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PubMed2005

The effect of GI bleeding on Helicobacter pylori diagnostic testing: a prospective study at the time of bleeding and 1 month later.

BACKGROUND: Some case series and cohort studies suggest that acute GI bleeding decreases the sensitivity of Helicobacter pylori diagnostic testing. OBJECTIVE: To assess H pylori biopsy testing in patients with acute upper-GI bleeding and 1 month later. DESIGN: Prospective cohort study using patients as their own controls. SETTING: Urban county hospital. PATIENTS: Sixty-one patients with acute variceal bleeding. INTERVENTIONS: Antral and body endoscopic biopsies at admission and 1 month later. MAIN OUTCOME MEASUREMENTS: CLOtest and histologic examinations were performed and biopsy specimens were coded and mixed for blinded histologic examination for H pylori density and inflammation. RESULTS: CLOtest results changed from H pylori negative at baseline to H pylori positive at 1 month in two patients (3%), from H pylori positive to H pylori negative in 6 patients (10%), and remained the same in 53 (87%). Histologic results changed from H pylori negative at baseline to H pylori positive at 1 month in two patients (3%), from H pylori positive to H pylori negative in 5 patients (8%), and remained the same in 54 (89%). Changes occurred only in patients with low H pylori density. No significant increase in H pylori density or change in inflammatory cell infiltration was seen. CLOtest sensitivity was 8% higher with bleeding vs. 1 month after bleeding (79% vs. 71%; 95% CI of difference was -11% to 27%; i.e., maximal potential decrease in sensitivity with bleeding is 11%). LIMITATIONS: The population is not one for which H pylori testing is recommended, and biopsy test performance was less consistent than expected. CONCLUSIONS: Acute-GI bleeding did not decrease the sensitivity of rapid urease testing, unless the effect lasts more than 1 month. Furthermore, bleeding did not produce falsely negative histologic examinations for H pylori, decrease H pylori density, or alter inflammatory cell infiltration. However, given the lower than expected overall CLOtest sensitivity and frequent use of proton pump inhibitors for GI bleeding, histology may be preferred in this setting.

Acute Disease↗

PubMed1996

The pathophysiology of bleeding disorders presenting as abnormal uterine bleeding.

Abnormal uterine bleeding is often the presenting complaint in women with underlying coagulopathies. A clear understanding of the pathophysiology of common bleeding disorders will help the practicing obstetrician/gynecologist in the diagnosis and treatment of these conditions. The normal hemostatic process can be divided into three phases. The first phase, primary hemostasis, consists of platelet adhesion and aggregation. After vascular injury, proteins in the subendothelium are exposed that promote platelet adhesion. Platelet adhesion is uniquely dependent on von Willebrand factor, a plasma protein that serves as a molecular bridge between components of the vessel wall and the platelet glycoprotein Ib/IX receptor. Activation of the adherent platelets promotes additional platelet recruitment, culminating in the formation of the platelet plug. Quantitative or qualitative defects in either the platelet or von Willebrand factor (von Willebrand disease) lead to defective primary hemostasis. Patients present with a prolonged bleeding time and mucocutaneous bleeding manifestations. In the next phase, secondary hemostasis, the plasma coagulation factors are sequentially activated, which leads to fibrin formation and cross-linking. These reactions take place primarily on the surface of activated platelets and are essential in maintaining the stability of the initial platelet plug. Defective secondary hemostasis arises from congenital or acquired deficiencies in coagulation factors. Although these defects are most often associated with bleeding into joints and soft tissues, other manifestations, including abnormal uterine bleeding, may be present. The prothrombin time and the activated partial thromboplastin time serve as initial screening tests for these coagulation disorders, although more specific tests, including factor levels, thrombin time, clot solubility, and mixing studies, are needed to fully define the defect. In the final phase of normal hemostasis, fibrinolysis, the fibrin clot undergoes an orderly process of degradation. Deficiencies in the normal inhibitors of fibrinolysis, such as alpha 2-antiplasmin or plasminogen activator inhibitor-1, may be underdiagnosed causes of delayed bleeding because they are not identified by the usual coagulation screening tests. Disorders of primary hemostasis, including thrombocytopenia and von Willebrand disease, are particularly important to consider when evaluating women with abnormal uterine bleeding. Patients with acquired or congenital deficiencies of either coagulation factors or the regulators of the fibrinolytic system may also present with menorrhagia. Accurate diagnosis of a bleeding disorder is essential to the design of an appropriate therapeutic regimen and is likely to have important clinical implications beyond that of the presenting gynecologic complaint.

