Plasma von Willebrand factor-collagen binding activity in normal dogs and in dogs with von Willebrand's disease.

A sensitive enzyme-linked immunosorbent assay was used for the simultaneous assessment of the amount of von Willebrand factor (vWF) in canine plasma and its ability to bind to canine collagen in vitro. In 60 normal dogs, there was close correlation between the concentration of vWF and its activity as determined by vWF-collagen binding. In 14 dogs with type I expressions of von Willebrand's disease, the ratio of vWF antigen to collagen binding activity was normal or only slightly increased. In 7 dogs with type II expressions of the disease, this ratio was consistently elevated suggesting a significant functional deficiency of the protein. Plasma from 3 dogs with type III von Willebrand's disease had little collagen binding activity because of the severe quantitative deficiency of the protein. The described assay permits the rapid assessment of both the quantity and quality of vWF in a dog. This information is necessary for the detection and characterization of canine von Willebrand's disease, particularly the type II expressions, which cannot be diagnosed by quantitative vWF assays alone.

Haemostatic abnormalities in horses with colic--their prognostic value.

The incidence and nature of coagulation abnormalities in horses presented with colic and the possible prognostic value of these abnormalities was investigated. A coagulogram was performed on each of 24 adult Thoroughbred or Standardbred horses. A coagulogram consisted of measurements of eight parameters; platelet count, plasma fibrinogen, plasma antithrombin III (AT), partial thromboplastin time (PTT), prothrombin time (PT), thrombin clotting time (TCT), soluble fibrin monomer (SFM) and fibrin-fibrinogen degradation products (FDP). Retrospective determination of the cause of the colic and outcome (survival vs non-survival) was carried out. All patients examined had at least one abnormal parameter with the frequency being: Increased SFM 67 per cent; prolonged PTT 63 per cent; prolonged TCT 50 per cent; elevated plasma fibrinogen 46 per cent; reduced platelet count 29 per cent; reduced plasma AT 29 per cent; prolonged PT 25 per cent; and elevated serum FDP 21 per cent. When survivor and non-survivor groups were compared there was little difference in the frequency of abnormalities such as elevated SFM, elevated fibrinogen and prolonged PTT. The abnormalities which had the greatest frequency difference between non-survivors and survivors, and therefore the greatest prognostic value, were decreased AT greater than prolonged TCT = prolonged PT greater than elevated FDP greater than reduced platelet count. The frequency of these abnormalities in non-survivors compared to survivors was 8.6:1, 7.1:1, 5.7:1 and 3.6:1, respectively. The average number of abnormal parameters in non-survivors (five) was significantly greater than in survivors (two).

Lupus-type "anticoagulant" in a dog with hemolysis and thrombosis.

A circulating anticoagulant was detected in a 2-year-old Chesapeake Bay Retriever with hemolytic anemia, nephrotic syndrome, thrombocytopenia, polyarthropathy, and pulmonary thromboembolism. A persistent prolongation of the activated partial thromboplastin time (aPTT) was detected, and it did not correct with repeated administration of fresh frozen plasma. The aPTT was still prolonged, with a 1:1 mixture of patient's plasma and normal dog plasma in vitro, suggesting the presence of a circulating inhibitor. Results of assays to characterize the inhibitor were compatible with those described for the lupus anticoagulant in human patients with systemic lupus erythematosus. Paradoxically, patients having the lupus anticoagulant are at increased risk for thrombosis. Pulmonary thromboembolism has been described as a frequent complication of immune-mediated hemolytic anemia in the dog, and the presence of a circulating anticoagulant should be considered as a potential mechanism.

The effects of desmopressin on hemostatic parameters in the normal dog.

Seven normal unanesthetized dogs were infused with desmopressin in saline (doses 0.2, 0.4 and 0.6 micrograms/kg i.v.) or saline alone, on separate occasions in order to determine the effects of desmopressin on circulating factor VIII coagulant and factor VIII-related antigen activities, on partial thromboplastin times and prothrombin times, on blood platelet count and packed cell volume, and on serum osmolarity. Desmopressin caused a rapid dose-dependent elevation in both factor VIII activities peaking at 30-60 minutes postinfusion. At a dosage of 0.6 microgram/kg desmopressin induced rises in factor VIII coagulant activity and factor VIII-related antigen of 150% and 198% of the preinfusion levels respectively, while the half disappearance times were approximately five and six hours respectively. The other parameters were not significantly affected by even the highest dose of desmopressin used. These results indicate that normal dogs respond to desmopressin in a manner similar to man. The major differences are in the dosage required to produce comparable effects (higher in dogs), and in the fact that the factor VIII-related antigen activity consistently responds to a greater degree than the coagulant activity. It is concluded that desmopressin may have particular value in stimulating elevations in plasma factor VIII-related antigen in dogs deficient in this plasma protein. Six dogs were pretreated with the endorphin inhibitor, naloxone, (0.04 mg/kg I.V.) or sterile saline, three minutes prior to infusion with desmopressin at a dose of 0.6 microgram/kg i.v.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitation of canine plasma von Willebrand factor antigen using a commercial enzyme-linked immunosorbent assay.

