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ED predictors of upper gastrointestinal tract bleeding in patients without hematemesis.

OBJECTIVES: In patients with gastrointestinal (GI) tract bleeding, the bleeding source is uncertain in the absence of hematemesis. We sought to identify clinical variables predictive of an upper GI bleeding source. METHODS: This retrospective cohort study involved patients admitted via the ED for GI tract bleeding without hematemesis, who underwent confirmatory testing. We used logistic regression analysis to identify clinical variables independently associated with an upper GI source. RESULTS: Among 325 patients, odds ratios for the strongest predictors were as follows: black stool, 16.6 (95% confidence interval [CI], 7.7-35.7); age less than 50 years, 8.4 (95% CI, 3.2-22.1); and blood urea nitrogen/creatinine ratio 30 or greater, 10.0 (95% CI, 4.0-25.6). Seven (5%) of 151 with none of these factors had an upper GI tract bleed, versus 63 (93%) of 68 with 2 or 3 factors. CONCLUSION: Black stool, age less than 50 years, and blood urea nitrogen/creatinine ratio of 30 or greater independently predict an upper GI tract bleeding source.

Adult↗

Assessment of bleeding events in clinical trials--proposal of a new classification.

Present classifications of bleeding events used in antithrombotic and/or antiplatelet clinical trials are based on the criteria developed by the Thrombolysis In Myocardial Infarction (TIMI) and Global Use of Strategies to Open Coronary Arteries (GUSTO) groups. Introduced more than a decade ago, the 2 classifications used the criteria to better categorize hemorrhagic events after therapy with thrombolytic agents. Recent advances in interventional cardiology, resulting in a domination of percutaneous intracoronary procedures over systemic drug-induced thrombolysis, have substantially changed the clinical characteristics and magnitude of bleeding complications. Moreover, disturbances of the coagulation cascade, as well as platelet inhibition caused directly by antithrombotic and antiplatelet agents, share very specific and well-recognized clinical features not reflected in the existing classifications. Bleeding events after aspirin or clopidogrel, and especially those after more delicate antiplatelet regimens with dipyridamole used in patients after ischemic stroke or transient ischemic attack, are impossible to classify by the present guidelines, other than categorically triaging them altogether to the "minor" category. Uniting entirely different bleeding events as "minor" under-rates their importance and diminishes affiliated risks, creating an illusion that they do not require monitoring and/or changes in antiplatelet or antithrombotic regimens. In reality, such unrecognized and unreported mild complications may transform into more serious bleeds or lead to noncompliance. Unauthorized withdrawal from antiplatelet agents in turn causes rebound platelet activation and higher risk for secondary vascular events. In conclusion, a new classification of bleeding events is introduced (the BleedScore), based on a point accumulation depending on the severity of hemorrhage, which is believed to be more suitable for the assessment of modern, more delicate antithrombotic and antiplatelet therapies, particularly for their realistic assessment in clinical trials.

Clinical Trials as Topic↗

Aprotinin reduces bleeding and blood product use in patients treated with clopidogrel before coronary artery bypass grafting.

BACKGROUND: An increased proportion of patients undergoing urgent coronary artery bypass graft surgery (CABG) is being treated with clopidogrel, an irreversible platelet inhibitor. Clopidogrel in combination with aspirin is known to augment bleeding, transfusion requirements, and reoperation rates after CABG. Aprotinin, a protease inhibitor, is approved for use in cardiac surgery to reduce bleeding. The aim of this study was to investigate whether or not intraoperative use of aprotinin decreases bleeding and number of transfusions after CABG in patients treated with clopidogrel less than 5 days before surgery. METHODS: We retrospectively reviewed the medical records of all consecutive patients, with preoperative clopidogrel exposure less than 5 days before surgery, who underwent urgent CABG at our institution during 1 year (n = 33). Eighteen patients received a full-dose aprotinin regime intraoperatively whereas 15 patients not receiving aprotinin served as a control group. RESULTS: The two groups were comparable with respect to baseline characteristics and operative data. Mean postoperative bleeding was 710 mL (95% confidence interval [CI]: 560 to 860) in the aprotinin group versus 1,210 mL (95% CI: 860 to 1550) in the control group (p = 0.004). The aprotinin group received fewer transfusions of packed red blood cells (0.9 U, 95% CI: 0.1 to 1.7, versus 2.7 U, 95% CI: 1.4 to 4.1; p = 0.01), platelets (0.1 U, 95% CI: 0 to 0.3, versus 0.6 U, 0.2 to 0.9; p = 0.02), and fewer blood product units (1.1 U, 95% CI: 0.1 to 2.0, versus 3.7 U, 95% CI: 2.1 to 5.4; p = 0.002). There were 3 reoperations for bleeding, all in the control group (p = 0.05). CONCLUSIONS: Aprotinin reduces bleeding, transfusion requirements of packed red blood cells, platelets, and total blood units in patients on clopidogrel undergoing urgent CABG.

