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PubMed1999

Cutaneous bleeding related to zinc deficiency in two cases of advanced cancer.

BACKGROUND: One patient with metastatic squamous cell carcinoma of the larynx and one with advanced non-Hodgkin lymphoma, both with poor nutritional status, developed ecchymoses and demonstrated prolonged bleeding time and abnormal aggregation of platelets. METHODS: On the basis of previous studies, the author measured the level of zinc in the serum and urine of these patients and the effect of zinc supplementation on the clinical symptoms and laboratory findings. Also studied were serum and urine zinc levels in 15 newly diagnosed, untreated cancer patients with no evidence of bleeding. RESULTS: The two patients were found to have very low serum and urine zinc levels, which were 6 and 9 microgram/dL and 28 and 22 microgram/24 hours, respectively, compared with normal average values of 70-150 microgram/dL and 150-1200 microgram/24 hours. The mean values of zinc in the serum and urine of the 15 patients newly diagnosed with cancer were 109.18 microgram/dL and 433.8 microgram/24 hours, respectively. Oral administration of zinc without any additional therapy was rapidly followed by control of bleeding, normalization of bleeding time, and platelet aggregation. Discontinuation of zinc caused the return of bleeding and abnormal laboratory findings, which again were corrected with zinc supplementation. CONCLUSIONS: Severe depletion of zinc in two patients with advanced cancer and malnutrition was accompanied by cutaneous bleeding and laboratory findings of platelet dysfunction, both of which were corrected by oral supplementation of zinc and reoccurred on discontinuing therapy. Zinc deficiency should be suspected in patients with advanced cancer demonstrating bleeding when a prolonged bleeding time is the only hemostatic abnormality.

Aged↗
PubMedDate not supplied

Association between prolonged bleeding time and gastrointestinal hemorrhage in 102 patients with liver cirrhosis: results of a retrospective study.

BACKGROUND: Gastrointestinal bleeding is a frequent complication of liver cirrhosis (LC) and represents an important warning sign of imminent death. Platelet dysfunction is an abnormality occurring prevalently in severe liver failure, and could well predispose to bleeding. METHODS: One hundred and two patients with liver cirrhosis diagnosed by needle liver biopsy were studied. According to the Child-Pugh classification, 23 were A class, 42 B class and 37 C class cases. Prothrombin activity, aPTT, fibrinogen, FDPs, XDP and platelet count were measured in each patient; bleeding time was measured in all but 17 of them. Forty (39%) had experienced gastrointestinal bleeding during the last 3 years (2 A class, 12 B class, 26 C class). RESULTS: Patients with a history of previous gastrointestinal bleeding showed lower values for prothrombin activity and fibrinogen, and higher percentage of elevated FDP and XDP levels; moreover, they presented lower platelet counts and more prolonged bleeding times than patients without gastrointestinal blood loss. CONCLUSIONS: While our findings confirm the relationship between hyperfibrinolysis and bleeding, the association between bleeding time prolongation and gastrointestinal blood loss suggests studying platelet function prospectively in LC in order to analyze its role, if any, in favoring hemorrhage activity.

Adult↗
PubMed1991

L-arginine, the precursor of nitric oxide, abolishes the effect of estrogens on bleeding time in experimental uremia.

We have reported previously that conjugated estrogens that are effective in shortening the prolonged bleeding time in uremic patients are also effective on bleeding time in a rat model of uremia. Using such a rat model we have recently demonstrated that nitric oxide (NO), an endothelium-derived vasodilator, is involved in mediating the bleeding tendency of uremia. With the present study we wanted to investigate whether conjugated estrogen mixture or its active component, 17 beta-estradiol, reduce uremic bleeding by interfering with the NO pathway. Our results showed that the shortening effect of conjugated estrogen and 17 beta-estradiol on bleeding time of uremic rats was completely reversed by giving the animals the NO precursor L-arginine, but not D-arginine, which is not a precursor of NO. Dexamethasone which at variance to progesterone inhibits the process of induction of NO-forming enzyme, shortened the prolonged bleeding time of uremic rats within 4 hours from injection. This effect was eliminated by L-arginine but not D-arginine administration. The glucocorticoid receptor antagonist cortexolone prevented the shortening of bleeding time induced by dexamethasone, suggesting that a receptor-mediated mechanism is involved in the hemostatic effect of dexamethasone as previously reported for estrogens. Unlike conjugated estrogens and dexamethasone, progesterone had no effect on bleeding time. All these findings would indicate that the effect of estrogens and dexamethasone on primary hemostasis in uremia might be mediated by changes in NO synthetic pathway.

