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Effect of 1-deamino-8-D-arginine vasopressin on the prolonged bleeding time in chronic renal failure.

The prolonged bleeding times of 12 patients with chronic renal failure were significantly shortened at 1 and 2 h after an infusion of 0.4 microgram/kg 1-deamino-8-D-arginine vasopressin (DDAVP). In 5 of these patients, the bleeding times 24 h after infusion had returned to approximate baseline values, suggesting that the effect of DDAVP is a temporary one. The levels of factor VIII coagulant activity, factor VIII related antigen activity, and factor VIII ristocetin cofactor activity were all normal or elevated prior to infusion, and a tendency to further elevation, although significant only for the factor VIII ristocetin cofactor activity, was observed after infusion of DDAVP. The latter observation suggests that the effect of DDAVP infusion on the bleeding time is unrelated to alteration of factor VIII activities.

Adult↗

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↗

Performance characteristics and clinical evaluation of an in vitro bleeding time device--Thrombostat 4000.

The performance characteristics of an in vitro bleeding time device--Thrombostat 4000 were evaluated and compared with the Simplate bleeding time in healthy individuals and patients with disorders of primary hemostasis. Reference ranges were established using 30 normal volunteers. Although there were variations between different filter batches, reproducibility was good within a single batch. There were no differences between the two channels of the instrument and between male and female subjects. Hematocrit correlated negatively with the initial flow (IF) and IF correlated positively with closure time (T) and bleeding volume (V). Aspirin could be detected only when the traditional addition of ADP was replaced with CaCl2. Both, closure time (T) or bleeding volume (V) were more sensitive than Simplate bleeding time and T was more sensitive than V in detecting patients with disorders of primary hemostasis. We conclude that the Thrombostat 4000 is a reproducible, reliable, sensitive and easy to use instrument. It is superior to the traditional in vivo bleeding times for investigations of disorders of primary hemostasis (screening, diagnosis, monitoring, etc.).

Aspirin↗

The influence of different amounts of n-3 polyunsaturated fatty acids on bleeding time and in vivo vascular reactivity.

Mesenteric bleeding time, mesenteric vascular reactivity, platelet and erythrocyte lipid fatty acid composition were measured at 2-3 weeks, 5-6 weeks and 11-22 weeks in normotensive Wistar rats, fed on high (6.5% energy) or moderate (1.6% energy) intakes of eicosapentaenoic acid (20:5n-3; EPA) as fish oil, compared with controls fed on a diet devoid of EPA. All diets contained the same level of linoleic acid (4% energy): the moderate- and high-EPA diets also contained 1.1 and 4.4% of the energy as docosahexaenoic acid (22:6n-3) respectively. Moderate, but not high, intakes of EPA increased mesenteric bleeding time. Similar reductions in erythrocyte and platelet arachidonic acid (20:4n-6) occurred in animals fed on either high or low amounts of EPA, but the proportion of EPA increased dose-dependently. At high intakes of EPA the proportion of oleic acid in platelets and erythrocytes was decreased. Blood pressure platelet counts, mesenteric vessel diameter and mesenteric vascular reactivity to vasopressin were unaffected by treatment. High intakes of fish oil led to a slight fall in packed cell volume. In a second experiment bleeding time and mesenteric vascular reactivity to noradrenaline were increased 2-4 weeks after receiving a moderate intake of EPA and these effects persisted 5-21 d after switching to a control diet. A similar increase in vascular reactivity to noradrenaline was observed in animals given indomethacin (6 mg/kg) but not in those given aspirin (20 mg/kg).

Animals↗

The bleeding time response to aspirin. Identifying the hyperresponder.

The authors measured the template bleeding time in 11 normal people before and 2, 4, 12, 24, and 48 hours after the subjects ingested a single dose of 74 mg of aspirin (ASA). The entire experiment was repeated twice at two-week intervals, with the dose of ASA increased to 325 mg and finally 3,900 mg. The mean increase was maximal at 4 and 12 hours, regardless of the dose administered, with a return to baseline by 48 hours. The authors then performed bleeding times in a prospective randomized double-blinded fashion on an additional 39 subjects at baseline and seven hours after they ingested either placebo or ASA 325 mg. The mean baseline bleeding time was 5.2 minutes (SD +/- 1.4), with a mean prolongation after ASA of 2.1 minutes (SD +/- 1.9). The authors identified 5 of 37 (14%) subjects as hyper-responders (HRs) using the criterion of a bleeding time prolongation of greater than 5.9 minutes (greater than 2 SD beyond the mean prolongation). Neither baseline bleeding time, threshold sensitivity of collagen-induced platelet aggregation, nor other tests of hemostatic function discriminated HRs from normals. The authors conclude that in subjects with normal baseline bleeding times, a prolongation of greater than 5.9 minutes when measured seven hours after the administration of a single dose of 325 mg of ASA can discriminate HRs from normals.

