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PubMed1987

Comparison of bleeding times performed on the arm and the leg.

The standardized bleeding time (SBT) is used to assess hemostatic function in patients suspected of having coagulation disorders. Because injury to the arm or the presence of intravascular cannulae often preclude the determination of SBTs on the upper extremity, the authors compared the SBT on the arm with the bleeding time on the leg to ascertain the efficacy of the lower extremity for this test. Thirty healthy volunteers were enrolled in the study. Bleeding times were performed on the forearm and on the medial aspect of the calf. The subjects then ingested 650 mg of aspirin, and the tests were repeated two hours later on the contralateral extremities. The mean preaspirin SBT (5.6 +/- 1.7 minutes did not differ significantly from the mean bleeding time on the leg (5.8 +/- 2.3 minutes) (P greater than 0.50), nor was there a significant difference between the mean postaspirin bleeding time on the arm (10.2 +/- 4.3 minutes) and that on the leg (9.9 +/- 3.7 minutes) (P greater than 0.50). On the basis of this study, the authors conclude that the arm and leg are equally reliable sites for determining bleeding times in normal persons and are equally sensitive for detection of aspirin-induced prolongation of bleeding.

Adult↗
PubMed1990

Differences in bleeding time, aspirin sensitivity and adrenaline between acute myocardial infarction and unstable angina.

STUDY OBJECTIVE - The objective was to measure platelet function in vivo (as cutaneous bleeding time), the role of catecholamines, and the effect of inhibiting thromboxane synthesis on bleeding time, in patients with myocardial infarction, unstable angina, and non-cardiac chest pain. DESIGN - Haemotological variables and plasma catecholamines were compared between patient diagnostic groups using the Kruskal-Wallis test, Conover's multiple comparison test, and Wilcoxon paired rank sum test. PATIENTS - 49 patients entered the study and 45 were assigned to three groups: myocardial infarction (n = 26), unstable angina (n = 9), and non-coronary chest pain (control) (n = 10). There were no significant differences between groups for age or sex. Patients with myocardial infarction smoked more than others. MEASUREMENTS and RESULTS - Compared to the controls, bleeding time in patients with myocardial infarction was shortened, while in unstable angina it was normal. Plasma adrenaline and noradrenaline concentrations were higher in the myocardial infarction group than in the unstable angina and control groups, but were not correlated with bleeding time. Bleeding time was remeasured 2 h after ingestion of 300 mg aspirin and increased in all subjects, especially in those with myocardial infarction, but it remained significantly shorter in the infarct group than in the comparison groups. Plasma adrenaline was inversely correlated with the bleeding time after aspirin in the infarct group. CONCLUSIONS - The shortened bleeding time may be an indicator of an increased prethrombotic tendency present in patients with myocardial infarction but not in those with unstable angina. The effect appears to be mediated by both thromboxane A2 and adrenaline.

Aged↗
PubMed1987

Platelet-mediated bleeding caused by broad-spectrum penicillins.

One hundred fifty-six hospitalized adult patients treated with ticarcillin, piperacillin, mezlocillin, or cefotaxime (control) were prospectively observed for determination of frequencies of platelet dysfunction and bleeding. Increases in bleeding times (greater than or equal to 5 min above pretreatment values) occurred in 73% of patients receiving ticarcillin, 43% receiving piperacillin, 25% receiving mezlocillin, and 17% receiving cefotaxime (P less than .0001); chemotherapy, thrombocytopenia, age of greater than or equal to 60 years, dose of greater than or equal to 12 g per day, and duration of treatment of six or more days were significant covariables. Significant bleeding occurred in 34% of patients treated with ticarcillin, 17% with piperacillin, 2% with mezlocillin, and 5% with cefotaxime (P = .0005); chemotherapy, thrombocytopenia, primary marrow disorders affecting platelet function, prolonged prothrombin time, and azotemia were significant covariables. Bleeding was associated with an elevated pretreatment bleeding time, an increase in bleeding time during treatment, and the maximal observed bleeding time during treatment (P less than .0001).