Animals↗
PubMedDate not supplied

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

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

Adult↗
PubMed1991

Incidence of breakthrough bleeding during oral contraceptive therapy.

A phase IV, open-label, multicenter survey of 983 obstetrician-gynecologists was conducted to evaluate the incidence of intermenstrual bleeding in 6,382 women receiving a low-dose monophasic oral contraceptive, ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms (EDA 1 mg with EE 35 micrograms) over a six-month period. Most patients (75%) did not experience intermenstrual bleeding during therapy. Follow-up questionnaires were sent to the physicians of the 1,526 women reporting breakthrough bleeding or spotting; 1,027 follow-up questionnaires (67%) were returned. The questionnaires revealed that approximately one-fifth of the patients were placed on EDA 1 mg with EE 35 micrograms to regulate preexisting bleeding; of them, 71% reported an improvement, 13% reported worsening, and 16% reported no change in their cycle regularity. Most breakthrough bleeding or spotting (91%) occurred in the first three months of therapy in women with preexisting irregular bleeding as well as in those using the oral contraceptive solely for birth control. Although a fair proportion of women experienced intermenstrual bleeding, very few (5.1%) discontinued therapy because of it. Thus, the study demonstrated that the incidence of breakthrough bleeding and spotting appears to be within or below the range reported for other monophasic and multiphasic oral contraceptives. Further, in agreement with previously published reports, the data suggest that cycle control will improve after three months of oral contraceptive use.

Contraceptives, Oral, Hormonal↗
PubMed1990

Bleeding times in rats treated with heparin, heparin fragments of high and low anticoagulant activity and chemically modified heparin fragments of low anticoagulant activity.

A template bleeding time study in the rat was undertaken to see if it is possible to correlate bleeding times with the molecular weight, anticoagulant activity or chemical composition of heparin or heparin-derived compounds. Heparin from porcine intestinal mucosa (PM-heparin) and from bovine lung (BL-heparin) as well as heparin fragments from these sources were compared. Heparin fragments of low anticoagulant activity were prepared by affinity chromatography on immobilized antithrombin as well as by chemical modification. A heparin fragment of high affinity for antithrombin (HA-fragment) caused a marked and dose-dependent increase in bleeding time while the corresponding heparin fragment with low affinity for antithrombin (LA-fragment) had a marginal and non-dose dependent effect on the bleeding time. Similar results were also obtained with PM-heparin with high and low affinity for antithrombin. A high anti-FXa activity was not always correlated with a marked bleeding tendency. Provided that a fragment was devoid of activated partial thromboplastin time (APTT) activity, it was not possible to provoke a bleeding time of 20 min or longer, although the compound was administered at a dose of 1,088 U/kg (anti-FXa activity). On the other hand, a N-acetylated chemically oversulphated heparin fragment, with a very low anti-FXa activity (1 U/mg) and with an APTT activity of 34 U/mg, caused a bleeding time of 20 min or longer in 70% of the animals after injection of the same number of APTT units, 1,088 U/kg. These data indicate that the APTT activity is a better and more sensitive indicator of the bleeding than is the anti-FXa activity.

Acetylation↗
PubMed1981

Aspirin-induced prolongation of bleeding time and perioperative blood loss.

One hundred twenty-nine patients undergoing total hip replacement were treated with aspirin at a level of either 300 mg four times a day (1.2 g/day) or 900 mg four times a day (3.6 g/day). Baseline bleeding times before aspirin treatment averaged 4.18 +/- 1.44 minutes. Two hours after 300 mg and 900 mg of aspirin, the bleeding times were 5.83 +/- 1.88 and 5.72 +/- 1.57 minutes, respectively. After three to five days of aspirin therapy at 1.2 g/day and 3.6 g/day, the bleeding times were 6.27 +/- 2.27 and 6.43 +/- 2.11 minutes, respectively. The bleeding times for all the aspirin-treated groups were longer than baseline times. No paradoxical shortening of the bleeding time was noted at the 3.6-g/day dose. Perioperative blood loss for those receiving aspirin was not increased in six of eight subsets by operation and anesthesia when compared with historical control subjects. Neither a bleeding time greater than ten minutes nor a prolongation of the bleeding time by aspirin of more than four minutes over baseline bleeding times was associated with increased perioperative blood loss.