Blood Coagulation Disorders↗

PubMed1991

Histometric analysis of epithelial alterations in bleeding and non-bleeding gingivae after probing and their corresponding stereomicroscopic findings of vasculature.

The present study was carried out to investigate and compare the thickness and number of rete pegs of the sulcular epithelium histometrically in bleeding and non-bleeding gingivae with special reference to comparisons of their relationship with corresponding stereomicroscopic findings. A total of 78 biopsies (40 bleeding and 38 non-bleeding gingival specimens) was obtained from 33 patients. Tissue sections with H&E stains were performed. Each gingival section was divided into three portions (coronal, middle and apical) along the gingival sulcular epithelium horizontally. The rete pegs were counted and the thickest and thinnest parts of the epithelium in three individual portions were also measured histometrically. The results show that the epithelial thickness of bleeding gingiva at the coronal and middle portions was significantly thinner than that of non-bleeding gingiva. There were also greater numbers of rete pegs of the sulcular epithelium in bleeding gingiva than of those in non-bleeding gingiva. However, there was no specific relationship between epithelial alterations of gingiva and the visibility of vasculature by stereomicroscopy. It is suggested that epithelial alterations of gingiva to some extent might be responsible for the gingival bleeding on probing clinically and highly associated with the volumetric density of underlying infiltrated connective tissue, but might not be related to the visibility of vasculature by stereomicroscopy.

Epithelium↗

PubMed1982

Massive rectal bleeding of colonic origin: localization of the bleeding site.

Fourteen patients with massive colonic bleeding underwent preoperative evaluation including visceral angiography and/or colonoscopy. Segmental for subtotal colectomy was performed in each case. The freshly excised colonic specimen was opened and washed clean, and the mucosal surface was closely examined by manually compressing the specimen segment by segment in order to detect the minute bleeding site(s), which were then marked with a suture for histologic sectioning. This maneuver was successful in 13 instances. In 11 of these, histologic identification was made; seven were cases of vascular malformations, and four were cases of diverticular bleeding. In 5 of these 11 cases, colonoscopy and/or visceral angiography failed to localize the bleeding sites; four were cases of bleeding of diverticular origin. Of the two patients in whom histologic identification was not made despite suture identification, one underwent a second colonic resection in which bleeding sites were histologically identified; the bleeding was not caused by vascular malformations or diverticula. The method of examining the freshly excised specimen described is useful for accurate histologic identification of the cause of colonic bleeding, particularly for diverticular bleeding. The method is also useful for immediate assessment of adequacy and appropriateness of surgical resection.

Angiography↗

PubMed2001

Effects of agents, used to treat bleeding disorders, on bleeding time prolonged by a very high dose of a direct thrombin inhibitor in anesthesized rats and rabbits.

Melagatran is the active form of the oral, direct thrombin inhibitor, H 376/95, that is under evaluation in clinical trials for the prevention and treatment of thromboembolism. In this study, a single dose, calculated on body weight basis, of antifibrinolytic treatment, factor VIIa, factor VIII with and without von Willebrand factor (vWF), factor IX, activated (APCC) or nonactivated (PCC) prothrombin complex concentrates was given intravenously to rats and rabbits, in an attempt to reverse the prolonged bleeding time during intensive anticoagulation with melagatran (2 micromol/kg/h). The doses used were at or above human therapeutic doses. The cutaneous tail bleeding time in the rat, as well as the ear incision bleeding time and cuticle bleeding time, and the blood loss in the rabbit were used for evaluation of the hemostatic effects of these agents. In vivo Feiba (APCC) and Prothromplex-T (PCC) shortened the prolonged cutaneous bleeding times in rats (P<.05); Feiba and Autoplex (APCC) shortened the cutaneous bleeding times in rabbits (P<.05). In contrast, Prothromplex-T prolonged bleeding times and blood loss in the rabbits (P<.05). Ex vivo Feiba, Autoplex and NovoSeven (rF VIIa) significantly (P<.05) shortened the prolonged whole blood clotting time (WBCT). Prothromplex-T significantly prolonged WBCT, activated clotting time (ACT) and activated partial thromboplastin time (APTT). Feiba, Autoplex, and Prothromplex-T increased thrombin generation measured as increased thrombin-antithrombin complex (TAT) formation. In conclusion, APCCs were found to be the most effective agents for reversing bleeding time induced by a very high plasma concentration of melagatran. APCC and recombinant activated factor FVII (rF VIIa) effectively shortened the prolonged WBCT. Thus, stimulating thrombin generation with the use of APCC may counteract the anticoagulant effect observed with a very high dose of a thrombin inhibitor.

