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Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding.

BACKGROUND AND METHODS: We compared propranolol therapy and endoscopic ligation for the primary prevention of bleeding from esophageal varices. This prospective, controlled trial included consecutive eligible patients who had large varices (>5 mm in diameter) that were at high risk for bleeding. The patients were assigned to either propranolol therapy, at a dose sufficient to decrease the base-line heart rate by 25 percent, or variceal ligation, to be performed weekly until the varices were obliterated or so reduced in size that it was not possible to continue treatment. RESULTS: Of the 89 patients, 82 of whom had cirrhosis of the liver, 44 received propranolol and 45 underwent variceal ligation. The mean (+/-SD) duration of follow-up in each group was 14+/-9 and 13+/-10 months, respectively. The mean time required to achieve an adequate reduction in the heart rate was 2.5+/-1.7 days; the mean number of sessions needed to complete variceal ligation was 3.2+/-1.1. After 18 months, the actuarial probability of bleeding was 43 percent in the propranolol group and 15 percent in the ligation group (P=0.04). Twelve patients in the propranolol group and four in the ligation group had bleeding. Three of the four in the ligation group had bleeding before their varices had been obliterated. Nine patients in the ligation group had recurrent varices, a mean of 3.7 months after the initial treatment. Five patients in each group died; bleeding from the varices was the cause of death of four patients in the propranolol group and of three in the ligation group. There were no serious complications of variceal ligation; in the propranolol group, treatment was stopped in two patients because of side effects. CONCLUSIONS: In patients with high-risk esophageal varices, endoscopic ligation of the varices is safe and more effective than propranolol for the primary prevention of variceal bleeding.

Adrenergic beta-Antagonists↗

Early administration of vapreotide for variceal bleeding in patients with cirrhosis.

BACKGROUND: In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue followed by endoscopic treatment are unknown. METHODS: We studied the effects of treatment with vapreotide, a somatostatin analogue, begun before endoscopic treatment in 227 patients with cirrhosis who were hospitalized for acute upper gastrointestinal bleeding. The patients were randomly assigned to receive vapreotide (a 50-microg intravenous bolus followed by an infusion at a rate of 50 microg per hour for five days) or placebo within a mean (+/-SD) of 2.3+/-1.5 hours after admission. All the patients received endoscopic treatment a mean of 2.6+/-3.3 hours after the infusion was begun. After the exclusion of 31 patients whose bleeding was not caused by portal hypertension, there were 98 patients in each group. RESULTS: At the time of endoscopy, active bleeding was evident in 28 of 91 patients in the vapreotide group (31 percent), as compared with 43 of 93 patients in the placebo group (46 percent) (P=0.03). During the five-day infusion, the primary objective--survival and control of bleeding--was achieved in 65 of 98 patients in the vapreotide group (66 percent) as compared with 49 of 98 patients in the placebo group (50 percent) (P=0.02). The patients in the vapreotide group received significantly fewer blood transfusions (2.0+/-2.2 vs. 2.8+/-2.8 units, P=0.04). Overall mortality rates at 42 days were not significantly different in the two groups. CONCLUSIONS: In patients with cirrhosis and variceal bleeding, the combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone as a method of controlling acute bleeding. However, the use of combination therapy does not affect mortality rates at 42 days.

Blood Transfusion↗

Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding.

BACKGROUND: Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients. METHODS: We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding. RESULTS: We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001). CONCLUSIONS: Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel.

Aged↗

Endoscopic injection therapy in bleeding Mallory-Weiss syndrome: a randomized controlled trial.

BACKGROUND: Endoscopic injection is widely used in the therapy of bleeding gastroduodenal ulcers, but its role in the management of bleeding Mallory-Weiss tears has not been properly assessed. METHODS: Sixty-three patients undergoing emergency endoscopy in whom there was a high index of suspicion that a Mallory-Weiss tear was the source of bleeding were randomly assigned to undergo endoscopic injection therapy (epinephrine and polidocanol) or no endoscopic therapy in 2 university-affiliated hospitals. Rates of recurrent bleeding, transfusion requirements, complications, mortality, and length of hospital stay were determined for both groups of patients. RESULTS: Bleeding recurred in 8 patients in the control group versus only 2 in the endoscopic treatment group (25.8% vs. 6.2%, p < 0.05). Hospital stay was longer for the control group (5.5 +/- 0.2, median 6.0, range 2.0-8.0 days vs. 3.4 +/- 0.2, median 3.0, range 2.0-6.0 days; p < 0.001). There was a trend toward a higher transfusion requirement after endoscopy in the control group versus the patients treated by injection (0.9 +/- 0.2, median 0.0, range 0.0-4.0 units vs. 0.2 +/- 0.1, median 0.0, range 0.0-2.0 units; p = 0.09). No complications or adverse events caused by endoscopic injection were noted. Two patients in the control group died of causes unrelated to bleeding. CONCLUSIONS: Endoscopic injection therapy is a useful option in the management of patients with Mallory-Weiss syndrome at high risk for recurrent bleeding.

