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Shortening of bleeding time by 1-deamino-8-D-arginine vasopressin in various bleeding disorders.

To evaluate the effect of 1-deamino-8-D-arginine vasopressin (DDAVP) in various bleeding disorders, 10 micrograms/m2 DDAVP was administered to subjects with von Willebrand disease (13), platelet function defects (12), von Willebrand disease and platelet defects together (8), or isolated prolongation of the bleeding time (5). DDAVP shortened the bleeding time similarly in all patient groups. Shortening of the bleeding time was also observed in 2 patients with aspirin-induced platelet defects and in 2 normal subjects. DDAVP administration was associated with falls in the platelet count, mean platelet volume, and partial thromboplastin time, and rises in platelet adhesion, factor VIII coagulant activity, factor VIII related antigen, and von Willebrand factor activity. The basal bleeding time was the only predictor of the magnitude of the bleeding-time correction. Normal haemostatis was achieved with DDAVP plus epsilon-aminocaproic acid and no blood product support during operations in 18 patients with bleeding disorders.

Adolescent↗

Synergistic shortening of the bleeding time by desmopressin and ethamsylate in patients with various constitutional bleeding disorders.

Desmopressin and ethamsylate were evaluated for possible synergistic effects on the bleeding time. The drugs were administered individually and together to 12 patients with markedly prolonged bleeding times known to be relatively or absolutely unresponsive to desmopressin alone. The bleeding disorders studied included Glanzmann's thrombasthenia (one), other disorders of platelet function (four), pseudo-von Willebrand disease (one), and von Willebrand disease type I (three), type II (two), and type III (one). Desmopressin alone shortened the bleeding time from 23.9 +/- 1.5 to 19.5 +/- 2.3 min (p = 0.03). Ethamsylate alone was without effect. Desmopressin and ethamsylate together shortened the bleeding time to 11.2 +/- 1.4 min (p less than 0.01 compared to baseline, p = 0.02 compared to desmopressin alone). The combination was ineffective in three patients, with Glanzmann's thrombasthenia (one), and von Willebrand disease type I (one) and type III (one). Toxic effects of the drugs were not observed. Five patients received desmopressin and ethamsylate prior to dental work with mandibular block (one), heart surgery requiring cardiopulmonary bypass (two), and adenotonsillectomy surgery (two). Normal hemostasis was achieved in each case. A synergistic shortening of the bleeding time was observed with the combination of desmopressin and ethamsylate in a wide range of bleeding disorders.

Adolescent↗

The outpatient bleeding risk index: validation of a tool for predicting bleeding rates in patients treated for deep venous thrombosis and pulmonary embolism.

BACKGROUND: Long-term anticoagulation prevents recurrent thrombosis in patients with idiopathic deep venous thrombosis or pulmonary embolism, but with a risk of clinically important so-called major bleeding. Physician- and patient-based decisions on the optimal duration of therapy are sensitive to the bleeding risk. The Outpatient Bleeding Risk Index potentially provides a means of calculating the potential risk of bleeding using easily elicited clinical findings, but, to our knowledge, the authors of the index have provided the only published validation of it. We sought to determine the accuracy of the index in our population of patients. METHODS: We prospectively applied the Outpatient Bleeding Risk Index to consecutive patients in our clinic who had been objectively diagnosed as having pulmonary embolism or deep venous thrombosis and who were about to undergo standard therapy. Standard therapy consisted of a minimum of 5 days of low-molecular-weight heparin therapy overlapped with warfarin sodium therapy, and continuation of warfarin therapy for at least 3 months, with a target international normalized ratio of 2.5. Patients were placed in 3 risk groups (low, moderate, or high), as defined by the index. The survival curves of the groups, using major hemorrhages as the events, were then compared by the log-rank test. RESULTS: Bleeding rates were lower than expected, but the index did discriminate between low- and moderate-risk groups (P =.03, log-rank test). The rate of major hemorrhage per 100 person-years was 0% (95% confidence interval, 0%-2.8%) in the low-risk group and 4.3% (95% confidence interval, 1.1%-11.1%) in the moderate-risk group. The rate in the high-risk group could not be defined because only 2 patients were at high risk. CONCLUSION: The Outpatient Bleeding Risk Index discriminates between low- and moderate-risk patients, and could be used to guide decisions on the optimal duration of anticoagulant therapy.