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↗

PubMed2000

Somatostatin or octreotide for acute bleeding oesophageal varices.

BACKGROUND: Somatostatin and its derivative, octreotide, are often used for emergency treatment of bleeding oesophageal varices in patients with cirrhosis of the liver. The placebo controlled trials have shown varying results, however, and their power has been quite low. An updated systematic review of a previously published meta-analysis was therefore performed. OBJECTIVES: To study whether somatostatin or octreotide improve survival or reduce the number of blood transfusions in patients with suspected or verified acute or recently bleeding oesophageal varices. SEARCH STRATEGY: MEDLINE and The Cochrane Library are searched every three months. Reference lists of articles and authors. SELECTION CRITERIA: All randomised trials comparing somatostatin or octreotide with placebo or no treatment in patients suspected of acute bleeding from oesophageal varices. DATA COLLECTION AND ANALYSIS: The effect variables extracted were: mortality, number of blood transfusions, number with balloon tamponade, number with initial haemostasis and number with rebleeding. Intention to treat analyses were conducted; a random effects analysis was preferred if there was significant heterogeneity between the trials (p<0.10). MAIN RESULTS: The meta-analysis comprised 820 patients. The active drugs had no effect on survival; a total of 91 patients died in the experimental groups vs 85 patients in the control groups (odds ratio 1.04, 95% confidence interval (CI) 0.74 to 1.46). The number of transfusions was less with drugs, the difference between experimental and control therapy was 1.2 units of blood products saved per patient (95% CI 0. 8 to 1.6). There were no significant differences in use of balloon tamponade (odds ratio 0.59, 95% CI 0.21 to 1.70), number of patients failing initial haemostasis (odds ratio 0.66, 95% CI 0.32 to 1.37) or number with rebleeding (odds ratio 0.73, 95% CI 0.30 to 1.79). It should be noted, however, that the trials were heterogeneous with respect to these secondary variables. REVIEWER'S CONCLUSIONS: The effect corresponded to one unit of blood saved per patient. This effect is small and treatment with these drugs in acute bleeding oesophageal varices is therefore of doubtful value. This does not suggest a need for further studies. On the other hand, the confidence interval for the effect on mortality was wide. Hence, a large placebo controlled trial is needed if one wishes to rule out the possibility that a worthwhile effect on mortality may have been overlooked.

Acute Disease↗

PubMed2000

Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Nonsteroidal anti-inflammatory drugs or prostaglandin synthetase inhibitors reduce prostaglandin levels which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea. OBJECTIVES: The primary objective of this review was to investigate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in achieving a reduction in menstrual blood loss in women of reproductive years with heavy menstrual bleeding (HMB). SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsychLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles and drug companies were approached for unpublished data. In most cases, the first author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of individual NSAIDs with either each other, placebo or other medical treatments in women of reproductive years with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment induced) causes for their heavy menstrual blood loss. DATA COLLECTION AND ANALYSIS: Sixteen RCTs were identified that fulfilled the inclusion criteria for this review. The reviewers extracted the data independently and odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of nine trials. The remaining seven trials were of crossover design with data unsuitable for pooling and their individual results were described in text form. MAIN RESULTS: As a group, NSAIDs were more effective than placebo at reducing heavy menstrual bleeding but less effective than either tranexamic acid or danazol. Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs but this did not appear to affect the acceptability of treatment. There was a non significant trend towards greater efficacy of NSAIDs compared to oral progestogen (luteal phase) and ethamsylate but no differences were demonstrated between NSAIDs and the progesterone releasing intra-uterine system (IUS) and the oral contraceptive pill, although these results were based on very small studies. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. REVIEWER'S CONCLUSIONS: NSAIDs reduce heavy menstrual bleeding when compared with placebo but are less effective than either tranexamic acid or danazol. However, adverse events are more severe with danazol therapy. In the limited number of small scale studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral progestogen given in the luteal phase, ethamsylate, oral contraceptive pill and the progesterone releasing IUS.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1986

