Characterization of a canine freeze-dried platelet-derived hemostatic agent: A preclinical model for surgical and traumatic hemorrhage.

INTRODUCTION: A freeze-dried, platelet-derived hemostatic agent (FPH) was developed for acute hemorrhage. The canine product (cFPH) was developed for use in preclinical models supporting human product (hFPH) investigations. MATERIALS AND METHODS: A carotid artery bypass graft (CABG) study in dogs compared 3 dosages of cFPH to canine liquid stored platelets (cLSP) and vehicle (VEH) control groups. Histopathological analysis and blood loss assessments were completed. A separate ex-vivo synthetic graft study assessed thrombogenicity via blood from human and canine donors that was combined with species-specific FPH or apheresis platelets. Characterization of cFPH and hFPH included thrombin generation, total thrombus formation, and scanning electron microscopy. RESULTS: Blood loss was reduced in CABG dogs receiving standard of care (cLSP) or cFPH treatment compared to VEH control; a cFPH dose effect signal was observed. Further, cFPH dosing up to 5 × 109 cells/kg was not associated with increased mortality or occlusion of the anastomosis sites, and histopathologic evidence of off-target thrombosis was not detected. When passed through a synthetic graft (ex vivo), whole blood combined with species-specific FPH did not result in thrombosis beyond that of whole blood control. In vitro testing and imaging of cFPH and FPH were comparable. CONCLUSIONS: A single dose of cFPH or cLSP reduced blood loss in a pilot surgical study and was well tolerated with no related adverse events. Further, the hemostatic activity and characteristics of cFPH are comparable to that of hFPH, suggesting that research findings from the canine product are likely to inform the development of the human product.

Lessons Learned From the Battlefield and Applicability to Veterinary Medicine - Part 2: Transfusion Advances.

Since the inception of recent conflicts in Afghanistan and Iraq, transfusion practices in human military medicine have advanced considerably. Today, US military physicians recognize the need to replace the functionality of lost blood in traumatic hemorrhagic shock and whole blood is now the trauma resuscitation product of choice on the battlefield. Building on wartime experiences, military medicine is now one of the country's strongest advocates for the principle of hemostatic resuscitation using whole blood or balanced blood components as the primary means of resuscitation as early as possibly following severe trauma. Based on strong evidence to support this practice in human combat casualties and in civilian trauma care, military veterinarians strive to practice similar hemostatic resuscitation for injured Military Working Dogs. To this end, canine whole blood has become increasingly available in forward environments, and non-traditional storage options for canine blood and blood components are being explored for use in canine trauma. Blood products with improved shelf-life and ease of use are not only useful for military applications, but may also enable civilian general and specialty practices to more easily incorporate hemostatic resuscitation approaches to canine trauma care.

In Vitro Compatibility of Canine and Human Blood: A Pilot Study.

Military working dogs (MWDs) are force multipliers that are exposed to the same risks as their human counterparts on the battlefield. Hemostatic resuscitation using blood products is a cornerstone of damage control resuscitation protocols for both humans and dogs. Canine-specific blood products are in short supply in mature theaters due to logistic and regulatory concerns and are almost nonexistent in austere environments, whereas human blood products are readily available at most surgical facilities. The objective of this study was to evaluate the in vitro compatibility of human and canine blood by using standard crossmatching techniques with the canine blood acting as the recipient and the human blood acting as the donor. Blood samples were collected from 20 government-owned canines (GOCs) and 7 healthy human volunteers in addition to washed red blood cells (RBCs) from a commercial blood typing kit. Major and minor crossmatches were conducted as well as a protein denatured crossmatch. All samples in this study showed strong cross-reactivity, with the majority demonstrating profound hemolysis and a minority showing substantial agglutination. Based on the results of this study, transfusion of human blood to an MWD cannot be recommended at this time.