Aged↗

Effective management of refractory postcardiotomy bleeding with the use of recombinant activated factor VII.

BACKGROUND: Severe coagulopathy after cardiovascular surgery may lead to intractable bleeding and is associated with increased mortality and morbidity. Recent studies have suggested that recombinant activated factor VII (rFVIIa) may play a role in decreasing postoperative bleeding. Herein we report our experience with the off-label use of rFVIIa in patients with refractory postcardiotomy bleeding. METHODS: From June 2003 to December 2005, 17 patients (mean age, 65 +/- 18 years) received rFVIIa for refractory bleeding after cardiac surgery. Preoperative risk factors for bleeding included reoperation (n = 7), emergency surgery (n = 7), and renal or hepatic failure (n = 3). Surgical procedures were aortic surgery (n = 7), complex valve operations (n = 7), coronary artery bypass grafting (n = 2), and cardiac tumor resection (n = 1). RESULTS: The average dose of rFVIIa was 103.1 +/- 30.2 microg/kg. After the administration of rFVIIa the blood loss was reduced and chest tube output decreased from an average of 300 mL/h to 60 mL/h (p = 0.024). Coagulation variables normalized (mean prothrombin time, 18 +/- 7 versus 14 +/- 3 seconds; p = 0.03; mean partial thromboplastin time, 94 +/- 50 versus 49 +/- 14 seconds; p = 0.02), and the need for blood products was significantly reduced. Only 1 patient required mediastinal reexploration. No thromboembolic complications occurred during hospitalization. CONCLUSIONS: This study suggests that rFVIIa is safe and efficacious in the management of refractory postcardiotomy bleeding. The use of rFVIIa is associated with reduced blood loss, rapid improvement of coagulation variables, and decreased need for blood products. Further studies are necessary to determine the safety and efficacy of this new hemostatic agent and its precise role in the treatment of severe postoperative coagulopathy.

Adult↗

Management of bleeding peptic ulcer: current status of intravenous proton pump inhibitors.

Over 80% of ulcer bleeding stops spontaneously, but associated mortality and morbidity remain high. Occurrence of re-bleeding increases mortality 10-fold. Endoscopic findings in those that have bled predict the risk of recurrent bleeding. Patients whose ulcers show a 'flat dot' or clean base (Forrest Class 3) rarely rebleed or need hospitalization. However, actively bleeding ulcers or those with evidence of recent hemorrhage (Forrest Classes 1 and 2) are likely to re-bleed and may need intensive care. Meta-analyses indicate that endoscopic hemostasis has reduced re-bleeding and surgical intervention by over 60% and mortality by 45%. Beyond these reductions, data indicate that (unlike H2-receptor antagonists use, largely devoid of benefits in this area) continuous intravenous infusions of high doses of proton pump inhibitors reduce rebleeding, re-endoscopy, blood transfusion and surgical intervention, but have little effect (beyond endoscopic therapy) on associated mortality, much of it due to conditions other than rebleeding.

Anti-Ulcer Agents↗

Prevention of the development of varices and first portal hypertensive bleeding episode.

Variceal bleeding is a serious complication in patients with cirrhosis. Although bleeding related mortality rates have fallen recently, it continues to be amongst the leading causes of death. Cirrhotics should be screened for varices at diagnosis. Data on preventing formation/growth of oesophageal varices (pre-primary prophylaxis) are conflicting, with insufficient evidence to use beta-blockers. In order to prevent first bleeding, there is strong evidence in patients with medium/large size oesophageal varices that either non-selective beta-blockers or banding ligation can be used. Banding is superior with respect to bleeding but mortality is similar. Non-selective beta-blockers should remain first line treatment being effective, cheap and without serious complications. In contrast banding ligation is more expensive, requires specialised staff, cannot prevent bleeding from portal hypertensive gastropathy and can cause iatrogenic bleeding. Patients with small varices, particularly if they have progressive liver disease also benefit from beta-blockers, but fewer studies confirm this therapeutic approach.

