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PubMed1994

Bleeding time and bleeding: an analysis of the relationship of the bleeding time test with parameters of surgical bleeding.

The bleeding time is currently the only clinically available comprehensive test to explore primary hemostasis. It is currently performed mostly as a screening procedure before surgery, to detect otherwise unknown defects in platelet-vessel wall interactions, but its use in this specific setting has been seriously questioned by recent reanalyses of previously published literature. We studied the relationship of the bleeding time from a standardized cutaneous incision with other parameters of bleeding derived from the analysis of the bleeding time curve and prospectively investigated possible correlations of these alternative parameters, as well as of the bleeding time, with a number of indices of actual bleeding during or after coronary bypass surgery. Four parameters (bleeding time, total bleeding, peak bleeding rate, and time to peak bleeding) were derived from the analysis of bleeding time curves measuring blood losses from a standardized cutaneous incision at 30-second intervals in 118 subjects. Parameters from the bleeding time curve were subsequently obtained in duplicate as a preoperative assessment in 40 patients with a negative bleeding history and no recent intake of non-steroidal anti-inflammatory drugs who were undergoing elective pure coronary bypass surgery performed by the same operator. These parameters were correlated in simple linear regression analysis with estimates of surgical bleeding (chest tube drainage, transfusion requirements, percentage of hematocrit, percentage of platelet level decrease, and times to hematocrit and platelet level nadir) and then, in multiple regression analysis, with indices of operation complexity (number of bypasses, total duration of the operation, and duration of the extracorporeal circulation). Bleeding time was significantly correlated, among parameters derived from the bleeding time curve, with total bleeding and peak bleeding rate, but not with time to peak bleeding. Bleeding time, total bleeding, and peak bleeding rate were similarly affected by acute interventions with intravenous aspirin (500 mg) and sublingual nitroglycerin (0.3 mg). None of these parameters, which were obtained in duplicate in each patient preoperatively, was significantly related to actual indices of bleeding at surgery. Thus, in patients with a negative history of bleeding and no recent intake of non-steroidal anti-inflammatory drugs, higher values for bleeding time and bleeding time-related parameters are not associated with higher indices of perioperative and postoperative bleeding at coronary bypass surgery. Therefore, we do not recommend the use of the test in this setting to predict perioperative or postoperative bleeding.

Aspirin↗
PubMed2006

Comparison of bleeding in patients with nonvalvular atrial fibrillation treated with ximelagatran or warfarin: assessment of incidence, case-fatality rate, time course and sites of bleeding, and risk factors for bleeding.

BACKGROUND: Ximelagatran is a novel direct thrombin inhibitor that can be administered as a fixed oral dose, without the need for anticoagulant monitoring. METHODS: We undertook a pooled analysis of 7329 patients with nonvalvular atrial fibrillation from the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation III and V trials to compare bleeding outcomes in patients who received ximelagatran, 36 mg twice daily, or warfarin sodium (target international normalized ratio, 2.0-3.0). We determined annual risk of bleeding (any, major), case-fatality rate, time course and anatomic sites of major bleeding, and risk factors for major bleeding with ximelagatran and warfarin treatment. RESULTS: Annual incidence of any bleeding was 31.75% with ximelagatran and 38.82% with warfarin (relative risk reduction, 18.2%; 95% confidence interval [CI], 13.0-23.1; P<.001). Annual incidence of major bleeding was 2.01% with ximelagatran and 2.68% with warfarin (relative risk reduction, 25.1%; 95% CI, 3.2-42.1; P = .03). Case-fatality rate of bleeding was comparable in ximelagatran- and warfarin-treated patients (8.16% vs 8.09%; P = .98). Cumulative incidence of major bleeding was higher with warfarin than ximelagatran after 24 months of treatment (4.7% vs 3.7%; P = .04). Anatomic sites of bleeding were comparable with both treatments. Risk factors for bleeding with ximelagatran were as follows (hazard ratios and 95% CIs in parentheses): diabetes mellitus (1.81; 1.19-2.77; P = .006), previous stroke or transient ischemic attack (1.78; 1.16-2.73; P = .008), age 75 years or greater (1.70; 1.33-2.18; P<.001), and aspirin use (1.68; 1.08-2.59; P = .02). Risk factors for bleeding in warfarin-treated patients were previous liver disease (4.88; 1.55-15.39; P = .007); aspirin use (2.41; 1.69-3.43; P<.001); and age 75 years or greater (1.26; 1.03-1.52; P = .02). CONCLUSIONS: Treatment with ximelagatran, 36 mg twice daily, is associated with a lower risk of bleeding than warfarin in patients with nonvalvular atrial fibrillation. Aspirin use and increasing age were associated with an increased risk of bleeding in ximelagatran- and warfarin-treated patients.

