A case of disseminated intravascular coagulation (DIC) in a cow with endometritis and fetal death

Acute disseminated intravascular coagulation (DIC) was diagnosed in a 3 1/2 year old cow of the Simmental breed. The cow was little less than 6 months pregnant and was admitted to the clinic because of severely disturbed general health. The most important clinical findings were increased heart and breathing rate, rectal temperature of 39.9 degrees C, nosebleed and petechiae on the nasal mucosa. Additionally, the cow showed petechiae on the vaginal mucosa, haemorrhage from the rectum lasting several hours after rectal examination and severe haemoglobinuria. Haematological and biochemical examinations showed increased liver enzymes and severe changes in all coagulation parameters (platelet count, PT, PTT, thrombin time, fibrinogen, fibrin degradation products). Based on the mentioned findings the diagnosis DIC was made. Possible causes were severe necrotic endometritis and placentitis combined with fetal death. High counts of Escherichia coli and Clostridium perfringens were determined in liver, lung and abomasal contents of the aborted fetus as well as in the placenta. Uterine secretion contained Actinomyces pyogenes besides.     

Disseminated intravascular coagulation (DIC) in rabbit haemorrhagic disease.

Seven rabbits experimentally infected with rabbit haemorrhagic disease virus were examined haematologically and histologically. Haematologically, activated partial thromboplastin time and prothrombin time were markedly prolonged in the terminal phase of the disease, just prior to death (all the animals died between 27 and 40 hr after inoculation with rabbit haemorrhagic disease virus). There was an increase in the titre of fibrin degradation products and a decrease in antithrombin III activity during the same interval. Acute necrotic hepatitis and disseminated intravascular coagulation (DIC) in many organs, including the lung, kidney, spleen and heart were the characteristic histopathological changes. Thus, the haematological and histological changes suggested that DIC was induced by rabbit haemorrhagic disease virus infection. Severe liver necrosis was considered to be a factor causing DIC by inducing a hypercoagulable condition in the systemic blood circulation.     

Liquoid-induced disseminated intravascular coagulation in the blue fox

The present experiments were performed to study the effects of a single high intravenous dose of Liquoid (10 mg/kg body weight) upon platelets, coagulation activities and hematocrit in blue foxes, and their correlation with the survival time. Both “short-living” (< 9 h) and “long-living” (24 h or more) blue foxes showed a marked consumption of coagulation factors, initial fall in fibrinogen, positive ethanol gel test and a gradual decrease in platelet counts. In addition “short-living” animals developed a marked rise in hematocrit, reflecting a considerable increase in vascular permeability. We conclude that activation of plasma proteases has as one of its effects increased permeability in microvasculatory vessels and that this may play a central role for the course and outcome of Liquoid-induced disseminated intravascular coagulation.     

Plasma fibronectin concentrations in dogs with disseminated intravascular coagulation

Plasma fibronectin concentrations were significantly (P less than 0.001) below the reference range in dogs with disseminated intravascular coagulation (DIC) secondary to nonlymphomatous neoplasia, acute necrotizing pancreatitis, sepsis, chronic active hepatitis, and heat stroke. There was no statistical evidence of a group effect. Decrease in fibronectin concentration was associated with severe DIC, although no attempt was made to correlate fibronectin concentration with prognosis. These findings parallel those reported for severely ill human beings with diseases associated with DIC. They exemplify the potential of spontaneous diseases in animals as models for the study of human disease.     

Haemophagocytic syndrome with disseminated intravascular coagulation in a dog

Clinical signs and haematological abnormalities of haemophagocytic syndrome of unknown origin are described for a male, nine-year-old rottweiler referred because of weakness, depression, mild weight loss and relapsing fever. Mucous membranes were pale and the spleen was enlarged. Ultrasonography revealed diffuse irregular structures in the enlarged spleen, and cytologlcal examination of multiple fine needle aspirates of the spleen demonstrated extramedullar haematopoiesis. Haematological examination revealed pancytopenia and disseminated intravascular coagulation. A bone marrow smear contained numerous marrow macrophages with a cytologically benign appearance, containing phagocytosed haematopoietic cells. The dog died one week after referral. The differential diagnosis is discussed.     

