Causes, diagnosis and therapy of common diseases in neonatal puppies in the first days of life: cornerstones of practical approach.

Neonatal diseases and losses are a common and often unavoidable problem within breeding kennels. Altogether, morbidity and mortality ranges, according to the literature, from 5 to 35%. Among non-infectious causes besides hypoxia during birth, hypothermia, hypoglycaemia and dehydration are mostly responsible for puppy diseases and losses. Approximately 90% of all deaths in hypoxaemic pups occur during the first 2 days. Of 183 pups with hypoxia, 63 died, 92.7% of them within 48 h after birth. Among infectious causes, bacterial infection is the most common cause of neonatal mortality. Escherichia coli, streptococci, staphylococci, Pseudomonas sp., Klebsiella sp., Enterobacter sp. and some other micro-organisms are regularly involved in neonatal infections. Post-mortem findings especially document E. coli, Staphylococcus sp. and Streptococcus sp. as responsible bacteria. The dam and the environment are suspected as sources of neonatal infections as it was shown by genetic relatedness of responsible bacterial strains isolated in both puppies and their dams. From a total of 517 puppies with bacterial infections, the treatment results documented that parenteral administration of amoxicillin/clavulanic acid in 308 neonates showed the best result. Diagnosis of diseases is often made difficult by the absence of variability in clinical signs contrary to adult dogs. Findings during a physical examination in pups differ from those in adults. Furthermore, treatment recommendations have to meet the special conditions in neonates concerning drug metabolism and excretion.

[Case report. Phenprocoumon (Marcumar, Falithrom) as an unusual reason for coumarin poisoning in a dog]. / Phenprocoumon (Marcumar, Falithrom) als ungewöhnliche Ursache einer Kumarinvergiftung beim Hund.

Coumarin poisoning in dogs is not unusual and is in most cases caused by warfarin, a coumarin derivative which is used as a rodenticide. Competitive inhibition of vitamin K with an incomplete synthesis of the coagulation factors II, VII, IX and X can lead to a significant bleeding tendency. We observed a 3-year old male West Highland White Terrier with a reduced general condition and dyspnoea together with a massive haemothorax. Administration of vitamin K1 (3 mg/kg) led to a rapid improvement of the condition. Coagulation analysis revealed a prolonged activated recalcification time (ARCT), prothrombin time (PT) and aPTT with uncharacteristic thrombin time (TT); factor II, VII and X activities were reduced while factor V activity was normal, all of which are characteristic for coumarin poisoning. HPLC did not reveal the presence of warfarin but of phenoprocoumon, a drug used for thromboembolic prophylaxis in humans. This observation has not been described for dogs to date.

Proteins invoked by vitamin K absence and clotting times in clinically ill cats.

The clinical utility of the Thrombotest, a method for determining the prothrombin time that is uniquely sensitive to the presence of proteins invoked by vitamin K absence (PIVKA), was prospectively evaluated and compared to routine coagulation tests in cats with clinically suspected bleeding tendencies. Abnormal PIVKA clotting values were determined by comparison to results of a concurrently evaluated pooled feline plasma sample and by use of an absolute cutoff value of 25.2 seconds. To be recognized as abnormal, PIVKA clotting values had to be >20% of the pooled feline plasma PIVKA clotting time (the "20% rule") or > or =25.2 seconds (mean + 2 standard deviations of 150 different pooled feline plasma samples). Among the disorders in the population examined were 74 cats with liver disease and 19 cats with severe inflammatory bowel disease. Overall, a prolonged PIVKA clotting time based on the 25.2-second cutoff was found in 39.3% of cats, and based on the 20% rule in 40.7% of cats. An abnormal prothrombin time (PT) developed in 5.8% of cats, an abnormal APTT in 14% of cats, subnormal fibrinogen in 8.8% of cats, and thrombocytopenia in 3.3% of cats. Bleeding tendencies were confirmed in 22 cats, of which abnormal PIVKA clotting times were recognized in 95.5%, abnormal PT in 21%, abnormal activated partial thromboplastin time in 25%, hypofibrinogenemia in 16.7%, and thrombocytopenia in 4.5%. Response to treatment with vitamin K was demonstrated in 21 of 24 cats with an abnormal PIVKA clotting time. In these cats, an abnormal PIVKA clotting time normalized within 3 to 5 days of parenteral vitamin K administration. Cats responding to vitamin K administration had hepatic lipidosis (n = 7), severe inflammatory bowel disease (n = 4), severe inflammatory bowel disease associated with cholangiohepatitis (n = 5), and miscellaneous disorders (n = 5). Using either endpoint, the PIVKA clotting time is more sensitive for the detection of cats with coagulopathies than routinely used coagulation assessments in our hospital. Our findings confirm that cats with hepatic lipidosis, severe cholangiohepatitis, and severe inflammatory bowel disease develop coagulopathies responsive to vitamin K administration.

