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A critical reappraisal of the bleeding time.

Since its initial invention by the French worker Milian in 1901, the bleeding time has been put forward as a clinically useful test in three contexts: diagnosis (particularly of platelet disorders), prediction of clinically important bleeding, and assessment of the adequacy of various forms of therapy. Attempting a complete review of the published experience with this test, we assessed 862 articles. Original bleeding time data appeared in 664 of these articles, from which we tabulated 1083 distinct studies in humans. ROC analysis, which characterizes the sensitivity and specificity of the test, was applied in every instance in which published data were adequate (34 studies). ROCs from 27 studies of the bleeding time in association with aspirin ingestion reveal high variability in the ability of the bleeding time to detect aspirin intake, and provide evidence against claims that recently devised bleeding time methods have improved discriminatory ability based on improved reproducibility. Two ROCs from surgical studies, in which the bleeding time was used to try to predict abnormal bleeding, were statistically indistinguishable from that of a completely noninformative test. In ROCs from five studies of abnormal bleeding in uremia, the test performed approximately the same as the platelet count or hematocrit (taken singly); in one of these studies, prothrombin consumption was determined and was a better predictor of bleeding than bleeding time, hematocrit, or platelet count. In the settings of renal biopsy (one study) and massive transfusion (one study), data allowed estimation of predictive value: in no instance was there evidence that the bleeding time significantly altered a priori estimates (based on prevalence) of the risk of bleeding. Linear regression analysis was applied to data from 23 studies relating platelet count to bleeding time, to assess published claims that the bleeding time and platelet count follow a predictively useful linear relationship. In 22 of 23 instances, the inverse relationship between bleeding time and platelet count was associated with broad statistical scatter, making it impossible to predict precisely one variable given the other. The pathophysiology of an abnormal bleeding time remains poorly understood. The bleeding time is affected by a large number of diseases, drugs, physiologic factors, test conditions, and therapeutic actions, not all of them platelet-related. The test is likely to remain widely used for the diagnosis of inherited disorders of platelet function, such as von Willebrand's syndrome, despite the lack of clear criteria for its use in this context.(ABSTRACT TRUNCATED AT 400 WORDS)

Bleeding Time↗

Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes.

Bleeding is a complication of current therapies for acute coronary syndrome (ACS). No studies have examined the effect of bleeding events on clinical outcomes. We analyzed pooled data from 4 multicenter, randomized clinical trials of patients who had ACS (n = 26,452) to determine an association between bleeding severity as measured by the GUSTO scale and 30-day and 6-month mortality rates using Cox proportional hazards modeling that incorporated bleeding as a time-dependent covariate. The analysis was repeated to examine procedure- and non-procedure-related bleeding and after censoring at the time of coronary artery bypass grafting. Of all the patients included, 27.6% had > or =1 bleeding episode. Patients who bled were older and sicker at presentation than were those who did not bleed. Unadjusted rates of 30-day and 6-month mortality increased as bleeding severity increased. There were stepwise increases in the adjusted hazards of 30-day mortality (mild bleeding, hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.3 to 1.9; moderate bleeding, HR 2.7, 95% CI l 2.3 to 3.4; severe bleeding, HR 10.6, 95% CI 8.3 to 13.6) and 6-month mortality (mild bleeding, HR 1.4, 95% CI 1.2 to 1.6; moderate bleeding, HR 2.1, 95% CI 1.8 to 2.4; severe bleeding, HR 7.5, 95% CI 6.1 to 9.3) as bleeding severity increased. Results were consistent after censoring for coronary artery bypass grafting and for procedure- and non-procedure-related bleeds. In conclusion, the GUSTO bleeding classification identifies patients who are at risk for short- and long-term adverse events. Therapies that minimize bleeding risk and maintain an anticoagulant effect may improve outcomes among patients who have ACS.

