study. Individual thrombin curves were calculated for undiluted blood and for different dilution scenarios. For every such curve, five standard quantitative parameters of thrombin generation were calculated and analyzed. RESULTS Thrombin generation parameters in diluted blood plasma displayed significant intersubject variability with a coefficient of variation up to approx. 28. Nevertheless, dilutional effects in the majority or all of the subjects in the study group were characterized by persistent patterns. In particular, the largest dilutioninduced change typically occurred in the maximum slope MS of the thrombin curve, followed by a change in thrombin peak height PH, whereas the smallest change often occurred in the area under the curve. The identified patterns demonstrated considerable robustness to variations in dilution scenario and tissue factor concentration.
- Medicine and Medical Research