Nature of the bleeding vessel in recurrently bleeding gastric ulcers.

An unselected consecutive series of 826 patients admitted for acute upper gastrointestinal bleeding underwent urgent endoscopy. Peptic ulcers were found in 402 (49%). Of the 329 ulcer craters that could be fully examined, visible vessels were identified in 156 (47%), other stigmata of recent hemorrhage in 66, and no stigmata of recent hemorrhage in 107. One hundred twenty-nine patients with stigmata of recent hemorrhage (93 of whom had visible vessels) randomly allocated to no endoscopic treatment were observed for evidence of further bleeding. Fifty-four of the 93 patients (58%) with visible vessels rebled, compared with 2 of 36 (6%) with other stigmata of recent hemorrhage. No patient without stigmata of recent hemorrhage rebled. Twenty-seven patients in whom a visible vessel in a gastric ulcer was identified at endoscopy underwent urgent partial gastrectomy because of recurrent bleeding. The vessel identified at endoscopy was found in 26 of 27 resection specimens (96%). The arterial vessel wall protruded above the surface of the ulcer crater in 10 specimens, and clot in continuity with a breach in the vessel wall protruded in a further 10 specimens. Postoperative angiography, when technically possible, showed that the breached artery ran across the base of the ulcer in all of these specimens. Pathological changes were common in the bleeding artery and included arteritis in 24 of 29 (83%) eroded arteries found in these specimens, with aneurysmal dilatation in 14 of 27 (52%) bleeding points that could be fully examined. The ulcer had penetrated to serosa in 13 specimens (45%). The bleeding artery had a mean external diameter of 0.7 mm with a range of 0.1-1.8 mm. This study provides new information about the nature of the bleeding vessel in gastric ulcers, and some of this information is relevant in planning studies of endoscopic therapy for bleeding peptic ulcers. It validates the endoscopic identification of a visible vessel, and confirms that such identification has a high predictive value for the development of recurrent hemorrhage.

Arteries↗

PubMed2006

Rectal bleeding after high-dose-rate brachytherapy combined with hypofractionated external-beam radiotherapy for localized prostate cancer: impact of rectal dose in high-dose-rate brachytherapy on occurrence of grade 2 or worse rectal bleeding.

PURPOSE: To evaluate the incidence of Grade 2 or worse rectal bleeding after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiotherapy (EBRT), with special emphasis on the relationship between the incidence of rectal bleeding and the rectal dose from HDR brachytherapy. METHODS AND MATERIALS: The records of 100 patients who were treated by HDR brachytherapy combined with EBRT for > or =12 months were analyzed. The fractionation schema for HDR brachytherapy was prospectively changed, and the total radiation dose for EBRT was fixed at 51 Gy. The distribution of the fractionation schema used in the patients was as follows: 5 Gy x 5 in 13 patients; 7 Gy x 3 in 19 patients; and 9 Gy x 2 in 68 patients. RESULTS: Ten patients (10%) developed Grade 2 or worse rectal bleeding. Regarding the correlation with dosimetric factors, no significant differences were found in the average percentage of the entire rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose from EBRT between those with bleeding and those without. The average percentage of the entire rectal volume receiving 10%, 30%, 50%, 80%, and 90% of the prescribed radiation dose from HDR brachytherapy in those who developed rectal bleeding was 77.9%, 28.6%, 9.0%, 1.5%, and 0.3%, respectively, and was 69.2%, 22.2%, 6.6%, 0.9%, and 0.4%, respectively, in those without bleeding. The differences in the percentages of the entire rectal volume receiving 10%, 30%, and 50% between those with and without bleeding were statistically significant. CONCLUSIONS: The rectal dose from HDR brachytherapy for patients with prostate cancer may have a significant impact on the incidence of Grade 2 or worse rectal bleeding.

