AAV gene therapy in companion dogs with severe hemophilia: Real-world long-term data on immunogenicity, efficacy, and quality of life.

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.

Evaluation of post-transfusion RBC alloimmunization in dogs using a gel-column crossmatch with and without anti-canine globulin enhancement.

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.

Analysis of vector genome integrations in multicentric lymphoma after AAV gene therapy in a severe hemophilia A dog.

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.

Effect of donor blood storage on gel column crossmatch in dogs.

Background: Compared with fresh blood, stored equine donor blood results in spurious tube crossmatch incompatibilities. Interpretation of blood crossmatch results is considered subjective.

Objectives: We aimed to determine if the duration of canine donor blood storage impacts compatibility testing using a standard gel column crossmatch and evaluate interobserver variation in the interpretation of crossmatch results.

Hemolytic anemia blunts the cytokine response to transfusion of older red blood cells in mice and dogs.

Background: Transfusion of red blood cells (RBCs) stored for longer durations induces hemolysis and inflammatory cytokine production in murine and canine models. Despite immune system activation by stored RBCs, human randomized trials suggest that fresher RBC transfusions do not improve clinical outcomes. We hypothesized that underlying recipient hemolysis may affect cytokine responses to older RBC transfusions.

2021 ISFM Consensus Guidelines on the Collection and Administration of Blood and Blood Products in Cats.

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.

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.

Prevalence of naturally occurring non-AB blood type incompatibilities in cats and influence of crossmatch on transfusion outcomes.

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.

Heterozygosity for P2Y12 receptor gene mutation associated with postoperative hemorrhage in a Greater Swiss Mountain dog.

A 3-year-old, female Greater Swiss Mountain dog developed a hemoperitoneum following an exploratory laparotomy and ovariohysterectomy. Platelet count, PT, APTT, and plasma von Willebrand factor antigen concentration were within RIs. A buccal mucosal bleeding time (BMBT) was prolonged.

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.

Warfarin therapy in a dog with acute arterial thrombosis and pyometra.

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.

Polymorphisms in canine platelet glycoproteins identify potential platelet antigens.

Human alloimmune thrombocytopenic conditions caused by exposure to a platelet-specific alloantigen include neonatal alloimmune thrombocytopenia, posttransfusion purpura, and platelet transfusion refractoriness. More than 30 platelet-specific alloantigens have been defined in the human platelet antigen (HPA) system; however, there is no previous information on canine platelet-specific alloantigens. Using the HPA system as a model, we evaluated the canine ITGB3, ITGA2B, and GP1BB genes encoding GPIIIa (β3), GPIIb (αIIb), and GPIbβ, respectively, which account for 21 of 27 HPA, to determine whether amino acid polymorphisms are present in the orthologous canine genes.

Evaluation of coagulation in dogs with partial or complete extrahepatic biliary tract obstruction by means of thromboelastography.

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.

Suspected epidural morphine analgesia induced chronic urinary and bowel dysfunction in a cat.

A 12-year-old male castrated domestic shorthair developed chronic urinary retention, constipation and a decreased perineal reflex following a single lumbo-sacral epidural injection of morphine during general anesthesia. Similar adverse effects have been reported in humans following epidural analgesia, but this is the first reported case of both urinary and bowel dysfunction in a cat purportedly from an epidural. The cat was medically managed with manual bladder expressions, intermittent enemas, and various medications including bethanechol, cisapride and stool softeners.

Canine platelet transfusions.

Objective: To review potential platelet storage options, guidelines for administration of platelets, and adverse events associated with platelet transfusions.

Data Sources: Data sources included original research publications and scientific reviews.

Human Data Synthesis: Transfusion of platelet concentrates (PCs) plays a key role in the management of patients with severe thrombocytopenia.

Effects of anticoagulant on pH, ionized calcium concentration, and agonist-induced platelet aggregation in canine platelet-rich plasma.

OBJECTIVE-To compare effects of 3.8% sodium citrate and anticoagulant citrate dextrose solution National Institutes of Health formula A (ACD-A) on pH, extracellular ionized calcium (iCa) concentration, and platelet aggregation in canine platelet-rich plasma (PRP). SAMPLE POPULATION-Samples from 12 dogs.

Clinical and clinicopathologic effects of plateletpheresis on healthy donor dogs.

Background: The safety and feasibility of plateletpheresis using a commercially available apheresis system (COBE Spectra, Gambro BCT) were evaluated in donor dogs, with characterization of its clinical and clinicopathologic effects.