Adolescent↗
PubMed1989

A reassessment of the bleeding time: association of age, hematocrit, platelet function, von Willebrand factor, and bleeding time thromboxane B2 with the length of the bleeding time.

In order to provide an overview of the relative contribution of platelet, von Willebrand factor, and other abnormalities to patients with clinical bleeding difficulties, we performed a retrospective survey of coagulation studies on 569 individuals referred to the University of Manitoba coagulation laboratory because they, or a closely related family member, showed clinical evidence of a bleeding disorder. There was a highly significant (p less than 0.001) negative correlation between the bleeding time and each of the following parameters: the platelet count; the hematocrit; the percent aggregation to collagen, epinephrine, ADP, and arachidonic acid; and the logarithm of von Willebrand factor antigen and a measure of its activity (ristocetin cofactor). A significant and independent inverse relationship between the length of the bleeding time and the extent of platelet adhesion to glass beads, patient age, and prothrombin consumption were also observed. Multivariate analysis of the ability of all parameters to predict the bleeding time showed an r2 of only 0.33. Bleeding time thromboxane B2, in a second smaller study of 70 patients, showed a negative correlation with the length of the bleeding time (p = 0.0001), and, when used together with the above parameters, significantly enhanced the ability to predict the length of the bleeding time (r2 = 0.55). Defects in platelet function, as measured in vitro, and significant enough to have an effect on the bleeding time, occurred with greater frequency than defects in von Willebrand factor in the Manitoba patients evaluated.

Adolescent↗
PubMed1988

"Haemostasis time", a modified bleeding time test and its comparison with the Duke and Ivy/template bleeding times. II. Application in bleeding disorders.

"Haemostasis time" (HT), the occlusion time of a Butterfly 25 short cannula inserted into the cubital vein, is a bleeding time modification comparable to the skin bleeding times according to Duke and Ivy/Mielke. It also measures platelet function and is not influenced more than the latter tests by clotting factors. In HT, subendothelium is replaced by a standard artificial surface. The technique was investigated in patients with haemophilia A and B, von Willebrand's disease (vWD), and defects of factors VII and XI. HT was prolonged in 9/16 patients with haemophilia A/B, but did not correlate with the factor VIII:C/IX:C values. However, it reflected the different bleeding tendencies in those patients as represented by early or late onset of bleeding symptoms and occurrence of spontaneous haemarthroses. Of the vWD patients, not classified by multimeric analysis, 15/31 had prolonged Simplate II bleeding times, 14/31 prolonged HTs. Only 20/31 patients had corresponding normal or prolonged bleeding times with both techniques. HT correlated significantly with the Duke bleeding time (p = 0.011), ristocetin cofactor activity (p = 0.003) and von Willebrand factor antigen (p = 0.022), while no correlations were found between these parameters and the Simplate II method. Statistical evaluation shows, that in vWD, HT can replace the less precise Duke bleeding time but not the non-related Ivy/Simplate techniques.

