Practical relevance:
Blood and blood products are increasingly available for practitioners to use in the management of haematological conditions, and can be lifesaving and therapeutically useful for ...patients with anaemia and/or coagulopathies. It is important for feline healthcare that donors are selected appropriately, and transfusions of blood or blood products are given to recipients that will benefit from them. Complications can occur, but can be largely avoided with careful donor management and recipient selection, understanding of blood type compatibility, and transfusion monitoring.
Clinical challenges:
Feline blood transfusion, while potentially a lifesaving procedure, can also be detrimental to donor and recipient without precautions. Cats have naturally occurring alloantibodies to red cell antigens and severe reactions can occur with type-mismatched transfusions. Blood transfusions can also transmit infectious agents to the recipient, so donor testing is essential. Finally, donors must be in good health, and sedated as appropriate, with blood collected in a safe and sterile fashion to optimise the benefit to recipients. Transfusion reactions are possible and can be mild to severe in nature. Autologous blood transfusions and xenotransfusions may be considered in certain situations.
Evidence base:
These Guidelines have been created by a panel of authors convened by the International Society of Feline Medicine (ISFM), based on available literature. They are aimed at general practitioners to provide a practical guide to blood typing, cross-matching, and blood collection and administration.
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.
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.
The hemophilias are the most common severe inherited bleeding disorders and are caused by deficiency of clotting factor (F) VIII (hemophilia A) or FIX (hemophilia B). The resultant bleeding ...predisposition significantly increases morbidity and mortality. The ability to improve the bleeding phenotype with modest increases in clotting factor levels has enabled the development and regulatory approval of adeno-associated viral (AAV) vector gene therapies for people with hemophilia A and B. The canine hemophilia model has proven to be one of the best predictors of therapeutic response in humans. Here, we report long-term follow-up of 12 companion dogs with severe hemophilia that were treated in a real-world setting with AAV gene therapy. Despite more baseline bleeding than in research dogs, companion dogs demonstrated a 94% decrease in bleeding rates and 61% improvement in quality of life over a median of 4.1 years (range 2.6–8.9). No new anti-transgene immune responses were detected; one dog with a pre-existing anti-FVIII inhibitor achieved immune tolerance with gene therapy. Two dogs expressing 1%–5% FVIII post gene therapy experienced fatal bleeding events. These data suggest AAV liver-directed gene therapy is efficacious in a real-world setting but should target expression >5% and closely monitor those with levels in the 1%–5% range.
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Doshi and colleagues demonstrate that AAV gene therapy in companion dogs in a real-world setting is safe and efficacious with decreased bleeding, no anti-transgene immune responses, and improved quality of life over a median of 4.1 years of follow-up. Bleeding rates are lower when factor VIII or IX expression is >5%.
Adeno-associated viral (AAV) vectors have traditionally been viewed as predominantly nonintegrating, with limited concerns for oncogenesis. However, accumulating preclinical data have shown that AAV ...vectors integrate more often than previously appreciated, with the potential for genotoxicity. To understand the consequences of AAV vector integration, vigilance for rare genotoxic events after vector administration is essential. Here, we investigate the development of multicentric lymphoma in a privately owned dog, PC9, with severe hemophilia A that was treated with an AAV8 vector encapsidating a B domain–deleted canine coagulation F8 gene. PC9 developed an aggressive B cell lineage multicentric lymphoma 3.5 years after AAV treatment. Postmortem analysis of the liver, spleen, and lymph nodes showed the expected biodistribution of the AAV genome. Integration events were found both in PC9 and a second privately owned hemophilia A dog treated similarly with canine F8 gene transfer, which died of a bleeding event without evidence of malignancy. However, we found no evidence of expanded clones harboring a single integration event, indicating that AAV genome integrations were unlikely to have contributed to PC9’s cancer. These findings suggest AAV integrations occur but are mostly not genotoxic and support the safety profile of AAV gene therapy.
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Samelson-Jones and colleagues found no evidence to suggest that adeno-associated viral (AAV) vector integrations contributed to the development of a fatal lymphoma 3.5 years after AAV treatment in a dog with hemophilia A. Although AAV vector integrations were identified, they did not appear to be genotoxic.