Epinephrine↗

Epinephrine versus epinephrine plus fibrin glue injection in peptic ulcer bleeding: a prospective randomized trial.

BACKGROUND: Peptic ulcer bleeding remains a disease with considerable morbidity and mortality. Epinephrine is the most widely used endoscopic injection agent, but bleeding recurs in 20% of high-risk cases. Fibrin glue might be an ideal injection agent, based on its physiologic properties, despite its demanding injection technique and high cost. The aim of this study was to determine whether the injection of fibrin glue in combination with epinephrine improves outcome for patients at high risk of recurrent bleeding. METHODS: Patients were prospectively randomized to injection of epinephrine alone (n = 70) or epinephrine plus fibrin glue (n = 65). Endoscopy was repeated daily until the ulcer base was clean. All patients were treated with high-dose omeprazole. RESULTS: Initial hemostasis was 100% in both groups. There was no significant overall difference in rates of recurrent bleeding (24.3% and 21.5%, respectively, for epinephrine and epinephrine plus fibrin). When patients were stratified according to Forrest criteria, no significant difference could be found, although there was a trend toward less recurrent bleeding after fibrin injection of actively bleeding ulcers. There was no significant difference in the proportions of patients who required surgery (10% and 6%, respectively, for epinephrine and epinephrine plus fibrin). Mortality was the same (3%) in each group. CONCLUSIONS: Adding fibrin glue to epinephrine for injection treatment of bleeding peptic ulcers does not improve outcome. Fibrin glue might be of some value in selected cases.

Adult↗

Endoscopic cryotherapy for the treatment of bleeding mucosal vascular lesions of the GI tract: a pilot study.

BACKGROUND: Thermal therapy is the cornerstone of endoscopic treatment of bleeding mucosal lesions of the GI tract. However, there is a 20% failure rate and contact devices may be cumbersome in the treatment of large bleeding areas. A pilot study was conducted to evaluate the safety and efficacy of endoscopic cryotherapy for bleeding mucosal vascular lesions. METHODS: Patients with recurrent bleeding from diffuse mucosal vascular lesions were treated with cryotherapy and had endoscopic and clinical follow-up. RESULTS: Twenty-six patients with gastric and duodenal arteriovenous malformations (n = 7), watermelon stomach (n = 7), radiation-induced gastritis (n = 5), and radiation-induced proctitis (n = 7) were treated with mean of 3.4 (1.6) sessions. The best results were achieved in patients with radiation-induced proctitis, with cessation of bleeding in all 7 patients. Cryotherapy was also effective in patients with multiple arteriovenous malformations (86%) and watermelon stomach (71%). It was less effective in patients with radiation-induced damage to stomach and duodenum, although all patients in this group were debilitated because of disseminated malignancy. CONCLUSIONS: Cryotherapy is a safe and effective treatment for bleeding from diffuse mucosal lesions of the GI tract. Bleeding from radiation-induced proctitis and multiple arteriovenous malformations is particularly responsive to endoscopic cryotherapy.

Aged↗

Usefulness of endoscopic band ligation for bleeding small bowel vascular lesions.

BACKGROUND: The optimal therapy for bleeding small bowel vascular lesions is controversial. This study investigated the efficacy and safety of endoscopic band ligation in this clinical condition. METHODS: Fourteen patients bleeding from angiodysplasia and 4 bleeding from Dieulafoy's lesions located in the small bowel were included in this pilot study. Endoscopic band ligation was performed by using less than 200 mBar negative pressure in suctioning the target lesion into the ligation cap just before band release. Mean follow-up was 18 months (range 6-31 months). OBSERVATIONS: Endoscopic band ligation achieved hemostasis in a single session in all patients. No adverse events occurred except for mild abdominal pain in two patients. Mortality was null, and no patient required further blood transfusion during the 40 days after endoscopic band ligation. No patient with Dieulafoy's lesion had further bleeding, whereas bleeding recurred in 6 of 14 (43%) patients with angiodysplasia during long-term follow-up. CONCLUSIONS: Endoscopic band ligation is safe and effective for treatment of acutely bleeding small bowel vascular lesions. Although endoscopic band ligation is definitive therapy for Dieulafoy's lesion, long-term efficacy in the treatment of GI bleeding from angiodysplasia is limited.

