The inheritance pattern of factor XII (Hageman) deficiency in domestic cats.

Measurements of coagulation factor XII levels in F1 progeny of a cat having factor XII deficiency revealed an autosomal recessive pattern similar to that reported in humans (Hageman trait). A study of the pedigree of the colony revealed that F1 kittens had approximately 50% factor XII activity while kittens produced by backcrossing with an F1 progeny possessed an average of 50% and a less than 2% factor XII activity in an approximate 1:1 ratio. Kittens having an average of 50% factor XII activity were postulated heterozygous for the trait while progeny with less than 2% activity were considered genetically homozygous.     

Inherited bleeding disorders of dogs and cats

The congenital bleeding disorders of domestic animals usually mimic closely the same disorders in man and are inherited in a similar fashion. Classical haemophilia (haemophilia A, factor VIII deficiency) and haemophilia B (factor IX deficiency) occur in both dogs and cats and are sex-linked conditions. Affected animals are almost always male and heterozygote females are asymptomatic carriers. Offspring of a carrier female have a 50 per cent chance of inheriting the defective X-chromosome and, on average, half of the sons will be affected and half of the daughters will be carriers. Diagnosis of affected animals is confirmed by specific factor assay. Carriers may be identified with a statistical certainty of greater than 80 per cent. Canine von Willebrand's disease is a less severe disorder due to a defect of platelet adhesion. It is an autosomal trait, inherited in most breeds in an incompletely dominant fashion.     

Deficiency of the contact phase of intrinsic coagulation in a horse

A 16-year-old gelding was examined because of weight loss, inappetence, and intermittent fever of 2 months' duration. Preliminary laboratory findings revealed anemia, hypoproteinemia, thrombocytopenia, and prolongation of the activated partial thromboplastin time. A deficiency or inhibition of coagulation factor XI, factor XII, or high molecular weight kininogen was diagnosed. This defect was not associated with a bleeding diathesis, but should be considered as a cause of prolongation of the activated partial thromboplastin time.     

Haemophilia A (factor VIII deficiency) in a litter of Weimaraners

Inherited coagulopathies are reported in a number of dog breeds. However, to date, there is no report of Weimaraners suffering factor VIII deficiency (haemophilia A). We report the discovery of haemophilia A in both males from a single litter of Weimaraners. Haemophilia A in human beings often results from a de novo stochastic mutation. We found no evidence using currently available screening tests of haemophilia A in relatives as far back as three generations making a stochastic mutation possible in this litter.     

Hemophilia A in two related quarter horse colts

Severe hemorrhagic diathesis caused by hemophilia A (factor VIII:C deficiency) was diagnosed in 2 related Quarter Horse colts. Clinical signs consisted of dyspnea and dysphagia attributable to cranial cervical hematoma in one colt and to intra-abdominal hemorrhage resulting in death of the second colt. Factor VIII:C deficiency, a defect of the intrinsic coagulation pathway, is suggested by results of coagulation studies--prolonged activated partial thromboplastin time, normal prothrombin time, and normal primary bleeding time. The diagnosis was confirmed by results of factor VIII:C assays. Hemophilia A is inherited as an X chromosome-linked trait.     

Haemophilia A (Factor VIII deficiency) in the cat

A case of haemophilia A (classical haemophilia, factor VIII deficiency) in a cat is described. The cat presented with persistent bleeding from an oral wound, and protracted haemorrhage after castration. The diagnosis and management of this case is described. Subsequent investigation of the dam and a recent litter identified a further affected male kitten.     

Factor XII deficiency and von Willebrand's disease in a family of miniature poodle dogs

The simultaneous occurrence of factor XII deficiency and von Willebrand's disease (VWD) is described in a family of Miniature Poodles affected concurrently with a familial non-spherocytic hemolytic anemia. Although there was a dominant distribution of factor XII deficiency in this family of dogs, only the dogs suffering from non-spherocytic hemolytic anemia had concurrent VWD gene expression. Neither the factor XII deficient dogs nor the VWD carrier dogs displayed bleeding tendencies.     

Haemophilia A (factor VIII deficiency) in German Shepherd dogs

Moderate haemophilia A (factor VIII deficiency) has been identified in eight male German Shepherd dogs. Of 12 related females, five were diagnosed as obligate or probable carriers. The diagnosis of haemophilia A, its pattern of inheritance and carrier detection are discussed.     

Hemophilia B (factor IX deficiency) with concomitant factor XII degradation in a male crossbreed cat

A male cat suffered from a severe haemorrhagic disorder manifesting as deep, partly infected cutaneous haematomas, enhanced and prolonged bleeding after injuries and subsequent lameness at several occasions. Bleeding resulted in severe anaemia with haematocrit falling to as low as 0.10 L/L. Haemophilia B was diagnosed based on factor IX deficiency with a functional residual activity of 5% and factor IX antigen of 8%, respectively. Additionally, factor XII activity was reduced to 32% of normal. The mutation 31217G==>A in exon 8 of the factor IX gene, predicting the amino acid exchange G366R was identified as the cause of moderate factor IX deficiency. This is the first mutation identified in cats with haemophilia B. Treatment was limited to local therapy and palliation, insufficient to prevent lethal outcome due to severe anaemia.     