Recognition and management of disseminated intravascular coagulation in horses

This article reviews normal hemostasis in order to provide the reader with the basis for understanding the pathogenesis and manifestations (both clinical and laboratory) of disseminated intravascular coagulation (DIC) in horses. DIC is subsequently discussed. The diagnosis and treatment of DIC in horses are also described.     

Thromboelastographic evaluation of hemostatic function in dogs with disseminated intravascular coagulation

BACKGROUND: There is considerable variation in the coagulation profile of dogs with disseminated intravascular coagulation (DIC), making it difficult to assess overall hemostatic function. OBJECTIVES: To characterize the overall hemostatic state in dogs with DIC, by use of tissue factor-activated thromboelastography (TF-TEG), and to determine whether there is an association between hemostasis and outcome. ANIMALS: 50 dogs with DIC. METHODS: Dogs admitted to the intensive care units, with an underlying disease known to predispose to DIC, were prospectively assessed with TF-TEG. Citrated blood samples were collected daily during hospitalization and an extended coagulation panel and TF-TEG were performed. Diagnosis of DIC was based on expert opinion. RESULTS: Hemostatic dysfunction was observed on the TF-TEG profile in 33/50 of the dogs, of which 22/50 were hypercoagulable and 11/50 were hypocoagulable based on the TF-TEG G value alone. There were significant differences in k, alpha, and MA values (P < .0001) among hypo-, normo-, and hypercoagulable dogs. There was a significant difference in case fatality rate between hypo- (64%) and hypercoagulable (32%) dogs (relative risk = 2.38; P= .04). Dogs that died had significantly lower antithrombin activity (P= .03) and higher d-dimer concentration (P= .03) than survivors. CONCLUSIONS: The most common overall hemostatic abnormality in dogs diagnosed with DIC was hypercoagulability, and there was significant difference in survival between hyper- and hypocoagulable dogs. The results suggest TF-TEG is valuable in the assessment of hemostatic function in dogs diagnosed with DIC.     

D-dimer concentrations in healthy dogs and dogs with disseminated intravascular coagulation

OBJECTIVE: To determine sensitivity and specificity of assays of D-dimer concentrations in dogs with disseminated intravascular coagulation (DIC) and healthy dogs and to compare these results with those of serum and plasma fibrin-fibrinogen degradation product (FDP) assays. ANIMALS: 20 dogs with DIC and 30 healthy dogs. PROCEDURE: Semi-quantitative and quantitative D-dimer concentrations were determined by use of latex-agglutination and immunoturbidometry, respectively. Fibrin-fibrinogen degradation products were measured by use of latex-agglutination. A reference range for the immunoturbidometric D-dimer concentration assay was established; sensitivity and specificity of the assay were determined at 2 cutoff concentrations (0.30 microg/ml and 0.39 microg/ml). RESULTS: Reference range for the immunoturbidometric D-dimer concentration assay was 0.08 to 0.39 microg/ml; median concentrations were significantly higher in dogs with DIC than in healthy dogs. Latex-agglutination D-dimer and serum and plasma FDP assays had similar sensitivity (85 to 100%) and specificity (90 to 100%); the immunoturbidometric assay had lower specificity (77%) at the 0.30 microg/ml cutoff and lower sensitivity (65%) at the 0.39 microg/ml cutoff. Sensitivity or specificity of the latex-agglutination D-dimer assay was not significantly improved when interpreted in series or parallel with FDP assays. CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of D-dimer concentrations by latex-agglutination appears to be a sensitive and specific ancillary test for DIC in dogs. Specificity of D-dimer concentrations in dogs with systemic disease other than DIC has not been determined, therefore FDP and D-dimer assays should be performed concurrently as supportive tests for the diagnosis of DIC in dogs.     