Administration, Oral↗
PubMed1995

Definition of the bleeding tendency in factor XI-deficient kindreds--a clinical and laboratory study.

Individuals with severe factor XI deficiency are prone to excessive bleeding after injury or surgery, but the existence of a haemorrhagic tendency in partial factor XI deficiency is controversial. In this study, 172 members of 30 kindreds (20 non-Jewish) transmitting factor XI deficiency in North West England were interviewed and a bleeding history questionnaire completed. Blood was taken for coagulation assays. The questionnaires were categorised independently by two assessors to determine presence or absence of a bleeding tendency, in the absence of information about the factor XI level or family history. Analysis shows that 48% of heterozygotes have a bleeding tendency. Eighteen (60%) families came to attention because of bleeding problems in heterozygotes. Comparison of histories between partially deficient and non-deficient individuals demonstrated a higher incidence of menstrual problems, an increase in significant bruising, and an increased likelihood of excessive bleeding after tonsillectomy and dental extractions. The incidence of von Willebrand's disease was not increased, but individuals with heterozygous factor XI deficiency who were bleeders tended to have lower levels of factor VIIIc and von Willebrand factor, and were more commonly of blood group 0. These features may contribute to the bleeding tendency. There was no evidence of alteration in factor VII activity (as defined by the ratio of activity to antigen) between the bleeders and non-bleeders. This is convincing evidence for abnormal bleeding in factor XI deficiency which is not confined to severely deficient patients.

Adolescent↗
PubMed1993

The effects of two synthetic glycoprotein IIb/IIIa antagonists, Ro 43-8857 and L-700,462, on platelet aggregation and bleeding in guinea-pigs and dogs: evidence that Ro 43-8857 is orally active.

In vitro platelet aggregation studies in whole blood were used to define the species-specificity profile of two synthetic GP-IIb/IIIa antagonists, Ro 43-8857 and L-700,462. Aggregation of rhesus monkey platelets was inhibited with a similar potency to human platelets, whereas both compounds were poor antagonists in mini-pig, rabbit or hamster blood. Compared to human platelets, Ro 43-8857 was 2-3-fold less active as an inhibitor of dog and guinea-pig platelet aggregation, whereas L-700,462 was, respectively, 4- and 14-fold less active in these species. In vivo investigations with these two compounds were performed in anesthetized guinea-pigs and conscious dogs, with bleeding times measured on small mesenteric arteries or on the inner jowl respectively. Ex vivo ADP-induced whole blood platelet aggregation was completely inhibited in guinea-pigs by Ro 43-8857 following intravenous administration of 0.1 mg/kg and intraduodenal administration of 3 mg/kg, with a duration of action exceeding 5 hours. Mesenteric bleeding times were prolonged by Ro 43-8857 only at doses causing supra-maximal inhibition of aggregation, suggesting these two effects could be partially dissociated. L-700,462 (3 mg/kg i.v.) was shorter acting than Ro 43-8857 in guinea-pigs (duration approximately 1 hour) and the anti-aggregatory effect was accompanied by mesenteric bleeding time prolongations. In conscious dogs, ex vivo aggregation was inhibited to approximately 80% by Ro 43-8857 (0.3 mg/kg i.v. or 10 mg/kg p.o.) and L-700,462 (1 mg/kg i.v.). However, bleeding time prolongations accompanied these anti-aggregatory effects with both compounds. In conclusion, we have shown clear differences between two synthetic GP-IIb/IIIa antagonists, both in terms of their species-specificity in vitro and in terms of their in vivo profile, and in particular the propensity to promote bleeding from mesenteric arteries in guinea-pigs. However, the ability of Ro 43-8857 to discriminate between anti-aggregatory and bleeding effects was not evident when the bleeding time measurements were performed on the dog jowl. This suggests that the species and/or vessels on which the bleeding time is performed, is also an important consideration when characterizing and comparing anti-platelet compounds, even with drugs acting via the same mechanism. These results are relevant for the future design of in vivo animal experiments to characterize this new class of compounds and in the interpretation of the data obtained to the clinical situation.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetates↗
PubMed1996

Limiting systemic plasminogenolysis reduces the bleeding potential for tissue-type plasminogen activators but not for streptokinase.

