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PubMedDate not supplied

Effect of desmopressin acetate on bleeding times and plasma von Willebrand factor in Doberman pinscher dogs with von Willebrand's disease.

Effects of desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]) on plasma von Willebrand factor (vWf) were studied in 12 purebred Doberman pinschers confirmed to have von Willebrand's disease (vWd) (plasma vWf antigen [vWf:Ag] concentrations, less than 30 U/dl). Twelve dogs had subnormal plasma botrocetin cofactor (BCf) activity and 11 dogs had prolonged buccal mucosa bleeding times. Tranquilization of three dogs with lenperone and three dogs with xylazine did not induce significant changes in mean plasma vWf:Ag concentrations or mean BCf activities. Thirty and 120 minutes after administration of DDAVP (1 micrograms/kg subcutaneously), there was significant shortening of the mean buccal mucosa bleeding time. Ten dogs responded to DDAVP with increases in BCf activity which exceeded 10 U/dl at 30 or 120 minutes, or both, after the drug was administered. At the same time, increases in plasma vWf:Ag concentrations were smaller than the increases in BCf activity. It was shown by multimeric analysis that primarily the higher molecular weight forms of vWf increased in plasma in response to DDAVP.

Animals↗

PubMed1987

The effects of diflunisal on bleeding time and platelet aggregation in a multidose study.

Diflunisal, a potent nonsteroidal anti-inflammatory agent, has been confirmed as an effective analgesic in oral surgery. It is generally stated that there is only slight impairment of coagulation at the recommended dosage of diflunisal; however, only a few multidose studies have been conducted, most being single dose studies. This report is of a multidose study of the effects of diflunisal on coagulation in 15 oral surgery patients, being the first such study reported. The results showed that the bleeding time was increased in 53% of the group, but in no case did the increase exceed the upper limit of normal. Additionally, platelet aggregation studies were affected in 38% of patients with increased bleeding time. The overall results substantiate the safety of diflunisal in relation to effect on coagulation, and are directly applicable to postoperative use in oral surgery.

Adolescent↗

PubMed1990

Recombinant human erythropoietin shortens the uraemic bleeding time without causing intravascular haemostatic activation.

Blood rheology and haemostasis have been investigated in 8 haemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). The aim was to elucidate the mechanism by which rHuEPO improves haemostasis, and to determine whether rHuEPO promotes intravascular coagulation. Investigations were performed before, and after 3 months of treatment. Haemoglobin and haematocrit rose significantly after rHuEPO (p less than 0.001) and there was a concurrent shortening of the bleeding time. No significant changes were observed in platelet aggregation, thromboxane generation, or platelet nucleotide content during the treatment period. Whole blood viscosity increased following rHuEPO (p less than 0.01), but plasma viscosity and red cell deformability were unchanged, as were markers of intravascular platelet activation and plasma levels of cross-linked fibrin derivatives. No patient suffered from thrombosis during the study period, and elevation of the haematocrit in uraemic patients up to 0.35 with rHuEPO did not appear to lead to intravascular coagulation. Shortening of the prolonged bleeding time in haemodialyzed patients following rHuEPO appeared to be due to the increase in circulating red cells, rather than to changes in platelet reactivity.

Adult↗

PubMed2004

D-003 and warfarin interaction on the bleeding time and venous thrombosis experimentally induced in rats.

D-003 is a mixture of higher aliphatic primary acids isolated and purified from sugarcane wax, the main component of which is octacosanoic acid. D-003 exhibits a cholesterol-lowering effect as well as antiplatelet and antithrombotic effects in experimental models. Warfarin is a coumarin derivative with anticoagulant activity that acts as a vitamin K antagonist. Since in clinical practice warfarin and D-003 could be administered together, the objective of this study was to evaluate the effects of the simultaneous administration of both drugs on the bleeding time and the venous thrombosis experimentally induced in rats. The combined therapy of minimally effective doses of D-003 and warfarin produced an antithrombotic effect significantly higher than those produced by each monotherapy. Likewise, the prolongation of bleeding time induced by warfarin was increased by the simultaneous administration with D-003, showing a synergistic effect between both drugs.

Animals↗

PubMedDate not supplied

The effects of n-3 fatty acid supplementation on bleeding time, plasma fatty acid composition, and in vitro platelet aggregation in cats.