Adrenergic beta-Antagonists↗

Effect of intermittent treatment with mifepristone on bleeding patterns in Norplant implant users.

A double-blind, placebo-controlled, randomized trial, was carried out in 120 Norplant users to evaluate the effect of mifepristone, 100 mg/day administered for 2 consecutive days every 30 days, on the vaginal bleeding pattern. Treatment was given from months 2-7 of implant use. Volunteers recorded bleeding and spotting days, during treatment and for the ensuing 6-month period. During treatment, women on mifepristone recorded the same frequency of bleeding/spotting episodes but significantly less prolonged bleeding episodes than placebo controls (mean +/- SD: 11 +/- 3 vs. 22 +/- 23 days) and their total number of bleeding days was 35% lower than in the placebo group. After the end of mifepristone use, bleeding patterns were similar in both groups. One pregnancy occurred in the mifepristone-treated group, in month 6 of treatment, the outcome was a healthy male baby. We conclude that intermittent administration of mifepristone can offer a clinically significant improvement of the vaginal bleeding pattern in Norplant users.

Administration, Oral↗

Biopsy of the prostate guided by transrectal ultrasound: relation between warfarin use and incidence of bleeding complications.

AIM: To determine the relation between warfarin use and the frequency of bleeding complications after biopsy of the prostate guided by transrectal ultrasound (TRUS). METHODS: Overall, 1022 consecutive patients with suspected prostatic disease were followed after biopsy. Warfarin and aspirin use was determined on the day of the procedure. A TRUS-guided biopsy was performed and patients were offered a questionnaire to complete 10 days after the procedure, to determine any immediate or delayed bleeding complications. Follow-up telephone calls were made to those who had not replied within the stipulated period. RESULTS: Of the 1000 patients who replied, 49 were receiving warfarin, 220 were receiving aspirin and 731 were not receiving any anticoagulant drugs. Of the 49 subjects reporting current use of warfarin, 18 (36.7%) experienced haematuria, compared with 440 (60.2%) of the patients receiving no anti-coagulant drugs who reported haematuria. This was statistically significant (p = 0.001). Of the group receiving warfarin, 4 (8.2%) experienced haematospermia whereas 153 (21%) of the group receiving no anticoagulant medication reported haematospermia. This difference also was statistically significant (p = 0.030). Rectal bleeding was experienced by 7 (14.3%) of the group receiving warfarin compared with 95 (13%) in the group without anticoagulant medication, but this was not statistically significant (p = 0.80). We also demonstrated that there was no statistically significant association between the severity of the bleeding complications and medication with warfarin. CONCLUSION: None of the group receiving warfarin experienced clinically important bleeding complications. Our results suggest that the frequency and severity of bleeding complications were no worse in the warfarin group than in the control group and that discontinuing anticoagulation medication before prostate biopsy may be unnecessary.

Aged↗

Somatostatin, somatostatin analogues and other vasoactive drugs in the treatment of bleeding oesophageal varices.

Somatostatin and its analogues have been compared with a variety of other treatments for the treatment of variceal bleeding in cirrhotic patients. Meta-analyses of studies comparing somatostatin or octreotide with vasopressin or terlipressin have shown that somatostatin is somewhat superior to vasopressin and equivalent to terlipressin in controlling bleeding and has significantly fewer side effects; no difference in mortality was observed. Octreotide was somewhat better than vasopressin and terlipressin in controlling bleeding, with similar mortality. Meta-analysis of trials comparing somatostatin or octreotide with endoscopic sclerotherapy shows that both drugs are equivalent to sclerotherapy for bleeding control, early rebleeding and survival. Complications are much less frequent with drug treatment. Nine trials have compared endoscopic therapy with therapeutic regimens combining endoscopic treatment with somatostatin, octreotide or vapreotide. Meta-analysis show that the combined regimens increase the 5 days bleeding control rate of endoscopic treatments by over 20%, although there is no difference in mortality. Comparisons of somatostatin and octreotide with combined regimens of sclerotherapy + somatostatin and sclerotherapy + octreotide have shown that the combined regimens were better than drug treatments alone in controlling bleeding and preventing early rebleeding, while complications were significantly less frequent with drug therapy.

