Background: Underlying conditions in dogs admitted to an intensive care unit (ICU) can cause hemostatic dysfunction. Thrombelastography (TEG) may be useful in detecting hemostatic alterations as compared with standard coagulation tests. Objectives: The purpose of this study was to compare TEG results and those of standard coagulation tests in identifying hemostatic dysfunction in dogs admitted to an ICU and to investigate associations among the variables measured. Methods: Tissue factor-activated TEG analysis, D-dimer and fibrinogen concentrations, antithrombin (AT) activity, prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count were measured using standard techniques on 27 dogs admitted to ICU with a disease known to be associated with hemostatic dysfunction and in 31 clinically healthy control dogs. Results were compared between groups using nonparametric tests and k analysis; principal component analysis (PCA) and Spearman rank correlation were used to measure associations among variables. Results: Fourteen of 27 ICU dogs had abnormal TEG tracings, which were used to classify the dogs as hypercoagulable (n = 11), hypocoagulable (n = 3), or normocoagulable (n = 13). Hypercoagulable dogs had significantly increased D-dimer (P =.03) and fibrinogen (P =.01) concentrations compared with normocoagulable dogs. In ICU dogs, positive associations were identified between maximum amplitude (MA), a-angle, fibrinogen concentration, and platelet count, and between PT, aPTT, and reaction time (R). Significant correlations were found between MA and fibrinogen (r s = .76, P o.001) and between reaction time (R) and PT (r s = .51, P =.003). Conclusions: TEG was useful in detecting hemostatic dysfunction in dogs in an ICU. Positive associations among variables may provide insight as to how overall coagulation status reflects alterations in clot strength and coagulation time. Dogs with TEG tracings indicative of hypercoagulability are likely in procoagulant states. Future studies of the incidence of thrombotic complications in dogs with hypercoagulable TEG tracings are warranted.

Administration of prednisone to healthy Beagles resulted in hypercoagulability as indicated by TEG tracings, whereas the effect on TG was more variable. Further studies are needed to determine the underlying mechanisms of hypercoagulability and its clinical impact.

Background: Thrombelastography (TEG) is used to evaluate the viscoelastic properties of blood during clotting and provides a global assessment of hemostasis and clot lysis. TEG analysis initiated with recombinant human tissue factor (TF) has not been evaluated in clinically healthy horses. Objectives: The purpose of this study was to determine whether TEG results are affected by the time elapsed between sampling and analysis (storage time) of equine blood samples and to establish a preliminary equine reference interval for a modified TEG assay, using recombinant human TF to initiate coagulation. Methods: Citrated blood samples were obtained from 20 clinically healthy adult horses. Thirteen samples were stored for 30, 60, and 120 minutes at room temperature before TEG analysis. Coagulation was initiated by adding 20 mL of CaCl 2 to 330 mL of blood and 10 mL of diluted recombinant TF for a final dilution of 1:3600. Reaction (R) and clotting (K) times, angle (a), and maximum amplitude (MA) were compared between time points. A preliminary reference interval (minimum-maximum values) was determined using data from all 20 horses after 30 minutes of sample storage. Results: There was a significant effect of storage time on R, K, and a but not MA. Reference intervals were: R, 3.65-6.4 minutes; K, 1.8-5.45 minutes; a, 33.4-66.21; MA, 41.2-64.1 mm; lysis at 30 minutes post-MA (LY30), o 2.75%; and lysis at 60 minutes post-MA (LY60), 1.55-9.5%. Conclusions: TEG can be performed on equine citrated blood samples using recombinant human TF to activate clot formation. TEG parameters were significantly affected by storage time, suggesting an incomplete inhibition of coagulation in citrated blood.While conventional coagulation tests evaluate the soluble or plasmatic components of coagulation, in vivo coagulation is the sum of complex interactions among coagulation factors, platelets, endothelial cells, erythrocytes, and even leukocytes.1,2 Thrombelastography (TEG) assesses the mechanical properties of the blood clot during its formation and subsequent lysis. [3][4][5] In human medicine, TEG is used to detect clinically significant coagulation disorders in patients perioperatively and in intensive care.6 TEG is commonly performed on native fresh whole blood within 5 minutes of collection.7 This constraint limits its use in clinical pathology laboratories and in many veterinary hospital facilities. More recently, the use of citrated whole blood has extended the time that may lapse between blood collection and initiation of coagulation. 7,8 TEG has been validated and used to predict the risk of bleeding and assess hypercoagulability in dogs [9][10][11][12] and has been used to monitor heparin therapy in cats.13 TEG also was used to evaluate a horse with a platelet dysfunction.14 Horses, like other species, can have congenital and acquired coagulation disorders 15 and TEG could be useful in the rapid diagnosis of coagulopathies associated with gastrointestinal disorders or neonatal sepsis. 16,17 The objectives of this study were to as...

