Control of severe intra-abdominal hemorrhage with an infusible platelet-derived hemostatic agent in a nonhuman primate (rhesus macaque) model.

Abstract

Hemorrhage remains the leading cause of potentially survivable trauma mortality. Recent reports indicate that injuries sustained in noncompressible anatomic locations (i.e., truncal and junctional) account for 86.5% of hemorrhage-related deaths. Infusible human platelet-derived hemostatic agents (hPDHAs) represent a promising strategy to reduce blood loss from noncompressible injuries. Here, we evaluate the hemostatic efficacy of a lyophilized hPDHA in a rhesus macaque model of severe, uncontrolled hemorrhage. Hemorrhage was induced via laparoscopic 60% left-lobe hepatectomy in anesthetized rhesus macaques (T = 0 minute). Treatment infusion began with an 11-mL bolus (T = 5-6 minutes) of either 5% albumin solution (control; n = 8) or hPDHA (1.2 × 10(10) platelet equivalents, n = 8), followed by 2.8-mL/min 0.9% normal saline at T = 6-20 minutes. Resuscitation continued with normal saline (0.22 mL/kg/min) to a total volume of 20 mL/kg at T = 120 minutes, at which time surgical hemostasis was achieved and percent blood loss quantified. Animals were monitored until T = 480 minutes and then euthanized, and necropsy was performed with emphasis on intravascular and end-organ thrombi. Data are expressed as mean ± SEM; significance, p < 0.05. Both groups exhibited a ∼70% decrease in mean arterial pressure (MAP) from T = 0-5 minutes. Percent blood loss was 44.2 ± 3.9% in hPDHA animals, and 44.3 ± 3.3% in controls. Survival rates were 4 of 8 for hPDHA animals and 7 of 8 for controls. Regardless of treatment, percent blood loss was greater (p < 0.02) in nonsurviving animals (55 ± 2%, n = 5) compared with surviving animals (42% ± 3%, n = 11). No pathologic intravascular thrombi were observed in either group. The isolated administration of hPDHA did not significantly reduce blood loss; however, thrombocytopenia was not present in the model, and clinically, platelets would be administered in combination with plasma. Mortality was not statistically different between groups (p = 0.14) but was related to blood loss. Future studies should consider the use of hPDHA in combination with additional therapeutics (e.g., factors) and a model that incorporates thrombocytopenia or platelet dysfunction.