Aged↗

PubMed1999

Endoscopic hydrogen peroxide spray may facilitate localization of the bleeding site in acute upper gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: A major problem encountered in the emergency endoscopic management of acute upper gastrointestinal (UGI) bleeding is poor localization of the bleeding site, which can be obscured by blood or clots. Traditional attempts to overcome this problem have been by physical methods, which have usually proved unsatisfactory. The aim of this prospective study was to show that hydrogen peroxide can be used as a dissolution agent, resulting in an alteration of the characteristics of blood clots and allowing a clearer visual field. PATIENTS AND METHODS: Twenty patients with acute UGI bleeding (13 male, seven female) were included in the study. The suspected site of bleeding was initially sprayed with 200 ml of saline and then with 25-175 ml of 3 % H2O2. Pictures of the visual field were taken before and after irrigation with both saline and H2O2. These pictures were evaluated by three gastroenterologists and scored using the following visual clearance scoring system: -3, marked worsening of visual field; -2, moderate worsening; -1, slight worsening; 0, no change; +1, slight improvement; +2, moderate improvement; + 3, marked improvement. In cases of active oozing or spurting, after initial hemostasis was achieved the bleeding point was injected with pure ethanol or cauterized with a heater probe. In order to assess the safety of 3 % H2O2 endoscopic biopsies of the antrum and the duodenal bulb were performed before and 30 minutes after its use and examined by a pathologist. RESULTS: There was a significant improvement in the mean visual clearance score after irrigation with H2O2 compared to irrigation with saline alone (2.13 vs. 0.43, P<0.001). During endoscopic examination there were 19 patients with active oozing from the ulcer base covered by an adherent blood clot; 12 of these (63.1%) achieved initial hemostasis after H2O2 spraying. Eleven of 18 (61.1 %) patients complained of a mild epigastric burning sensation during H2O2 irrigation. There was no clinically significant change in the histology of the antrum and the duodenal bulb after H2O2 therapy. CONCLUSIONS: We concluded that H2O2 is a safe and effective way to clear the visual field, facilitating the localization of the bleeding site during emergency endoscopy for acute UGI bleeding, with only mild side effects. In some cases H2O2 therapy can also induce temporary hemostasis. We recommended the use of hydrogen peroxide to improve endoscopic visualization, especially in cases where an adherent blood clot covers the suspected bleeding site.

Adult↗

PubMed1999

Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers.

BACKGROUND AND METHODS: After endoscopic treatment to control bleeding of peptic ulcers, bleeding recurs in 15 to 20 percent of patients. In a prospective, randomized study, we compared endoscopic retreatment with surgery after initial endoscopy. Over a 40-month period, 1169 of 3473 adults who were admitted to our hospital with bleeding peptic ulcers underwent endoscopy to reestablish hemostasis. Of 100 patients with recurrent bleeding, 7 patients with cancer and 1 patient with cardiac arrest were excluded from the study; 48 patients were randomly assigned to undergo immediate endoscopic retreatment and 44 were assigned to undergo surgery. The type of operation used was left to the surgeon. Bleeding was considered to have recurred in the event of any one of the following: vomiting of fresh blood, hypotension and melena, or a requirement for more than four units of blood in the 72-hour period after endoscopic treatment. RESULTS: Of the 48 patients who were assigned to endoscopic retreatment, 35 had long-term control of bleeding. Thirteen underwent salvage surgery, 11 because retreatment failed and 2 because of perforations resulting from thermocoagulation. Five patients in the endoscopy group died within 30 days, as compared with eight patients in the surgery group (P=0.37). Seven patients in the endoscopy group (including 6 who underwent salvage surgery) had complications, as compared with 16 in the surgery group (P=0.03). The duration of hospitalization, the need for hospitalization in the intensive care unit and the resultant duration of that stay, and the number of blood transfusions were similar in the two groups. In multivariate analysis, hypotension at randomization (P=0.01) and an ulcer size of at least 2 cm (P=0.03) were independent factors predictive of the failure of endoscopic retreatment. CONCLUSIONS: In patients with peptic ulcers and recurrent bleeding after initial endoscopic control of bleeding, endoscopic retreatment reduces the need for surgery without increasing the risk of death and is associated with fewer complications than is surgery.