Adolescent↗
PubMed2000

Antifibrinolytics for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is an important cause of ill health in women. Medical therapy, with the avoidance of possibly unnecessary surgery, is an attractive treatment option. A wide variety of medications are available to reduce heavy menstrual bleeding but there is considerable variation in practice and uncertainty about the most appropriate therapy. Plasminogen activators are a group of enzymes that cause fibrinolysis (the dissolution of clots). An increase in the levels of plasminogen activators has been found in the endometrium of women with heavy menstrual bleeding compared to those with normal menstrual loss. Plasminogen activator inhibitors (antifibrinolytic agents) have therefore been promoted as a treatment for heavy menstrual bleeding. There has been a reluctance to prescribe tranexamic acid due to possible side effects of the drugs such as an increased risk of thrombogenic disease (deep venous thrombosis). Long term studies in Sweden, however, have shown that the rate of incidence of thrombosis in women treated with tranexamic acid is comparable with the spontaneous frequency of thrombosis in women. OBJECTIVES: To determine the effectiveness of antifibrinolytics in achieving a reduction in heavy menstrual bleeding. SEARCH STRATEGY: All studies which might describe randomised controlled trials of antifibrinolytic therapy for the treatment of heavy menstrual bleeding were obtained by electronic searches of the MEDLINE 1966-1997, EMBASE 1980-1997 and the Cochrane Library. Companies producing antifibrinolytics and experts within the field were contacted for reference lists and information on unpublished trials. SELECTION CRITERIA: Randomised controlled trials in women of reproductive age treated with antifibrinolytic agents versus placebo, no treatment or any other medical (non-surgical) therapy for regular heavy menstrual bleeding within either the primary, family planning or specialist clinic settings. Women with post menopausal bleeding, intermenstrual bleeding, iatrogenic or pathological causes of heavy menstrual bleeding were excluded. DATA COLLECTION AND ANALYSIS: Fifteen eligible trials were assessed by three reviewers and eight of these did not meet with the inclusion criteria. Of the seven remaining trials, four of these could be included within the meta-analysis. The remaining three trials had a crossover design and despite contacting the authors and appropriate companies, we were unable to extract the results in a format suitable to include these within the meta-analysis. However the results are included within the text of the review for discussion. MAIN RESULTS: Antifibrinolytic therapy compared to placebo showed a significant reduction in mean blood loss (WMD -94.0 [-151.4, -36.5]) and significant change in mean reduction of blood loss (WMD -110.2 [-146. 5, -73.8]). This objective improvement was not mirrored by a patient perceived improvement in monthly menstrual blood loss (RR 2.5 [0.9, 7.3]) in the one study which recorded this outcome ( approximately approximately Edlund 1995 approximately approximately ). Antifibrinolytic agents were compared to only three other medical (non-surgical) therapies: mefenamic acid, norethisterone administered in the luteal phase and ethamsylate. In all instances, there was a significant reduction in mean blood loss (WMD -73.0 [-123.4, -22.6], WMD -111.0 [-178.5, -43.5] and (WMD -100 [-143.9, -56.1] respectively) and a strong, although non-significant trend in favour of tranexamic acid in the participants' perception of an improvement in menstrual blood loss. There were no significant differences in the frequency of reported gastrointestinal side effects with tranexamic acid when compared to either NSAIDs (RR 0.9 [0.4, 2.1], oral luteal phase progestagens (RR 0.4 [0.1, 1.2]) or ethamsylate (RR 0.88 [0.3, 2.9]) when these treatments were used for heavy menstrual bleeding. (ABSTRACT TRUNCATED)

Antifibrinolytic Agents↗
PubMed2003

Acute small bowel bleeding: a distinct entity with significantly different economic implications compared with GI bleeding from other locations.

BACKGROUND: Historically, acute lower intestinal bleeding has incorporated small bowel with colonic sources. This potentially obscures the unique characteristics of small bowel bleeding, which are eclipsed by the attributes of the much more common colonic bleeding. Separating acute lower intestinal bleeding into small bowel and colonic sources may delineate characteristics of each, thereby making it possible to determine whether clinical outcomes vary by anatomic level of bleeding. METHODS: A total of 29 consecutive patients (15 women, 14 men; age 68.6 +/-2.4 years) with acute small bowel bleeding were compared with two other groups, each with 29 consecutive patients, with either acute colonic bleeding or acute upper GI bleeding. Clinical presentation, outcomes, and resource utilization for small bowel bleeding were compared with similar parameters for acute colonic bleeding and upper GI bleeding. RESULTS: Although the clinical presentation did not always distinguish the 3 groups, resource utilization was significantly higher in the small bowel bleeding group. The latter group required a higher number of diagnostic procedures (p < 0.001) and blood transfusions (p < 0.001), remained in hospital longer (p < 0.05), and had a higher cost of hospitalization (p < 0.001) compared with the colonic bleeding and upper GI bleeding groups. The mortality rate for patients with small bowel bleeding was 10%. Although none of the patients with upper GI bleeding and only 14% of those with colonic bleeding required greater than 3 diagnostic procedures, 79% of patients with small bowel bleeding required 4 procedures for diagnostic localization (p < 0.0001). CONCLUSIONS: Small bowel bleeding ("mid-intestinal bleeding") is a distinct clinical entity with significantly worse outcomes compared with colonic bleeding and upper GI bleeding. The focus of the investigation should be directed to the small bowel, with enteroscopy or capsule endoscopy, when 3 investigative procedures fail to localize recurrent overt GI bleeding.