Dietary supplementation with fish and fish oils rich in the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to alter eicosanoid metabolism and impair platelet function in several species. As an initial step in evaluating the antithrombotic effect of these n-3 fatty acids in cats, purified EPA and DHA were administered daily to 8 clinically normal cats for 2 months. Platelet function was evaluated biweekly by determining mucosal bleeding time and in vitro platelet aggregation parameters. Plasma fatty acid profiles were obtained before fish oil supplementation and at the termination of the study. In spite of significant increases (P < .0001) in the plasma concentrations of EPA and DHA after n-3 fatty acid supplementation, there were no significant changes in platelet aggregation or bleeding times. Although it is tempting, based on extrapolation of data from other species, to recommend dietary supplementation with fish oil for cats prone to arterial thromboembolism, these results indicate that administration of large doses of purified EPA and DHA once daily does not inhibit platelet function in normal cats and is unlikely to prevent thrombosis in cats with cardiovascular disease. Additional studies are recommended to ascertain whether more frequent administration of these purified n-3 fatty acids or continual feeding of diets high in n-3 fatty acid content will impair platelet function.

Administration, Oral↗

PubMed2000

PECAM-1 (CD31) expression modulates bleeding time in vivo.

PECAM-1 is a 130-kd member of the Ig superfamily present on endothelial cells, platelets, polymorphonuclear leukocytes, monocytes, and lymphocytes. Its expression begins early in development and persists through adulthood. PECAM-1 functions as an adhesion and signaling molecule between adjacent endothelial cells and between endothelial cells and circulating blood elements. Antibodies directed against PECAM-1 have been shown to affect angiogenesis, endothelial cell migration, and polymorphonuclear leukocyte transmigration. Furthermore, its dimerization is associated with the modulation of integrin affinity. Antibody inhibition studies suggest that PECAM-1 plays a role in modulating thrombosis; however, recent in vitro aggregation studies performed on platelets harvested from PECAM-1-deficient mice revealed no abnormalities. In this report we demonstrate prolonged in vivo bleeding times in PECAM-1-deficient mice. This abnormality was not corrected when wild-type hematopoietic precursors were engrafted into marrow-ablated PECAM-1-deficient mice. Furthermore, normal bleeding times were observed when marrow-ablated wild-type mice were engrafted with hematopoietic precursors harvested from PECAM-1-deficient mice. These studies are consistent with a role for PECAM-1 in modulating thrombosis in the vasculature, which is potentially mediated by endothelial cell PECAM-1 expression.

Animals↗

PubMed1994

[Ex-vivo bleeding time as a control for platelet transfusion].

Thrombocytopenia is the most common cause of bleeding tendency and, if due to impaired platelet production, is best treated by platelet transfusion. For patients with acute leukemia prophylactic platelet transfusion should be considered if platelet count is below 20 x 10(9)/l. This will be underlined by a retrospective analysis at our clinic of 231 patients suffering from acute myelocytic leukemia (AML FAB M1-7) and showing an early-death rate of 7.7% by bleeding complications. To estimate the effectiveness of platelet transfusions, not only stopping of bleeding symptoms and corrected count increment (CCI) should be taken into account but also whether the patient has fever, sepsis, hepato-splenomegaly or has taken special drugs. Measuring the in vivo bleeding time is of little use for low reproduction and is stressing for patients. In 1985 Kratzer described a new and sensitive method for the evaluation of platelet function. After modifying this method it is now possible to test platelet function even with platelet counts below 50 x 10(9)/l.

Bleeding Time↗

PubMed1992

Disturbed platelet aggregation to collagen associated with an antibody against an 85- to 90-Kd platelet glycoprotein in a patient with prolonged bleeding time.

We studied a 5-year-old girl presenting with a markedly prolonged bleeding time. Her platelets were refractory to collagen stimulation, but the response to other agonists was normal. There were no coagulation abnormalities as measured by standard tests. Two-dimensional electrophoresis showed no abnormalities of the patient's platelet membrane glycoproteins. When the patient's plasma or purified plasma IgG was mixed with normal platelets, collagen-induced platelet aggregation was blocked. Western blotting showed the presence of an antibody in the patient's plasma directed against a protein of molecular weight 85 to 90 Kd under both reducing and nonreducing conditions. This protein comigrated with glycoprotein (GP) IV immunoprecipitated by OKM5 from 125I-labeled platelets. Immunoprecipitation of 125I-labeled normal platelet glycoproteins with the patient's IgGs also yielded an 85- to 90-Kd protein that migrated on the diagonal following nonreduced/reduced two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Despite similarities in electrophoretic behavior, the antigen was not demonstrated to be GPIV, since purified GPIV was not recognized by the antibody.

Antibodies↗

PubMed1999

[Effect of unfractionated and low-molecular-weight heparin on platelet aggregation and in vitro bleeding time in dogs].