Esophageal and Gastric Varices↗

Somatostatin and its analogues in peptic ulcer bleeding: facts and pathophysiological aspects.

Peptic ulcer bleeding remains a common medical emergency and despite recent advances in management is still associated with high mortality. Endoscopic treatment remains the cornerstone for the effective management of high-risk patients. Recent evidence suggests that potent antisecretory drugs that inhibit gastric acid secretion, such as proton pump inhibitors, may be of help alone or in combination with endotherapy in the management of peptic ulcer bleeding. Somatostatin appears to offer a distinct advantage over antisecretory drugs, as it inhibits both acid and pepsin secretion and combines these effects with a reduction in gastroduodenal mucosal blood flow which seems to be important in the pathophysiology of peptic ulcer bleeding. Additionally, the inhibition of pepsin secretion might induce a decreased proteolytic activity preventing the dissolution of freshly formed clots at the site of bleeding. Despite its theoretical advantages, there has been very little evidence in the recent past in setting of randomised, controlled, clinical trials. In reviewing the available data, we found that the efficacy of somatostatin and its analogue octreotide are different in the control of peptic ulcer bleeding and this might be due to the different distribution of its receptors through the GI tract. Further studies are needed to define the exact role, if any, of somatostatin and its analogues, in high-risk patients with peptic ulcer bleeding and this might be a rather interesting area for future research.

Gastrointestinal Agents↗

Predictive value of rectal bleeding for distal colonic neoplastic lesions in a screened population.

The aim of this study was to determine the diagnostic value of rectal bleeding for distal colorectal cancer (CRC), or large (> or =10 mm) adenomas among an average-risk population. A cross-sectional survey was conducted among individuals aged 55-64 years, who attended sigmoidoscopy (FS) screening in the context of a multicentre randomised trial of FS screening for CRC. Sensitivity, specificity and positive predictive value (PPV) of rectal bleeding for large distal adenomas or CRC were calculated. Rectal bleeding was reported by 8.8% of 8507 patients examined (15% of those with large adenomas and 29% of those with CRC). The risk of CRC was increased when bleeding was associated with an altered bowel habit: odds ratio (OR)=10.42; 95% Confidence Interval (CI): 4.08-26.59; the corresponding OR for isolated bleeding was 5.29 (95% CI: 2.28-12.30). Rectal bleeding carries an increased risk of distal neoplastic lesions. However, most lesions are detected among asymptomatic subjects. This finding suggests that screening represents the optimal strategy to detect CRC or large adenomas in the distal colon in the targeted age range.

Colonic Neoplasms↗

The length of menstrual bleeding and the risk of urogenital infections in the context of the activity of hemoglobin-derived microbicidal peptides.

OBJECTIVE: Well-known natural unspecific antimicrobial factors acting in the vagina are additionally reinforced during menstrual bleeding by hemocidins--a recently discovered novel class of microbicidal peptides generated proteolytically from hemoglobin. The aim of the presented research was to investigate the relation between the average length of menstrual bleeding and the frequency of urogenital infections. We expected that the shorter menstrual bleeding might increase the risk of urogenital infections because is synonymous with the shorter period of exposition on bactericidal action of hemocidins. STUDY DESIGN: The study contains statistical analysis of an average declared length of menstrual bleeding in the group of 267 young, sexually active women with the symptoms of urogenital infections. The control group consisted of 300 young healthy women. RESULTS: The length of menstrual bleeding in the group of patients with urogenital infections (average 4.35 days) was statistically significantly shorter than in the control group (average 4.95 days). The average length of the menstrual cycle was equal and counted ca. 28 days in both groups. CONCLUSION: The length of menstrual bleeding seems to be a significant factor in the vaginal ecology maintenance.

Adolescent↗

Risk of preterm delivery in relation to vaginal bleeding in early pregnancy.

