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PubMed1991

Bleeding time prolongation and bleeding during infusion of recombinant tissue-type plasminogen activator in dogs: potentiation by aspirin and reversal with aprotinin.

Thrombolytic therapy is associated with a bleeding tendency that may be exacerbated by adjunctive antiplatelet agents. The effect of recombinant tissue-type plasminogen activator (rt-PA) alone or in combination with aspirin on serial measurements of template bleeding time, ex vivo platelet aggregation and coagulation factors and the frequency of bleeding was studied in dogs. During infusion of rt-PA (15, 30 or 60 micrograms/kg per min for 90 min), a dose-related increase in bleeding time was observed. In a randomized blinded study of 25 dogs, the baseline bleeding time (mean +/- SD) was 3.5 +/- 1 min in control animals and 4 +/- 2 min after oral aspirin (15 mg/kg body weight). Infusion of rt-PA (15 micrograms/kg per min for 90 min) prolonged the bleeding time to a maximum of 15 +/- 12 min. In contrast, combined aspirin and rt-PA therapy produced an increase to greater than 30 min during infusion, reverting to 13 +/- 10 min within 2 h after cessation of infusion. Recurrent continuous bleeding from incision sites occurred in one of six dogs given aspirin alone, two of seven given rt-PA alone and all six dogs given both aspirin and rt-PA (p = 0.02). Bleeding time greater than 9 min correlated significantly with bleeding frequency (p less than 0.0001), with a sensitivity of 100% and a specificity of 87%. Intravenous bolus injection of aprotinin (20,000 kallikrein inhibitor units/kg body weight) in six dogs given both rt-PA and aspirin produced a decrease in bleeding time from greater than 30 min to 9.5 +/- 9 min and resulted in cessation of bleeding. Thus, bleeding and bleeding time prolongation in this canine model are potentiated by a marked interactive effect of rt-PA and aspirin that is rapidly reversible. Template bleeding times may provide a useful quantitative index for monitoring the bleeding tendency associated with thrombolytic therapy.

Animals↗
PubMed1999

Is the bleeding time predictive of bleeding prior to a percutaneous renal biopsy?

The bleeding time is used by many nephrologists to predict risk of hemorrhage before percutaneous kidney biopsy. Developed in 1910, the bleeding time is a nonspecific test that may be prolonged in multiple disease states. When accompanied by a platelet count, hematocrit, and a thorough investigation of family or personal history of bleeding, the bleeding time is the best predictor of hemorrhagic risk in patients with kidney disease. Because there is a small but significant risk of bleeding with percutaneous kidney biopsy, a prolonged bleeding time should be treated with 1-deamino-8-D-arginine vasopressin, cryoprecipitate, estrogens, or dialysis as indicated before biopsy. Treating all patients with 1-deamino-8-D-arginine vasopressin without checking bleeding times may be cost-ineffective when compared with treating only those patients with prolonged bleeding times.

Biopsy↗
PubMed1989

Correlation between template bleeding times and spontaneous bleeding during treatment of acute myocardial infarction with recombinant tissue-type plasminogen activator.

The purpose of this study was to correlate bleeding complications during and after treatment with recombinant tissue-type plasminogen activator (rt-PA) with serial template bleeding time measurements, with ADP-induced platelet aggregation, with clinical characteristics, and with hemostatic parameters. Fifty-two of 55 consecutive patients with acute myocardial infarction and template bleeding times (Ivy method) of less than 9.5 minutes were treated with rt-PA in a total dose of 55-212 mg (mean, 109 mg) over 90 to 360 minutes (median, 240 minutes) combined with heparin. The mean bleeding time was significantly prolonged at 90 minutes (from 5.0 +/- 1.9 to 8.2 +/- 4.3 minutes, p less than 0.0001) but returned toward baseline after 4 hours (from a median of 8.0 to 7.0 minutes, p less than 0.05). Thirteen patients (25%) suffered relatively minor but spontaneous bleeding that did not correlate with age, hypertension, smoking, partial thromboplastin time, platelet count, ADP-induced platelet aggregation, steady-state rt-PA level, or extent of fibrinogen degradation. In multivariate analysis, only the 90-minute bleeding time correlated with spontaneous bleeding (p = 0.01). Prolongation of the 90-minute bleeding time to greater than or equal to 9 minutes, which occurred in 21 patients, correlated with spontaneous bleeding with a sensitivity of 69% (95% confidence interval, 39-90%) and a specificity of 69% (95% confidence interval, 52-83%). Retrospective analysis revealed that in 14 patients taking aspirin, the bleeding time at 90 minutes was significantly more prolonged (p less than 0.05) and spontaneous bleeding significantly more frequent (p less than 0.01) than in patients not taking aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1990

