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An Ongoing Series




                        Hemoglobin-Based Oxygen Carrier for the Reconstitution of
                    Canine Freeze-Dried Plasma in an In Vitro Model of Resuscitation


                            Thomas H. Edwards, DVM, MS, DACVECC*; Michael A. Meledeo, PhD;
                               Grantham C. Peltier, MS; Alice F. Henderson; Rachel M. Hammill;
                                           Colby S. McIntosh; James A. Bynum, PhD






              ABSTRACT
              Military working dogs (MWDs) are force multipliers that are   restoration of effective circulating volume while minimizing the
              at risk for severe trauma when employed on the battlefield.   aforementioned complications from crystalloids and colloids.
                                                                                                               2,3
              When in severe hemorrhagic shock, MWDs require both oxy-  However, traditional blood products have logistical challenges
              gen-carrying capacity and replacement of vascular volume and   to include the requirement of different cold storage conditions
              coagulation factors. The objective of this study was to evaluate   for different products and relatively short shelf lives. 4,5
              the hemostatic capacity of canine freeze-dried plasma (cFDP)
              with a Food and Drug Administration (FDA)-approved hemo-  Previous studies have documented the injuries sustained by
              globin-based oxygen carrier (HBOC) in an in vitro model of re-  military working dogs (MWDs) on the battlefield, which are
              suscitation. Whole blood (WB) was collected from 10 MWDs,   similar to those sustained by their human counterparts.  Rec-
                                                                                                           6–8
              and these samples were diluted by 10%, 25%, or 40% with   ommendations have been made that severely injured MWDs
              either cFDP (reconstituted with water), HBOC, cFDP (reconsti-  (and canines in general) would likely benefit from similar he-
              tuted with HBOC), or an equal volume of a 1:1 ratio of cFDP   mostatic resuscitation protocols that are recommended for
              (reconstituted with water) and HBOC. Hemostatic parameters   severely injured people in hemorrhagic shock. 9–11  Though
              were minimally changed based on evaluation of prothrombin   veterinary medical and surgical resources are well established
              time, activated partial thromboplastin time, fibrinogen and   for MWDs in mature theaters, resources are lacking in highly
              thromboelastography at the 10% and 25% dilutions, and pa-  tactical and far-forward environments. These austere environ-
              rameters consistent with a hypocoagulability were seen at di-  ments complicate the logistics of getting canine specific blood
              lutions of 40%. Based on the results of this study, additional   products to injured MWDs.  This has led to interest in find-
                                                                                      12
              research is warranted to determine if cFDP reconstituted with   ing blood products or blood substitutes that do not pose sig-
              HBOC is a viable resuscitation product in canine trauma.  nificant logistical hurdles. The Department of Defense (DoD)
                                                                 has sponsored two companies to develop cFDP, and a recent
              Keywords:  canine; hemoglobin-based oxygen carrier; freeze-  study showed that one of the products, when reconstituted
              dried plasma; oxyglobin; thromboelastography; dogs  with sterile water per manufacturer’s specifications, performs
                                                                                                13
                                                                 similarly to canine fresh frozen plasma.  An HBOC that is
                                                                 FDA approved for use in dogs (HB-200-Oxyglobin) is no lon-
                                                                 ger commercially available but may become available in the
              Introduction
                                                                 future. This product has a long track record of successfully
              Fluid resuscitation is a cornerstone of hemorrhagic shock man-  treating anemic dogs with few significant side effects. 14–16  Ox-
              agement in both humans and animals. The use of crystalloid   yglobin  has  the  advantage  of  long  shelf  life  (labeled  for  36
              and colloid solutions to restore effective circulating volume   months), is stable at room temperature, and can be infused
              has been the standard of care for years. However, crystalloids   without the concern for transfusion mismatch while delivering
              and synthetic colloid-based resuscitation strategies can cause   oxygen-carrying capacity to the recipient. 17
              a hypocoagulability by way of a significant hemodilution of
              red blood cells, platelets, and coagulation factors as well as   The combination of cFDP and HBOC is an extremely attrac-
              impaired platelet function and fibrin formation.  Alternatively,   tive option for resuscitating severely injured canines, particu-
                                                  1
              resuscitation with blood products to include whole blood,   larly in austere environments. This combination of products
              packed red blood cells, platelet products, and plasma allow for   potentially allows for both oxygen carrying capacity as well
              *Correspondence to ugadvm2006@hotmail.com
              LTC (Ret) Thomas H. Edwards, Dr Michael A. Meledeo, Grantham C. Peltier, SPC Alice F. Henderson, SSG Rachel M. Hammill, Colby S.
                McIntosh, and Dr James Bynum are all affiliated with the US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX. LTC (Ret)
              Edwards is also an adjunct professor at Lincoln Memorial University College of Veterinary Medicine and a critical care specialist at BluePearl
              Veterinary Specialists in San Antonio, TX.

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