Acute Disease↗
PubMedDate not supplied

Heavy bacterial loads of H. pylori may precipitate duodenal ulcer bleeding but not bleeding severity.

BACKGROUND/AIMS: To determine whether severity of Helicobacter pylori (H. pylori) infection is aggravated during acute duodenal ulcer bleeding and related to bleeding severity. METHODOLOGY: One hundred and thirty-eight patients with H. pylori-infected bleeding duodenal ulcer and 112 non-bleeding cases were included in the study. A comparison was made of the anti-H. pylori IgG titer, endoscopic finding, density of H. pylori (range: 1-5) in the antrum, and severity of antral gastritis (score: 0-3) between bleeding and non-bleeding cases. The role of H. pylori in bleeding cases was further analyzed to survey its relationship to the severity of bleeding judged by clinical parameters. The H. pylori status of patients with rebleeding within the first week was compared to that of the non-rebleeding cases as well. RESULTS: The anti-H. pylori IgG titer and H. pylori density of the non-bleeding group were lower than those of the bleeding group (0.466+/-0.288 vs. 0.912+/-0.559, p<0.001; 2.13+/-1.02 vs. 3.34+/-1.32, p<0.001). The percentages of bleeding ulcers in the study cases increased in a trend as the density of H. pylori increased (density: 1-5; 32.7%, 33.8%, 57.4%, 81.3%, 91.4%, p<0.001). Although the severity of gastritis and density of H. pylori disclosed an upward trend as bleeding severity increased, only ulcer size was significantly associated with bleeding severity (p<0.05). The 10 cases with recurrent bleeding had higher bacterial density and serological titer than the 128 non-rebleeding cases (p<0.005). CONCLUSIONS: Heavy bacterial loads of H. pylori infection may precipitate bleeding episodes of duodenal ulcer. However, in bleeding duodenal ulcer, the status of H. pylori infection is not strongly associated with initial bleeding severity before therapeutic endoscopy. With the aim of enhancing hemostasis and preventing rebleeding, further studies could focus on diminishing the bacterial load of H. pylori during bleeding episodes.

Adult↗
PubMed1990

A bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting anticoagulant therapy.

PURPOSE: To construct and test prospectively a bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting long-term anticoagulant therapy. PATIENTS AND METHODS: In an inception cohort of 617 patients starting long-term anticoagulant therapy in one hospital, data were gathered retrospectively and bleeding was classified using reliable explicit criteria. We constructed a bleeding risk index by identifying and weighting independent predictors of major bleeding using a multivariate proportional-hazards model. The bleeding risk index was tested in 394 other patients prospectively identified in a second hospital. The index was compared to physicians' predictions. RESULTS: Major bleeding developed before discharge in 61 of all 1,011 patients (6%). The bleeding risk index included four independent risk factors for major in-hospital bleeding: the number of specific comorbid conditions; heparin use in patients aged 60 years or older; maximal prothrombin or partial thromboplastin time 2.0 or more times control; liver dysfunction worsening during therapy. In the testing group, the index predicted major bleeding, which occurred in 3% of 235 low-risk patients, 16% of 96 middle-risk patients, and 19% of 63 high-risk patients (p less than 0.001). The bleeding risk index performed as well as physicians' predictions, and integration of the bleeding risk index with physicians' predictions led to a classification system that was more sensitive (p = 0.03) than physicians' predictions alone. In 86% of patients with a high risk of major bleeding, we identified specific ways of improving therapy, e.g., avoiding overanticoagulation and nonsteroidal anti-inflammatory agents. CONCLUSION: The bleeding risk index provides valid estimates of the probability of major bleeding in hospitalized patients starting long-term anticoagulant therapy and complements physicians' predictions. The possibility that bleeding can be prevented in high-risk patients warrants prospective evaluation.

Aged↗
PubMed2001

Nonlocalized lower gastrointestinal bleeding: provocative bleeding studies with intraarterial tPA, heparin, and tolazoline.