Non-occlusive bleeding times may improve the value of Ivy bleeding times.

The present studies measured bleeding times, without venous occlusion, in a series of patients, whose bleeding times (+ venostasis) consistently exceeded 20 min. During these tests, the amount of blood loss (expressed as mg/min) was also quantitated. To allow comparison, normal controls were studied before and following aspirin ingestion. In normal controls, the mean standard Ivy bleeding time was 5.0 with a range of 2.5 to 7.5 min. Two hours after aspirin (650 mg), this increased to 7.3 min (range 4.0-12.0). For comparison, the non-occlusive bleeding time averaged 3.8 min (1.0-6.5) and after aspirin 5.3 min (2.5-11.5). The measured amount of blood loss was 5.0 mg/min (0-10.5 mg/min) under all of the above conditions. At the other extreme, patients with severe bone marrow failure had occluded and non-occluded bleeding times in excess of 20 min. Moreover, these were often associated with excess blood loss. By contrast, patients with "Ivy" values greater than 20 min in association with platelet counts greater than 10,000/microliters had unpredictable bleeding parameters. In the latter group, the non-occluded values ranged from 1 to greater than 20 min. Of particular note, the non-occlusive times appeared to correlate with spontaneous bleeding manifestations. Only a rare patient (1/37), whose non-occluded value was less than 20 min, had worrisome bleeding. By contrast, serious bleeding manifestations were observed in 39% whose non-occluded value exceeded 20 min. This was even higher (64%) in those with a non-occluded value greater than 20 min and excess blood loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Arm↗
PubMed1994

The skin bleeding time test as a predictor of brain bleeding time in a rat model.

Previous studies have indicated that the skin bleeding time test does not accurately reflect visceral bleeding time (BT). The present study examines the predictive value of the skin bleeding time for brain bleeding tendency. Sixteen Sprague-Dawley rats were divided into equal groups. The first group (controls) underwent standardized skin and brain bleeding time tests under general anesthesia. Mean skin BT was found to be 168.8 sec with a standard deviation of +/- 20.8 sec. Mean brain BT was found to be 172.5 sec with a standard deviation of +/- 19.6 sec. The second group was given 23.2 mg/kg of aspirin per day for five days prior to skin and brain BT testing. Mean skin BT in this group was 315 seconds with a standard deviation of +/- 72.2 sec which proved to be significantly different from the control skin BT (P = 0.0005). Brain BT in the aspirin treated group was 155.6 sec with a standard deviation of +/- 22.6 sec. Brain BT in both control and aspirin treated groups was not significantly different (P = 0.13). All animals were euthanized 30 minutes after brain BT and their brains harvested. One animal in the control group showed evidence of a small subcortical hemorrhage upon brain sectioning. Sectioned brains in the aspirin-treated group showed no evidence of subcortical hematoma. The results indicate that skin BT is prolonged by aspirin administration, but brain bleeding time is unaffected. Brain hemostasis is likely more dependent on intrinsic procoagulant than platelet function. The skin BT test may therefore be of little utility as a preoperative screening test for neurosurgical patients.

Animals↗
PubMed1995

Beneficial effect of low-dose transdermal estrogen on bleeding time and clinical bleeding in uremia.