The purpose of this study was to evaluate a commercial enzyme-linked immunosorbent assay (ELISA) for human von Willebrand factor antigen (vWF:Ag) with respect to its potential value in quantitating the protein in canine plasma. The assay was a sandwich technique using F(ab')2 fragments specific for von Willebrand factor (vWF) and a peroxidase conjugated rabbit anti-vWF second antibody, with a microplate as the support surface. Canine plasmas were assayed by ELISA, and by Laurell electroimmunoassay (EIA), our reference methodology. The ELISA had a within-day variation of 1.21-4.44% and a between-day variation of 0.85-4.88% depending on the level of vWF:Ag. The sensitivity of the assay was less than 0.1% vWF:Ag. The range of vWF:Ag concentrations in plasmas from 24 clinically normal dogs compared favorably with the range for the same plasmas when assayed by EIA (ELISA = 60-152% of normal; EIA = 50-142% of normal). In 121 canine plasmas with vWF:Ag concentrations (as assessed by EIA) ranging from undetectable levels (less than 6% of normal) to 142% of normal, there was good correlation with measurements made by ELISA (correlation coefficient = 0.835). It was concluded that this commercial ELISA technique could be used to provide reliable, same-day measurements of canine plasma vWF:Ag. Since it requires no special equipment other than a microplate reader and washer it is particularly suitable for laboratories lacking the electrophoretic expertise or equipment required for EIA.

Comparative effects of the human protein C activator, Protac, on the activated partial thromboplastin clotting times of plasmas, with special reference to the dog.

The commercial snake venom extract, Protac, is a specific activator of the anticoagulant zymogen, protein C (PC) in human plasma. This specific action has led to its use in developing coagulation-based and amidolytic-based assays for the diagnosis of quantitative and/or qualitative PC deficiency states in human beings. The purpose of the present study was to compare the effects of Protac on the activated partial thromboplastin times (APTT) of human, bovine, equine, and canine plasmas in order to determine the potential value of this venom extract as an activator in functional PC assays in these domestic animal species. As expected, Protac significantly prolonged the APTT of normal human plasma, but had no effect on plasma known to be devoid of PC. Clotting times were prolonged by 34%-214% with concentrations of venom activator ranging from 0.1-1.0 U/mL. Under identical conditions, Protac prolonged the APTT of equine plasma by 11%-98% over control times. Even more dramatic was the inhibitory effect of Protac on the clotting of bovine plasma, extending the APTT more than 3-fold at a venom concentration of 0.1 U/mL. At higher venom concentrations, most bovine plasmas remained unclotted after 300 s (control time 34.1 s). Under similar conditions, the canine APTT was unaffected by Protac, even when the venom concentration was increased to 3 U/mL. In order to determine the reason for the lack in response of canine plasma, the concentration of the APTT reagent was altered (decreased), exposure time of the plasma to the Protac was increased from 2 min to 9 min, and the plasma was diluted to assess for the potential existence of plasma PC inhibitors. Protac caused an unexpected shortening of the APTT when the contact activator reagent was diluted. Increasing the exposure time had no effect. Although a slight prolongation of the canine APTT was detected when the plasma was diluted, the presence of strong plasma PC inhibition was considered an unlikely cause of the lack of significant anticoagulant action. The failure of Protac to exert a strong inhibitory effect on the canine APTT, as well as to generate amidolytic activity, suggests that this venom extract does not stimulate the production of activated PC activity in canine plasma. This may result from molecular differences in the canine PC molecule that prevent the formation of the stoichiometric complex of venom extract, APTT reagent, and canine protein, a complex thought to be essential for the PC-activating function of Protac. Protac may be suitable as an activator of PC in bovine and equine plasmas; however, it appears ineffective in generating anticoagulant activity in canine plasma.