PURPOSE: The purpose of this study was to assess the efficacy and safety of provocative mesenteric angiography with tissue plasminogen activator (tPA), heparin, and tolazoline in patients with nonlocalized lower gastrointestinal (LGI) bleeding. Results were examined to assess the clinical impact of the study on patients who had positive or negative results from elective provocative bleeding studies. MATERIALS AND METHODS: Seventeen provocative bleeding studies for occult LGI bleeding were performed in 16 patients, nine of whom were women, aged 44-79 years. All patients had negative results from previous endoscopic and angiographic studies. Patients' requirements for blood transfusion ranged from 6 to 69 units. Studies were performed electively. Blood group matching and cross-matching were performed for all patients. To provoke bleeding, a combination of intravenous heparin, intraarterial tolazoline, and intraarterial tPA was used. Doses used included 3,000-10,000 U heparin, 25-100 mg intraarterial tolazoline, and 10-50 mg intraarterial tPA (mean, 20.3 mg). Duration of follow-up was 3-34 months. RESULTS: Seventeen elective provocative studies were performed in 16 patients with occult LGI bleeding, leading to provoked bleeding in six patients (37.5%). In addition, two previously undiagnosed vascular abnormalities were diagnosed, which did not bleed during provocation. Therefore, an abnormality was identified in eight of 16 patients (50%) overall. There were no procedural complications encountered during or after any of the 17 procedures. In six patients in whom bleeding was successfully provoked, four bleeding episodes occurred in the large bowel and two occurred in the small bowel. Five of the positively provoked patients had a previously positive tagged red cell scintigraphic study. Three patients had superselective embolization at the time of provoked bleeding. Two were treated with estrogen therapy, and one patient was treated palliatively. Five of these six patients required no further therapy for LGI bleeding. Ten patients (including two with vascular abnormalities) did not bleed during the provoked study with tPA. Follow-up of the group of eight patients with completely normal study results ranged from 3 to 34 months in duration, and during the follow-up period, five patients experienced repeated bleeding and one had no further bleeding. One patient was diagnosed with an ileal vascular lesion during subsequent intraoperative enteroscopy and underwent surgical resection. One patient was lost to follow-up. CONCLUSION: Intraarterial provocative mesenteric angiography with heparin, vasodilator, and tPA identified the site of bleeding in 37.5% of patients in our study group and contributed to treatment in 50%. This small study indicates that the procedure appears to be safe, with no complications encountered in this series. Larger prospective studies are needed to fully assess the safety and efficacy of the technique and to optimize the pharmacologic protocol and patient selection.

Adult↗
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↗
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↗
PubMed2004

Patterns of bleeding after endoscopic sphincterotomy, the subsequent risk of bleeding, and the role of epinephrine injection.

BACKGROUND: The patterns of bleeding following endoscopic sphincterotomy (ES) and their predictive value for subsequent bleeding are poorly understood. Similarly, the efficacy and side effects of epinephrine (E) injection for persistent bleeding have not been well studied. METHODS: Over a 44-month period, all patients undergoing ES were prospectively assessed and followed-up. The character of bleeding (pulsatile, oozing, trickle, none) was recorded immediately, 5 minutes following ES and at the completion of the procedure. Patients with persistent bleeding at the time the procedure was completed (5 minutes or greater) received E injection(s) (1:10,000 concentrations) into the bleeding point with a sclerotherapy needle. ES was performed in all patients with a single electrosurgical generator Valleylab (Force 1B) using pure cutting current. RESULTS: 506 patients (68% females, mean age 54 years) who underwent 550 ES were studied. Bleeding patterns immediately following ES were: 6% pulsatile, 42% oozing, 27% trickle, and 24% none. E (median 0.5 cc; range 0.5-4 cc total) was injected during 79 procedures (14%); none of these patients had complications nor delayed bleeding. For all patients, delayed bleeding occurred in 8 (1.6%, 95% CI 0.57-0.0269); of these 8 delayed bleeders, 1 had no bleeding after ES, and only 1 had any bleeding at 5 minutes. The only variable associated with bleeding after ES was abnormal labs (thrombocytopenia, elevated creatinine concentration, hypoprothrombinemia). CONCLUSIONS: The pattern of bleeding following ES may not predict the risk of late bleeding. Abnormal labs are associated with visible bleeding. Epinephrine injection is safe and appears to provide effective hemostasis.

Adult↗
PubMed1987

Bleeding rates necessary for detecting acute gastrointestinal bleeding with technetium-99m-labeled red blood cells in an experimental model.