Clinical experience suggests that thrombolytic-induced bleeding is associated with systemic activation of the thrombolytic system. Using fibrin specific variants of tissue-type plasminogen activator (t-PA) and making use of the apparent fibrin specificity of streptokinase (SK) in the rabbit we tested the hypothesis that minimizing systemic plasmin production and fibrinogenolysis will decrease hemorrhages in models of peripheral bleeding and embolic stroke. t-PA consumed 51% of the available fibrinogen; caused cerebral bleeds and increased peripheral bleeding time. Fibrin-specific variants of t-PA depleted less than 20% of the fibrinogen and did not cause peripheral or cerebral bleeding. However, an equipotent dose of SK converted only 12% of the available fibrinogen but increased bleeding time and caused hemorrhagic conversion in 75% of embolic stroke model animals treated. The data suggest that bleeding associated with tissue-type plasminogen activators is linked to systemic plasmin generation and subsequent fibrinogenolysis. This hypothesis does not explain the mechanism(s) of SK-induced bleeding.

Animals↗
PubMed1981

Upper gastrointestinal tract bleeding. Predisposing factors, diagnosis, and therapy.

The mortality from upper gastrointestinal (GI) tract bleeding has remained constant at 10% during the past 40 years. Many drugs may precipitate upper GI tract bleeding by disrupting the gastric mucosal barrier. Aspirin-induced injury to the gastric mucosa and GI tract bleeding have been documented in many studies; some of the mechanisms involved are known, but others are still being investigated. An approach to the bleeding patient is suggested; initial resuscitation, history taking, physical examination, determination of bleeding levels, and diagnostic procedures to determine the cause of bleeding are reviewed. Also described are available therapies for GI tract bleeding-gastric lavage, drug therapy, endoscopic control, electrocautery, thermal probe, tissue adhesive, and laser photocoagulation. The merits of the argon laser and the neodymium-yttrium aluminum garnet laser (both still in experimental stages) are described and compared. No pharmacologic or endoscopic therapies for upper GI tract bleeding have been proved effective.

Angiography↗
PubMed2000

Use of calcium channel blockers and risk of hospitalized gastrointestinal tract bleeding.

BACKGROUND: We conducted a case-control study of the association between calcium channel blocker use and gastrointestinal (GI) tract bleeding in hypertensive members of a health maintenance organization. METHODS: Case patients (n=174) were treated hypertensive health maintenance organization members hospitalized for GI tract bleeding between January 1992 and December 1994. Case patients were identified using computerized diagnosis codes and were confirmed by medical record review. Control subjects (n=771) were treated hypertensive members selected from ongoing studies at the health maintenance organization. Computerized pharmacy data and medical records were used to assess medication use and other risk factors for GI tract bleeding. RESULTS: Compared with beta-blocker users, calcium channel blocker users had an age-, sex- and calendar year-adjusted relative risk (RR) of GI tract bleeding of 2.60 (95% confidence interval [CI], 1.71-3.96). The RR associated with calcium channel blocker use was 2.05 (95% CI, 1.33-3.17) after further adjustment for number of recent visits, diastolic blood pressure, chronic congestive heart failure, and duration of hypertension. No significant dose-response relationship was observed. Compared with beta-blocker users, angiotensin-converting enzyme inhibitor users had an RR of 1.22 (95% CI, 0.75-1.97). Calcium channel blocker use tended to be more strongly associated with risk of lower GI tract bleeding (RR, 2.56; 95% CI, 1.08-6.05) than with risk of upper GI tract bleeding (RR, 1.54; 95% CI, 0.91-2.59) or peptic ulcer-related bleeding (RR, 1.17; 95% CI, 0.62-2.21), although these results were compatible with chance. CONCLUSIONS: Calcium channel blocker use might be associated with an elevated risk of GI tract bleeding. These findings require confirmation in randomized studies.

Adrenergic beta-Antagonists↗
PubMed2003

Anticoagulant-related bleeding in older persons with atrial fibrillation: physicians' fears often unfounded.

