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

Background: 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. METHODS: Hemorrhage was induced via laparoscopic 60% left-lobe hepatectomy in anesthetized rhesus macaques (T = 0 minute). Treatment infusion beganwith an 11-mL bolus (T = 5-6minutes) of either 5%albumin solution (control; n = 8) or hPDHA (1.2×10¹⁰ 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. RESULTS: 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. CONCLUSION: 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.