Adult↗
PubMed1995

Effects of temperature on bleeding time and clotting time in normal male and female volunteers.

OBJECTIVE: This study was done to assess the effects of temperature on bleeding time and clotting time in normal male and female volunteers. DESIGN: Open study utilizing normal volunteers. SETTING: University research laboratory. SUBJECTS: Fifty-four healthy male and female volunteers, ranging in age from 19 to 35 yrs, who were not receiving medications. The study was done and the samples of venous blood and shed blood collected at the template bleeding time site were obtained at a convenient time for each volunteer. INTERVENTIONS: Skin temperature was changed from +20 degrees to +38 degrees C and blood samples were obtained from the antecubital vein of each volunteer. MEASUREMENTS AND MAIN RESULTS: The effect of local skin temperature ranging from +20 degrees to +38 degrees C on bleeding time was evaluated in 38 normal volunteers (19 male and 19 female). Skin temperature was maintained at +20 degrees to +38 degrees C by cooling or warming the forearm. At each temperature, measurements were made of complete blood count, bleeding time, and thromboxane B2 concentrations in shed blood collected at the template bleeding time site and in serum and plasma isolated from blood collected from the antecubital vein. Clotting time studies were measured in 16 normal volunteers (eight male and eight female) at temperatures ranging from +22 degrees to +37 degrees C. At +32 degrees C, the bleeding time was longer and hematocrit was lower in female than in male volunteers. However, at local skin temperatures of < +32 degrees C, both the males and females exhibited significantly increased bleeding times, which were associated with a reduction in shed blood thromboxane B2. Each 1 degree C decrease in temperature was associated with a 15% decrease in the shed blood thromboxane B2 concentration. Clotting times were three times longer at +22 degrees C than at +37 degrees C. Each 1 degree C reduction in the temperature of the clotted blood was associated with a 15% reduction in the serum thromboxane B2 concentration. CONCLUSION: Our data indicate that during surgical procedures, it is important to maintain normothermia to ensure that platelets and clotting proteins function optimally.

Adult↗
PubMedDate not supplied

DDAVP therapy controls bleeding in Ehlers-Danlos syndrome.

PURPOSE: Patients with Ehlers-Danlos syndrome (EDS), especially types IV, VI, and VIII, are at increased risk of bleeding, and most do not have specific hemostatic deficiencies that would be amenable to replacement therapy. We have investigated the ability of DDAVP (desmopressin acetate) to control bleeding in EDS. PATIENTS AND METHODS: Two children with EDS, types VIII and VI, presented with hemorrhagic symptoms and scheduled surgical procedures. Ivy bleeding times (BTs) were measured before and after intravenous (i.v.) DDAVP challenge, and i.v. DDAVP was used prophylactically for their procedures. Laboratory testing was performed to rule out other hemostatic disorders. RESULTS: Both patients had prolonged BTs that corrected following i.v. DDAVP therapy; all other laboratory values were normal. Both patients had excellent clinical hemostasis with surgery, and one has continued to use intranasal DDAVP to control epistaxis and gingival bleeding. CONCLUSIONS: The bleeding time in both patients was corrected with DDAVP, and the patients did not have any postoperative bleeding. DDAVP should be considered in other patients who have EDS with bleeding tendencies.

Bleeding Time↗
PubMed2006

Upper gastrointestinal bleeding associated with antiplatelet drugs.

