| abstract |
It has been discovered that by temporarily blocking one or more natural anticoagulants, such as the activation of intrinsic protein C, subsequent surgical blood loss from a microvascular surgical or traumatic wound can be substantially reduced. Other natural anticoagulants include thrombomodulin, antithrombin III, and tissue factor inhibitor pathway. The effects of protein C blockade were compared to the standard therapy, topical thrombin, and to the experimental topical agent, tissue thromboplastin. Domestic pigs were blindly pretreated with intravenous HPC4 or saline then underwent partial-thickness skin graft harvesting to create a reproducible microvascular wound. It was found that blocking the activation of protein C significantly reduces surgical blood loss compared to saline control animals. Intravenous HPC4 performed equally as well as topical thrombin or tissue thromboplastin. In addition, topical thrombin acted synergistically with HPC4 to further reduce blood. |