Patients with renal failure frequently manifest a hemorrhagic diathesis characterized by prolonged bleeding time (BT). Oral and intravenous estrogens have been shown to correct this abnormality, but both estrogens have real and potential disadvantages, especially for long-term use. We examined the effectiveness of transdermally applied 17 beta-estradiol on clinical bleeding and BT in renal failure patients. Six patients with renal insufficiency and prolonged BT were included in the study. Four patients had recurring gastrointestinal bleeding from telangiectasias. Two patients anticipated percutaneous renal biopsy. Transdermal estradiol 50 or 100 micrograms/24 hr was applied every 3.5 days for a period of 2 months. Bleeding times were measured just prior to estrogen administration (pre-estradiol) and again on cessation of clinical bleeding or prior to renal biopsy (post-estradiol). Differences were analyzed using a paired t-test. Erythrocyte transfusion requirement 2 months before and 2 months after estradiol application also was observed. Hemorrhage in all four actively bleeding patients ceased or improved, as reflected by the reduced need for transfusion. Bleeding time improved significantly (P = 0.008) when comparing before (day 0) with after (days 1 to 17) estradiol application. No adverse reactions associated with estradiol occurred over 2 months of therapy. In conclusion, transdermal application of 17 beta-estradiol is a safe and effective means to reduce BT and clinical hemorrhage in patients with renal failure and prolonged BT.

Administration, Cutaneous↗
PubMed1984

Prolonged bleeding time.

The bleeding time is the most frequently used test of platelet function. This review of the literature relating to the bleeding time outlines the causes and management of prolonged bleeding time. The bleeding time appears to have its greatest utility in evaluation of a patient with active bleeding or one with a well-documented bleeding history. It should not be used as a substitute for a clinical history, since there is insufficient information available to calculate its sensitivity, specificity, or predictive value with regard to peri- or postoperative hemorrhage.

Aspirin↗
PubMed1986

Effect of alternate-day regular and enteric-coated aspirin on platelet aggregation, bleeding time, and thromboxane A2 levels in bleeding-time blood.

The effectiveness of low-dose aspirin for primary prevention of cardiovascular mortality is being assessed among the nearly 22,000 United States physicians currently participating in the Physicians' Health Study. Because of occasional reports of gastric irritation among study participants, two enteric-coated aspirin preparations were tested as possible alternatives to regular compressed aspirin for platelet inhibition. Thirty-three volunteers were assigned randomly to one of four treatment groups: regular aspirin (325 mg), placebo, and two enteric-coated aspirin preparations (325 mg). Pills were administered every other day, duplicating the regimen used in the Physicians' Health Study. Bleeding times, platelet aggregation, and thromboxane A2 levels produced by aggregating platelets in vitro, as well as in collected bleeding-time blood, were determined. Measurements were taken before and after a single dose as well as after seven alternate-day doses. Regular and enteric-coated aspirin preparations were equally efficacious in prolonging the bleeding time, inhibiting platelet aggregation, and suppressing thromboxane A2 production. There was virtually complete suppression of thromboxane A2 production (over 99 percent), by platelets in vitro and in collected bleeding-time blood. The levels were still profoundly reduced (89 percent) 48 hours after the last dose. Enteric-coated aspirin may provide an alternative to regular aspirin in a low-dose regimen designed to inhibit platelet activity.

Adult↗
PubMed1998

Interobserver Reproducibility and Biological Variability of the Surgicutt II Bleeding Time.

The bleeding time is a readily and easily performed clinical test with immediate results, but there is a degree of subjectivity in its performance and interpretation. We performed a study on 27 volunteers designed to determine the normal range, interobserver reproducibility, and biological variability of the test. Bleeding times in these normal subjects ranged from as low as 129 seconds to as high as 803 seconds. The interobserver variability was 106 seconds (2 standard deviations of the mean of the differences of paired results of repeated measurements), and the coefficient of variation was 18%. For bleeding times taken on the same subjects 6 weeks apart, when the same nurse performed the test at both visits, the difference was 150 seconds (2 standard deviations of the mean of the differences of paired samples) and the coefficient of variation was 27%, and they were essentially the same if a different nurse performed the tests at each visit. There is a wide range in the bleeding times among subjects. However, within individuals there is little biological variability, and most of the difference over time is due to interobserver variability. This suggests that changes in bleeding time are clinically useful in predicting platelet responsiveness in individual patients.