OBJECTIVE: To examine the relationship between vaginal bleeding during early pregnancy and preterm delivery. METHODS: Study subjects (N=2678) provided information regarding socio-demographic, biomedical, and lifestyle characteristics. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Any vaginal bleeding in early pregnancy was associated with a 1.57-fold increased risk of preterm delivery (95% CI: 1.16-2.11). Vaginal bleeding was most strongly related with spontaneous preterm labor (OR=2.10) and weakly associated with preterm premature rupture of membrane (OR=1.36) and medically induced preterm delivery (OR=1.32). As compared to women with no bleeding, those who bled during the first and second trimesters had a 6.24-fold increased risk of spontaneous preterm labor; and 2-3-fold increased risk of medically induced preterm delivery and preterm premature rupture of membrane, respectively. CONCLUSION: Vaginal bleeding, particularly bleeding that persists across the first two trimesters, is associated with an increased risk of preterm delivery.

Adult↗

Histological characteristics and altered expression of interleukins (IL) IL-13 and IL-15 in endometria of levonorgestrel users with different uterine bleeding patterns.

OBJECTIVE: To determine the relationship between uterine bleeding patterns in levonorgestrel users with endometrial histology and expression of interleukins (IL) IL-13 and IL-15. DESIGN: Prospective observational study. SETTING: Academic research center. PATIENT(S): Questionnaires were sent to patients (n = 578) who had levonorgestrel implants concerning bleeding patterns; 35 of these patients were identified to have regular cycle (n = 13), amenorrhea (n = 8), or metrorrhagia (n = 14). INTERVENTION(S): Endometrial biopsies, serum, histology, and immunostaining. MAIN OUTCOME MEASURE(S): Endometrial histological assessment and immunostaining for IL-13 and IL-15 and for blood levonorgestrel, E2, and progesterone levels by ELISA or RIA. RESULT(S): No correlation was found between circulating levonorgestrel, E2, or progesterone levels with the bleeding patterns, although a trend toward a lower E2 level was observed in patients with amenorrhea who had inactive endometrium. There was a direct correlation between bleeding patterns and endometrial histology, as well as IL-13 and IL-15 expression in patients with regular cycles and metrorrhagia, demonstrating secretory and proliferative endometrium, respectively. Some patients in each group were also identified as demonstrating endometritis. CONCLUSION(S): Endometrial histology may assist directing therapy and subsequently increasing compliance in progestin-only contraceptive users with irregular bleeding who fail to respond to standard therapies. Altered endometrial expression of IL-13 and IL-15, key cytokines in inflammatory and immune cell trafficking, may influence events, leading to irregular bleeding.

Amenorrhea↗

Impact of capsule endoscopy in obscure small-bowel bleeding: defining strict diagnostic criteria for a favorable outcome.

BACKGROUND: The most frequent indication for capsule endoscopy is to diagnose the cause of obscure GI bleeding. The objective of the study was to determine the impact of capsule endoscopy on the outcome of patients with GI bleeding of obscure origin. METHODS: Ninety-six patients (53 men, 43 women; mean [standard deviation] age, 60.84 years [16.55 years]) were enrolled in the study. All patients have been subjected to gastroscopy, colonoscopy, small-bowel barium follow-through or enteroclysis, and push enteroscopy; no bleeding site had been identified. Capsule endoscopy was performed with the Given M2A video capsule system. By using strict criteria, studies were classified as having positive findings, findings of uncertain significance, and no findings. Outcome was defined as continued or complete resolution of bleeding. RESULTS: Positive findings, findings of uncertain significance, and no findings were identified in 41.7%, 20.8%, and 37.5% of our study population, respectively. The most common lesions seen were angiodysplasias of the small intestine. Therapeutic intervention was possible in 82.5% of patients with positive findings and in 35.0% of patients with findings of uncertain significance. Complete resolution of bleeding, after a median (interquartile range) follow-up period of 14 months (9-17 months), occurred significantly more often in patients with positive findings (68.4%) compared with patients with findings of uncertain significance and no findings (40.8%, p = 0.009). CONCLUSIONS: Capsule endoscopy increases the diagnostic yield in the workup of patients with obscure small-bowel bleeding. Strictly defined positive findings are associated with a favorable outcome.

Endoscopes, Gastrointestinal↗

Obscure gastrointestinal bleeding.