Disseminated intravascular coagulation in experimentally induced feline infectious peritonitis

Disseminated intravascular coagulation was induced in kittens by intraperitoneal inoculation of feline infectious peritonitis virus (FIPV). Kittens seronegative to FIPV survived significantly (P less than 0.05) longer than those seropositive to FIPV. Pyrexia, anemia, icterus, hyperbilirubinemia, and elevated concentrations of liver-specific enzymes were detected in the inoculated cats. Lesions induced included disseminated fibrinonecrotic and pyogranulomatous inflammation, hepatic necrosis, and widespread phlebitis and thrombosis. Localization of FIP viral antigen and immunoglobulin G was demonstrated in foci of heptic necrosis by immunofluorescence miroscopy. Lymphopenia, thrombocytopenia, hyperfibrinogenemia, and increased quantities of fibrin-fibrinogen degradation products were present in cats after the onset of clinical illness. Depression of factor VII, VIII, IX, X, XI, and XII plasma activities and prolongation of prothrombin and partial thromboplastin times also developed in infected cats. The accelerated onset of clinical disease and mortality in seropositive kittens vs seronegative kittens and the association of virus and antibody in multiple foci of hepatic necrosis suggest an immune-mediated component is involved in the pathogenesis of this disease.     

Prekallikrein deficiency in a dog

A 15-year-old male dog with chronic hematuria was found to have prolonged activated partial thromboplastin time. Results of plasma coagulation assays indicated a deficiency of prekallikrein, a plasma protein that modulates the rate of activation of factors XI and XII in the intrinsic clotting system. Patients with prekallikrein deficiency rarely have manifestations of hemorrhage. The hematuria was the result of a renal transitional cell carcinoma.     

Reproductive capacity of free-roaming domestic cats and kitten survival rate

OBJECTIVE: To determine reproductive capacity of naturally breeding free-roaming domestic cats and kitten survival rate. DESIGN: Prospective cohort and retrospective cross-sectional study. ANIMALS: 2,332 female cats brought to a trap-neuter-return clinic for neutering and 71 female cats and 171 kittens comprising 50 litters from a cohort study of feral cats in managed colonies. PROCEDURE: Data collected for all cats included pregnancy, lactation, and estrus status and number of fetuses for pregnant cats. Additional data collected for feral cats in managed colonies included numbers of litters per year and kittens per litter, date of birth, kitten survival rate, and causes of death. RESULTS: Pregnant cats were observed in all months of the year, but the percentage of cats found to be pregnant was highest in March, April, and May. Cats produced a mean of 1.4 litters/y, with a median of 3 kittens/litter (range, 1 to 6). Overall, 127 of 169 (75%) kittens died or disappeared before 6 months of age. Trauma was the most common cause of death. CONCLUSIONS AND CLINICAL RELEVANCE: Results illustrate the high reproductive capacity of free-roaming domestic cats. Realistic estimates of the reproductive capacity of female cats may be useful in assessing the effectiveness of population control strategies.     

Transmission of feline immunodeficiency virus from infected queens to kittens.

This study demonstrates the transmission of feline immunodeficiency virus (FIV) from infected queens to kittens in two separate litters. Queen 1 was infected by intravenous administration of FIV at 22 days prior to parturition. Two out of three kittens from the litter were found to be viremic at 10 weeks of age as detected by culture isolation and polymerase chain reaction detection of FIV DNA in peripheral blood mononuclear leukocytes. The third kitten remained aviremic through 40 weeks of age. Queen 2 was infected by subcutaneous administration of FIV 2 days prior to parturition. This litter also had two out of three kittens infected with FIV; however, viremia was not detected in one of the kittens until 21 weeks of age. Culture isolation was found to be superior to polymerase chain reaction for the early detection of FIV, and viremia was found to precede seroconversion by up to 4 weeks. Although all infected kittens have remained healthy, depressed CD4:CD8 lymphocyte ratios suggest that clinical disease may develop. This study suggests that FIV infection in cats may be a useful model system for the study of HIV transmission from mothers to infants.     

Genetics of equine bleeding disorders

Genetic bleeding disorders can have a profound impact on a horse's health and athletic career. As such, it is important to understand the mechanisms of these diseases and how they are diagnosed. These diseases include haemophilia A, von Willebrand disease, prekallikrein deficiency, Glanzmann's Thrombasthenia and Atypical Equine Thrombasthenia. Exercise-induced pulmonary haemorrhage also has a proposed genetic component. Genetic mutations have been identified for haemophilia A and Glanzmann's Thrombasthenia in the horse. Mutations are known for von Willebrand disease and prekallikrein deficiency in other species. In the absence of genetic tests, bleeding disorders are typically diagnosed by measuring platelet function, von Willebrand factor, and other coagulation protein levels and activities. For autosomal recessive diseases, genetic testing can prevent the breeding of two carriers.     