The effects of desmopressin on plasma factor VIII/von Willebrand factor activity in dogs with von Willebrand's disease.

Eight unanesthetized normal dogs and seven dogs with von Willebrand's disease (vWD) were given desmopressin (0.6 micrograms/kg, IV) in order to determine the effects of this drug on plasma Factor VIII/vWF activity. Seven of the normal dogs and four of the vWD dogs were administered an equal volume of saline (control infusion) on another occasion. The other three vWD dogs underwent major surgery after treatment with desmopressin. Plasma FVIII coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), and FVIII-ristocetin co-factor activity (FVIII:RC) were quantitated before infusion and at 60 minutes postinfusion. Activities were expressed as a percentage of the activity of a pooled canine plasma (12 dogs) arbitrarily designated as having 100% FVIII:C, vWF:Ag, and FVIII:RC activity. Plasma FVIII:C activity increased by 28% in the normal dogs and by 37% in the dogs with vWD. Plasma vWF:Ag increased more than twofold in normal dogs after desmopressin treatment. In the vWD dogs the average increase was also twofold, however there was much greater variability between dogs with increases ranging from 1.2 fold to 2.4 fold. Plasma FVIII:RC activity almost doubled in normal dogs, however like vWF:Ag, the increases in vWD dogs were more variable. One vWD dog had no increase in FVIII:RC while in the remaining six dogs FVIII:RC increases ranged from 1.8 to 2.9 fold. The results of this study indicate that a single intravenous dose of desmopressin (0.6 micrograms/kg) causes a significant elevation in plasma vWF:Ag and FVIII:RC activity and a much lesser increase in FVIII:C activity in normal unanesthetized dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of sodium pentobarbital anesthesia to alter 1-desamino-8-D-arginine vasopressin-induced elevations of plasma factor VIII/ von Willebrand factor in normal dogs.

The vasopressin analog 1-desamino-8-D-arginine stimulates elevations in plasma Factor VIII/ von Willebrand factor in normal dogs. In order to study the effects of general anesthesia on this response, six dogs were anesthetized with sodium pentobarbital or given an equivalent amount of saline then challenged with an intravenous dose of 1-desamino-8-D-arginine (0.6 micrograms/kg body weight). Factor VIII coagulant activity, von Willebrand factor antigen, and ristocetin cofactor activity were quantitated before anesthesia (or saline infusion), 20 min after induction (pre-1-desamino-8-D-arginine), and at 30 and 60 min post-1-desamino-8-D-arginine. Anesthesia did not significantly affect the elevations in plasma Factor VIII/ von Willebrand factor induced by 1-desamino-8-D-arginine. Sodium pentobarbital appeared however to prevent the rise in Factor VIII coagulant activity seen following saline treatment. The results of this study suggest that when 1-desamino-8-D-arginine is to be used in normal dogs to boost basal plasma von Willebrand factor levels, it is not necessary to administer it prior to induction of general anesthesia with sodium pentobarbital.

Hemostatic studies in racing standardbred horses with exercise-induced pulmonary hemorrhage. Hemostatic parameters at rest and after moderate exercise.

The purpose of this study was to determine whether a defect in hemostasis might be a factor in the etiology of exercise-induced pulmonary hemorrhage (EIPH). Hemostatic parameters were evaluated in 22 EIPH-positive and ten EIPH-negative racing horses while in a rested state. Nineteen EIPH-positive and ten EIPH-negative horses were further evaluated just before and immediately after a 15 min exercise period on a 260 m oval track. When EIPH-positive and EIPH-negative horses were compared at rest, there was no significant difference in any of the coagulation and fibrinolytic parameters studied. There was however, a significant difference in platelet function as assessed by aggregometry. The platelets from affected horses were significantly less responsive than those from nonaffected horses when exposed in vitro to the platelet agonists adenosine diphosphate, collagen and platelet activating factor. Exercise tended to increase the packed cell volume and factor VIII/von Willebrand factor and to decrease platelet aggregation responses to low concentrations of adenosine diphosphate. These effects of exercise however were quantitatively similar in both EIPH-positive and EIPH-negative horses. Reduced platelet function may therefore be a contributing factor in the bleeding characteristic of horses with EIPH.

Evaluation of the effect of storage at -70 degrees C for six months on hemostatic function testing in dogs.