Obscure GI bleeding is a relatively common problem facing internists, gastroenterologists, and surgeons in a typical clinical practice. The etiology is occasionally suggested by the patient's age, history, and medications. Management is complicated and typically requires a team-oriented approach, with input from the internist, gastroenterologist, radiologist, and surgeon alike. SBFT and enteroclysis seem to have a limited role, unless there is a high suspicion of a small bowel mass lesion or Crohn's disease. Scintigraphy may be performed in patients with active bleeding in whom endoscopy has failed oris contraindicated. Angiography may be used in patients with an early positive nuclear imaging or failed endoscopic therapy. Provocative angiography probably has a lower diagnostic yield than previously reported, and should be performed only in experienced centers. Helical CT is a new and potentially important option in patients with obscure bleeding, but is currently considered experimental. All patients with obscure GI bleeding should undergo repeat upper endoscopy and perhaps colonoscopy to rule out missed lesions. SBE seems to be complementary to capsule endoscopy, and it is unknown whether this should be performed before capsule endoscopy or only if capsule endoscopy yields a positive proximal small bowel finding. Double balloon enteroscopy seems promising, but the technique requires further study. Surgery should be reserved for patients who have a positive capsule endoscopy requiring surgical therapy or patients who have persistent GI bleeding requiring recurrent blood transfusions in whom all other modalities have failed. Treatment for vascularectasias, the most common cause of obscure GI bleeding, is currently inadequate,and typically requires a combination of multiple management approaches.

Algorithms↗

Impact of mean rectal dose on late rectal bleeding after conformal radiotherapy for prostate cancer: dose-volume effect.

PURPOSE: To identify the clinical and dosimetric factors predictive of a greater risk of Grade 2 or worse late rectal bleeding in patients with localized prostate cancer treated with three-dimensional conformal radiotherapy in a prospective dose-escalation study. METHODS AND MATERIALS: We performed a retrospective analysis of the clinical records and dose-volume histograms of 107 patients with Stage T1c-T3 prostate cancer treated at our institution with three-dimensional conformal radiotherapy who had a minimal follow-up of 1 year. Of the 107 patients, 21 were treated at dose level 1 (70.0 Gy), 57 at dose level 2 (72.0 Gy), and 29 at dose level 3 (75.6 Gy). The mean International Commission on Radiation Units and Measurements reference dose was 76.5 Gy (range, 69.8-82.6 Gy). RESULTS: The 4-year actuarial incidence of Grade 2 or worse late rectal bleeding was 7.7% +/- 2.5%. The results of the multivariate analysis indicated that the mean rectal dose (rectal D(mean); p = 0.003) and the percentage of rectum receiving >60 Gy (Vr(60); p = 0.002) correlated with Grade 2 or worse rectal bleeding. The receiver operating characteristic curve analysis showed that this logistic regression model using both Vr(60) and rectal D(mean) had good reliability to predict the risk of late rectal bleeding. The area under the curve for Vr(60) and rectal D(mean) was 0.889 and 0.892, respectively. CONCLUSION: The results of the present study provide clear evidence of a dose-volume effect and the importance of intermediate doses (60.0 Gy) on the risk of rectal bleeding at this prescription dose level. On the basis of these results, new constraints have been implemented in our institution to keep the risk of developing Grade 2 rectal bleeding reasonably low (rectal D(mean) 50.0 Gy and Vr(60) 42%).

Adenocarcinoma↗

Ultrasound assessment of the endometrium for irregular vaginal bleeding.

Irregular vaginal bleeding is a common symptom of women seeking gynecologic care. Etiologies of irregular vaginal bleeding can be classified into the following categories: pregnancy related (retained products of conception, threatened or missed abortion, or ectopic pregnancy), hormonal (disorders of ovulation, menopause, or hormonal contraceptive use), structural (polyps, myomas, or arteriovenous malformation), neoplasm (endometrial cancer), and infection (endometritis). After the history and physical examination, the initial evaluation of irregular vaginal bleeding has traditionally involved an endometrial biopsy. Transvaginal ultrasound has revolutionized the evaluation of the gynecologic ultrasound examination by providing a minimally invasive means to determine the etiology for the bleeding. Transvaginal ultrasound assessment of the endometrial cavity allows treatment to be tailored to the specific cause of irregular vaginal bleeding, thus saving women time, money, and exposure to unnecessary interventions. The purpose of this article is to give the clinician critical information regarding the capabilities of ultrasound to evaluate women with irregular vaginal bleeding.

Abortion, Incomplete↗