Aged↗

Hirudin causes more bleeding than heparin in a rabbit ear bleeding model.

This study was undertaken to determine the appropriateness of the current practice of using the activated partial thromboplastin time (APTT) to select hirudin doses. A rabbit bleeding ear model was used to compare the effects of various doses of heparin and hirudin on the relationship between the APTT and bleeding. In addition, the effects of these agents on the thrombin clotting time (TCT) and factor Xa clotting time also were examined. Both heparin and hirudin produced a concentration-dependent increase in bleeding. When bleeding was plotted as a function of APTT ratio, even a small increase in APTT ratio within the therapeutic range of 1.5 to 2.5 resulted in a marked increase in bleeding with hirudin but not with heparin. The TCT was more responsive than the APTT or factor Xa clotting time to increases in hirudin-induced bleeding. In this model, hirudin produces more bleeding than heparin when the agents are used in doses that increase the APTT ratio to the same extent. These studies highlight the pitfalls of extrapolating from experience with heparin when choosing a test to monitor new antithrombotics. Our findings also suggest that the TCT may be more responsive than the APTT for monitoring hirudin therapy.

Animals↗

Sequential subtraction scintigraphy with 99Tcm-RBC for the early detection of gastrointestinal bleeding and the calculation of bleeding rates: phantom and animal studies.

To improve the detectability of gastrointestinal (GI) bleeding, we have developed a new method, 'sequential subtraction scintigraphy' (SSS) with 99Tcm-labelled red blood cells (RBC). Sequential subtraction scintigrams were obtained by subtracting 5 min interval images from each other using a digital gamma camera. With this method, we are able to detect the bleeding site and calculate the bleeding rate earlier because of the lower background activity. The results of the present study demonstrate that the minimum detectable bleeding rate was 0.05 ml min-1 in both a phantom and an animal model. The minimum detectable activity volumes within 10 min were 0.5 ml by SSS and more that 3 ml by conventional non-subtraction scintigraphy (CNS). The bleeding rates calculated with the subtraction method correlated well with the actual syringe pump rates. The detectability of GI bleeding by SSS and CNS in animal models was compared using the area under receiver operator characteristic (ROC) curves. The results showed that SSS significantly increased the area under the ROC curves from 0.55 +/- 0.05 to 0.79 +/- 0.04 for the 10 min image set and from 0.65 +/- 0.05 to 0.83 +/- 0.04 for the 30 min image set (Z = 5.45, P < 0.0001 and Z = 4.36, P < 0.0001, respectively). These results suggest that sequential subtraction scintigraphy with 99Tcm-RBC is an effective method for the early detection of GI bleeding when compared with the conventional non-subtraction method.

Adult↗

Histometric analysis of infiltrated connective tissue in bleeding and non-bleeding gingivae after probing.

The present study was carried out to evaluate and compare the volumetric densities of subepithelial infiltrated connective tissue (ICT) geographically in bleeding and non-bleeding gingivae with special reference to comparisons of the relationships with their corresponding stereomicroscopic findings. A total of 51 biopsies (25 bleeding and 26 non-bleeding gingival specimens) was obtained from 33 patients. After stereomicroscopic examinations, tissue sections were obtained with H&E stain. On each section, the density of ICT was calculated by volumetric analysis. The results showed that the volume of ICT in bleeding-gingiva was significantly greater than that in non-bleeding gingiva. However, there was no specific relationship between the ICT of gingiva and the visibility of vasculature by stereomicroscopy. These results suggest that increased infiltrated inflammatory volumes of gingiva may play a role in the presenting of bleeding on clinical probing, but appear not to be related to the visibility of vasculature by stereomicroscopy.

Adult↗

Heparin assays and bleeding complications in treatment of deep venous thrombosis with particular reference to retroperitoneal bleeding.