The incidence of disseminated intravascular coagulation in dogs with malignant tumor

The incidence of DIC in 208 dogs with a malignant tumor was evaluated. The incidence of DIC was 9.6% in dogs with a malignant tumor which was a solid tumor in all. In 164 dogs with a malignant solid tumor, the incidence of DIC was 12.2%. The incidence of DIC in dogs with hemangiosarcoma, mammary gland carcinoma and adenocarcinoma of the lung was significantly higher than that in dogs with other malignant tumors. These results suggested that special care in looking for DIC should be taken in dogs with a malignant solid tumor.     

Diagnosis of disseminated intravascular coagulation in dogs admitted to an intensive care unit.

OBJECTIVE: To describe and evaluate hemostatic function in critically ill dogs with clinical signs of diseases that predispose to disseminated intravascular coagulation (DIC). DESIGN: Prospective case series. ANIMALS: 59 critically ill dogs (affected dogs) with clinical signs of diseases known to predispose to DIC and 52 clinically normal dogs (control dogs). PROCEDURE: Activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin clotting time (TCT), plasma fibrinogen concentration, serum concentration of fibrin and fibrinogen-related antigens (FRA), and plasma antithrombin III (AT III) activity were determined for all dogs. Results from affected dogs were compared with those of control dogs. In some affected dogs, postmortem tissue specimens were examined for evidence of microvascular thrombosis. A diagnosis of DIC was made by fulfilling at least 3 of the following criteria: 1) abnormal aPTT, PT, or TCT value, 2) low plasma fibrinogen concentration, 3) low plasma AT III activity, 4) high serum FRA concentration, or 5) low platelet count. To evaluate the severity of hemostatic dysfunction, 3 arbitrary categories (mild, moderate, and severe) were proposed. RESULTS: A diagnostic strategy based on moderate hemostatic dysfunction identified DIC in 16 of 59 (27.1%) affected dogs. The AT III activity was < 70% in 15 of 16 dogs with DIC. Microvascular thrombosis was observed in tissue specimens from 7 of 8 affected dogs. Serum FRA and plasma fibrinogen concentrations did not contribute in establishing a diagnosis of DIC. CONCLUSIONS AND CLINICAL RELEVANCE: A diagnosis of DIC can be made when hemostatic dysfunction is moderate in dogs with clinical signs of diseases associated with DIC.     

Clinicopathologic evidence of disseminated intravascular coagulation in horses with acute colitis

OBJECTIVE: To detect subclinical disseminated intravascular coagulation (DIC) in horses with colitis and to determine any association between the diagnosis of subclinical DIC and outcome or occurrence of complications in horses with colitis. DESIGN: Prospective study. ANIMALS: 37 horses admitted to a veterinary teaching hospital for treatment of acute colitis. PROCEDURE: Coagulation profiles were obtained on each horse 0, 24, and 48 hours after admission. Six tests were performed: platelet count, plasma fibrinogen concentration, prothrombin time, activated partial thromboplastin time, antithrombin activity, and serum fibrin degradation products concentration. RESULTS: A clinicopathologic diagnosis of subclinical DIC was made if 3 of the 6 tests had abnormal results at any 1 sample period. No horse had clinical signs of DIC at the time of sampling. Twelve of 37 (32%) horses met the criteria for diagnosis of subclinical DIC within a 1-year period. Outcome was defined as survival or nonsurvival. Five of 12 horses with subclinical DIC and 2 of 25 horses without subclinical DIC did not survive. Crude odds ratio analysis revealed a horse with acute colitis was 8 times as likely to die or be euthanatized if a diagnosis of subclinical DIC was made. CONCLUSIONS AND CLINICAL RELEVANCE: Clinicopathologic evidence of DIC is common and is significantly associated with a poor outcome in horses with acute colitis. Treatment of subclinical DIC may influence outcome in horses with acute colitis.     