Proponents of [99mTc]sulfur colloid for GI bleeding studies argue that, although labeled red blood cells are useful for intermittent bleeding, they are not capable of detecting low bleeding rates. Studies of dogs with experimental GI bleeding have indicated bleeding rates of 0.05 ml/min can be detected with [99mTc]sulfur colloid. Since similar data in the dog model were unavailable for 99mTc-labeled red blood cells, we undertook this study. To simulate lower GI bleeding, catheters were inserted into the bowel lumen. Each dog's blood was labeled with 99mTc using an in vitro technique. Venous blood was then withdrawn and re-infused into the lumen of the bowel using a Harvard pump. Fourteen dogs were studied, ten receiving a bleeding rate from 4.6-0.02 ml/min in the descending colon and four with proximal jejunal bleeds of 0.20-0.02 ml/min. Bleeding rates of 4.6-0.2 ml/min were detected within 10 min in the colon and bleeding rates as low as 0.04 ml/min were seen by 55 min. Slower bleeding rates were not detected. Similar findings were noted for proximal jejunal bleeds. Based on the time of appearance, a minimum volume of approximately 2-3 ml labeled blood was necessary to detect bleeding. We conclude that 99mTc-labeled RBCs are sensitive for low bleeding rates in the dog model. The rates are comparable to those described for [99mTc]sulfur colloid in this experimental setting. The time of appearance of activity is related to the bleeding rate.

Animals↗
PubMed1999

Increased bleeding associated with protease inhibitor therapy in HIV-positive patients with bleeding disorders.

The use of protease inhibitor (PI) drugs in treatment regimens for HIV-infected patients with hereditary bleeding disorders has been associated with an increased bleeding tendency. To characterize the nature of this bleeding tendency, a retrospective case record analysis was performed on 67 HIV-positive patients with hereditary bleeding disorders who had been treated with PI therapy. 34 patients (51%) developed an increased bleeding tendency on PI therapy, usually within the first few weeks of treatment. As well as an increase in usual joint bleeds, patients developed spontaneous atypical small joint, soft tissue and muscle bleeds. Haematuria was also common. Bleeding episodes tended to respond suboptimally to factor concentrate replacement. Ritonavir was most likely to be associated with bleeding. Nine patients switched first-line PI therapy as a direct consequence of bleeding and seven had no further bleeding problem on their second PI. Factor concentrate usage was significantly increased during the first 6 months of PI therapy compared to the 6 months preceeding treatment. PI therapy is frequently associated with increased bleeding in patients with hereditary bleeding disorders. The mechanism of the bleeding tendency remains to be elucidated.

Adolescent↗
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↗
PubMed1986

"Haemostasis time", a modified bleeding time test and its comparison with the Duke and Ivy/template bleeding times. I. Normal values, application in thrombocytopenic patients and evaluation of heparin and aspirin effects.

The occlusion time ("haemostasis time" - HT) of a thin, short cannula inserted into the cubital vein, was compared with the skin bleeding times of the Duke and Ivy/template techniques. 25 male and 25 female volunteers without a history of bleeding were divided into 5 equally large age groups ranging from 10 to over 50 years of age. They exhibited a range of 46 s-6 min 38 s (95% tolerance interval), while the Duke and Ivy/template bleeding times, which were simultaneously determined, corresponded to values given by other authors. HT is different from the skin bleeding times in that endothelium is replaced by a standard foreign surface which allows better standardization of the method. Similar results were obtained with HT compared to the skin bleeding times. These and a similar, non-significant heparin response with all three techniques suggest that HT is not more influenced by clotting factors than the Duke and Ivy/template bleeding times and, indeed, may be regarded as a bleeding time modification. HT, like both of the skin bleeding times, reflected lowered platelet counts and is even more sensitive in this respect. As tested in a group of 20 male and 20 female volunteers, HT showed a significant prolongation two hours after ingestion of 1 g aspirin. While male individuals exhibited longer bleeding times than females with the Ivy/template technique (sex-related difference p = 0.01), no male to female differences were found both with HT and the Duke bleeding time. HT is easy to perform, inexpensive, leaves no scars and is safe even for the patient with severe bleeding. Moreover, compared to the skin bleeding times, it permits a differential evaluation of vessel wall and tissue effects.

Adolescent↗
PubMed2001

Timing and volume of fluid administration for patients with bleeding following trauma.