BACKGROUND: The risk of major upper gastrointestinal bleeding associated with various antiplatelet drugs and the protection conferred by gastroprotective agents are not well defined. AIM: To estimate the risk of upper gastrointestinal bleeding associated with the use of antiplatelet drugs and its prevention by gastroprotective agents. METHODS: In a case-control study, we compared all cases of upper gastrointestinal bleeding from a gastric or duodenal lesion in patients over 18 years of age (2813 cases), with 7193 matched controls. Odds ratios of upper gastrointestinal bleeding for individual antiplatelet drugs with adjustment for potential confounders were estimated. RESULTS: The individual risks of upper gastrointestinal bleeding were cardiovascular acetylsalicylic acid 4.0 (3.2-4.9), clopidogrel 2.3 (0.9-6.0), dipyridamole 0.9 (0.4-2.0), indobufen 3.8 (1.2-12.2), ticlopidine 3.1 (1.8-5.1) and triflusal 1.6 (0.9-2.7). Concomitant proton pump inhibitors decreased all risk estimates. For acetylsalicylic acid plus a proton pump inhibitor, the odds ratio was 1.1 (0.5-2.6). As a group, antiplatelet drugs accounted for 14.5% of all cases of upper gastrointestinal bleeding, i.e. 58 per million per year (334 per million per year among those older than 70 years). CONCLUSIONS: The risk of upper gastrointestinal bleeding is substantially decreased by the concomitant use of proton pump inhibitors. The risk of acetylsalicylic acid plus a proton pump inhibitor seems lower than that of ticlopidine or clopidogrel.

Adult↗
PubMed1985

Low haematocrit and prolonged bleeding time in uraemic patients: effect of red cell transfusions.

This study demonstrates that a low haematocrit is the main determining factor of the prolonged bleeding time often encountered in uraemic haemodialysed patients. Thirty-three patients submitted to regular haemodialysis and having a platelet count greater than 100 X 10(9)/l were investigated with the following tests: simplate bleeding time, blood cell count, platelet aggregation induced by ADP, collagen and sodium arachidonate, arachidonate induced MDA synthesis, tests for detection of an acquired storage pool disease, and factor VIII complex level. The results were compared to two other groups; one of uraemic patients not yet subjected to haemodialysis and another of healthy volunteers. The results were basically identical in the two groups of uraemic patients. The only consistent abnormality was a 30-35% reduction in the platelet MDA synthesis in comparison with control subjects. There was a negative correlation between the log bleeding time and the haematocrit (r = 0.78, P less than 0.01). Fourteen uraemic patients having a prolonged bleeding time were submitted to a red cell transfusion programme and were investigated a second time under identical conditions. There was no change in any of the platelet function tests or in the factor VIII complex level, but the bleeding time was normalized when the post-transfusion haematocrit was over 26% (nine patients). This study emphasizes the role of anaemia in the pathogenesis of the prolonged bleeding time in uraemia and suggests that red cell transfusion can be a long-term efficient therapeutic measure to stop bleeding in these patients.

Adolescent↗
PubMed1992

Sustained correction of the bleeding time in an afibrinogenaemic patient after infusion of fresh frozen plasma.

We have evaluated the duration of the effect of replacement therapy with two different doses of fibrinogen on the prolonged bleeding time of an afibrinogenaemic patient and the relationship between changes in bleeding time and plasma and platelet fibrinogen concentrations. The infusion of 40 mg/kg fibrinogen, as fresh frozen plasma (FFP), corrected the prolonged bleeding time of the patient from longer that 30 min to 8 min. The bleeding time was still normal 9 d after infusion, at a time when the plasma and platelet fibrinogen levels were low (0.13 g/l and 27 micrograms/10(9) platelets; normal ranges 1.6-4.0 and 60-190). Two months later, the infusion of a smaller dose of fibrinogen (4 mg/kg) also corrected the bleeding time, which remained normal until the second day after infusion, despite the fact that plasma and platelet fibrinogen were very low (0.02 g/l and 3.4 micrograms/10(9) platelets). The bleeding time returned to the prolonged baseline values only by day 6 post-infusion, when plasma and platelet fibrinogen levels were 4 x 10(-4) g/l and 1.4 micrograms/10(9) platelets. Therefore, sustained correction of the prolonged bleeding time may be obtained in afibrinogenaemic patients with a single infusion of fibrinogen at lower doses than usually recommended.

Adult↗
PubMed1981

Vaginal bleeding disturbances associated with the discontinuation of long-acting injectable contraceptives. From the World Health Organization Special Programme for Research, Development, and Research Training in Human Reproduction; Task Force on Long-acting Systemic Agents for the Regulation of Fertility.

