Bernard F. Feldman

General Principles of Small Animal Blood Component Administration

Administration of blood components instead of whole blood has become the most important means of transfusion support in dogs and in some settings in cats as well. Component administration entails the transfer of biological material and carries an inherent risk of disease transmission and adverse reactions. This article reviews the indications, pretransfusion considerations, and follow up in small animal patients receiving blood component therapy.

Cloning of a cDNA encoding bovine erythropoietin and analysis of its transcription in selected tissues

A bovine cDNA encoding erythropoietin (Epo) was isolated by polymerase chain reaction (PCR) amplification and screening of a bovine kidney cDNA library. The sequenced cDNA has a length of 1312 bp and an open reading frame that encodes a predicted 192-amino-acid (aa) protein, including a putative signal sequence of 25 aa. A mature protein of 167 aa (18.4 kDa) results upon cleavage of the putative signal peptide. The deduced bovine mature Epo peptide exhibits 96, 88, 83, 82 and 79% sequence identity to that of sheep, swine, human, monkey and rat, respectively. The expression of the bovine Epo gene in tissues from a severely anemic calf, bovine fetus and a healthy steer was analysed by a competitive RT-PCR method. In kidneys of the severely anemic calf, Epo mRNA levels increased 60-fold relative to that from the kidneys of the healthy steer. Epo mRNA levels were threefold higher in the liver of the bovine fetus than that in its kidneys. Low levels of Epo transcripts were detected in RNA from spleen of the severely anemic calf and the bovine fetus. No Epo transcripts were detectable in spleen from the healthy steer.

Demographics of canine immune-mediated haemolytic anaemia in the Southeastern United States

Detailed examination of the records of 57 dogs referred to our clinic with the diagnosis of immunemediated haemolytic anaemia was accomplished. Only untreated dogs or dogs who had only received supportive therapy were included in the study group comprising 30 male dogs and 27 female dogs. Age distribution followed the general age distribution of our patient population. There was no within-breed sex or age predilection. The youngest dog was 11 months of age and the oldest dog was 13 years of age. Overall mortality rate among the study population was 51% (29 dogs). Certain canine breeds were over-represented in this study and these same breeds had high mortality rates. Included were 11 cocker spaniels (19%; 82% mortality rate, 9 of 11 dogs), nine dogs with terrier in their name (16%; 78% mortality rate, 7 of 9 dogs), six German shepherds (11%; 50% mortality rate, 3 of 6 dogs), five doberman pinschers (9%; 60% mortality rate, 3 of 5 dogs), and five miniature schnauzers (9%; 60% mortality rate, 3 of 5 dogs). Immune-mediated haemolytic anaemia was considered secondary to hepatic disease in 16 dogs (28%), septicaemia in 10 dogs (18%) and neoplasia in six dogs (11%), i.e. signs and data supporting these processes were reported to have preceded anaemia. A total of 29 dogs (51%) also had thrombocytopenia (platelet counts less than 60000 cells/µl), eight (14%) dogs had major venous thrombosis, eight (14%) dogs had associated disseminated intravascular coagulation, and 24 (42%) of the dogs had evidence of renal disease — proteinuria and cylinduria. About 35% (20 dogs) of the patients were treated from June to August, and 63% (36 dogs) of the patients were direct antiglobulin positive (immunoglobulin G with or without complement). A variety of red cell morphological changes were observed including stomatocytes, bowl forms, knizocytes, schistocytes and spherocytes. Spherocytes were observed in 11 dogs (19%). Absolute reticulocytosis was observed in 26 dogs (46%). A variety of treatment combinations including glucocorticoids, azathioprine, cyclophosphamide, anabolic steroids, heparin, intravenous human gamma globulin, and blood component therapy were used without identifiable success associated with any given protocol.

Haemostasis and parturition revisited: Comparative profiles in mammals

The influence of parturition on plasma concentrations of fibrinogen, fibronectin and von Willebrand factor is compared in the canine, porcine, equine, bovine and human species. The significance of the alterations in these proteins at parturition is discussed in relation to their role in haemostasis, cellular adhesion reactions, and as acute-phase reactant proteins. The effect of hormones on the expression of these proteins in whole animal and cultured cell systems is briefly reviewed

von Willebrand’s disease

Abstractvon Willebrand’s disease (vWd) is the most frequent inherited bleeding disorder in people and in dogs, but has also been described in other species (pig, rabbit, horse, cow and cat). Patients affected by von Willebrand’s disease have a reduced quantity of functional von Willebrand factor (vWf). This deficiency produces impaired platelet adhesion to exposed subendothelium and subsequent platelet aggregation. The coagulation factor VIII (FVIII) circulates bound to vWf in plasma. The half-life of this factor is shorter without vWf. Clinical signs vary with severity of disease (in terms of vWf status), type of vWd, genotype, and concurrent diseases. Definitive diagnosis of vWd requires specific determination of plasma vWf concentration (with a result lower than 49 canine units (CU)/dl compared to the reference pool considered to be 100 CU/dl). Transfusion therapy, specifically cryoprecipitate (cryo) as vWf is concentrated in this blood product, is the treatment of choice in vWd in the dog. The advantage of cryo is the low volume needed to infuse a large quantity of vWf (1 unit/10 kg body weight as needed). If cryo is not available, fresh frozen plasma is indicated (6–10 ml/kg body weight bid or tid) or fresh whole blood (12–25 ml/kg/day) especially if marked haemorrhage has occurred.