Bleeding complications occurred in 30 (11%) out of 280 patients who received continuous heparin infusion for deep venous thrombosis (DVT). 22 (8%) had minor while 8 patients (3%) had major bleeding complications (1 intrathoracic [fatal], 2 gastrointestinal and 5 retroperitoneal). Heparin activity, in daily drawn blood samples, was determined by four assays (chromogenic substrate [CS] assay, activated partial thromboplastin time [APTT], thrombin time with citrated plasma [CiTT] and thrombin time with recalcified plasma [CaTT]). The differences in median heparin activity between patients with minor bleeding and patients with no bleeding did not reach significance for any of the tests. In patients with major bleeding, the differences were significant with the CS (p = .011) and the CaTT (p = .030) assays. Patients with retroperitoneal bleeding had significantly increased median activity judged by all four assays: CS (p = .002), CaTT (p = .003), APTT (p = .010), CiTT (p = .029). The difference was most pronounced after four days of heparin treatment, but there was a considerable overlap with patients without bleeding.

Adult↗

Bleeding time in uremia: a useful test to assess clinical bleeding.

Modified Ivy bleeding time (template) and platelet aggregation to ADP, epinephrine, and collagen were studied in 26 uremic patients who had not recently ingested anti-platelet drugs. Regardless of the aggregating agent used, the abnormalities in platelet aggregation were often mild, even with advanced uremia, and frequently less severe than the effects of common anti-platelet drugs. The inhibition of collagen-induced aggregation was significantly correlated with both increased bleeding time and blood urea nitrogen. Platelet aggregation was not discriminative between clinically bleeding and non-bleeding groups of patients, but the bleeding time was helpful in this regard. In certain cases, the aggregometric patterns differed between drug-induced and uremic thrombocytopathies. Platelet aggregometry appears to be of little help clinically in assessing the severity of the uremic bleeding diathesis.

Adenosine Diphosphate↗

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↗

Reversible prolonged skin bleeding time in acute gastrointestinal bleeding presumed due to NSAIDs.

The purpose of this research was to look for a possible mechanism whereby NSAIDs, and particularly ASA, might cause gastrointestinal bleeding. A total of 34 hospitalized GI bleeders and 29 age- and sex-matched controls were studied. Skin bleeding time (SBT) was measured within 6 h of coming to hospital and before any blood products were given. All patients and controls were questioned regarding current NSAID use. This history was supplemented by estimation of serum salicylate and of platelet cyclooxygenase activity to detect unreported current aspirin (ASA) use. Various aspects of platelet function were also tested by lumiaggregation in 28 controls and, after recovery, in 27 of the bleeders. Of 34 bleeders, 26 bled from the upper GI tract, (13 from peptic ulcer) and eight from the lower GI tract, 30 (88%) had a current intake of NSAIDs and of these 22 (73%) used ASA, some in combination with other NSAIDs, whereas 12 of 29 controls were using NSAID's, 11 of which were ASA. SBT in the bleeders was 9.0 +/- 1.02 min versus 4.8 +/- 0.42 min in the controls (p < 0.001). SBT measured 6.6 days later in 28 bleeders was 4.7 +/- 0.22 min (p < 0.0006), and of those tested after recovery all but one had fallen to 6.5 min or less. None had any residual constitutional platelet abnormalities as tested by lumiaggregation. By logistic regression, NSAID intake was strongly associated with prolonged SBT to > 6 min (odds ratio [OR], 16.7; p < 0.0002), whereas NSAID intake (OR 14.6; p < 0.0003) and SBT > 6 min (OR 1.8; p < 0.005) contributed to a bleeding outcome. Almost 90% of GI bleeders had recently consumed NSAIDs, mostly ASA, on an average 15 h before onset of bleeding. Although most of the nonbleeders who had used NSAIDs did not have a prolonged SBT, most of the bleeders who used NSAIDs had an abnormal elevation of SBT, suggesting a possible mechanism for GI bleeding. Retesting approximately 7 days after recovery from bleeding showed normalization of the SBT, indicating that the defect was transient and spontaneously reversible.