The aim of the present study was to examine the influence of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) on the function of canine thrombocytes. This was performed by adding different concentrations of UFH or LMWH to platelet rich plasma (PRP) or blood of healthy dogs: 0.2, 0.5, 1, 2, 5, 10, 20, and 50 I.U./ml UFH or Anti-FXaU/ml LMWH, respectively (aggregation induced by thrombin additionally: 0.025, 0.05, and 0.1 I.U./ml UFH or Anti-FXaU/ml LMWH.) Platelet aggregation induced by ADP, collagen or thrombin with the BORN method (n = 11) as well as the in vitro bleeding time using the analyzer PFA-100 (n = 5) were examined. Additionally, a specific test assay for ADP induced platelet aggregation was performed which enabled an individual adjustment of the aggregation maximum at 30-40% in the control measurements (n = 6). The most prominent effect was noted in the platelet aggregation induced by thrombin. The aggregation maximum of the platelet aggregation induced by 1 I.U./ml thrombin (final concentration) was significantly lower in all of the testet UFH concentrations > or = 0.025 I.U./ml UFH in comparison to control measurements. If the aggregation was induced by 10 I.U./ml thrombin a significant reduction of the aggregation maximum was restricted to UFH concentrations > or = 0.5 I.U./ml. The addition of LMWH to canine PRP resulted in a distinct decrease (p < 0.01) of the maximum aggregation induced by 1 I.U./ml thrombin in concentrations > or = 0.2 Anti-FXaU/ml LMWH. A slight decrease of the maximum aggregation induced by collagen was only found for UFH at activities > or = 20 I.U./ml. No significant systematic influence could be demonstrated for LMWH on the aggregation induced by collagen as well as for LMWH and UFH on the platelet aggregation induced by ADP. Capillary in vitro bleeding time (closure time) was prolonged only after adding high concentrations of UFH (> or = 10 I.U./ml) and LMWH (> or = 50 Anti-FXaU/ml) to the sample material. The results document the unimportant influence of therapeutic levels of UFH and LMWH on platelet function in dogs. Therefore, the remarkable inhibition of the aggregation induced by thrombin reflects mainly the antithrombin effect.

Animals↗

PubMed1985

Effect of Bordetella pertussis vaccine on bleeding time, whole blood coagulation time and platelet aggregation in animals.

Bordetella pertussis vaccine, a hypoglycemic agent significantly prolonged the bleeding time and whole blood coaguistion time in rabbits and dogs when administered intraperitonially. The vaccine also affects platelet aggregation in rats 4 days after its intraperitonial administration. The effect on platelet aggregation is thought to be due to its beta adrenargic receptor blocking action which may also contribute to the hypoglycemia.

Animals↗

PubMed1997

Dissociation of antithrombotic effect and bleeding time prolongation in rabbits by inhibiting tissue factor function.

Inhibition of the tissue factor/factor VIIa (TF/F.VIIa) complex attenuates thrombosis in different animal models of arterial thrombosis. However, it remains unclear to what extent the antithrombotic effects are associated with changes in hemostatic functions and how this compares with inhibition of thrombin, an enzyme acting at a later stage in the coagulation cascade. The antithrombotic and the antihemostatic effects of a monoclonal anti-TF antibody (AP-1) were compared in a model of arterial thrombosis to those of a direct thrombin inhibitor (napsagatran) and heparin. In anesthetized rabbits transient arterial thrombi were induced by mechanical damage to the subendothelium of a moderately stenosed carotid artery. Recurrent formation and dislodgement of thrombi resulted in cyclic flow variations (CFVs) which were monitored over 2 hours. Rabbits received intravenously either a placebo (control), a monoclonal anti-rabbit TF antibody (AP-1, 0.05 mg/kg as an i.v. bolus repeated every 15 min, a specific low molecular weight thrombin inhibitor (napsagatran, 3 microg/kg/min) or heparin (3 and 13 microg/kg/min). The effect of the inhibitors on the hemostatic system was studied in a separate set of rabbits by measuring template bleeding times (BT) in the ear arterioles, marginal ear vein and the nail cuticle of the foreleg. AP-1 and napsagatran showed a similar antithrombotic activity (78% and 80% abolition of the CFVs, respectively), whereas either low or high dose heparin was poorly effective (43% and 40% inhibition of CFVs, respectively). At these antithrombotic doses and even at 4-fold higher dosage, AP-1 did not significantly alter the BT, whereas napsagatran and heparin prolonged the ear vessels and cuticle BT in a dose-dependent manner. These results suggest that in contrast to direct thrombin inhibition, the blockade of the TF/F. VIIa function did not result in a concomitant prolongation of the bleeding time. Thus, dissociation of antithrombotic and antihemostatic effects indicates that inhibition of the coagulation system at its initial stage represents a promising approach for the development of new anticoagulants.

Animals↗

PubMed1952