Acute Disease↗

The risk of bleeding in thrombocytopenic patients with acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: Patients with acute myeloid leukemia are at risk of bleeding. The risk factors for different severities of bleeding are poorly studied. DESIGN AND METHODS: Data from Rebulla et al. were analyzed in an exploratory analysis using multivariate Cox regression analyses for time-to-first bleed with time-depend- ent covariates reflecting measures of clinical and laboratory variables on the previous day. The relationships of the variables with three bleeding categories were studied: mild bleeding (WHO grades 1 and 2) clinically significant (bleeding grades 2, 3 and 4) and severe (bleeding grades 3 and 4). RESULTS: Bleeding of any severity occurred in 149 (58.4%) of 255 patients. There were 743 days of bleeding over 7335 patient-days of observation. Risk factors for mild bleeding included increased body temperature and decreased platelet count; the risk was decreased with administration of antifungal medication or platelet transfusion on the previous day. Risk factors for clinically significant bleeding included grade 1 bleeding on the previous day, decreased platelet count and elevated body temperature. Decreased platelet count and mild bleeding on the previous day were risk factors for severe bleeding. Higher hemoglobin values were associated with a delay in the time-to-first clinically significant bleed. INTERPRETATION AND CONCLUSIONS: These results support clinical guidelines for increasing the platelet transfusion threshold in the presence of fever and support the use of milder bleeding symptoms as an outcome in clinical trials. The suggestion that hemo- globin concentration maybe predictive of bleeding risk supports the hypothesis that this maybe a valuable intervention in anemic thrombocytopenic patients at high risk of bleeding.

Adolescent↗

The clinical usefulness of the preoperative bleeding time.

OBJECTIVES: To determine the clinical utilization of the Simplate bleeding time test as a preoperative screen, to examine the clinical utilization of the bleeding time test by multiple surgical services, and to correlate the indicators of bleeding risk (bleeding history, thrombocytopenia, prolonged prothrombin time/activated partial thromboplastin time, increased creatinine, and medications known to interfere with platelet function) with the bleeding time and the occurrence of clinically significant perioperative bleeding. DESIGN: Retrospective data analysis. SETTING: A large tertiary-care hospital. PATIENTS: One hundred sixty-seven consecutive surgical patients tested for preoperative bleeding time. MAIN OUTCOME MEASURES: The occurrence of clinically significant perioperative bleeding and the positive and negative predictive value of the preoperative screening bleeding time test. RESULTS: Patients with a positive bleeding history were more likely to have an abnormal bleeding time (P = .04), but there was no statistically significant association between patients with an abnormal bleeding time and the other indicators of bleeding risk examined or the occurrence of clinically significant perioperative bleeding. The positive predictive value of the preoperative bleeding time was 5%, and the negative predictive value was 95%. CONCLUSIONS: Screening for preoperative bleeding time is not a reliable test for assessing the risk of clinically significant perioperative bleeding and should not be used for this purpose.

Bleeding Time↗

Bleeding complications in oral anticoagulant therapy. An analysis of risk factors.

BACKGROUND: Insufficient data are available about the safety of oral anticoagulant therapy. The specialized organization of thrombosis services in the Netherlands can provide important information on the bleeding risk and various risk factors for bleeding in patients receiving oral anticoagulant therapy. METHODS: In a follow-up study over a 12-month period beginning in January 1988 on all patients treated by the Leiden Thrombosis Service, the frequency of bleeding complications was assessed. A Poisson regression model was used to assess the relative contribution to the bleeding risk of age, sex, target zone (intensity of anticoagulant effect aimed at), achieved intensity of anticoagulant therapy (International Normalized Ratio), and the type of coumarin derivative used. RESULTS: Six thousand eight hundred fourteen patients experienced 1003 bleeding complications (16.5 per 100 treatment-years), 162 of which were major bleeds (2.7 per 100 treatment-years). Bleeding increased significantly with age (32% increase for all bleeding, 46% for major bleeding for every 10-year increase in age in comparison with age < 40 years). Women had more minor bleeding complications than men, whereas both sexes experienced major bleeding in an equal frequency. There was no influence of target zone, while every one-point increase in International Normalized Ratio gave 42% more major bleeding (54% more regarding all bleeding). Use of acenocoumarol resulted in fewer bleeds (26% less regarding all bleeding and 46% less regarding major bleeding) than use of phenprocoumon. CONCLUSIONS: The risk of anticoagulant therapy in a routine, real-life situation is similar as in the setting of several well-organized clinical trials. The risk of bleeding complications rises significantly with age and with the achieved intensity of anticoagulation, and is dependent on the type of coumarin derivative that is used.