Acute Disease↗

Usefulness of the bleeding time to predict the risk of clinical bleeding in patients with uraemia.

In a prospective study of haemostatic status of 15 uraemic Nigerians a highly significant prolongation of bleeding time (p less than 0.001) and significantly lower haematocrit levels (p less than 0.001) were detected in comparison to healthy controls. A highly significant positive correlation (r = +0.778) between prolongation of bleeding time and blood urea was present. Six patients had overt clinical bleeding with significantly prolonged bleeding time (p less than 0.01) compared to uraemics without overt bleeding. Blood urea was significantly different in both groups (p greater than 0.1). Platelet count, prothrombin time, partial thromboplastin time and Hess tourniquet test did not differ between the uraemic patients and controls. Haemostatic dysfunction has been noted in Nigerian uraemics we studied. Bleeding time is a useful but simple means of assessing such dysfunction.

Adolescent↗

Bleeding time and concentrations of von Willebrand factor in patients with acute upper gastrointestinal bleeding.

OBJECTIVE: To evaluate the prevalence of impaired primary haemostasis in patients with acute upper gastrointestinal bleeding. DESIGN: Prospective open study. SETTING: County hospital, Sweden. SUBJECTS: 160 consecutive patients admitted with haematemesis or melaena, or both. INTERVENTIONS: Diagnosis verified on admission by endoscopy. Consumption of non-steroidal anti-inflammatory drugs (NSAID), transfusion requirements, presence of chronic liver disease, and age were recorded. MAIN OUTCOME MEASURES: Skin bleeding time was measured on admission with a modified Ivy method using the Simplate II bleeding time device; von Willebrand factor and routine haematological tests were analysed. RESULTS: In 31 of the patients (19%) the skin bleeding time was prolonged (over 10 minutes), and these patients also had a significantly lower packed cell volume on admission. In all patients the concentration of von Willebrand factor was increased which might explain why there was no significant difference in bleeding time between those who did and those who did not take NSAIDs. CONCLUSION: We recommend measurement of bleeding time in patients who present with haematemesis or melaena, or both, to detect those with impaired primary haemostasis.

Aged↗

Clinical performance and menstrual bleeding patterns with three dosage combinations of a Nestorone progestogen/ethinyl estradiol contraceptive vaginal ring used on a bleeding-signaled regimen.

OBJECTIVE: We examined the clinical performance of contraceptive vaginal rings (rings) delivering Nestorone (NES) progestin and ethinyl estradiol (EE). Ring removal times were signaled by menstrual events. Bleeding patterns, adverse events, patterns of use and continuation rates were the principal parameters evaluated. METHODS: In a two-stage 6-month trial, subjects were randomized to use rings releasing 50 microg/day of NES and either 10 (50/10) or 20 (50/20) microg/day of EE. Subjects were to keep rings continuously in situ until menstrual bleeding or prolonged spotting-signaled removal. Reinsertion was to occur 96 h later. After the randomized stage, an open-label 6-month trial of rings releasing 150 microg/day of NES and 15 microg/day of EE (150/15) began with the same menstrually signaled regimen. RESULTS: Two-hundred forty-six subjects participated in the trial. Six-month pregnancy rates ranged by ring dose from 1.3 to 3.9 per 100. For each ring dose combination, 6-month continuation rates were above 80 per 100. Bleeding and spotting (B+S) days in women with the 50 microg/day NES rings were similar in number to those experienced by cycling women not using contraception. Nevertheless, in the initial 90 days, fewer B+S days were reported by subjects with the 50/20 ring than by subjects with the 50/10 ring (p < .05). Throughout the trial, subjects using the 150/15 ring reported significantly fewer B+S episodes than did subjects with either 50 microg/day NES ring. CONCLUSION: Combined contraceptive rings used with a bleeding-signaled regimen led to few terminations attributed to bleeding problems and to acceptable continuation rates. The 150/15 ring appeared to induce fewer bleeding problems than did the lower-dose NES combination rings, but no important difference in 6-month continuation rates among the three doses was noted.