Vitamin K-dependent coagulopathy in a British Devon rex cat.

Deficiencies of the vitamin K-dependent coagulation factors were identified in a Devon rex cat which had bled after castration. Haemorrhage was controlled by plasma transfusion. Clotting times were normalised by oral administration of vitamin K. This report confirms the existence of this bleeding disorder in a Devon rex cat in the United Kingdom.

Vitamin deficiencies in cattle.

Deficiencies of vitamins A, D, K, E and thiamin can cause severe limitations in beef production. In particular, vitamin A and E can be common causes of lost profit, secondary to limitations of reproductive and growth potential. Prolonged dry periods will reduce available A and E in pasture forage, as can ensiling and prolonged storage of harvested feedstuffs. Polioencephalomalacia is a thiamin responsive disorder, associated with high concentrate feeding and lush pastures. Antimetabolites, such as amprolium, will cause thiamine deficiency when fed in excess. Recent information has shown improved performance with supplemental beta carotene and niacin. The positive responses in reproductive performance, noted with cattle fed supplemental beta carotene, was independent of vitamin A. Supplementation of vitamins above National Research Council recommendations can be justified. However, proper evaluation of feed and animal status, and documentation of a response to supplementation is necessary before diagnosing deficiencies of specific nutrients.

Vitamin K-dependent multifactor coagulopathy in Devon Rex cats.

A coagulopathy attributable to a deficiency of vitamin K-dependent clotting factors (II, VII, IX, and X) was diagnosed in 3 Devon Rex cats. There was no evidence for exposure to vitamin-antagonist-related rodenticides. The cats did not have evidence of hepatic disease, gastrointestinal disease, or fat malassimilation. Oral treatment with vitamin K1 resulted in normalization of clotting factor concentrations. However, when treatment was discontinued in 2 cats, prothrombin and activated partial thromboplastin values became prolonged again, although the cats did not have clinical signs of a bleeding disorder.

[Secondary effects caused by feed medication in swine]. / Nebenwirkungen durch Futtermedikation beim Schwein.

Giving medical feed to weanling pigs it is possible to produce a vitamin K-deficiency as a side effect, which is caused by destruction of the intestinal flora. In this investigation the effect of different drugs in a vitamin K-deficient diet on blood coagulation of weanling pigs was examined. In a first trial clinical symptoms of a vitamin K-dependent coagulation disorder could be seen in five from six animals after feeding a combination of sulfadimidine, tylosin, furazolidone and arsanilic acid. Animals showed haemorrhages, when they were housed on flatdecks as well as on concrete floor. This indicated that coprophagy plays no role in pigs for supply of vitamin K. Feeding these drugs in other combinations or one of the drugs alone caused no clinical signs in a second trial. Significant differences to untreated control pigs were found only in one group (sulfadimidine/arsanilic acid) for activities of coagulation factors. Other groups demonstrated only prolongation of clotting times in single animals. Pigs, which received sulfadimidine within their ration, were more often affected than other animals. In a third trial suckling pigs were treated over a period of three weeks with a drug combination used in the first trial to allow an adaptation of the intestinal flora. Same treatment after weaning was unable to produce any clinical symptoms, but led to distinct coagulation disorders in pigs treated before as well as in untreated animals. It is supposed that the development of a vitamin K-deficiency depends on faecal bacterial count and on the specific resistance of intestinal flora in individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Probable vitamin K--deficient bleeding in two cats with malabsorption syndrome secondary to lymphocytic-plasmacytic enteritis.

Two cats with intestinal malabsorption developed a hemorrhagic diathesis. Although unsubstantiated, the probable cause of bleeding was a chronic malabsorption of fat and the fat-soluble vitamin K. When treated with vitamin K1 per os, one cat's clotting times were only partially corrected. Since vitamin K1 is actively absorbed in the proximal small intestine, the incomplete response of this case to orally administered vitamin K1 was predictable. The infrequent occurrence of bleeding in animals with malabsorption is, in part, attributable to the ileal and colonic absorption of bacterially derived vitamin K2. For this reason, nonspecific use of antibiotics in these animals is contraindicated. Since long-chain, polyunsaturated fats impair vitamin K absorption, dietary fat given to animals with malabsorption should be restricted to medium- and short-chain, saturated fats. Vitamin K should be administered subcutaneously to these animals if prolonged clotting times or active bleeding is present, and routinely prior to surgery. Oral supplementation with vitamin K3, which is absorbed in the colon and less lipid soluble than vitamin K1, should be given to animals with malabsorption that are maintained as outpatients. Adequate dosage levels of vitamin K3, however, are yet to be established for the cat, and dose-dependent hemolytic anemia is a probable toxic manifestation.