Flow cytometric evaluation of disseminated intravascular coagulation in a canine endotoxemia model

Sepsis is associated with substantial morbidity and mortality in dogs. Alterations in hemostasis by systemic inflammation play an important role in the pathophysiology of sepsis. To evaluate the functional hemostatic changes in sepsis, we evaluated coagulation profiles and flow cytometric measurement of P-selectin (CD62P) expression on platelets, as well as platelet-leukocyte aggregation from a lipopolysaccharide (LPS)-induced endotoxemia model in dogs (n = 7). A sublethal dose of LPS [1 mg/kg body weight (BW)] induced thrombocytopenia and increased activated partial thromboplastin time (aPTT), prothrombin time (PT), and D-dimer concentrations. Flow cytometry analysis showed a significant increase in P-selectin expression on platelets between 1 and 24 h of a total 48 h of the experiment. In addition, platelet-leukocyte aggregation was significantly increased in the early stage of endotoxemia (at 1 and < 6 h for platelet-monocyte aggregation and at 3 h for platelet-neutrophil aggregation). Our results suggest that CD62P expression on platelets and platelet-leukocyte aggregation, as measured by flow cytometry, can be useful biomarkers of disseminated intravascular coagulation (DIC) in canine sepsis. These functional changes contribute to our understanding of the pathophysiology of hemostasis in endotoxemia.     

Laboratory diagnosis and differential diagnosis of disseminated intravascular coagulation in the dog]

The laboratory diagnostic possibilities for characterization of disseminated intravascular coagulation (DIC) in dogs are reviewed. A DIC can be demonstrated by means of: 1. Simultaneous consumption of platelets, fibrinogen, coagulation factors and inhibitors of coagulation 2. Increased plasma levels of the specific reaction products fibrin monomers and fibrinopeptides 3. Secondary hyperfibrinolysis, especially an increase in plasma concentrations of fibrin(ogen) degradation products 4. Presence of schistocytes in the blood smear 5. Improvement in the coagulation values during an efficacious anticoagulant therapy 6. Indication of enhanced turnover and formation of microthrombi in different organs by radioisotopically detected coagulation components. Different principles of the laboratory diagnostic procedure in DIC are illustrated by the results of an animal experiment and clinical case reports. Concerning differential diagnosis among other things a deprivation- and dilution effect as well as a disturbance of synthesis have to be considered. One must especially bear in mind that a DIC may also be caused by different coagulator disturbances, e.g. of prothrombin complex synthesis. A DIC can mask such a defect in laboratory diagnostic findings, thereby complicating the diagnosis.     

Evaluation of point-of-care tests for diagnosis of disseminated intravascular coagulation in dogs admitted to an intensive care unit.

OBJECTIVE: To evaluate the accuracy of point-of-care tests for the diagnosis of disseminated intravascular coagulation (DIC) in dogs and assess the correlation and agreement of results between point-of-care and laboratory tests in the evaluation of hemostatic function. DESIGN: Prospective case series. ANIMALS: 59 critically ill dogs (affected dogs) with clinical signs of diseases known to predispose to DIC and 52 clinically normal dogs. PROCEDURES: Accuracy of the point-of-care tests (activated clotting time [ACT], estimated platelet count and number of schizocytes from a blood smear, plasma total solids [TS] concentration, and the protamine sulfate test) was evaluated, using receiver operating characteristic curves and likelihood ratios. A strategy, using likelihood ratios to calculate a posttest probability of DIC, was tested with 65% used as a threshold for initiation of treatment. Results of laboratory tests (coagulogram and plasma antithrombin III activity) were used as the standard for comparison in each dog. RESULTS: ACT and estimated platelet count provided the best accuracy for detection of DIC. The plasma TS concentration, schizocyte number, and protamine sulfate test had poor accuracy. The strategy using post-test probability of DIC identified 12 of 16 affected dogs that had DIC. Estimated platelet count was correlated and had acceptable clinical agreement with automated platelet count (r = 0.70). The plasma TS (r = 0.28) concentration and serum albumin (r = 0.63) concentration were not accurate predictors of plasma antithrombin III activity. The ACT did not correlate with activated partial thromboplastin time (r = 0.28). CONCLUSIONS AND CLINICAL RELEVANCE: Strategic use of likelihood ratios from point-of-care tests can assist clinicians in making treatment decisions for dogs suspected to have DIC when immediate laboratory support is unavailable.     