A randomized comparative trial of 832 women receiving norethisterone oenanthate (NET-OEN) and 846 women receiving depot medroxyprogesterone acetate (DMPA) injections at 12 week intervals was conducted in 10 centers. The pregnancy rate with NET-OEN was significantly higher than with DMPA. The termination rate for amenorrhoea was substantially lowe with NET-OEN than DMPA, whereas the discontinuation rates for bleeding problems were similar with the two drugs. Analysis of bleeding patterns among continuing and discontinuing users suggests that women tolerated frequent bleeding episodes, but found prolonged bleeding or prolonged bleeding-free intervals unacceptable. Bleeding for more than 30 days during an injection interval and complete amenorrhoea for a whole injection interval were jointly associated with 43.7% of all terminations among NET-OEN users and 64.5% of all terminations among DMPA users. In future efforts to improve the acceptability of long-acting injectable contraceptives, more attention should be given to the control of prolonged amenorrhoea and prolonged bleeding.

Amenorrhea↗
PubMed1985

Shortened bleeding time in acute myocardial infarction and its relation to platelet mass.

The bleeding time, using the Simplate method, horizontal incision, and venostasis, was measured in a study of 51 patients admitted to a coronary care unit within 12 hours of the onset of chest pain. The bleeding time was significantly shorter in the 28 patients who were found to have definite myocardial infarction compared with the 23 others with chest pain but no definite infarction (p less than 0.0005). A bleeding time of less than 212 seconds correctly classified 84% of patients (sensitivity for definite myocardial infarction 89%) presenting to the coronary care unit with chest pain. Multiple regression analysis showed the bleeding time in all patients to be determined independently (and with high significance) by the following variables in order of importance: diagnostic group, platelet mass (platelet count X mean volume), and age. Packed cell volume was not a significant determinant. In the group with definite myocardial infarction considered alone the same order of variables was observed in predicting bleeding time, but none of them was significant. A major variable reducing bleeding time in acute myocardial infarction remains to be determined. There was no association between bleeding time and creatine phosphokinase activity or infarct size in the group with definite myocardial infarction.

Aged↗
PubMed1993

Nafamostat mesilate: a regional anticoagulant for hemodialysis in patients at high risk for bleeding.

107 hemodialysis patients at high risk for intradialytic bleeding due to previous surgery or active bleeding from other sites were treated with nafamostat mesilate (FUT-175; FUT) as hemodialysis anticoagulant for 2 weeks. In contrast to heparin. FUT prolonged clotting times only in the extracorporeal circuit. Clotting times were not prolonged even at the conclusion of the treatment, and bleeding from the puncture site after removal of the needle was shorter than with heparin. The exacerbation of bleeding by hemodialysis was noted in only 21 out of 573 hemodialysis procedures (3.7%), and 134 of 145 hemodialysis procedures (92.4%) with active bleeding were successfully completed without increasing the bleeding. Adverse effects of FUT were noted in only 6 cases (5.6%) or 1.2% of HD procedures. These results indicate that FUT is a very useful anticoagulant for HD, especially in patients with high risk of bleeding.

Aged↗
PubMed1983

Quantification of blood from skin bleeding time determinations: effects of fish diet or acetylsalicylic acid.

The Simplate II technique for measuring bleeding time was adapted to quantify the volume of blood as a function of time and for determining how this parameter was affected by either acetylsalicylic acid (ASA) or a dietary supplement of fish. Both increased the bleeding time significantly. Irrespective of the final bleeding time, the rate of blood loss increased for about the first 2 min and then decreased almost linearly until bleeding stopped. This time course was not affected by either ASA or the fish diet. The lack of effect by ASA suggests that the initial increase in bleeding time, presumably due to reversal of vasoconstriction, does not involve prostaglandin derivatives. After ASA the rate of blood loss was significantly greater throughout, probably caused by deceleration of platelet aggregation. During the fish diet, when bleeding time was increased, there was no change in the rate of blood loss until the last 2-3 min during which bleeding continued at a very low rate. The results support the conclusion that the delay in primary haemostasis produced by a fish diet is due to a different mechanism than that produced by ASA.