Aged↗

Reduction in the need for hospitalization for recurrent ischemic events and bleeding with clopidogrel instead of aspirin. CAPRIE investigators.

BACKGROUND: Repeat hospitalizations of patients with atherosclerosis represent a considerable burden on the health care system. We sought to determine whether clopidogrel compared with aspirin decreases the need for rehospitalization for ischemia and bleeding. METHODS AND RESULTS: The Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial was a randomized, blinded, multicenter, trial of 19,185 patients with atherosclerotic disease manifested as recent ischemic stroke or myocardial infarction or symptomatic peripheral arterial disease. Without any double-counting of events, the number of rehospitalizations for ischemic events (defined as angina, transient ischemic attack, or limb ischemia) or bleeding events was determined for the entire cohort. There was a significant reduction in the total number of rehospitalizations for ischemic events or bleeding with clopidogrel use compared with aspirin (1502 vs 1673; P =.010) over an average of 1.6 years of treatment. This reduction in rehospitalization was consistent across individual outcomes of angina, transient ischemic attack, limb ischemia, and bleeding. Compared with aspirin, clopidogrel also resulted in a 7.9% relative risk reduction in a combined end point of vascular death, stroke, myocardial infarction, or rehospitalization for ischemic events or bleeding (15.1% to 13.7% at 1 year; P =.011). Adjusting for baseline prognostic variables, clopidogrel therapy was an independent predictor for reduction of vascular death, stroke, myocardial infarction, or rehospitalization for ischemic events or bleeding (P =.009). CONCLUSIONS: Treatment with clopidogrel results in a significant decrease in the need for rehospitalization for ischemic events or bleeding compared with aspirin. This meaningful end point tracks well with other, more traditional measures of outcome and has incremental value beyond such end points.

Aspirin↗

Reduced vaginal bleeding in postmenopausal women who receive combined norethindrone acetate and low-dose ethinyl estradiol therapy versus combined conjugated equine estrogens and medroxyprogesterone acetate therapy.

OBJECTIVE: The purpose of this study was to compare the effects on vaginal bleeding patterns of continuous combined hormone replacement therapy with norethindrone acetate and ethinyl estradiol versus conjugated equine estrogens and medroxyprogesterone acetate. STUDY DESIGN: Three hundred fifty-seven postmenopausal women were selected randomly (in a blinded manner) to 12 months of treatment with 1 mg norethindrone acetate/5 microg ethinyl estradiol, placebo, or open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (conjugated equine estrogens/medroxyprogesterone acetate [CEE/MPA]; Prempro). The incidence and duration of vaginal bleeding were assessed throughout the study. Statistical analyses used Cochran-Mantel-Haenszel methodology and analysis of variance. RESULTS: At 3 months, 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy reduced the incidence of bleeding (12% vs 23%; P <.029) and bleeding and/or spotting (22% vs 44%; P <.001), compared with conjugated equine estrogens/medroxyprogesterone acetate therapy. The mean duration of bleeding and bleeding and/or spotting were also reduced with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate (P =.004 and P <.001, respectively). The incidence of cumulative amenorrhea at every monthly interval was significantly better with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate therapy (P <.05). Associated adverse event (ie, headache, breast pain) incidence rates were similar in the 2 active treatment groups. CONCLUSION: The 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy provides significantly better control of vaginal bleeding than conjugated equine estrogens/medroxyprogesterone acetate therapy at all time points investigated in this 12-month study.

Adult↗

Simulation of bleeding in endoscopic procedures using virtual reality.

