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Hetastarch, the currently marketed preparation of hydroxyethyl starch, affects coagulation by prolonging partial thromboplastin, prothrombin, and bleeding times; by lowering clotting proteins such as fibrinogen via hemodilution; by lowering clotting factor VIII (coagulant, von Willebrand antigen, and von Willebrand activity) to a greater degree than can be explained simply by hemodilution (i.e., presumably factor VIII affected by both hemodilutional plus additional, independent effects); and, finally, by shortening thrombin, reptilase, and urokinase-activated clot lysis times. Pentastarch, a new analog of hetastarch, was found to exert lesser effects on blood coagulation, despite its greater hemodiluting properties. When compared with hetastarch, pentastarch had little effect on factor VIII (except that due to hemodilution), shortened thrombin times to a significantly lesser degree, exerted no effect on the urokinase-activated clot lysis time, and did not prolong the bleeding time. Even when plasma hydroxyethyl starch levels were similar, pentastarch seemed to alter the results of coagulation assays to lesser degree than did hetastarch, which suggests the possibility of greater safety. Therefore, pentastarch may be a desirable drug, not only for leukapheresis, but also for plasma volume expansion in trauma and surgical patients who often have additional hemostatic abnormalities that place them at increased risk of hemorrhage.