Aged↗

PubMed2002

Relationship between bleeding time test and postextraction bleeding in a healthy control population.

OBJECTIVE: We sought to determine whether cutaneous bleeding time (BT) is related to bleeding outcome measures after a single tooth extraction. STUDY DESIGN: This was a prospective clinical pilot study of 30 subjects. Cutaneous BT was evaluated before a single tooth extraction. After extraction, an oral BT was determined. Subjects were contacted 3 to 7 hours and 2 days after extraction to assess further postoperative bleeding. RESULTS: The mean cutaneous BT was 5.9 minutes (range 1.5-10.0 minutes). The mean oral BT was 7.5 minutes (range 0-20 minutes). Cutaneous BT did not correlate with oral BT or any of our measures of postoperative bleeding. However, the oral BT correlated with the number of hours of bleeding after surgery (R(s) = 0.54, P =.03). The time necessary to perform the extraction correlated with the extraction site bleeding 3 to 7 hours after surgery (R(s) = 0.67, P =.0006). CONCLUSION: Cutaneous BT did not correlate with measures of postoperative bleeding in the present study, but oral BT immediately after extraction correlated with the duration of subsequent postoperative bleeding.

Adult↗

PubMed1995

Bleeding risks, risk factors and management of bleeding complications after treatment with anticoagulants, specific antithrombins, thrombolytics IIb-IIIa receptor blockers.

Assessment of the risks of new antithrombotic therapies is best undertaken by evaluating risk factors for bleeding in individual patients, and risks associated with specific antithrombotic agents. This forms the basis for the development of a management strategy for major bleeding complications. Patient-related risk factors for bleeding with oral anticoagulants include: trauma, invasive procedures, history of bleeding disorder, high anticoagulant intensity, concomitant use of antiplatelet drugs, presence of underlying severe disease, advanced age, and prior history of cerebrovascular accident, or gastrointestinal bleeding. Weight-adjusted and other nomograms are more successful in achieving a balance between therapeutic effect and safety with intravenous heparin. The most important complication of thrombolytic therapy is intracranial haemorrhage, and the risks increase with age > 65 years, weight under 70 k, hypertension on admission and the use of tissue plasminogen activator: this profile is helpful in assessing risk-benefit ratio amongst individual patients. Recent experience with the experimental use of antithrombin agents such as hirudin, indicates a delicate dose-response relationship as it relates to the risk of cerebral haemorrhage, when used in conjunction with thrombolytic agents. A definitive answer regarding the role of hirudin and the balance of safety and efficacy awaits completion of ongoing trials. Novel IIb/IIIa platelet inhibitors appear to offer a significant therapeutic advance: major bleeding is variable and depends in part on the use of concomitant procedures, and heparin therapy. It is important to identify the source and severity of bleeding with the use of antithrombotic therapy and its haemodynamic consequences in constructing a management plan. Well developed treatment algorithms for patients with severe bleeding exist, and although laboratory testing may be helpful, it is on balance of marginal benefit since patients usually require urgent therapy. Future investigation promises more readily available, rapid and specific laboratory testing, and newer antithrombotic agents that are easier to administer and monitor. Molecular targeting with fusion proteins that attract to a specific antigen, thereby delivering more effective and safe therapy, offer new promise.

Anticoagulants↗

PubMed1996

Optimizing the time-frame for the definition of bleeding-related death after acute variceal bleeding in cirrhosis.