Efficacy of low molecular weight heparin in a canine model of thromboplastin-induced acute disseminated intravascular coagulation

The aim of this study was to test the efficacy of different dosages of low molecular weight heparin (LMWH) in acute DIC which was induced in anaesthetised dogs by 4 h infusions of a canine lung thromboplastin extract. In all animals during the first 2 h, development of acute DIC was characterised by decreasing fibrinogen concentrations, platelet numbers, factor V- and antithrombin activities. Two hours after starting the thromboplastin infusion, intravenous LMWH treatment in different dosages started in groups 2 and 3 to achieve plasma levels between 0.27+/-0.01 and 0.36+/-0.02 anti-FXaUml(-1) or 0.62+/-0.08 and 0.90+/-0.07 antiFXaUml(-1) (mean+/-SD), respectively, during the time period of parallel administration of thromboplastin and LMWH (group 1=control; 4 dogs/group). In this time period, changes in factor V activity and fibrinogen concentration did not differ between group 2 and the control group. This was in contrast to group 3. The results of this study indicate that an efficacious interruption of the consumption reaction in cases of severe canine DIC requires high plasma heparin levels.     

Disseminated intravascular coagulation in cats

The purpose of this study was to describe the clinical characteristics of cats with disseminated intravascular coagulation (DIC), including associated diseases and hemostatic abnormalities, and to identify risk factors for death and treatments that potentially altered outcome. Medical records for cats with DIC from 1990-2004 were evaluated retrospectively. Inclusion criteria were the presence of an underlying disorder associated with DIC and either postmortem examination findings of intravascular fibrin deposition or thrombosis, or both of 2 or more organs or coagulation profiles that meet 3 of 5 criteria: prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), presence of fibrin degradation products (FDP), low plasma fibrinogen (FIB) concentration, and thrombocytopenia (<160,000 platelets/microL). Signalment, historical data, clinical findings, clinicopathologic data, underlying disorders, management, and outcome were recorded. Forty-six cats fulfilled the criteria for DIC. Cats ranged in age from 7 weeks to 17 years (median, 9 years). Hemorrhage was noted in 7 of 46 cats (15%). Three of 46 cats (7%) survived, whereas 43 of 46 (93%) died or were euthanized. The most common underlying disorders were lymphoma, other forms of neoplasia, pancreatitis, and sepsis. There was no association detected between outcome and signalment; underlying disease; hemorrhage; abnormalities in aPTT, FIB, FDPs, platelet count; transfusion of blood products; and heparin therapy. However, the median PT of nonsurvivors was more prolonged than in survivors (P < .005). DIC in cats can result from a variety of neoplastic, infectious, and inflammatory disorders, and is associated with a high case fatality rate.     

Mammary gland carcinoma in a dog with peripheral blood and bone marrow involvement associated with disseminated intravascular coagulation

A 7-year-old female Leonberger dog was referred to the National Veterinary School of Lyon Teaching Hospital with a 2-day history of anorexia and bleeding. A mammary mass had been removed 7 months earlier, but histologic examination was not performed. On physical examination, the dog was depressed and had pale mucous membranes and numerous petechiae and hematomas. Significant laboratory findings were moderate thrombocytopenia, prolonged prothrombin, activated partial thromboplastin, and thrombin times, hypofibrinogenemia, and increased concentration of fibrin(ogen) degradation products. A peripheral blood smear, buffy coat preparation, and bone marrow aspirate contained low numbers of large atypical cells that had moderate nuclear:cytoplasmic ratios, oval nuclei with multiple prominent nuclei, and basophilic cytoplasm with villous projections. A small nodule was found in the left inguinal mammary gland, and a fine-needle aspirate contained cells similar to those in blood and bone marrow. In samples of blood, bone marrow, and the mammary mass, the neoplastic cells were immunoreactive for cytokeratin. The diagnosis was mammary carcinoma with secondary disseminated intravascular coagulation (DIC) and disseminated tumor cells in bone marrow and circulating tumor cells in blood; this diagnosis was not confirmed by histopathologic examination. Owing to clinical deterioration and the poor prognosis, the dog was euthanized and a necropsy was not performed. This is the first report of a canine mammary carcinoma with circulating tumor cells and secondary DIC.