BACKGROUND: Treatment of haemorrhagic shock involves maintaining blood pressure and tissue perfusion until bleeding is controlled. Different resuscitation strategies have been used to maintain the blood pressure in trauma patients until bleeding is controlled. However, while maintaining blood pressure may prevent shock, it may worsen bleeding. OBJECTIVES: To assess the effects of early versus delayed, and larger versus smaller volume of fluid administration in trauma patients with bleeding. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the specialised register of the Injuries Group, MEDLINE, EMBASE, the National Research Register and the Science Citation Index. We checked reference lists of identified articles and contacted authors and experts in the field. SELECTION CRITERIA: Randomised trials of the timing and volume of intravenous fluid administration in trauma patients with bleeding. Trials in which different types of intravenous fluid were compared were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: We did not combine the results quantitatively because the interventions and patient populations were so diverse. Early versus delayed fluid administration: Three trials reported mortality and two coagulation data. In the first trial (n=598) relative risk (RR) for death with early fluid administration was 1.26 (95% confidence interval of 1.00-1.58). The weighted mean differences (WMD) for prothrombin time and partial thromboplastin time were 2.7 (95% CI 0.9-4.5) and 4.3 (95% CI 1.74-6.9) seconds respectively. In the second trial (n=50) RR for death with early blood transfusion was 5.4 (95% CI 0.3-107.1). The WMD for partial thromboplastin time was 7.0 (95% CI 6.0-8.0) seconds. In the third trial (n=1309) RR for death with early fluid administration was 1.06 (95% CI 0.77-1.47). Larger versus smaller volume of fluid administration: Three trials reported mortality and one coagulation data. In the first trial (n=36) RR for death with a larger volume of fluid resuscitation was 0.80 (95% CI 0.28-22.29). Prothrombin time and Partial thromboplastin time were 14.8 and 47.3 seconds in those who received a larger volume of fluid as compared to 13.9 and 35.1 seconds in the comparison group. In the second trial (n=99) RR for death with a high (100 mm Hg) compared to low (70 mm Hg) systolic blood pressure resuscitation target was 1.02 (95% CI 0.27-3.85). In the third trial (n=25) there were no deaths. REVIEWER'S CONCLUSIONS: We found no evidence from randomised controlled trials to support early or larger volume of intravenous fluid administration in uncontrolled haemorrhage. There is continuing uncertainty about the best fluid administration strategy in bleeding trauma patients. Further randomised controlled trials are needed to establish the most effective fluid resuscitation strategy.

Hemorrhage↗
PubMed2004

Rectal bleeding after hypofractionated radiotherapy for prostate cancer: correlation between clinical and dosimetric parameters and the incidence of grade 2 or worse rectal bleeding.

PURPOSE: To investigate the incidence and severity of rectal bleeding after high-dose hypofractionated radiotherapy (RT) for prostate cancer, and to explore the factors affecting the incidence of Grade 2 or worse rectal bleeding. METHODS AND MATERIALS: The data of 52 patients who had been treated by external beam RT for localized prostate cancer between 1999 and 2002 were analyzed. All the patients had received hypofractionated external beam RT to a total dose of 69 Gy in 3-Gy fractions, three fractions weekly. The clinical and dosimetric factors affecting the incidence of Grade 2 or worse late rectal bleeding were analyzed by univariate and multivariate analyses. The effect of the percentage of the whole rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose (V(30), V(50), V(80), and V(90), respectively) on the incidence of rectal bleeding was evaluated. RESULTS: Of the 52 patients, 13 (25%) developed Grade 2 or worse rectal bleeding. One patient who needed laser coagulation and blood transfusion for the treatment of rectal bleeding was classified as having Grade 3 rectal bleeding. The median time to the development of Grade 2 or worse rectal bleeding was 11 months. The results of the univariate analysis revealed that the presence of a history of diabetes mellitus (p < 0.001), and V(30) >/= 60%, V(50) >/= 40% (p < 0.05), V(80) >/= 25%, and V(90) >/= 15% (p < 0.001) were statistically significant risk factors for the occurrence of Grade 2 or worse rectal bleeding. The results of the multivariate analysis revealed that a history of diabetes mellitus was the most statistically significant risk factor for the occurrence of rectal bleeding after hypofractionated RT for prostate cancer (p < 0.05). CONCLUSION: A history of diabetes mellitus was the most statistically significant risk factor for the occurrence of Grade 2 or worse rectal bleeding after high-dose hypofractionated RT, although dosimetric factors were also closely associated with the risk of rectal bleeding.

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