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 session on the hemostatic system focused on new developments in coagulation and platelet biology as well as how therapeutic agents may affect hemostasis. The classic cascade model of coagulation was compared with the more recent models of cell-based and vascular-based coagulation, which may provide better insight on how the coagulation cascade works in vivo. A review of platelet biology highlighted that, as platelets age, desialylated platelets form and are recognized by Ashwell-Morell receptor (AMR), leading to hepatic uptake and subsequent increase in thrombopoietin (TPO) production. Administration of therapeutics that induce thrombocytopenia was also discussed, including Mylotarg, which is an antibody-drug conjugate that was shown to decrease human megakaryocyte development but had no effect on platelet aggregation. An acetyl co-A carboxylase inhibitor was shown to cause thrombocytopenia by inhibiting de novo lipogenesis, which is critical for the formation of the megakaryocyte demarcation membrane system responsible for platelet production. It was also illustrated how preclinical translation models have been very helpful in the development of adeno-associated virus (AAV) hemophilia B gene therapy and what old and new preclinical tools we have that can predict the risk of a prothrombotic state in people.
Fibrin and fibrinogen degradation products (FDPs) are the end products of primary fibrinogenolysis (cleavage of fibrinogen and non-crosslinked fibrin) or secondary lysis of cross-linked fibrin clots. Elevated FDP concentrations indicate either fibrinogenolysis or fibrinolysis, and may be observed in horses with disseminated intravascular coagulation (DIC), severe inflammatory processes and hemorrhagic disorders. Measurement of FDPs has been largely replaced in practice by D-dimer assays, which detect specific, domains of cross-linked fibrin, and are more specific indicators of plasmin's action on fibrin rather than fibrinogen. Commercial assays for D-dimers demonstrate higher sensitivity and specificity, and have largely replaced FDP measurement in clinical practice. Blood for FDP or D-dimer measurement should be collected via minimally traumatic venipuncture into tubes containing sodium citrate (3.2 or 3.8%) anticoagulant (blue top tube). FDPs and D-dimer will be elevated in response to any process that activates the coagulation cascade and results in clot formation and subsequent fibrinolysis.
Summary During a study period from 1985 through 1988, plasma von Willebrand's factor antigen (vWF:Ag) concentration was measured as a marker for prevalence of the von Willebrand's disease (vWD) trait in Doberman Pinschers (doberman, n = 5,554), Scottish Terriers (scottie, n = 1,363), and Shetland Sheepdogs (sheltie, n = 4,279). Significant increase in prevalence of the trait was seen in scotties and shelties during this period. In 1988, 73% of dobermans, 30% of scotties, and 28% of shelties tested had abnormal vWF:Ag concentration (<50% vWF:Ag). We found significant differences between breeds with respect to age and vWF:Ag concentration of clinically affected dogs at time of diagnosis. The affected dobermans were older (doberman mean age, 4.6 years; scottie mean age, 1.7 years; sheltie mean age, 1.9 years) and had higher concentration of plasma vWF:Ag (doberman mean vWF:Ag, 15%; scottie mean vWF:Ag, 0%; sheltie mean vWF:Ag, 8%). Bleeding in affected dogs of all 3 breeds was observed predominantly from mucosal surfaces and from cutaneous sites of surgery or trauma. The most common site of mucosal bleeding in scotties and shelties was oral or nasal cavity, and in dobermans was the urogenital tract. Differences in clinical manifestations of vWD in purebred dogs may reflect heterogeneous defects within the vWF gene, causing a variety of abnormalities in production, structure, and function of vWF protein. Analogous to vWD in human beings, acquired deficiencies of vWF may also contribute to the clinical variability of vWD in dogs.
Thirteen dogs with primary immune-mediated hemolytic anemia received fresh-frozen plasma within 12 hours of admission, in addition to unfractionated heparin and other therapies, such as prednisone, azathioprine, and packed red blood cell transfusion. Antithrombin activity was quantified prior to transfusion and at 30 minutes and 48 hours after transfusion. Plasma antithrombin activity did not change significantly after a single plasma transfusion. There were no deaths in the first 48 hours of treatment. Thromboembolism was identified at necropsy in six of 10 dogs that died within 12 months of admission. There was no significant difference in the incidence of thromboembolism between the current treatment group and a historical control group.
The current feline genotyping array of 63 k single nucleotide polymorphisms has proven its utility for mapping within breeds, and its use has led to the identification of variants associated with Mendelian traits in purebred cats. However, compared to single gene disorders, association studies of complex diseases, especially with the inclusion of random bred cats with relatively low linkage disequilibrium, require a denser genotyping array and an increased sample size to provide statistically significant associations. Here, we undertook a multi-breed study of 1,122 cats, most of which were admitted and phenotyped for nine common complex feline diseases at the Cornell University Hospital for Animals. Using a proprietary 340 k single nucleotide polymorphism mapping array, we identified significant genome-wide associations with hyperthyroidism, diabetes mellitus, and eosinophilic keratoconjunctivitis. These results provide genomic locations for variant discovery and candidate gene screening for these important complex feline diseases, which are relevant not only to feline health, but also to the development of disease models for comparative studies.