Adult↗
PubMed2004

An association of candidate gene haplotypes and bleeding severity in von Willebrand disease (VWD) type 1 pedigrees.

von Willebrand disease (VWD) type 1 is difficult to diagnose because of bleeding variability and low heritability of von Willebrand factor (VWF) levels. We compared a bleeding severity score and bleeding times to candidate gene haplotypes within pedigrees of 14 index cases, using a covariance components model for multivariate traits (Mendel: QTL Association). These pedigrees included 13 affected and 40 unaffected relatives, as defined by plasma ristocetin cofactor (VWF:RCo) levels. The bleeding severity score was derived from a detailed history. Donors were genotyped using a primer extension method, and 9 candidate genes were selected for analysis. VWF:RCo levels had the strongest influence on bleeding severity score and bleeding time. ITGA2 haplotype 2 (807C) and ITGA2B haplotype 1 (Ile(843)) were each associated with increased bleeding severity scores (P < .01 and P < .01, respectively). GP6 haplotype b (Pro(219)) was also associated with increased scores (P = .03) after adjustment for donor age. No association was observed with 6 other candidate genes, GP1BA, ITGB3, VWF, FGB, IL6, or TXA2R. Increased plasma VWF:Ag levels were associated with VWF haplotype 1 (-1793G; P = .02). These results establish that genetic differences in the adhesion receptor subunits alpha(2), alpha(IIb,) and GPVI can influence the phenotype of VWD type 1.

Bleeding Time↗
PubMed1992

Prolonged bleeding time of Chediak-Higashi cats corrected by platelet transfusion.

Cats with the Chediak-Higashi syndrome (CHS) have a platelet storage pool deficiency (SPD). Ten CHS cats were transfused with a concentrate of 51Cr-labeled platelets prepared from normal donor cats. One hour after transfusion, the donor platelet count in CHS recipient cats was 40,000-60,000/microliters. Bleeding time before transfusion was 9.1 +/- 3.0 min. When donor platelet count in CHS cats was 50,000/microliters, bleeding time was 1.7 +/- 0.2 min. Bleeding time of normal cats was 1.4 +/- 0.3 min. Bleeding time increased to 3.3 +/- 0.2 min and to 5.3 +/- 0.2 min when the platelet count was 30,000/microliters, and 15,000/microliters, respectively. The close inverse relationship between bleeding time and number of donor platelets in CHS cats (r = -0.92), suggests that prolonged bleeding time is due to a platelet abnormality, that platelet transfusion can effectively correct prolonged bleeding time in an animal model of platelet SPD and that CHS cats may be an appropriate animal model to evaluate hemostatic capabilities of transfused platelets.

Animals↗
PubMed1992

[Bleeding time].

Bleeding time indicates the interaction of the platelets with the damaged vessel wall and the subsequent formation of the primary hemostatic plug. Bleeding time has been widely used in the diagnosis of bleeding disorders, especially thrombocytopenia, abnormalities in platelet function, vascular disorders, and von Willebrand's disease. There are a number of methods to perform the bleeding time test, but there are significant problems concerning sensitivity, specificity, and reproducibility. To study the inhibitory effects of monoclonal antibodies (anti-vWF, anti-GPIb, and anti-GPIIb/IIIa) on primary hemostasis, these antibodies were infused to normal pigs. Anti-vWF and anti-GPIb antibodies markedly prolonged the bleeding time and inhibited hemostatic plug formation. The anti-GPIIb/IIIa antibody completely inhibited ADP-and collagen-induced platelet aggregation, but no or only mild prolongation of bleeding time was observed. The quantitative bleeding time which measures both the time and the amount of blood loss is useful in the diagnosis of hemorrhagic disorders and in judging the efficacy of the treatment. It will provide important information to understand the mechanism of primary hemostasis.

Animals↗
PubMed2006

Ex vivo evaluation of anti-GPVI antibody in cynomolgus monkeys: dissociation between anti-platelet aggregatory effect and bleeding time.