Abstract.A 12-year-old Persian cat was examined for a firm swelling of the right tarsal region and enlargement of the corresponding right popliteal lymph node. Cytologic evaluation demonstrated a population of malignant cells consistent with large cell lymphoma. Necropsy revealed a multilobulated subcutaneous mass involving the tarsus with some extension into adjacent deep muscular tissue. Histologically, the mass was composed of round cells with eosinophilic cytoplasm and pleomorphic anisokaryotic nuclei. Evidence of articular and nodal infiltration by these cells was observed. Differential diagnoses included synovial sarcoma and histiocytic sarcoma. Neoplastic cells were negative for cytokeratin, CD79a, and CD3 and positive for CD18, vimentin, lysozyme, and alpha-1-antitrypsin, most consistent with a diagnosis of histiocytic sarcoma. This is the first report of a histiocytic sarcoma involving a joint of a cat. The final diagnosis was based on the light microscopic appearance in combination with the immunohistochemical stains.

Our study demonstrates that thrombin generation can be measured in canine plasma and may be useful in assessing the degree of anticoagulation provided by UFH.

Background: Hyperadrenocorticism (HAC) has been associated with thrombotic disease in dogs. Hypothesis: The purpose of this study was to use thromboelastography (TEG) and measurement of thrombin generation (TG) to characterize the hypercoagulable state in dogs with HAC. We hypothesized that dogs with HAC would have a hypercoagulable profile on TEG tracings and an increase in thrombin generation as measured by endogenous thrombin potential (ETP).Animals: Sixteen dogs with HAC. Dogs were compared with a population of normal dogs used to obtain reference intervals.Methods: TEG tracings on citrated whole blood were obtained from 15 dogs, and TG measurements on frozen-thawed platelet-poor plasma (PPP) were obtained from 15 dogs.Results: For the TEG analysis, when results of individual dogs were compared with the reference interval, 12/15 dogs had at least 1 parameter associated with hypercoagulability. When the population of HAC dogs was compared with a population of healthy dogs, HAC dogs had decreases in R and K and increases in a and MA values. The ETP was increased when the HAC group was compared with a population of normal dogs. However, only 3/15 dogs had an ETP above reference interval, and 1/15 had a decreased lag time.Conclusion and Clinical Importance: Of 16 dogs with HAC, 12/15 had evidence of hypercoagulability when evaluated by TEG, 4/15 when evaluated by TG, and 2 dogs had increases in ETP and MA.

The p75 CCAAT-displacement protein/Cut homeobox (CDP/ Cux) isoform was previously reported to be overexpressed in human breast cancers. To investigate its oncogenic potential, we engineered two transgenic mouse lines expressing p75 CDP/Cux under the control of the mouse mammary tumor virus-long terminal repeat. The FVB strain of mouse is generally used in the generation of mouse models for breast cancer. The transgene was introduced into the hprt locus of 129/Ola embryonic stem cells and, following germ line passage, was backcrossed onto the FVB and C57BL/6 mouse strains. Here, we describe the phenotype of p75 CDP/Cux transgenic virgin female mice of the first backcross generations. We report that after a long latency period, f33% of mice from two independent transgenic lines and from backcrosses into either the FVB or the C57BL/6 strains succumbed to a similar disease characterized by splenomegaly, hepatomegaly, and frequent infiltration of leukocytes into nonhematopoietic organs like the kidneys and lungs. Although an excess of B or T cells was observed in three diseased mice, in 17 other cases, histologic and flow cytometry analyses revealed the expansion of a population of neutrophils in the blood, spleen, and bone marrow. The increase in neutrophils correlated with signs of anemia and thrombocytopenia, whereas there was no indication of a reactive process. Therefore, p75 CDP/Cux transgenic mice displayed heightened susceptibility to a disease defined as a myeloproliferative disease-like myeloid leukemia. These results indicate that the overexpression of p75 CDP/Cux could alter homeostasis in the hematopoietic compartment.

The mouse response to acute Salmonella typhimurium infection is complex, and it is under the influence of several genes, as well as environmental factors. In a previous study, we identified two novel Salmonella susceptibility loci, Ity4 and Ity5, in a (AcB61 × 129S6)F2 cross. The peak logarithm of odds score associated with Ity4 maps to the region of the liver and red blood cell (RBC)–specific pyruvate kinase (Pklr) gene, which was previously shown to be mutated in AcB61. During Plasmodium chabaudi infection, the Pklr mutation protects the mice against this parasite, as indicated by improved survival and lower peak parasitemia. Given that RBC defects have previously been associated with resistance to malaria and susceptibility to Salmonella, we hypothesized that Pklr is the gene underlying Ity4 and that it confers susceptibility to acute S. typhimurium infection in mice. Using a fine mapping approach combined with complementation studies, comparative studies, and functional analysis, we show that Pklr is the gene underlying Ity4 and that it confers susceptibility to acute S. typhimurium infection in mice through its effect on the RBC turnover and iron metabolism.