Adult↗

Hysteroscopy in women with abnormal uterine bleeding on hormone replacement therapy: a comparison with postmenopausal bleeding.

OBJECTIVE: To determine the role of outpatient diagnostic hysteroscopy in patients with abnormal uterine bleeding (AUB) on hormone replacement therapy (HRT) and to contrast this with a control group of women presenting with postmenopausal bleeding. DESIGN: Comparative observational study. SETTING: Outpatient hysteroscopy clinic in a university hospital. PATIENTS: Three hundred ten patients undergoing outpatient hysteroscopy. INTERVENTIONS: Outpatient diagnostic hysteroscopy with endometrial biopsy when indicated. MAIN OUTCOME MEASURES: Hysteroscopic findings, need for cervical dilatation and local anaesthesia, correlation between hysteroscopy and histologic diagnosis. RESULTS: There were 157 (7.1%) patients with AUB on HRT and another 153 (6.9%) with postmenopausal bleeding out of 2,203 outpatient hysteroscopies. Hysteroscopy was successful in 97% and 92% of patients, respectively, and intrauterine pathology was diagnosed in 46.7% and 39.7% of these cases. Functional endometrium was noted significantly more often with HRT and endometrial atrophy with postmenopausal bleeding. Overall, local anesthesia was used in 126 (40.6%) and shown to be associated significantly with the need for cervical dilatation. Endometrial biopsy was attempted in 125 (80%) and 119 (78%) patients in the study and control groups, but was unsuccessful significantly more often with postmenopausal bleeding (38.7%) versus 16%). There were six cases of endometrial carcinoma, all in the control group. CONCLUSION: There is a high incidence of intrauterine abnormalities in women with menstrual symptoms while taking HRT, but the pathology differed from those with postmenopausal bleeding. As focal lesions are found commonly in such patients, their detection by diagnostic hysteroscopy should improve compliance with HRT as it would allow individualization of treatment.

Biopsy↗

Helicobacter pylori infection is a protective factor for bleeding gastric ulcers but not for bleeding duodenal ulcers in NSAID users.

BACKGROUND: The effect of Helicobacter pylori infection on NSAID-induced gastroduodenal damage is unclear. AIM: To determine the role of H. pylori and NSAID use in complicated peptic ulcers. METHODS: A total of 185 consecutive patients with bleeding peptic ulcers and 185 hospitalized matched controls were studied prospectively. Additionally, 75 consecutive uncomplicated peptic ulcers and 75 community controls were also studied. Active H. pylori infection was determined by urea breath test and/or both urease test and histology. Serum CagA and VacA status were determined at random in 135 infected patients and 82 controls. NSAID use was determined by structured data collection. RESULTS: H. pylori (odds ratio [OR]=5. 98; 2.9-12.3) and NSAID use (OR=5.74; 3.4-9.7) were independent risk factors for duodenal ulcer bleeding, whereas NSAID use was the main risk factor for bleeding gastric ulcers (OR=12.4; 5.5-27.9). Interaction of both factors was associated with reduced risk for bleeding gastric ulcers (OR=0.19; 0.04-0.88) but not for bleeding duodenal ulcers, which showed a similar risk to any one factor alone. This was observed for all types of NSAID use, including low-dose aspirin, and infection by CagA positive strains. H. pylori was the only factor involved in common uncomplicated duodenal ulcers. CONCLUSION: Interaction of both H. pylori infection and NSAID use decreases the risk of bleeding due to gastric ulcers, but not that due to duodenal ulcers.

Duodenal Ulcer↗

Prospective trial of endoscopic clips versus combination therapy in upper GI bleeding (PROTECCT--UGI bleeding).