Administration, Oral↗

Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention.

OBJECTIVE: To review (1) the clinical epidemiology of bleeding during anticoagulant therapy with heparin or warfarin, (2) data useful in estimating the risk for bleeding in individual patients, and (3) the efficacy of methods for its prevention. METHODS: Relevant literature was identified by a computerized search of the Medline database and by review of the bibliographies of original and review articles. Studies were classified according to their design. Estimates of the risk for bleeding during anticoagulant therapy, compared with the risk without therapy, were obtained from randomized trials. Estimates of the frequency of bleeding during the course of anticoagulant therapy and information about risk factors for bleeding were obtained primarily from longitudinal studies of inception cohorts of patients followed from the start of therapy. MAIN RESULTS: The average daily frequencies of fatal, major, and major or minor bleeding during heparin therapy were 0.05%, 0.8%, and 2.0%, respectively; these frequencies are approximately twice those expected without heparin therapy. The average annual frequencies of fatal, major, and major or minor bleeding during warfarin therapy were 0.6%, 3.0%, and 9.6%, respectively; these frequencies are approximately five times those expected without warfarin therapy. The risk for anticoagulant-related bleeding is highest at the start of therapy: during warfarin therapy, the risk for major bleeding during the first month of therapy is approximately 10 times the risk after the first year of therapy. An individual patient's risk for major anticoagulant-related bleeding can be estimated on the basis of specific risk factors such as the intensity of the anticoagulant effect achieved and the presence of serious comorbid diseases, especially cerebrovascular, kidney, heart, and liver disease; older age and concurrent medicines may also be independent risk factors. Major bleeding most often affects the gastrointestinal tract, soft tissues, and urinary tract. Diagnostic evaluation of gastrointestinal bleeding and gross hematuria leads to identification of previously unknown lesions in approximately one-third of cases, even when the prothrombin time is elevated. Intracranial bleeding is rare, but it is frequently fatal. The frequency of bleeding during warfarin therapy is reduced by less intense therapy achieving a prothrombin time with an International Normalized Ratio of 2.0 to 3.0, which is efficacious for most indications. CONCLUSION: Anticoagulant-related bleeding is common and often serious. The risk for bleeding can be estimated in an individual patient, giving the primary physician a quantitative basis for weighing the risks and benefits of therapy and for optimizing patient management. The frequency of anticoagulant-related bleeding is reduced by less intense warfarin therapy. Future studies should evaluate new approaches to management that may further reduce complications while maintaining efficacy.

Anticoagulants↗

Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions.

Bleeding related to percutaneous coronary intervention (PCI) occurs relatively frequently. We retrospectively investigated the incidence, predictors, and prognostic impact of periprocedural bleeding and transfusion in 10,974 patients who underwent PCI. Bleeding definitions were based on Thrombolysis In Myocardial Infarction (TIMI) criteria: (1) major bleeding (n = 588; 5.4%): if patients had a hemorrhagic stroke or if hematocrit decreased >15 points or by 10 to 15 points with clinical bleeding; (2) minor bleeding (n = 1,394; 12.7%): if hematocrit decreased <10 points with clinical bleeding or by 10 to 15 points without clinical bleeding; and (3) no bleeding (n = 8,992; 81.9%): if hematocrit decreased <10 points without clinical bleeding. Patients with major bleeding were older than patients with minor or no bleeding (67.8 +/- 11 vs 65.9 +/- 11 vs 63.6 +/- 11 years, respectively; p <0.001) and more often experienced intraprocedural complications, such as emergency use of an intra-aortic balloon pump (13.6% vs 6.5% vs 2.3%, respectively; p <0.001). Multivariate logistic regression analysis identified the use of an intra-aortic balloon pump (odds ratio [OR] 3.0, p <0.0001), procedural hypotension (OR 2.9, p <0.001), and age >80 years (OR 1.9 compared with age <50 years, p = 0.001) as the strongest predictors for major bleeding. Patients who had major bleeding had higher in-hospital and 1-year mortality compared with patients with minor or no bleeding. Bleeding was an independent predictor of in-hospital death. Thus, periprocedural major bleeding occurs relatively frequently and is associated with adverse outcomes. Patients >80 years of age who experience intraprocedural complications are at particularly high risk.