Adult↗

The effect of regular and enteric-coated aspirin on bleeding time, thromboxane, and prostacyclin.

We compared the effect of different aspirin schedules, dosages, and formulations on various bleeding time parameters including bleeding time, plasma and total blood volume, and levels of the stable metabolites of thromboxane A2 (TXA2) and prostacyclin (PGI2) (respectively, TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha)) to determine the optimal dosage and formulation of aspirin to inhibit TXA2 production while sparing PGI2. In a randomized, parallel study, 52 healthy male volunteers (62 independent observations) with no history of bleeding disorders were given 80 mg or 325 mg of regular aspirin, or 325 mg of enteric-coated aspirin to ingest daily (14 pills) or every other day (7 pills) for a continuous 14 day period. Bleeding times were performed on day 1 before aspirin, 6 h after aspirin on day 1, and before aspirin on day 14. Bleeding times, plasma volume, and total volume increased significantly from before aspirin to after 6 h and 14 days (p < 0.0001 for all parameters) for all aspirin formulations. For day 1 before aspirin ingestion to 6 h later, both TX and PGI2 (p < 0.008) decreased significantly. 6 h after ingestion of aspirin on day 1 to day 14, both TX and PGI2 levels also significantly decreased (p < 0.0001). There was a highly significant decrease in PGI2 production on every other day aspirin schedules (p = 0.0001) particularly with 80 mg of aspirin, while the decrease in PGI2 production on daily aspirin was not significant (p = 0.10). The most favourable ratio of 6-keto-PGF1 alpha to TXB2 occurred with 80 mg daily.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

An interobserver and intraobserver study of buccal mucosal bleeding time in Greyhounds.

Two observers experienced with the buccal mucosal bleeding-time technique using a standardised device (Surgicutt) performed the test on 20 Greyhounds, to evaluate interobserver and intraobserver repeatability. The interobserver and intraobserver repeatability were both about 2 minutes. The results indicated that, for any two readings within a dog, the buccal mucosal bleeding time may differ by up to +/- 2 minutes. A single reading was accurate to within +/- 80 seconds. Sixty-one Greyhounds were used to establish a reference interval for the buccal mucosal bleeding time, and to assess the relationship between the buccal mucosal bleeding time and plasma von Willebrand factor concentration. The mean was 129.5 (SD 44.2) seconds. The reference interval was 53 to 235 seconds, which was slightly lower than non-greyhounds. No significant correlation (r=-0. 18, P=0.17) between the buccal mucosal bleeding time and plasma von Willebrand factor concentration was found in the 61 Greyhounds, where plasma von Willebrand factor concentration was in the range 29 to 160 Canine Units dL(-1).

Animals↗

Bleeding time, stroke and myocardial infarction: the Caerphilly prospective study.

The stressed bleeding time is a simple 'global' test of haemostasis, dependent upon platelet function, rheology, thrombosis and intimal function. It could be of considerable value in clinical practice if it were shown to be predictive of vascular disease events. A stressed bleeding time test was done on 1319 men aged 55-69 years in the Caerphilly Cohort Study of Heart Disease, Stroke and Cognitive Decline. The men were followed-up and during the following 7-10 years 155 men had a myocardial infarction (MI) and 72 an ischaemic stroke. The mean bleeding time was 323 (SD 113)s. This was shorter in men who smoked by an average of 45 s, and lengthened in men who took aspirin daily by 40s. After making statistical adjustments for numerous possible confounding factors, the relative odds (ROs) of an MI within the third of men with the longest bleeding times, compared to the third with the shortest times, was 0.90 (0.40-2.03). For ischaemic stroke, the ROs in the third of men with the longest times were 1.42 (0.39-5.21). The stressed bleeding time does not predict either MI or ischaemic stroke. It has no place in health screening.

Aged↗

A study of aspirin induced changes in bleeding time, platelet aggregation, and Sonoclot coagulation analysis in humans.