Study Design And Methods: Fourteen adult dogs (18-27.7 kg) underwent a plateletpheresis procedure.

Hereditary factor VII deficiency in the Alaskan Klee Kai dog.

Background: Hereditary factor VII (FVII) deficiency is characterized as a mild bleeding disorder in Beagles, caused by a missense mutation in exon 5 of the FVII gene. An Alaskan Klee Kai dog with severe bleeding after trauma was diagnosed with FVII deficiency based on coagulation testing. Molecular analyses were undertaken to identify the genetic basis of the defect in this breed.

Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs.

Objective: To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs.

Animals: 8 client-owned dogs with clinical signs of osteoarthritis.

Procedures: Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.

Multiple papillomavirus-associated epidermal hamartomas and squamous cell carcinomas in situ in a dog following chronic treatment with prednisone and cyclosporine.

A 4-year-old, spayed female toy fox terrier developed multiple epidermal hamartomas and squamous cell carcinomas in situ following chronic immunosuppressive therapy with prednisone and cyclosporine for management of an immune-mediated nonregenerative anaemia. Immunohistochemical staining was positive for papillomavirus antigen within both benign (n = 19) and malignant (n = 8) cutaneous lesions that developed during a 3-year period of observation, with positive staining most often seen in keratinocytes in the granular cell layer. Treatment of the papillomavirus infection with interferon-alpha was discontinued after 2 weeks because of diarrhoea and a further increase in liver enzymes.

Effect of desmopressin on von Willebrand factor multimers in Doberman Pinschers with type 1 von Willebrand disease.

Objective: To assess the effect of desmopressin (DDAVP) administration in Doberman Pinschers with type 1 von Willebrand disease (vWD) on plasma von Willebrand factor (vWF) multimers through determination of vWF collagen binding activity (vWF:CBA; a functional vWF assay dependent on the presence of high-molecular-weight [HMWI multimers), comparison of vWF antigen concentration (vWF:Ag) to vWF:CBA, and vWF multimer size distribution.

Animals: 16 Doberman Pinschers with type 1 vWD and 5 clinically normal control dogs.

Procedure: Plasma vWF:Ag and vWF:CBA assays and vWF multimer analysis were performed before and 1 hour after administration of DDAVP (1 microg/kg, SC).

Evaluation of a canine D-dimer point-of-care test kit for use in samples obtained from dogs with disseminated intravascular coagulation, thromboembolic disease, and hemorrhage.

Objective: To evaluate a canine D-dimer point-of-care (cD-d POC) test kit for use in healthy dogs and dogs with disseminated intravascular coagulation (DIC), thromboembolic disease (TED), and hemorrhage.

Animals: 12 healthy dogs, 18 dogs with DIC, 23 dogs with TED (19 acute and 4 chronic), and 18 dogs with hemorrhage.

Procedure: The cD-d POC, canine D-dimer ELISA (cD-d ELISA), human D-dimer latex agglutination (hD-d LA), and fibrin degradation product (FDP) tests were performed on citrated plasma.

Clinical application of a hemoglobin-based oxygen-carrying solution.

Oxyglobin, a hemoglobin-based oxygen-carrying fluid, is indicated in the treatment of anemia in dogs and may be life saving if compatible red blood cells are not available for transfusion. The colloidal properties of Oxyglobin allow for expansion of the circulatory volume, which may be helpful in patients with hypovolemia, especially hemorrhagic shock. Oxyglobin's colloidal properties can also lead to circulatory overload, with development of pulmonary edema and pleural effusion, however, necessitating careful monitoring of the rate of administration and of the respiratory rate and effort of the patient.

Effect of desmopressin acetate administration on primary hemostasis in Doberman Pinschers with type-1 von Willebrand disease as assessed by a point-of-care instrument.

Objective: To evaluate primary hemostasis following administration of desmopressin acetate (DDAVP) to Doberman Pinschers with type-1 von Willebrand disease (vWD).

Animals: 16 nonanemic Doberman Pinschers with type-1 vWD.

Procedure: Closure time (CT), defined as time required for occlusion of an aperture by a platelet plug assessed within the point-of-care instrument, plasma von Willebrand factor (vWF) concentration, and buccal mucosal bleeding time (BMBT) were determined before and 1 hour after administration of DDAVP (1 microg/kg, SC).