BACKGROUND: Many studies have documented the underuse of anticoagulant (ie, warfarin sodium) therapy as stroke prophylaxis in older persons with atrial fibrillation. Failure to prescribe anticoagulant agents to these patients is often due to physicians' perceiving the risk of major bleeding as unacceptably high because of the presence of such clinical risk factors as hypertension, falls, a history of gastrointestinal tract bleeding, and lack of assurance about compliance. OBJECTIVES: To critically appraise whether the presence of additional clinical factors that increase the risk of bleeding affects the chance of anticoagulant-related hemorrhage, and to develop an approach to the use of anticoagulant agents in older patients with atrial fibrillation who have any of these factors. METHODS: Systematic MEDLINE literature search from January 1966 to March 2002. RESULTS: Many of the factors that are purported to be barriers to anticoagulant therapy in older persons with atrial fibrillation probably should not influence the choice of stroke prophylaxis in these patients. These include previous episodes of upper gastrointestinal tract bleeding, predisposition to falling, and old age in itself. For some other factors, such as alcoholism, participation in activities that predispose to trauma, the presence of a bleeding diathesis or thrombocytopenia, and noncompliance with monitoring, there is little or conflicting evidence about their effect on anticoagulant-related bleeding. However, they should be considered in the clinical decision-making process. CONCLUSIONS: For many older patients with atrial fibrillation, physicians' fears of the risk of bleeding in association with anticoagulant therapy are often exaggerated and unfounded. Therefore, the salient issue in selecting older patients with atrial fibrillation for anticoagulation is accurately estimating their stroke risk, with bleeding risk during anticoagulation being a lesser issue, relevant to only a few patients.

Aged↗
PubMed2005

Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction.

BACKGROUND: Combinations of aspirin with thienopyridine derivatives (clopidogrel bisulfate or ticlopidine hydrochloride) and/or warfarin sodium are increasingly being used in various cardiac conditions. However, little is known about the bleeding risks associated with these combinations, particularly in elderly individuals at the population level. This study estimates the bleeding risks associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients. METHODS: We conducted a population-based observational cohort study using linked administrative databases. A total of 21,443 elderly survivors of acute myocardial infarction between 1996 and 2000 were studied. Patients were divided into 5 groups according to drug exposure: aspirin alone, warfarin alone, aspirin plus a thienopyridine derivative (antiplatelet combination), aspirin plus warfarin (anticoagulant combination), and aspirin plus warfarin plus a thienopyridine derivative (3-drug combination). Hospitalizations for bleeding events were examined. RESULTS: Hospitalizations for bleeding were observed in 1428 patients (7%). Compared with rates of patients receiving aspirin alone (0.03 per patient-year), rates of bleeding were higher among patients receiving the antiplatelet combination (0.07 per patient-year), the anticoagulant combination (0.08 per patient-year), and the 3-drug combination (0.09 per patient-year). Compared with aspirin alone, the adjusted odds ratios (95% confidence intervals) for bleeding were 1.65 (1.02-2.73) for patients receiving the antiplatelet combination and 1.92 (1.28-2.87) for patients receiving the anticoagulant combination. Only 1 of 141 patients in the 3-drug combination group had a bleeding event. CONCLUSION: In practice, antiplatelet and anticoagulant combinations lead to modest increases in bleeding risk in elderly patients, but the overall risk is small.

Age Factors↗
PubMed1996

Correcting prolonged bleeding during renal transplantation with estrogen or plasma.

OBJECTIVE: To determine the efficacy and relative effectiveness of conjugated entrogens (CE) and fresh-frozen plasma (FFP) in normalizing prolonged preoperative bleeding times during renal transplantation. DESIGN: Prospective, randomized trial. SETTING: A university regional referral center for transplantation. PATIENTS: Patients scheduled for renal transplantation with preoperative bleeding times greater than 10 minutes (normal, < 7 minutes) following informed consent were asked to participate in the randomized protocol. Those with bleeding times of 8 to 9.5 minutes were asked, following informed consent, to be a control group receiving neither CE nor FFP. INTERVENTIONS: Following induction of anesthesia and drawing of baseline laboratory tests, patients were administered randomly, using a table of random numbers, either 50 mg of CE or 2 U of FFP. MAIN OUTCOME MEASURES: Bleeding time measurements and other laboratory tests were repeated at the end of surgery as well as at 24 and 48 hours postoperatively. RESULTS: Treatment with CE and FFP decreased the patients' bleeding times from 16.68 +/- 0.8 (SEM) and 17.13 +/- 0.85 minutes to 7.67 +/- 0.79 (P < .001) and 10.50 +/- 1.27 minutes (P < .001), respectively, by the end of surgery. At 24 and 48 hours postoperatively, the CE group had bleeding times of 9.77 +/- 0.99 and 9.81 +/- 1.24 minutes (P < .001 for both), respectively, whereas the FFP group bleeding times were 12.76 +/- 1.57 (P = .003) and 12.14 +/- 1.56 minutes (P = .001), respectively. There were no statistical differences for the control group compared with baseline either at the end of surgery or at 24 hours. CONCLUSIONS: Although both CE and FFP significantly decreased prolonged preoperative bleeding times during renal transplantation, CE might be preferred because of lower risk and cost, as well as a longer duration of action.