The purpose of this study was to determine whether or not a newer test of platelet function, Sonoclot coagulation analysis, can identify the patients who develop significant prolongation of bleeding time after aspirin ingestion. Template bleeding time, platelet aggregation in response to arachidonic acid, collagen, epinephrine, adenosine diphosphate, and ristocetin, and Sonoclot coagulation analysis were performed before and after ingestion of aspirin in 22 adult volunteers. Mean bleeding time increased from 5.32 +/- 2.16 min to 7.34 +/- 2.1 min, but remained within normal range (2.5 to 9 min). There was marked intersubject variability in the effect of aspirin on bleeding time, and difference between men and women was not significant. There was significant decrease in platelet aggregation in response to arachidonic acid, collagen and epinephrine. Sonoclot coagulation analysis did not show significant effect of aspirin administration. There was no correlation among changes in bleeding time, platelet aggregation, and Sonoclot coagulation analysis. Five patients with known platelet function disorders and prolonged bleeding times (mean = 18.5 min, range 14 to 22) without any other coagulation abnormalities were also studied. In four of these patients who had normal platelet count, Sonoclot graphs were morphologically similar to those in the volunteers with normal bleeding times, but in one patient with thrombocytopenia, morphology was altered. It is our conclusion that Sonoclot coagulation analysis is unlikely to identify patients with prolonged bleeding time in whom platelet count and other coagulation factors are normal.

Adult↗

Thromboxane A2 in skin-bleeding-time blood and in clotted venous blood before and after administration of acetylsalicylic acid.

The 'Simplate' technique for measuring skin bleeding time was adapted to quantify thromboxane A2 in the emerging blood as the stable degradation product thromboxane B2 in twelve Swedish and ten English volunteers. During the bleeding time thromboxane B2 concentrations increased, but as the rate of blood loss fell the rate of production of thromboxane A2 was constant. The English subjects had shorter bleeding times and produced more thromboxane A2 than the Swedish subjects. When the Swedish subjects were grouped according to bleeding times those with the shortest had more thromboxane A2 than those with longer bleeding times. Clotting venous blood in vitro produced much more thromboxane A2 than bleeding-time blood and there was no correlation with bleeding time. Determination of the capacity of clotting blood to form thromboxane A2 is therefore irrelevant to in-vivo haemostasis. Acetylsalicylic acid greatly diminished the appearance of thromboxane A2 in the bleeding time and prevented the increase of thromboxane A2 concentration with time.

Adenosine Diphosphate↗

Template bleeding time and clinical hemorrhage in myeloproliferative disease.

In 32 patients with myeloproliferative disorders (MPD), correlations were made among clinical observations of hemorrhagic tendency, template Ivy bleeding time, and platelet aggregation studies. Bleeding time was commonly prolonged, particularly in myelofibrosis. In two cases, this prolongation appeared to reflect a defect in platelet function, which resulted in clinical bleeding. Prolongation of bleeding time did not correlate with degree of thrombocytosis. Two patients with thrombocytosis had serious clinical bleeding at a time when bleeding time was normal. Of the patients, 35% had abnormal findings from aggregation studies, but there was no correlation between aggregation studies and prolongation of bleeding time or clinical hemorrhage. We conclude that bleeding in MPD arises either from a defect in platelet function, which is reflected in a prolonged bleeding time, or from thrombocytosis.

Blood Cell Count↗

A study of bleeding time in 120 long-term aspirin trial patients.

The bleeding time was measured in 120 patients participating in a longterm randomised double-blind trial of aspirin in thromboembolic prophylaxis (UK-TIA aspirin Study). In 70 patients taking aspirin 300 mg or 1,200 mg daily for a mean duration of 35 months the bleeding time averaged 228 seconds. In comparison with 30 patients randomised to placebo and not taking aspirin whose bleeding time averaged 217 seconds, there was no significant difference. Stratification of bleeding time estimation by duration of treatment suggested no significant trend in either placebo or aspirin groups over several years. These results suggest that the longterm trials of aspirin should be looked at again from the point of view of efficacy of treatment by time from randomisation.

Aged↗

An assessment of the sensitivity of 3 bleeding time techniques.

The sensitivity of 3 bleeding time techniques to an aspirin-induced defect of platelet function has been assessed in 35 normal volunteers. A carefully standardised Ivy technique was compared with 2 commercial devices for a template bleeding time, the Simplate II and the Thrombolette. The standardised Ivy and the Simplate II were found to have a similar sensitivity; the Thrombolette tended to be less sensitive but the difference was not significant.

Aspirin↗

Subcutaneous desmopressin (DDAVP) shortens the bleeding time in uremia.

The intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) is used as a nontransfusional form of treatment in patients with congenital and acquired bleeding disorders, including patients with uremia associated with prolonged bleeding times. Since uremic patients experience minor bleeding episodes that might be self-managed at home (particularly epistaxis, gingival bleeding, and menorrhagia), we carried out a double-blind, placebo-controlled crossover study in nine uremics to evaluate whether the prolonged bleeding times could be shortened by subcutaneous injections of DDAVP. One hour after administration, the bleeding time was significantly shortened (P less than .01) and became normal in seven of nine patients. After 4 hr, the bleeding time was still shorter than baseline (P less than .01), but in only three patients was it still normal. There was no significant bleeding time change after placebo. When the same patients were treated with the same dose of DDAVP infused intravenously, the bleeding times were not significantly different from those measured after subcutaneous administration. Hence, subcutaneous DDAVP is an alternative method for short-term shortening of the bleeding time in uremia, at least as effective as intravenous DDAVP but with the possibility of self-administration by the patients at home.