BACKGROUND AND PURPOSE: An image-based approach has been developed to represent bleeding in a simulator for transurethral resection of the prostate (TURP). Whereas previous groups attempted to simulate bleeding mathematically over tissue surfaces or in blood vessels, our approach focused on macroscopic visualization of bleeding in a fluid environment. The TURP is an ideal procedure for simulator-based training because of its importance as a skill to acquire as well as its long learning curve. The most challenging step in creating a realistic TURP simulator is simulated bleeding. MATERIALS AND METHODS: We took an image-based approach in which we generated blood flow movies of bleeding vessels having different severity and position under variable fluid flow conditions and processed them to separate the blood flow from the background anatomy. We then organized the movies into a parametric database. During the running of the simulation, resection systematically triggers the playback of a blood flow movie (bleeding event). The movie is texture mapped onto a virtual surface that is positioned, oriented, morphed, composited, and looped into the virtual scene. RESULTS AND CONCLUSION: The technique produced an accurate depiction of bleeding vessels one would encounter during a TURP. The image changes readily according to the fluid flow state.

Blood Loss, Surgical↗

Laparoscopy-assisted exploration of obscure gastrointestinal bleeding after capsule endoscopy: the Korean experience.

BACKGROUND: Obscure gastrointestinal bleeding (OGB) is generally defined as recurrent acute or chronic bleeding for which no source has been identified by routine radiologic and endoscopic examination. The aim of this study was to report our early experiences detecting small bowel bleeding by capsule endoscopy (CE) and the results of laparoscopy assisted surgery for OGB. MATERIALS AND METHODS: Seventy-five patients with OGB were examined by CE. Twelve of 24 patients in the active bleeding group underwent laparoscopic or laparoscopy assisted surgery and we carried out intraoperative enteroscopy to find the focus of the bleeding. RESULTS: Laparoscopic localization of the lesion was successful for 4 patients-those with Meckel's diverticulum, gastrointestinal stromal tumor, lymphoma, and ischemic necrosis. In 3 cases in which there was no natural passage of the capsule endoscope, lesions were identified by small bowel exploration through simple palpation by hand. Intraoperative enteroscopy was performed extracorporeally in 5 cases through a minilaparotomy window using an extended incision of a port site less than 7 cm in length. The lesions that were identified by CE preoperatively were resected successfully, via laparoscopic or laparoscopy-assisted surgery. The gastrointestinal bleeding has not recurred during the postoperative follow-up period (mean, 10.6 months). CONCLUSION: The laparoscopic approach can be chosen for surgical management of OGB patients with active bleeding whose lesions have been identified by CE. This approach allows minimally invasive surgical treatment for ongoing OGB.

Adolescent↗

Economic impact of bleeding complications and the role of antithrombotic therapies in percutaneous coronary intervention.

The economics of bleeding complications and the role of antithrombotic therapies in percutaneous coronary intervention (PCI) are discussed. More than 1 million PCI procedures are performed annually in the United States, at a mean cost of hospitalization of approximately $9,000 and billions of dollars in total health care costs. Ischemic complications have been reduced to the point that bleeding has become the most common complication. Bleeding complications and transfusions are also among the most costly complications in PCI, accounting for an incremental cost of hospitalization after PCI that may exceed $10,000, due to increased length of stay and the use of additional resources such as ultrasound evaluation and surgical repair of the vascular site. Anemia and transfusions are also associated with increased morbidity and mortality, contributing to additional treatment costs beyond those directly attributable to correcting the bleeding complication. In the past decade, significant reductions in heparin dose and warfarin use were associated with reduced bleeding complications, but glycoprotein IIb/IIIa inhibitors have been shown to increase the clinical and economic costs of bleeding complications. The replacement of heparin with bivalirudin is associated with significant reductions in the costs of antithrombotic therapy and in complications. Reductions in bleeding complications have become a primary target for further improvements in both clinical and economic outcomes.

Angioplasty, Balloon, Coronary↗

Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel.

It has been suggested that the administration of an anti-progesterone might improve bleeding patterns in women with irregular bleeding while using low-dose progestin-only contraception. We report the findings of a double-blind, randomized, placebo-controlled trial of mifepristone 50 mg taken once every 4 weeks in 100 Chinese women (50 subjects and 50 controls) complaining of frequent and irregular bleeding while using a levonorgestrel-releasing subdermal contraceptive implant. In all women, regardless of treatment, the frequency of bleeding decreased significantly over 360 days of observation. Women recorded significantly shorter episodes of bleeding (P: < 0.0002) during mifepristone treatment than during the 90 days before treatment started. In contrast, the duration of bleeding episodes fell more gradually in placebo-treated controls. Women using mifepristone were more likely to find treatment acceptable than women receiving a placebo tablet (P: < 0.01). Despite concern that anti-progestogenic effects may jeopardize contraception, there were no pregnancies. This approach may offer a useful strategy to improve continuation rates by alleviating unwanted side-effects until bleeding patterns improve spontaneously with time.