Journal Article↗
PubMed1990

Oral estrogens decrease bleeding time and improve clinical bleeding in patients with renal failure.

PURPOSE: A prolonged bleeding time is associated with platelet dysfunction and clinical bleeding in patients with renal failure. Parenteral estrogens have been shown to shorten the prolonged bleeding time in patients with chronic renal failure, although the mechanism of action is unknown. We conducted a study to evaluate the efficacy of oral conjugated estrogens in this setting. PATIENTS AND METHODS: Four patients with renal failure, prolonged bleeding time, and clinical bleeding were given 50 mg of conjugated estrogen (Premarin) daily. RESULTS: Bleeding time normalized in two cases and was reduced to less than 50% of the pretreatment value in one of the remaining two cases. Bleeding stopped in all patients within two days. Ten dialysis patients with prolonged bleeding time were randomized to a course of 50 mg of Premarin daily or placebo. The bleeding time in all five patients in the Premarin group normalized or decreased to below 50% of the pretreatment value after 7.0 +/- 4.2 days of therapy. The bleeding time did not normalize in the five patients treated with placebo. No side effects attributable to therapy were reported. CONCLUSION: We conclude that orally administered conjugated estrogens effectively improve the bleeding tendency in patients with chronic renal failure.

Administration, Oral↗
PubMed1993

New bleeding time devices with retractable blades evaluated in children, healthy volunteers and patients with prolonged bleeding time.

The Simplate II-R and the Simplate Paediatric, are two new Simplate bleeding time devices with retractable blades. In this study we compared the Simplate II-R with the Simplate II bleeding time and found a good correlation when performed by the same technician both in 30 healthy volunteers and in 7 patients with prolonged bleeding time. The same normal ranges may be applied for the Simplate II-R as for the Simplate II bleeding time. The Simplate II-R bleeding time was highly reproducible in healthy volunteers when performed by the same technician. We found no correlation between age and bleeding time, and no significant difference in bleeding time between males and females. We performed the Simplate Paediatric bleeding time test and calculated the normal ranges in 84 healthy children in 4 age groups: 3 days, 3 months, 1 year and 3-6 years of age. The Simplate Paediatric bleeding times were shorter in the children than the Simplate II-R bleeding times in the adults. We found no significant correlation between bleeding time and the inverse platelet count, and no significant difference in bleeding time between boys and girls. The retractable blades in the Simplate II-R and the Simplate Paediatric reduce the risk of accidental cuts. Both devices yield reproducible bleeding time measurements and can be used instead of older Simplate variants.

Adult↗
PubMed1980

A sex difference in the bleeding time.

The bleeding time by a modified Ivy technique was estimated on 128 normal volunteers, 59 men and 69 women. The bleeding time was found to be significantly longer in women than men (p < .001). This was not attributable to a difference in platelet count nor to any detectable difference in platelet aggregability. It is likely that a difference in blood vessels or supporting tissues is responsible for the observed difference.

Adolescent↗
PubMedDate not supplied

Training anesthesia personnel to perform bleeding times.

Template bleeding time results generated by residents in anesthesiology correlate well with those obtained by trained laboratory personnel (p less than 0.002). Anesthesia personnel can accurately perform bleeding time tests when laboratory support is not available. The results of these tests can be used to guide clinical decisions.

Anesthesiology↗
PubMed1995

Low-dose aspirin in nulliparous women: safety of continuous epidural block and correlation between bleeding time and maternal-neonatal bleeding complications. National Institute of Child Health and Human Developmental Maternal-Fetal Medicine Network.