Freezing is a routine method of storage for plasma that is to be used in evaluating certain aspects of hemostatic function in many species. The purpose of this study was to evaluate the effect of storage at -70 degrees C for 6 mo on canine plasma samples. On fresh and frozen plasma from 12 clinically healthy dogs, prothrombin time, activated partial thromboplastin time, thrombin clotting time, fibrinogen determination, antithrombin III activity, fragment D and E assay, and protamine sulfate test were performed. Clinical agreement analysis was utilized to determine the effect of such storage on all assays. Individual differences detected between fresh and frozen samples were all within 2 standard deviations of the mean difference. With the exception of the activated partial thromboplastin time, storing canine plasma at -70 degrees C for 6 mo has no significant effect on hemostatic function, as assessed by these tests.

Hemostatic abnormalities in equine colic.

Hemostatic profiles were determined in 30 horses with clinical colic. Blood samples were obtained at the time of the animal's admission, and the following hemostatic tests were done: blood platelet count, plasma fibrinogen, plasma antithrombin, prothrombin time, partial thromboplastin time, thrombin time, protamine sulfate test for soluble fibrin monomer, and fibrin-fibrinogen degradation products. The patients were categorized in retrospect, according to the cause of the colic: group 1--colic associated with colitis and/or severe diarrhea, group 2--colic associated with torsion or obstruction of the intestine, and group 3--colic associated with impaction of the intestine or the presence of enteroliths. Of the 30 horses with colic, 28 had at least 1 abnormality in their coagulogram--the most frequent abnormalities being high plasma fibrinogen concentration, high circulating soluble fibrin monomer, or a long partial thromboplastin time or thrombin time. The horses in group 1 seemed to have the most severe coagulopathies, as indicated by the average number of demonstrable abnormalities. The horses in group 3 showed the fewest abnormalities--usually a high plasma concentrations of fibrinogen and/or soluble fibrin monomer. The results indicated that hemostatic abnormalities are not uncommon in horses with gastrointestinal disease and colic--the degree of severity depending to some extent on the cause of the colic.

Breed, age, and gender differences in plasma antithrombin-III activity in clinically normal young horses.

Plasma antithrombin-III activity was quantitated in plasma samples obtained from 165 clinically normal horses 3 years old or younger. In the horses as a group, antithrombin-III activity ranged from 63 to 131% of a species-specific reference plasma. Thoroughbred horses had significantly higher antithrombin-III activity (103.3 +/- 18.3; mean +/- SD) than did Standardbred horses (92.3 +/- 14.2). The plasma antithrombin-III activities were significantly lower in horses younger than 16 months old when compared with those in more mature horses (3 years old). There was no statistically significant gender-related effect on plasma antithrombin-III activity. Breed and age factors should therefore be taken into consideration when interpreting plasma antithrombin-III activity in horses.

Effects of aspirin and propranolol alone and in combination on hemostatic determinants in the healthy cat.

The effects of aspirin (75 mg orally/average-size cat) and propranolol (5 mg orally every 8 hours/average-size cat) alone and in combination on hemostatic determinants in healthy cats were studied. In cats, aspirin alone did not cause a significant effect in platelet numbers, plasma fibrinogen, activated partial thromboblastin time, prothrombin time, thrombin time, or platelet aggregation response to adenosine diphosphate. Aspirin did, however, significantly reduce the degree of aggregation induced by acid soluble collagen. Propranolol alone or in combination with aspirin did not cause a significant effect on platelet numbers, plasma fibrinogen, activated partial thromboblastin time, prothrombin time, thrombin time, or platelet aggregation in response to acid soluble collagen, adenosine diphosphate, or adrenaline. It was concluded that aspirin alone at the recommended dosage of one-quarter of a 5-grain tablet (1.25 grains or 75 mg) every other day will significantly affect platelet function and may be of value in the prevention of thromboembolic disease in the cat.

Room temperature storage and cryopreservation of canine platelet concentrates.