BACKGROUND: It is not known if combination therapy of epinephrine injection and multipolar electrocoagulation or hemoclips are a more efficient or effective treatment for patients with acute nonvariceal upper gastrointestinal (GI) bleeding. METHODS: Adult patients with active nonvariceal upper GI bleeding, a nonbleeding visible vessel, or after removal of an adherent clot findings of active bleeding or a visible vessel were studied. Patients were randomized to either therapy and the outcomes were assessed at 30 days. RESULTS: Forty-seven patients were studied: 26 patients randomized to hemoclips and 21 to combination therapy. There were 22 patients with active bleeding, 13 with a nonbleeding visible vessel, and 12 with an adherent clot. The median duration of endoscopic therapy was 17 min in the hemoclip group versus 20 min for the combination therapy, p= 0.29. Primary hemostasis with successful initial control of bleeding occurred in 26 (100%) of 26 hemoclip patients and 20 (95.2%) of 21 combination therapy patients, p= 0.45. The rebleeding rates were: 4 (15.4%) of 26 hemoclip patients versus 5 (23.8%) of 21 combination therapy patients, p= 0.49. Overall, the length of hospital stay, units of blood transfused, surgery rates, and mortality were not different. CONCLUSIONS: In this prospective, randomized controlled trial of endoscopic hemoclips versus combination therapy in the nonvariceal upper GI bleeding, the efficiency, efficacy, and complications of the two treatment modalities were not significantly different.

Aged↗

Risks of gastrointestinal bleeding during secondary prevention of vascular events with aspirin--analysis of gastrointestinal bleeding during the UK-TIA trial.

From 1979 to 1985 2435 patients having had transient ischaemic attacks (TIAs) or minor ischaemic strokes, were enrolled in the UK TIA trial and were randomised to receive either aspirin 300 mg, daily or aspirin 1200 mg or placebo. Analysis of reported upper gastrointestinal bleeding events (defined as haematemesis or melaena, or both) showed a risk of bleeding in a dose dependent manner, odds ratios (95% CI) for 300 mg of aspirin = 3.3 (1.2 to 9.0) and for 1200 mg = 6.4 (2.5 to 16.5) and, as would be expected, an increased risk of hospitalisation because of bleeding also in a dose dependent manner, odds ratio = 3.6 (0.7 to 17.2) for 300 mg and 8.7 (2.0 to 37.6) for 1200 mg. Further analysis suggested greater risks of bleeding from duodenal ulcers than gastric ulcers and that bleeding is more likely early in the course of treatment with aspirin used as secondary prevention. There was also an increased risk of lower gastrointestinal bleeding, defined as fresh blood per rectum for both doses of aspirin, odds ratio 1.8 (0.5 to 6.1) for 300 mg of aspirin, and 1.5 (0.4 to 5.3) for 1200 mg of aspirin.

Aspirin↗

Excessive bleeding and transfusion in a prior cardiac surgery is associated with excessive bleeding and transfusion in the next surgery.

If there is a genetic predisposition to excessive bleeding, there should be an association in excessive blood loss between multiple cardiac surgeries. We retrospectively determined in 174 patients the association of excessive bleeding between 2 cardiac surgeries with cardiopulmonary bypass between January 19, 1990 and June 25, 2002. Excessive bleeding was defined by 2 criteria: (a) postoperating room chest tube blood loss over 24 h more than or equal to 750 mL (chest tube drainage [CTD] > or = 750) and (b) transfusion of any non-red blood cell (RBC) blood products. Logistic regression was used to estimate the association between excessive bleeding at the first and second cardiac procedures. The logistic regression models for CTD > or = 750 in the second surgery determined that CTD > or = 750 in the first surgery compared to CTD < 750 had an unadjusted odds ratio of 2.18 (P = 0.03) and an odds ratio of 2.42 (P = 0.03) when adjusted for age, sex, body surface area, preoperative anticoagulant use, cardiopulmonary bypass duration, and procedure type at second surgery. The logistic regression model for any non-RBC use in the second surgery determined that any non-RBC use in the first surgery compared with no non-RBC use had an unadjusted odds ratio of 2.32 (P = 0.02) and an odds ratio of 2.55 (P = 0.02) when adjusted for age, sex, body surface area, preoperative anticoagulant use, cardiopulmonary bypass duration, and procedure type at second surgery. We conclude that a history of excessive bleeding during the first operation is associated with more than two times increased risk for excessive bleeding in the second surgery.

Adult↗