Avitaminosis K and the lack of heart lesions in poultry.

Poultry susceptibility to avitaminosis K-induced granulomatous endocardial lesions was studied in broiler and layer chicks. They were fed either a practical corn-soybean meal diet with and without added vitamin K (vit K), or a 61% raw sugar-isolated soybean protein diet (RS-IS) with no added vit K for 10 weeks. Heart lesions were not found in birds fed any of the experimental diets. Mortality, body weight gain, and prothrombin time did not differ significantly between birds fed the practical diet regardless of vit K supplementation. In contrast, the RS-IS diet significantly increased mortality, prothrombin time, and markedly decreased growth. Furthermore, more than a third of the birds fed the high sugar diet had subcutaneous edema, which resembled exudative diathesis. Compared with swine, poultry are apparently less susceptible to granulomatous endocardial lesions induced by a vit K deficiency.

A haemorrhagic syndrome in recently weaned pigs ascribed to hypovitaminosis K.

An outbreak of a haemorrhagic syndrome involved recently weaned, mixed-breed pigs in a large piggery. The pigs were fed a pelleted complete ration containing antibacterial drugs. Affected pigs failed to grow, became pale and developed large, subcutaneous haematomas. Some pigs became lame and one had epistaxis. The monthly mortality rate in the weaner house, which was previously less than 2%, exceeded 6% during the outbreak. Coagulation time, activated partial thromboplastin time and prothrombin time were prolonged in blood from some of the pigs. The outbreak resolved promptly after supplementation of the diet with vitamin K3.

Fatal myocarditis in mice fed rancid purified feed.

An outbreak of disease characterized by diarrhea, severe myocarditis, and high mortality occurred in a group of 800 male B6C3F1/ Har mice fed powdered purified diets. A total of 292 animals died. No evidence of an infectious agent was found, and the disease was reproduced in healthy mice by feeding the purified diets, suggesting a nutritional deficiency or toxicity. Analysis of the feed revealed adequate levels of vitamin E, reduced levels of thiamine, and elevated levels of lipoperoxide. It was concluded that mortality was due to myocarditis associated with the ingestion of rancid feed.

Preparation, properties and biological activity of beta-cyclodextrin inclusion complex of menadione.

The molar ratio of menadione (vitamin K3) to beta-cyclodextrin in the microcrystalline inclusion complex showed this to be 1:3 with a menadione content of approximately 4.1-4.3%. Complexes with higher vitamin content could not be prepared. Bound and free vitamin can be readily separated by sublimation in vacuum. The menadione is highly stable in complexed form; in dry state it is released only when cyclodextrin is destroyed by heating to about 300 degrees C. Complexed menadione does not react with amino acids. Solubility and dissolution rate are strongly increased. Treating hypovitaminotic chickens with equivalent doses of menadione or menadione-beta-cyclodextrin complex and monitoring blood clotting times, recalcification times and prothrombin times the complex proved to be at least as effective as--or even somewhat more potent than--free vitamin. 1.5-2.0 micrograms/animal/d free or complexed menadione was sufficient to cover the daily vitamin K needs of chickens.

Vitamin K deficiency syndromes in warfarin-resistant brown rats (Rattus norvegicus).

Resistance to the anticoagulant rodenticide warfarin and an increased vitamin K requirement appear to be pleiotropic effects of the gene Rw2. A comparison of pup mortality in F2 (Rw1Rw2 x Rw1Rw2) and backcross (Rw1Rw2 x Rw1Rw1 or reciprocal) matings of wild brown rats in the laboratory revealed significantly greater losses in the F2 litters at 4-8 weeks of age. Some deaths could be attributed directly to haemorrhage resulting from vitamin K deficiency. A newborn warfarin-resistant rat from an F2 litter showed bleeding from the umbilicus and the anus, and died from internal haemorrhage at 18 weeks of age. Another warfarin-resistant male rat dying at the same age had a grossly enlarged skull.