OBJECTIVE: To determine whether in vitro viability and function, and microbiological sterility, of canine platelet concentrates (PC) could be retained during storage at 20 to 24 C (room temperature [RT]) for up to 7 days and cryopreservation for 6 months. ANIMALS: 14 mature dogs. PROCEDURE: PC prepared by centrifugation of fresh blood were stored for 7 days at RT with continuous agitation. An aliquot of each was cryopreserved with 6% dimethyl sulfoxide at -74 C for 6 months. Fresh PC (day 0) were tested by microbial culture and measurement of platelet count, mean platelet volume, pH, glucose and lactate concentrations, lactate dehydrogenase activity, response to hypotonic stress, and aggregation. Tests were also performed on PC stored at RT on days 3, 5, and 7, and on the cryopreserved aliquots after thawing. RESULTS: After 7 days at RT, microbial growth was not evident, and decrease in platelet number was not significant. On the basis of pH and glucose and lactate concentrations, metabolic activity was maintained throughout RT storage. On the basis of mean platelet volume and lactate dehydrogenase activity, platelet swelling and membrane damage had occurred. Aggregatory responses decreased during RT storage, and platelets recovered poorly from hypotonic stress. After cryopreservation for 6 months, microbial growth was not evident, but platelet numbers were significantly decreased. Mean platelet volume and lactate dehydrogenase activity were significantly greater, compared with values for day-0 PC. Crypreserved platelets aggregated poorly and did not respond to hypotonic stress. CONCLUSIONS: Platelet viability and microbiological sterility are retained in canine PC stored for 7 days at RT, but platelet function pregressively decreases and day-7 platelets are substantially damaged. Crypreservation of PC results in considerable damage, compared with that of PC stored at RT. CLINICAL RELEVANCE: Similar to human PC, canine PC stored at RT for up to 5 days can be recommended for treatment.

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.

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.

Clinical and laboratory diagnosis of bleeding disorders.

The diagnosis of hemostatic abnormalities requires a detailed clinical and laboratory evaluation of the patient. The clinical assessment includes a detailed history and a thorough physical examination. The patient's history may provide clues as to the time of onset of the bleeding tendency, the clinical severity of the abnormality, and the possible contributing role of other disease processes or of drugs. The nature of the bleeding symptoms may provide clues as to the nature of the hemostatic defect. Hemostatic screening tests are invaluable in helping to differentiate between platelet, vascular, coagulation, and fibrinolytic abnormalities. Specific tests, including specific factor assays, platelet aggregometry, and antiplatelet antibody assays are usually required to characterize the exact nature and severity of hemostatic defects.

Canine Von Willebrand's Disease: A Common Inherited Bleeding Disorder in Doberman Pinscher Dogs.

Von Willebrand's disease is the most common inherited bleeding disorder of dogs occurring with particularly high frequency in Doberman pinscher dogs. Because of its method of transmission (autosomal incomplete dominant), the clinical and laboratory severity of the disease varies considerably. "Stress" may be required to make the increased bleeding tendency clinically apparent. This report describes five cases of Von Willebrand's disease in Doberman pinscher dogs and illustrates the variety of clinical expressions that the disease may take.

Desmopressin enhances the binding of plasma von Willebrand factor to collagen in plasmas from normal dogs and dogs with type I von Willebrand's disease.

A new in vitro von Willebrand factor-collagen binding activity (vWF:CBA) assay was used to assess qualitative changes in vWF in normal dogs and dogs with Type I von Willebrand's disease (vWD) following treatment with desmopressin acetate (DDAVP). Although DDAVP induced increases in vWF antigen concentrations at 1 hour postinfusion in both normal and vWD dogs (57% and 60% increases, respectively), there were disproportionately greater increases in vWF:CBA (96% and 103% increases). These results support the hypothesis that the enhanced hemostatic activity induced by DDAVP is, at least in part, due to the selective release of more functionally active vWF multimers. The assay, as described, provides a convenient means of simultaneously assessing vWF quantity and function before and after DDAVP administration.

Disseminated intravascular coagulation in a horse with postpartum ulcerative colitis and laminitis.

Hemostatic studies were conducted on a five year old Belgian mare presented two days postpartum with colic and laminitis that was unresponsive to treatment.The mare was moderately thrombocytopenic with plasma fibrinogen levels more than twice that of a normal control horse. Platelet function as evaluated by aggregometry indicated that the circulating platelets were markedly hyporesponsive. Activated partial thromboplastin times and prothrombin times were prolonged. Para-coagulation tests (protamine sulfate and ethanol gelation) were strongly positive and fibrin degradation products were significantly elevated in the serum.The laboratory data suggested that the clinical bleeding was the result of the development of disseminated intravascular coagulation. The data were compatible with intravascular activation of the clotting mechanism, consumption of hemostatic factors, inhibition of platelet function and enhanced stimulation of the fibrinolytic mechanism.This report illustrates the complexity of the hemostatic abnormalities associated with pathological overactivation of the hemostatic mechanism. Factors such as tissue thromboplastins and/or endotoxins can stimulate disseminated intravascular coagulation, particularly during pregnancy or in the early postpartum period when a physiological "hypercoagulable" state already exists.