Adult↗
PubMed2002

Danazol for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is an important cause of ill health in pre menopausal women. Medical therapy, with the avoidance of possibly unnecessary surgery is an attractive treatment option, but there is considerable variation in practice and uncertainty about the most effective therapy. Danazol is a synthetic steroid with anti-oestrogenic and anti progestogenic activity, and weak androgenic properties. Danazol suppresses oestrogen and progesterone receptors in the endometrium, leading to endometrial atrophy (thinning of the lining of the uterus) and reduced menstrual loss and to amenorrhoea in some women. OBJECTIVES: To determine the effectiveness and tolerability of danazol when used for heavy menstrual bleeding in women of reproductive years. SEARCH STRATEGY: All studies which might describe randomised controlled trials of danazol for the treatment of heavy menstrual bleeding were obtained by electronic searches of MEDLINE, EMBASE, Current Contents, CINAHL, National Research Register and the Menstrual Disorders and Subfertility Group's Specialist Register of controlled trials (on 6 November 2001). Attempts were also made to identify trials from citation lists of included trials and relevant review articles. In most cases the first author of each included trial was contacted for unpublished additional information. SELECTION CRITERIA: Randomised controlled trials of danazol versus placebo, any other medical (non-surgical) therapy or danazol in different dosages for heavy menstrual bleeding in women of reproductive age with regular HMB measured either subjectively or objectively. Trials that included women with post menopausal bleeding, intermenstrual bleeding and pathological causes of heavy menstrual bleeding were excluded. DATA COLLECTION AND ANALYSIS: Nine RCTs, with 353 women, were identified that fulfilled the inclusion criteria for this review. Quality assessment and data extraction were performed independently by two reviewers. The main outcomes were menstrual blood loss, the number of women experiencing adverse effects, weight gain, withdrawals due to adverse effects and dysmenorrhoea. If data could not be extracted in a form suitable for meta-analysis, they were presented in a descriptive format. MAIN RESULTS: Most data were not in a form suitable for meta analysis, and the results are based on a small number of trials, all of which are under-powered. Danazol appears to be more effective than placebo, progestogens, NSAIDs and the OCP at reducing MBL, but confidence intervals were wide. Treatment with danazol caused more adverse events than NSAIDs (OR 7.0; 95% CI 1.7, 28.2) and progestogens (OR 4.05, 95% CI 1.6, 10.2), but this did not appear to affect adherence to treatment. Danazol was shown to significantly lower the duration of menses when compared with NSAIDs (WMD -1.0; 95% CI -1.8, -0.3) and a progesterone releasing IUD (WMD -6.0; 95% CI -7.3, -4.8). There were no randomised trials comparing danazol with tranexamic acid or the levonorgestrel-releasing intrauterine system. REVIEWER'S CONCLUSIONS: Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments, though it is uncertain whether it is acceptable to women. The use of danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. Overall no strong recommendations can be made due to the small number of trials, and the small sample sizes of the included trials.

Danazol↗
PubMed2003

H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer.

