Influence of canine donor plasma hemostatic protein concentration on quality of cryoprecipitate

Background Cryoprecipitate (CRYO) is a plasma component containing high concentrations of factor VIII (FVIII), von Willebrand factor (VWF), and fibrinogen. Because Greyhounds are reported to have lower plasma VWF and fibrinogen concentrations, their plasma may not yield high potency CRYO. Objectives To determine if plasma hemostatic protein concentration is a good predictor of CRYO potency and if a difference exists in quality of CRYO prepared from Greyhounds versus non‐Greyhounds. Animals Twenty Greyhounds and 20 non‐Greyhounds. Methods A 450 mL unit of blood was collected from each donor, centrifuged to prepare fresh frozen plasma (FFP), and processed to CRYO. Aliquots of FFP and CRYO were analyzed for FVIII, VWF, and fibrinogen content and factor recovery. Results A positive correlation was found among donor plasma FVIII, VWF and fibrinogen concentration, and CRYO factor content (P < .001). Mean recovery was highest for VWF (67%), followed by fibrinogen (47%), and FVIII (37%). No breed difference was found in mean CRYO FVIII content, but CRYO VWF and fibrinogen were lower in Greyhounds (P = .004 and P < .001, respectively). No difference was found between Greyhounds and non‐Greyhounds for the number of CRYO units meeting human blood banking standards. Conclusions and Clinical Importance Factor concentration in FFP is associated with CRYO potency, suggesting that prescreening of blood donors may enhance CRYO quality. Despite lower VWF and fibrinogen content, CRYO prepared from Greyhounds is acceptable based on blood banking standards for humans, indicating that Greyhound FFP does not need to be excluded from CRYO production

Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs.

Severe hemophilia A (HA) is an inherited bleeding disorder characterized by <1% of residual factor VIII (FVIII) clotting activity. The disease affects several mammals including dogs, and, like humans, is associated with high morbidity and mortality. In gene therapy using adeno-associated viral (AAV) vectors, the canine model has been one of the best predictors of the therapeutic dose tested in clinical trials for hemophilia B (factor IX deficiency) and other genetic diseases, such as congenital blindness. Here we report our experience with liver gene therapy with AAV-FVIII in two outbred, privately owned dogs with severe HA that resulted in sustained expression of 1-2% of normal FVIII levels and prevented 90% of expected bleeding episodes. A Thr62Met mutation in the F8 gene was identified in one dog. These data recapitulate the improvement of the disease phenotype in research animals, and in humans, with AAV liver gene therapy for hemophilia B. Our experience is a novel example of the benefits of a relevant preclinical canine model to facilitate both translational studies in humans and improved welfare of privately owned dogs

Humoral response to AAV8 capsid in hemophilia A dogs before and after intravascular delivery of AAV8-cFVIII-BDD.

<p>Humoral response to AAV8 capsid in hemophilia A dogs before and after intravascular delivery of AAV8-cFVIII-BDD.</p

Bleeding episodes and transfusion events prior to gene therapy in privately owned dogs with severe hemophilia A.

<p>Bleeding episodes and transfusion events prior to gene therapy in privately owned dogs with severe hemophilia A.</p

Time course of canine FVIII activity following intravenous injection of AAV8-cFVIII-BDD in severe hemophilia A dogs.

<p>Time course of canine FVIII activity following intravenous injection of AAV8-cFVIII-BDD in severe hemophilia A dogs.</p

Summary of liver gene therapy by AAV8 encoding canine FVIII in privately owned severe hemophilia A dogs.

<p>Summary of liver gene therapy by AAV8 encoding canine FVIII in privately owned severe hemophilia A dogs.</p

sj-pdf-1-vdi-10.1177_10406387231222895 – Supplemental material for Evaluation of post-transfusion RBC alloimmunization in dogs using a gel-column crossmatch with and without anti-canine globulin enhancement

Supplemental material, sj-pdf-1-vdi-10.1177_10406387231222895 for Evaluation of post-transfusion RBC alloimmunization in dogs using a gel-column crossmatch with and without anti-canine globulin enhancement by Alison Thomas-Hollands, Rebecka S. Hess, Nicole M. Weinstein, Samantha Fromm, Nicole A. Chappini, Kimberly Marryott and Mary Beth Callan in Journal of Veterinary Diagnostic Investigation</p