Congenital factor XI deficiency in a domestic shorthair cat

A 6-month-old, female, domestic shorthair cat was examined after onychectomy and ovariohysterectomy because of bleeding from the paws. Prolonged activated partial thromboplastin time was discovered, Coagulation factor analyses revealed deficiency of factor XI coagulant activity. Plasma mixing studies indicated factor deficiency or dysfunction rather than factor inhibition. Feline factor XI deficiency in one adult cat has been previously reported but was attributed to factor XI inhibitors. The signalment, lack of primary disease, and the finding of persistent factor XI deficiency in the absence of coagulation inhibitors were considered compatible with congenital factor XI deficiency in the cat of this report.     

Factor IX deficiency in an Alaskan Malamute

Factor IX deficiency, consistent with hemophilia B, was detected in a 6-month old male Alaskan Malamute with a 2-week history of persistent oozing from an oral wound. Laboratory studies disclosed an intrinsic coagulation defect. Hemophilia A was initially suspected. Further evaluation demonstrated normal factor VIII activity and factor VIII-related antigen, but factor IX activity was only 1.3% of normal.     

A 37XO chromosome complement in a kitten

In two kittens from the same litter with spina bifida and meningocoele the phenotypic male was found to have a normal 38XY chromosome complement whilst the phenotypic female had a 37XO chromosome complement. It was concluded that the spina bifida condition was due to the manx ancestry and not to the 37XO karyotype. The possible effect of the XO complement in cats is discussed.     

Transmission of feline leukaemia virus in the milk of a non-viraemic cat

The possibility of the transmission of feline leukaemia virus (FeLV) from latently infected cats was studied. Five female cats with latent infections were examined for evidence of transmission of the virus to their kittens. One of the cats infected members of four consecutive litters of kittens which subsequently became persistently viraemic and transmitted the virus to other susceptible kittens by contact. Shortly after birth its kittens were apparently FeLV-free since neither viral antigen nor infectious virus was detected in their blood and no virus was found in cell cultures made from aspirates of bone marrow. The kittens became viraemic from 45 days of age onwards at a time when their passively acquired colostral FeLV neutralising antibodies were no longer detectable. Transmission of the virus occurred via the milk since both FeLV antigen and infectious virus were found in milk samples taken six weeks after kittening and the virus was transmitted to a fostered kitten. Eleven weeks after the birth of the fourth litter the cat became viraemic. The intermittent presence of FeLV antigens detected by the Leukassay F test, but not infectious virus, in the plasma of this cat over the previous months and a low level of serum neutralising antibodies distinguished it from four other latently infected queens which did not transmit infection to their kittens. These factors may indicate a risk of milk transmission and reactivation of latent virus.     

Attempted transmission of Toxoplasma gondii infection from pregnant cats to their kittens

Sixteen 1- to 7-week-old pregnant specific-pathogen free cats were inoculated orally with Toxoplasma gondii cysts. Fetuses and neonatal kittens were examined for toxoplasma infection by inoculating suspensions of their tissues into mice. Toxoplasma gondii was not isolated from 23 fetuses and 16 newborn kittens from 13 queens. Six (3 litters) of the 15 kittens from the 3 remaining queens were killed on the day of or a day after birth, and the remaining 9 kittens were housed with their mothers for 7 to 33 days. None of the 9 kittens from the 2 litters examined between 0 and 33 days of age was infected with T gondii. In the other litter, T gondii was isolated from 3 kittens killed at 9, 16, and 22 days of age but not from 3 littermates killed on days 1, 1, and 22. Internal organs from the 3 kittens with proved toxoplasma infectivity in mice were examined histologically. Multifocal granulomatous encephalitis, hepatitis, nephritis, myocarditis, myositis, and interstitial pneumonia were found in all 3 kittens. Toxoplasma forms were demonstrated histologically in the tissues of 2 of these kittens. The mode of toxoplasma infection in newborn kittens was not determined but did not appear to be either transplacental or via fecal contamination from oocysts excreted by the mother cat. Evidence obtained in these experiments suggests that transplacental toxoplasma infection in the cat is not an important epidemiologic factor in perpetuation of the disease in the feline population.     

Vitamin K deficiency in cats fed commercial fish-based diets

Clinical signs of vitamin K deficiency have been observed in cats offered two commercial canned diets high in salmon or tuna. Some of the queens and kittens offered these diets had died while survivors had increased coagulation times. Necropsies revealed hepatic and, or, gastrointestinal haemorrhages. Coagulation times of survivors returned to normal after vitamin K therapy. The purpose of this study was to induce a vitamin K deficiency in kittens and determine the dietary requirement. Kittens were offered vitamin K-deficient purified diets containing antibiotics and, or, substances inherent in canned fish diets that may have contributed to the deficiency. Clinical signs of vitamin K deficiency were not observed, even though one purified diet contained only 4 μg K₁/kg diet compared with 60 μg in the commercial tuna diet. Therefore, a minimum vitamin K requirement could not be determined using purified diets; nevertheless, canned commercial diets formulated primarily with fish should contain more than 60 μg K₁/kg diet.