BACKGROUND: Peptic ulcer is the main cause for upper gastrointestinal haemorrhage, and Helicobacter pylori infection is the main etiologic factor for peptic ulcer disease. Maintenance antisecretory therapy has been the standard long-term treatment for patients with bleeding ulcers to prevent recurrent bleeding. On the other hand, the precise efficacy of H. pylori eradication for the prevention of rebleeding from peptic ulcer is unknown. OBJECTIVES: To compare the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (the Cochrane Library issue 1, 2003), MEDLINE (January 1966 to March 2003), EMBASE (January 1988 to March 2003), CINAHL (January 1982 to March 2003), and reference lists of articles. We also conducted a manual search from several congresses. SELECTION CRITERIA: Controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. DATA COLLECTION AND ANALYSIS: Extraction and quality assessment of studies were done by two reviewers. Study authors were contacted for additional information. MAIN RESULTS: Six studies with a total of 355 patients were included in the first meta-analysis: mean percentage of rebleeding in H. pylori eradication therapy group was 4.5%, and in the non-eradication therapy group without subsequent long-term maintenance antisecretory therapy it was 23.7% (OR 0.18, 95% CI 0.09 to 0.37; there was no statistical evidence of heterogeneity; NNT was 5, 95% CI 4 to 8). Three studies with a total of 470 patients were included in the second meta-analysis: mean percentage of rebleeding in H. pylori eradication therapy group was 1.6%, and in non-eradication therapy group with long-term maintenance antisecretory therapy it was 5.6% (OR 0.25, 95% CI 0.08 to 0.76; heterogeneity was not demonstrated; NNT was 20, 95% CI 12 to 100). Subanalysis. Excluding patients taking non-steroidal anti-inflammatory drugs (NSAIDs) at the time of recurrent bleeding resulted in a rebleeding rate of 4% (first meta-analysis) or 0.78% (second meta-analysis) in the group receiving H. pylori eradication therapy. When only patients with H. pylori eradication success were included, rebleeding rate was 1% in H. pylori eradication therapy group, and NNT decreased from 5 to 4. In some cases, recurrence of H. pylori infection seemed to be responsible for recurrence of bleeding. REVIEWER'S CONCLUSIONS: Treatment of H. pylori infection is more effective than antisecretory non-eradicating therapy (with or without long-term maintenance antisecretory therapy) in preventing recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori infection, and eradication therapy should be prescribed to H. pylori-positive patients.

Anti-Ulcer Agents↗
PubMed2004

H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer.

BACKGROUND: Peptic ulcer is the main cause for upper gastrointestinal haemorrhage, and Helicobacter pylori infection is the main etiologic factor for peptic ulcer disease. Maintenance antisecretory therapy has been the standard long-term treatment for patients with bleeding ulcers to prevent recurrent bleeding. On the other hand, the precise efficacy of H. pylori eradication for the prevention of rebleeding from peptic ulcer is unknown. OBJECTIVES: To compare the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (the Cochrane Library issue 4, 2003), MEDLINE (January 1966 to January 2004), EMBASE (January 1988 to January 2004), CINAHL (January 1982 to January 2004), and reference lists of articles. We also conducted a manual search from several congresses. SELECTION CRITERIA: Controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. DATA COLLECTION AND ANALYSIS: Extraction and quality assessment of studies were done by two reviewers. Study authors were contacted for additional information. MAIN RESULTS: Seven studies with a total of 578 patients were included in the first meta-analysis: mean percentage of rebleeding in H. pylori eradication therapy group was 2.9%, and in the non-eradication therapy group without subsequent long-term maintenance antisecretory therapy it was 20% (OR 0.17, 95% CI 0.10 to 0.32; there was no statistical evidence of heterogeneity; NNT was 7, 95% CI 5 to 11). Three studies with a total of 470 patients were included in the second meta-analysis: mean percentage of rebleeding in H. pylori eradication therapy group was 1.6%, and in non-eradication therapy group with long-term maintenance antisecretory therapy it was 5.6% (OR 0.25, 95% CI 0.08 to 0.76; heterogeneity was not demonstrated; NNT was 20, 95% CI 12 to 100). SUBANALYSIS: Excluding patients taking non-steroidal anti-inflammatory drugs (NSAIDs) at the time of recurrent bleeding resulted in a rebleeding rate of 2.7% (first meta-analysis) or 0.78% (second meta-analysis) in the group receiving H. pylori eradication therapy. When only patients with H. pylori eradication success were included, rebleeding rate was 1.1% in H. pylori eradication therapy group, and NNT decreased from 7 to 6. In some cases, recurrence of H. pylori infection seemed to be responsible for recurrence of bleeding. REVIEWERS' CONCLUSIONS: Treatment of H. pylori infection is more effective than antisecretory non-eradicating therapy (with or without long-term maintenance antisecretory therapy) in preventing recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori infection, and eradication therapy should be prescribed to H. pylori-positive patients.

Anti-Ulcer Agents↗