Adolescent↗

The effect of a change in the dose of trimegestone on the pattern of bleeding in estrogen-treated post-menopausal women: 6 month extension of a dose-ranging study.

BACKGROUND: Abnormal bleeding pattern is one major reason for non-compliance with hormone replacement therapy (HRT) in post-menopausal women. We have previously documented that the dose of trimegestone is the main determinant of the pattern of bleeding in women treated with estradiol (E(2)) and sequential combined trimegestone administered in four doses. The objectives of this study were to test the effect of changing the dose of trimegestone and the duration of treatment on the pattern of bleeding in these women who then entered a 6 month extension phase where a single dose of trimegestone was given sequentially combined with E(2). METHODS: The menstrual diaries of 134 post-menopausal women who completed a dose-ranging study of trimegestone and then entered a 6 month extension phase were analysed. In the 6 month extension study, all women were given one dose of trimegestone (0.25 mg) in a sequential fashion (day 15-28) combined with continuous E(2) (2 mg/day). RESULTS: Women who had received trimegestone 0.25 mg/day during the first 6 months experienced no change in the bleeding pattern in the 6 month extension. Women who had been treated with 0.5 mg/day dose experienced earlier onset, and more prolonged bleeding (P < 0.0001) following the change to 0.25 mg/day. Women who previously received trimegestone doses of 0.05 and 0.1 mg experienced a later onset of bleeding, which was lighter and of shorter duration (P < 0.001) during the extension phase as compared with the first 6 months. CONCLUSION: The dose of trimegestone, and not the duration of treatment, appears to be the important determinant of the pattern of bleeding in post-menopausal women on this HRT regimen.

Dose-Response Relationship, Drug↗

Correlation between endometrial histology, microvascular density and calibre, matrix metalloproteinase-3 and bleeding pattern in women using a levonorgestrel-releasing intrauterine system.

BACKGROUND: The main reason for discontinuation of the levonorgestrel-releasing intrauterine system (LNG-IUS) is unpredictable bleeding pattern. METHODS: The objective of the study was to evaluate the endometrial histology, microvascular density and calibre, and the quantification of matrix metalloproteinase (MMP-3) in long-term users of LNG-IUS, with and without bleeding. Endometrial biopsies were obtained from 58 healthy women, 29 who maintained some degree of endometrial bleeding and 29 who were amenorrhoeic. RESULTS: In the histological analysis, the majority of samples displayed a progestin-modified appearance. The major glandular diameter and the perimeter were significantly greater in the group of women with amenorrhoea. A significantly higher number of leukocytes was found in the group with bleeding (P = 0.014). No significant correlation was observed between the microvascular density or calibre and the bleeding pattern. MMP-3 showed a significantly higher number of reactive cells (P = 0.005) in the group who maintained some degree of bleeding. CONCLUSIONS: Women using LNG-IUS who maintained endometrial bleeding during its use presented a higher number of leukocytes and MMP-3 in the endometrium when compared to women using LNG-IUS who became amenorrhoeic. However, the results did not provide evidence for microvascular pattern changes.

Adult↗

Increased serum levels of nitric oxide metabolites among users of levonorgestrel-releasing implants [corrected] a possible role in progestin-induced bleeding.

BACKGROUND: Nitric oxide (NO) is a potent angiogenic and vasodilator factor that could be involved in progestin-induced bleeding. This study aimed to assess possible changes in the serum levels of NO metabolites in users of levonorgestrel-releasing implants (LNG-implants) [corrected] and to identify any correlation between some of their clinical characteristics and NO metabolite levels. METHODS: This cross-sectional study included 37 LNG-implants [corrected] users; a single 5 ml venous blood was collected at different periods of [corrected] use. Women were divided into users with acceptable menstrual bleeding (n 5 13) [corrected] and those having abnormal bleeding patterns (n 5 24) [corrected] The controls are 13 age-matched healthy women; they were fertile, had regular menstruation and did not use any contraceptive method in the previous 3 months. NO was determined by the evaluation of its oxidation products (nitrites and nitrates) where the nitrates were reduced to nitrites with cadmium filings; total serum concentrations of nitrites were measured by using the Griess reaction. RESULTS: The mean serum levels of NO metabolites were significantly higher in the LNG-implants [corrected] users than in the controls (mean+/-SE) 34.9+/-11.3 versus 6.1+/-1.5 mumol/l (P<0.001) [corrected] The mean serum levels of NO metabolites were significantly higher in the LNG-implants [corrected] users with abnormal bleeding patterns than in those with normal bleeding patterns (mean+/-SE) 41.3+/-7.4 versus 23.2+/-5.8 mumol/l (P<0.001) [corrected] There was a positive correlation between NO levels and both prolonged spotting and heavy/prolonged bleeding days (P<0.001 and P<0.01, respectively) and negative correlation between NO levels with the duration of use and length of the menstrual cycle (P<0.05). CONCLUSION: The significantly increased serum levels of NO metabolites among LNG-implants [corrected] users may primarily reflect an increase in its endometrial production, possibly secondary to its increased liberation by systemic vascular endothelium. This may result in enhanced endometrial angiogenesis and vascular dilatation which can induce and perpetuate abnormal excessive/prolonged uterine bleeding.