Recent progress in the understanding of thrombus formation has suggested an important role of glycoprotein (GP)VI. In contrast to its pivotal role in collagen-induced platelet activation, it has been suggested that its blockade does not induce massive bleeding tendency. To demonstrate the dissociation between inhibitory effect on platelet aggregation and bleeding by GPVI blockade, we examined the effects of Fab fragment of OM2, an anti-human GPVI monoclonal antibody on ex vivo collagen-induced platelet aggregation and skin bleeding time after intravenous injection in cynomolgus monkeys. In a dose-escalation study, OM2 potently (> 80%) inhibited collagen-induced platelet aggregation at the cumulative dose of 0.2 mg/kg with a slight prolongation of bleeding time (1.3 times baseline value). Furthermore, at 18.8 mg/kg, the highest dose tested, prolongation of bleeding time was still mild (1.9 times). In contrast, abciximab, Fab fragment of anti-GPIIb/IIIa antibody prolonged bleeding time by 5.0 times at 0.35 mg/kg, the lowest effective dose on platelet aggregation. In a pharmacodynamic study, a bolus injection of OM2 at 0.4 mg/kg produced potent inhibition of collagen-induced aggregation up to six hours after injection, showing longer half-life than that of abciximab. The injection of OM2 Fab did not induce thrombocytopenia and GPVI depletion in monkeys. These results suggest that blockade of GPVI by antibody can exert a potent inhibitory effect on collagen-induced platelet aggregation with a milder prolongation of bleeding time than blockade of GPIIb/IIIa. This study indicates that OM2 has the potential to be developed as a new class of therapeutic tool.

Animals↗
PubMed2006

Assessment of PFA-100 system for the measurement of bleeding time in oral surgery.

UNLABELLED: The common diagnostic methods to know primary hemostasis have been classified as invasive, depending on the operator, difficult to reproduce and at times not very reliable. Thus, different systems have been proposed to assess bleeding time, one of them being the PFA-100 device, which we present in this paper. OBJECTIVE: Compare specificity between the traditional Ivy method with the PFA-100 system to measure bleeding time. MATERIAL AND METHOD: We obtained a sample of 33 patients between the age of 24-80 years receiving anti-platelet treatment who needed to undergo oral surgery. Bleeding time was obtained by the Ivy method, an INR by an analysis done on the same day and a Coagucheck one hour before surgery as well as measurement of bleeding time with the PFA-100 system. RESULTS: Mean value of bleeding time through the Ivy method was 406.36 sec.. Mean bleeding time with the PFA-100 system for the collagen/epinephrine cartridge was 226.91 sec. and for the collagen/ADP cartridge was 110.27 sec.. All these values were within normality. We observed very high standard deviations with the Ivy method and more regular ones for the PFA-100 system, indicating its greater specificity. We also obtained a large correlation between collagen/epinephrine cartridge and acetylsalicylic acid. CONCLUSIONS: We found greater specificity of the analyzer of PFA-100 platelet function for the measurement of bleeding time in relationship with the traditional Ivy method.

Adult↗
PubMed1990

Subcutaneous desmopressin (DDAVP) shortens the prolonged bleeding time in patients with liver cirrhosis.

The intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) shortens the prolonged bleeding time in patients with congenital or acquired bleeding disorders, including patients with uremia or liver cirrhosis. We carried out a double-blind, placebo-controlled crossover study in ten patients with liver cirrhosis to evaluate whether or not their prolonged bleeding times could be shortened by subcutaneous injections of DDAVP (0.3 microgram/kg), a more practical route of administration than intravenous infusions. One hour after DDAVP injection the bleeding time was significantly shortened (p less than 0.05). After 4 h, however, the bleeding time shortening was no longer statistically significant. There was no bleeding time change after placebo. Plasma levels of von Willebrand factor antigen (vWF:Ag) did not significantly increase after DDAVP or placebo. The study shows that subcutaneous DDAVP is an alternative method for short-term shortening of the bleeding time in liver cirrhosis.

Adolescent↗