Homocysteine, fibrinogen and physical activity in human males with coronary artery disease

Elevated homocysteine (Hcy) concentration has been identified as an independent risk factor for premature coronary artery disease (CAD). Associations between Hcy concentrations and established cardiovascular risk factors have occasionally, but not consistently, been demonstrated. Plasma fibrinogen and total Hcy concentrations, along with other risk factors, folate and B-vitamin supplements and medications, were recorded for 40 males (mean age±SD: 65±9.8 years) with CAD. Physical activity was assessed using the Modifiable Activity Questionnaire (MAQ), a written questionnaire which appraises leisure and occupational activities by recall for a 12-month period. Subjects in the upper tertile of physical activity had significantly lower fibrinogen concentrations than those in the lower tertile (274.7±38 mg/dl vs. 320.2±63, respectively,p-0.04). Univariate analyses revealed those subjects on beta-blocker therapy (n=12) had lower fibrinogen concentrations than those not on these medications (n=28) (277.7±16.7 vs. 316.1±10.9 mg/dl respectively,p=0.04). There was also a trend for those on beta-blockade to have lower Hcy concentrations (8.3±0.66 vs 9.7±0.43 μmol/l, respectively,p=0.058). Homocysteine concentration was found to be positively associated with age (p=0.0008). No significant associations were established with multivariate analyses among fibrinogen. Hcy, physical activity, age, BMI, B-vitamin and folate supplements, beta-blocker therapy, total cholesterol, high density lipoprotein (HDL), low density protein (LDL), triglycerides, and TC/HDL ratio. These results support the hypothesis that hyperhomocysteinaemia is independent of other CAD risk factors. Future studies should consider the favourable effects of beta-blockade, which may be a confounding factor, on Hcy and fibrinogen concentrations. Knowledge of associations may contribute towards understanding of the pathogenesis of CAD.

Disseminated Intravascular Coagulation: Present and Future Perspective

The haemostatic response could be considered a defensive function: it prevents or avoids blood loss from damaged vasculature (haemorrhage) and ensures adequate blood flow, maintaining the vascular tree free of obstruction (thrombosis). Procoagulant activity (inactive haemostatic proteins) is modulated or inhibited by several mechanisms. Endothelial cells play a key role in the control of these functions. The adequate equilibrium between activation and inhibition of haemostasis depends on interactions between endothelial cells, platelets, circulating blood cells, coagulation activators and inhibitors. Disseminated intravascular coagulation (DIC) may represent loss of haemostatic equilibrium induced by numerous clinical entities resulting in life-threatening consequences. This review summarises the data recently obtained concerning the aetiology, pathophysiology, clinical findings and laboratory diagnostics as regards DIC. Current and future DIC diagnostic and treatment modalities are discussed. It should be realised at the outset that disease presents differently among a continuum of events. Patients may undergo DIC anywhere in this continuum and, depending on the position in the continuum, exhibit radically different clinical and laboratory effects.

Large Granular Lymphoma with Toxoplasmosis in a Cat

A five-year-old domestic cat with generalised toxoplasmosis and severe leukaemia (145 × 109 WBC/1) is described. The liver was necrotic with tissue cysts and a localised lymphoma.Toxoplasma gondii organisms were found in all organs investigated. Tumour cells containing large cytoplasmic, azurophilic granules were observed in the blood. Erythrophagocytosis by tumour cells was also seen.

Biological monitoring of three antithrombotic drugs: single dose therapy

A randomised study using 40 New Zealand White male rabbits was performed to compare the effects of three antithrombotic drugs on eight clinical haemostatic function tests. The animals were divided into four treatment groups. The treatment groups were saline (control), unfractioned heparin (UFH), low-molecular-weight heparin (LMWH), and recombinant hirudin (r-hirudin).Blood samples were collected 2 and 12 h after administration of the drugs. The following tests were performed: bleeding time (BT), platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen concentration (Fg), antithrombin III (ATIII), and antifactor Xa activity (antiXa activity). Effects attributable to drug treatment for each analyte were determined by comparison with the control group.At 2 h after medication, in the UFH treated group, TT was moderately prolonged (p<0.05) and antiXa activity was significantly higher (p<0.05) than the respective values of the control group. In the LMWH-treated group the antiXa activity was significantly higher (p<0.01) than that of the control group. In the r-hirudin-treated group, the APTT and TT were significantly prolonged (APTT,p<0.01; the TT samples did not clot) when compared to the control group. However, 12 h after administration, no significant differences (p>0.05) between groups were observed for any of the studied analytes. It might be concluded that the antiXa assay has the potential of being a sensitive screen for heparin therapy and that the absence of changes in the bleeding time, antithrombin III, and antiXa assays —with a markedly prolonged thrombin time - indicates that,in vivo, r-hirudin acts as a specific inhibitor of thrombin.