Adult↗

Endometrial lysosomal enzyme activity in ovulatory dysfunctional uterine bleeding, IUCD users and post-partum women.

The aim of this study was to evaluate the role of lysosomal enzymes in excessively heavy menstruation by comparing women with menorrhagia due to dysfunctional bleeding or intrauterine contraceptive device (IUCD) use with those with normal menstrual periods or with amenorrhoea associated with breastfeeding. This was a prospective cohort investigation of the activity of four endometrial lysosomal enzymes in three contrasting groups: (i) women with ovulatory dysfunctional uterine bleeding and users of intrauterine contraceptive devices; (ii) breastfeeding post-partum women in whom there are long periods of amenorrhoea, particularly in the early months post-partum; and (iii) normal cycling women. It was found that the total activity of lysosomal enzymes, particularly acid phosphatase and N-acetyl-beta-D-glucosaminidase, was markedly elevated (P < 0.001) in IUCD-exposed endometrium, and endometrium from women with dysfunctional uterine bleeding when compared with endometrium from women with a history of entirely normal menstrual periods or that in post-partum breastfeeding women. The activity of alpha-L-fucosidase was moderately elevated in IUCD users (P < 0.05) and ovulatory dysfunctional uterine bleeding (P < 0.05), whereas alphaD-mannosidase activity was elevated in ovulatory dysfunctional uterine bleeding (P < 0.05), but decreased in IUCD users (P < 0.01). No significant differences were observed in the lysosomal enzyme activities of breastfeeding post-partum women and normal cycling women. These results show that total endometrial tissue activity of four lysosomal enzymes was substantially increased throughout the cycle in most circumstances in women with two different causes for increased menstrual bleeding. This suggests a contributory role to the increased bleeding.

Acetylglucosaminidase↗

Maternal cigarette smoking as a risk factor for placental abruption, placenta previa, and uterine bleeding in pregnancy.

The authors carried out an epidemiologic study to evaluate the role of maternal cigarette smoking as a potential risk factor for placental abruption, placenta previa, and uterine bleeding of unknown etiology in pregnancy. Data for this prospective cohort study were obtained from women seeking prenatal care at any of the two tertiary, seven regional, or 17 community hospitals in the province of Nova Scotia, Canada, between January 1, 1986, and December 31, 1993. A total of 87,184 pregnancies (among 61,667 women) were registered in the database. Women who smoked during pregnancy (33%) were compared with nonsmokers, and all women were followed until the termination of pregnancy. Placental abruption was indicated in 9.9 per 1,000 pregnancies, while placenta previa and uterine bleeding of unknown etiology were indicated in 3.6 and 58.9 per 1,000 pregnancies, respectively. Women who smoked had a twofold increase in the risk of abruption (relative risk = 2.05, 95% confidence interval (CI) 1.75-2.40) in comparison with nonsmokers, while the relative risk for placenta previa was 1.36 (95% CI 1.04-1.79). However, cigarette smoking was not found to be associated with uterine bleeding of unknown etiology (relative risk = 1.01, 95% CI 0.94-1.08). There was no evidence for an increased risk of uteroplacental bleeding disorders with increasing numbers of cigarettes smoked. All analyses were adjusted for potentially confounding factors through logistic regression models based on the method of generalized estimating equations. The study confirms a positive association between cigarette smoking and placental abruption and a weak association with placenta previa but not with other uterine bleeding. The distinct pattern of results for placental abruption, placenta previa, and uterine bleeding of unknown origin suggests that these three uteroplacental bleeding disorders do not have a common etiology in relation to cigarette smoking.

Abruptio Placentae↗