Objective-To characterize in vitro coagulation status in a cohort of dogs with extrahepatic biliary tract obstruction (EHBO) and to evaluate these patients for hypercoagulability by means of ...thromboelastography. Design-Prospective cohort study. Animals-10 dogs with EHBO and 19 healthy control dogs. Procedures-Partial or complete EHBO was confirmed via exploratory celiotomy. Venous blood samples were collected for evaluation of prothrombin time (PT) and activated partial thromboplastin time (APTT); fibrinogen and D-dimer concentrations; protein C and antithrombin activities; and factor VII, VIII, and XI coagulant activities in plasma as well as thromboelastography in whole blood. Thromboelastography variables were measured from the thromboelastography tracing, and a coagulation index was calculated. Thromboelastography results were compared with those of healthy control dogs previously evaluated by the same laboratory. Results-Hypercoagulability was diagnosed in all dogs with EHBO on the basis of a high coagulation index. Thromboelastography variables, including maximal amplitude, α-angle, and coagulation index, were significantly higher, and K (clot formation time) and R (reaction time) were significantly lower in these dogs than in control dogs. All dogs with EHBO had PT and APTT within respective reference ranges. Plasma D-dimer and fibrinogen concentrations were above reference ranges in 8 and 7 dogs, respectively, and protein C and antithrombin activities were below reference ranges in 3 and 1 dogs, respectively. Conclusions and Clinical Relevance-In vitro hypercoagulability was commonly detected in dogs with naturally occurring EHBO. The traditional view of EHBO as a disease that causes hypocoagulability may need to be reconsidered.
A blood crossmatch is essential to ensure RBC compatibility for previously transfused dogs. There is no gold standard crossmatch method for dogs, although the standards used most commonly by academic ...institutions and reference laboratories are the tube and gel-column crossmatches. Addition of anti-canine globulin (ACG) has been suggested to increase detection of RBC incompatibilities. Our objective was to determine if there is a correlation between results of a standard and an ACG-enhanced gel-column crossmatch in detecting post-transfusion RBC alloimmunization. Pre- and post-transfusion serum or plasma samples were obtained from 33 dogs for major crossmatches to 1–6 (median: 3) blood donors. Crossmatches were performed with (n = 202) and without (n = 202) ACG, with results scored by 4 observers, 3 of whom were anonymized. Ten of 33 (30%) dogs had major crossmatch incompatibilities post-transfusion. RBC incompatibilities (2–4+ agglutination) were detected only with ACG in 4 dogs, only without ACG in 3 dogs, and with both methods in 3 dogs. There was fair correlation between crossmatch methods for determination of compatibility (ρ = 0.34; p < 0.001) and incompatibility (ρ = 0.35; p < 0.001) scores. Among 4 observers, there was near-perfect agreement in determining compatibility (κ = 0.97; p < 0.001) and substantial agreement in overall scoring of incompatibility (κ = 0.77; p < 0.001). Our results suggest that detection of RBC incompatibilities in dogs can be maximized by performing a gel-column crossmatch both with and without ACG enhancement.
This report describes the presentation of acute arterial thrombosis causing triparesis in a 6-year-old female Chihuahua with pyometra and its successful management in combination with warfarin ...therapy. This is the first case report of a dog with arterial thrombosis associated with pyometra.
Background
Recognition of the feline red blood cell (RBC) antigen Mik and the presence of naturally occurring anti‐Mik antibodies resulting in acute hemolytic transfusion reactions prompted the ...recommendation to perform a crossmatch before a cat's first RBC transfusion, but this guideline has not yet become a standard practice.
Objective
To determine the prevalence of naturally occurring non‐AB alloantibodies detectable by tube crossmatch, and to compare transfusion outcomes in cats with and without a crossmatch performed.
Animals
Three hundred cats that received an RBC transfusion, with or without a major crossmatch performed.
Methods
Retrospective study.
Results
Major crossmatch incompatibilities were documented in 23 of 154 transfusion‐naive cats (14.9%) and in 15 of 55 previously transfused cats (27%; P = 0.042). Type‐specific packed RBCs (pRBCs) were administered to 167 and 82 cats with and without a crossmatch, respectively. Median volume of pRBCs administered during the first transfusion was 5.3 mL/kg (range, 2.4‐18 mL/kg). Median change in PCV scaled to dose of pRBCs was +0.8%/mL/kg; administration of crossmatch‐compatible pRBCs was not associated with a greater increase in PCV. Febrile transfusion reactions occurred more often in cats that received non‐crossmatched (10.1%) compared to crossmatched (2.5%) pRBCs (P = 0.022). Seventy‐six percent of cats that received pRBC transfusions survived to hospital discharge. A crossmatch was not associated with improved survival to discharge or at 30 or 60 days posttransfusion.
Conclusions and Clinical Importance
The prevalence of naturally occurring non‐AB incompatibilities is sufficiently high to justify the recommendation to perform a crossmatch before all (including the first) RBC transfusions in cats.
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