Adult↗

Acquired platelet dysfunction may be an aetiologic factor in Heyde's syndrome--normalization of bleeding time after aortic valve replacement.

BACKGROUND: There is a well-documented relationship, with unknown aetiology, between aortic valve stenosis and occult gastrointestinal bleeding in elderly patients. Despite several studies attempting to determine the prevalence and to discuss the aetiology, there are still many unanswered questions. METHODS: A total of 288 consecutive patients with valvular aortic stenosis--mean age 73 +/- 9 years aortic stenosis group (ASG)--were compared with 129 pacemaker-treated patients, mean age 73 +/- 9 years control group (CG). Screening for occult blood in stools was performed in both groups. Those with a positive Hemocult test or a history of gastrointestinal bleeding were scheduled for further examination including upper endoscopy and colonoscopy. Template bleeding time was performed on patients in both groups and in patients with a prolonged bleeding time with an extended coagulation evaluation was carried out. Patients referred to aortic valve replacement and with a preoperatively prolonged bleeding time were re-examined after surgery. RESULTS: There was a significant difference in the number of subjects with prolonged bleeding time between groups (ASG 19; CG 2; P = 0.028). Re-examination of the bleeding time after aortic valve surgery revealed normalized values in nine of 12 (P = 0.0003). The number of patients with positive Hemocult test did not differ between groups (ASG 29; CG 12; NS). Comparison of the pressure gradient over the aortic valve demonstrated a significantly higher maximal gradient amongst patients with a preoperatively prolonged bleeding time (113 mm HG vs. 90 mmHG; P = 0.005). CONCLUSION: Prolonged bleeding time is related to valvular aortic stenosis and seems to be caused by acquired platelet dysfunction. The normalization of the bleeding time after valve surgery supports the hypothesis that the calcified cusps may interact with the platelet function.

Aged↗

An in vitro measurement of bleeding time.

An in vitro method of measuring the bleeding time is described. The test, called the machine bleeding time (MBT), is not affected by heparin and detects the same types of hemostatic abnormalities as the template bleeding time. It is sensitive to thrombocytopenia, aspirin administration, and von Willebrand's disease. It is a reproducible test suitable for replicate and serial determinations and permits in vitro evaluation of the addition of drugs.

Aspirin↗

Shortening of the bleeding time in rabbits by hydrocortisone caused by inhibition of prostacyclin generation by the vessel wall.

The effect of hydrocortisone on thrombocytopenic bleeding has been studied in rabbits using a jugular vein bleeding-time technique and a microvascular bleeding-time technique. An inverse relationship was found between the bleeding time and platelet count with both techniques in rabbits made thrombocytopenic by either X-irradiation or injection of heterologous platelet antiserum. Hydrocortisone shortened both bleeding times in thrombocytopenic animals when given in single large doses intravenously (25-100 mg/kg), in daily doses (6 mg/kg) intramuscularly, and shortened the jugular bleeding time when applied to the outside of the jugular vein or instilled intraluminally into the vein. This effect was also noted in normal animals. The effect on thrombocytopenic bleeding was dose related. When given daily, the effect was greater when hydrocortisone was given for 10 d than for 5 d. Both indomethacin and tranylcypromine also reduced the jugular vein bleeding time when instilled intraluminally into the jugular vein, whereas exogenously provided arachidonic acid reversed the effect of hydrocortisone but did not reverse the effect of indomethacin or tranylcypromine. Exogenously provided linoleic acid did not have any effect. Perfusion of the vessel segment with prostacyclin (PGI(2)) reversed the effect of intraluminally administered hydrocortisone, indomethacin, and tranylcypromine. Similarly, hydrocortisone, indomethacin, and tranylcypromine all reduced the rate of loss of fluid from a standard wound in isolated vessels emptied of blood and perfused with saline under constant pressure. PGI(2) reversed the action of these three agents, however, arachidonic acid reversed only the effect of hydrocortisone and did not reverse the effect of indomethacin and tranylcypromine. The generation of PGI(2)-like material and 6-keto-prostaglandinF(1) alpha from jugular vein strips was prevented by prior exposure of the animals or vessel wall to hydrocortisone. These results are compatible with the hypothesis that the vessel wall releases smooth muscle-relaxing prostaglandins when injured and that inhibition of prostaglandin formation by hydrocortisone enhances hemostasis by allowing vasoconstriction to be maintained.

Animals↗

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↗