OBJECTIVE: Our purpose was to determine the frequency and safety of the use of epidural anesthesia and the correlation between bleeding time and maternal-neonatal bleeding complications in a group of pregnant women who participated in a multicenter trial of low-dose aspirin in pregnancy. STUDY DESIGN: Data regarding type of anesthesia used for labor and delivery were available in 1629 nulliparous women who were randomly assigned at 13 to 27 weeks to receive 60 mg/day aspirin or a placebo. A total of 891 (55%) received epidural anesthesia, and the remaining 738 did not. RESULTS: Among the 891 women known to have received epidural anesthesia, 451 were assigned to low-dose aspirin and 440 to placebo. There was no instance of bleeding related to epidural use. In addition, there were no differences in maternal and neonatal complications between those receiving or not receiving epidural anesthesia. Within the group receiving epidural anesthesia there were no differences in bleeding complications between those assigned to aspirin on placebo. One of the five centers also obtained bleeding times in 303 women (149 received aspirin and 154 received placebo). The mean +/- SD bleeding time in women assigned to low-dose aspirin was significantly higher than in women assigned to placebo (6.99 +/- 2.95 minutes vs 5.99 +/- 2.43 minutes, p = 0.004). In addition, the frequency of women having a bleeding time > 10 minutes was higher in the aspirin group (14.1% vs 5.2%, p = 0.01). Interestingly, women who received an epidural anesthetic had a lower bleeding time than those not receiving an epidural (p = 0.003), irrespective of the treatment used. CONCLUSIONS: In women assigned to low-dose aspirin there were no adverse effects related to epidural anesthesia. In spite of an increased bleeding time in a subset of pregnant women assigned to low-dose aspirin, maternal-neonatal bleeding complications were not increased.

Analysis of Variance↗
PubMed1997

A method for measuring capillary bleeding time in non-anaesthetized dogs: prolongation of the bleeding time by acetylsalicylic acid.

A reproducible standardized method for measuring capillary bleeding time (CBT) in dogs is presented. The skin was punctured at the toe from a forelimb of non-anaesthetized dogs parallel to the edge of the horny skin of the pad. Before the procedure, a cuff of a sphygmometer was placed above the antibrachium and a hyperaemie agent was applied to the shaved area. The normal CBT in non-anaesthetized dogs was 2.25 +/- 0.76 min (x +/- SD). After injection of acetylsalicylic acid (ASA) (20 mg/kg body weight), CBT was prolonged up to 25 min. Platelet aggregation in response to 10 micrograms collagen/ml was decreased in parallel after treatment with ASA.

Animals↗
PubMed1996

Bleeding time does not predict gastrointestinal bleeding in patients with cirrhosis. The CALC Group. Coagulation Abnormalities in Liver Cirrhosis.

BACKGROUND/AIMS: Bleeding time, a laboratory test which explores primary hemostasis, may be prolonged in cirrhosis, but whether abnormal bleeding time identifies patients with cirrhosis who are at risk of bleeding has never been investigated. The aim of this study was to analyze the relationship between bleeding time and the risk of gastrointestinal bleeding. METHODS: Eighty consecutive patients with liver cirrhosis (47 males, 33 females; age, 60 +/- 9 years; range 31 to 83 years) and esophageal varices were enrolled in the study. RESULTS: In the whole series of patients bleeding time was 11 +/- 6 min; it increased as the degree of liver deficiency increased, from low to severe (p = 0.007). During 14 +/- 9 (median (range): 12 (1-34) months of follow-up, 28 (35%) patients experienced gastrointestinal bleeding. They had a longer bleeding time, higher incidence of previous bleeding, more severe liver failure and larger variceal size than patients who did not bleed. However, multivariate analysis (Cox's model) showed that only previous bleeding, liver failure and variceal size were independently associated with bleeding. Similar data were obtained in patients with moderate-severe liver insufficiency (B and C degree according to Child-Pugh's classification). In patients who had never bled (n = 54), the severity of liver failure and variceal size were independent predictors of bleeding. CONCLUSIONS: This study shows that bleeding time is not a predictor of gastrointestinal bleeding in patients with cirrhosis.

Adult↗