OBJECTIVE: To identify the best time-frame for defining bleeding-related death after variceal bleeding in patients with cirrhosis. DESIGN: Prospective long-term evaluation of a cohort of 155 patients admitted with variceal bleeding. SETTING: Eight medical departments in seven hospitals in north-eastern Italy. METHODS: Non-linear regression analysis of a hazard curve for death, and Cox's multiple regression analyses using different zero-time points. RESULTS: Cumulative hazard plots gave two slopes, the first corresponding to the risk of death from acute bleeding, the second a baseline risk of death. The first 30 days were outside the confidence limits of the regression curve for the baseline risk of death. Using Cox's regression analysis, the significant predictors of overall mortality risk were balanced between factors related to severity of bleeding and those related to severity of liver disease. If only deaths occurring after 30 days were considered, only predictors related to the severity of liver disease were found to be of importance. CONCLUSION: Thirty days after bleeding is considered to be a reasonable time-frame for the definition of bleeding-related death in patients with cirrhosis and variceal bleeding.

Adult↗

PubMed1999

The higher risk of bleeding in lung transplant recipients from bronchoscopy is independent of traditional bleeding risks: results of a prospective cohort study.

STUDY OBJECTIVE: To determine whether recipients of lung transplants have a higher risk of bleeding from fiberoptic bronchoscopy (FOB) than other patients who undergo the procedure. DESIGN: Prospective cohort study. SETTING: Bronchoscopy services of Johns Hopkins Hospital, a tertiary referral center and Johns Hopkins Bayview Medical Center, a community hospital. PATIENTS: All adult patients (18 years) who underwent FOB between July 1, 1996 and June 30, 1997 by the full-time pulmonary medicine staff were included. A total of 720 procedures were performed, including 38 in lung transplant recipients. MEASUREMENTS: Bleeding was assessed by reviewing physician reports of bloody drainage after the procedure and whether the procedure was terminated early for bleeding. Patient reports of hemoptysis were assessed using questionnaires administered pre- and post-FOB. Predictor variables included patient demographics, bleeding parameters (platelets, prothrombin time, and activated partial thromboplastin time), immunosuppressive medications, aspirin use, use of transbronchial biopsy, and the time length of the procedure. RESULTS: Lung transplant recipients were significantly more likely to have used aspirin prior to FOB (18.4 vs 7.2%, p < 0.05) and to undergo transbronchial biopsy (64.9 vs 26.8%, p < 0.001). Lung transplant patients were more likely to have new or worsened hemoptysis (53.8 vs 24.6%, p < 0.001), to have > 25 mL of blood loss (44.5 vs 17.5%, p < 0.001) and to have the procedure terminated early for bleeding (5.4 vs 1.0%, p < 0.05). In multivariate analysis, predictors of new or worsened hemoptysis included lung transplant, longer procedure time, and older patient age. Independent predictors of greater blood loss included lung transplant, performance of transbronchial biopsy, longer procedure time, and older patient age. CONCLUSIONS: Lung transplant recipients are at higher risk of bleeding from bronchoscopy than are other patients. This propensity to bleed is independent of coagulation parameters, platelet count, immunosuppressive medication use, aspirin use, or performance of transbronchial biopsy. The higher risk of bleeding should be considered when assessing the risks and benefits of bronchoscopy in lung transplant recipients.

Adult↗

PubMed1995

Premature extravasation. A bleeding site identified during the dynamic phase of Tc-99m red blood cell bleeding scintigraphy.

Tc-99m RBC scintigraphy is favored by many investigators because it provides the ability to image the abdomen over a prolonged period of time, thereby allowing identification of delayed bleeding sites that are frequently encountered due to the intermittent nature of gastrointestinal bleeding. The authors describe a case of bleeding scintigraphy with labeled red blood cells in which the bleeding site was identifiable only on the dynamic blood-flow and first static images. On later images, the labeled blood cells had spread throughout the colon, rendering localization of the actual bleeding site impossible. Two previous red blood cell scintigraphies and a subsequent contrast angiogram did not reveal sites of active bleeding. As illustrated by this unusual case, factors governing timing and visualization of abnormal bleeding sites are discussed, as is a differential diagnosis of abnormal foci of activity seen on the dynamic phase of bleeding scintigraphy.

Adult↗

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↗