Age Factors↗

Gastrointestinal bleeding in the hospitalized patient: a case-control study to assess risk factors, causes, and outcome.

PURPOSE: To determine the risk factors, etiology, and outcome of clinically important gastrointestinal bleeding that occurs after hospital admission (nosocomial gastrointestinal bleeding). PATIENTS AND METHODS: Cases consisted of consecutive patients who developed gastrointestinal bleeding more than 24 hours after admission to the hospital. Cases were compared with two control populations: a set of hospitalized patients without gastrointestinal bleeding matched with cases for age, gender, and length of stay; and all patients admitted to the hospital with clinically important gastroduodenal ulcer bleeding during the study period. Case and controls were compared with respect to risk factors for gastrointestinal bleeding and outcomes. Data were obtained through a comprehensive review of medical records. RESULTS: Clinically important nosocomial gastrointestinal bleeding occurred in 67 inpatients after a mean hospital length of stay of 14 +/- 10 days. The majority (64%) of the patients were not hospitalized in the intensive care unit at the onset of the bleeding. Seventy-two percent of the patients who developed bleeding had been receiving some form of bleeding prophylaxis. In a multivariate analysis, a prior intensive care unit stay (odds ratio 2.5; 95% confidence interval 1.0 to 6.1; P <0.05) and mechanical ventilation (OR 3.4; 95% CI 1.1 to 10.7; P = 0.03) were independent risk factors for the onset of bleeding. Nosocomial gastrointestinal bleeding was associated with poor outcome, with an associated mortality of 34%. Duodenal ulcer disease was the most common source of nosocomial gastrointestinal bleeding, accounting for 36% of cases overall. Nosocomial ulcer bleeders were less likely to have a previous history of ulcer disease (13% versus 50%; P <0.05) Helicobacter pylori infection (14% versus 62%; P <0.0001), chronic active gastritis (29% versus 91%; P <0.0001), or to be taking NSAIDs (48% versus 68%; P <0.08) than patients admitted to the hospital with ulcer bleeding. CONCLUSIONS: Gastrointestinal bleeding remains an important complication of hospitalization, with a high associated mortality. Our current approaches to prevention of this complication are imperfect. Bleeding tends to occur after a prolonged hospital stay and is more likely to occur in patients with more severe underlying illnesses. Duodenal ulcer disease is the most common source of this bleeding. Nosocomial gastroduodenal ulcer disease is distinct in etiology from the ulcer disease that occurs in outpatients.

Adult↗

Management of abnormal uterine bleeding.

Patients treated for dysfunctional uterine bleeding are separated into two groups: those with acute bleeding episodes and those with chronic repetitive bleeding problems. An acute bleeding episode is best controlled with the use of high-dose estrogen. A curettage is indicated for patients with acute bleeding resulting in hypovolemia, and a curettage or hysteroscopically directed biopsies is indicated for women with risk factors for endometrial cancer who have persistent bleeding problems. The management of anovulatory dysfunctional uterine bleeding is determined by the needs of the patient. In the adolescent medroxyprogesterone acetate is administered orally once a day for 10 days each month for > or = 3 months, and the patient is monitored closely thereafter. Oral contraceptives are used for women of reproductive age with anovulatory bleeding episodes who also require contraception. Clomiphene citrate is used for women of reproductive age with anovulatory bleeding who want to conceive. Oral medroxyprogesterone acetate is administered 10 days each month for 6 months for the treatment of anovulatory dysfunctional uterine bleeding alone in this age group. For the perimenopausal patient dysfunctional uterine bleeding may be treated by the administration of cyclic progestin or cyclic conjugated equine estrogens for 25 days with the concomitant administration of medroxyprogesterone acetate for days 18 to 25. The perimenopausal patient with dysfunctional uterine bleeding who is a nonsmoker and does not have evidence of vascular disease may also be treated with low-dose combination oral contraceptives. The long-term treatment for women with ovulatory dysfunctional uterine bleeding is the most difficult type of dysfunctional uterine bleeding to manage. The long-term therapy is directed at the reduction in menstrual blood loss. For these patients prolonged progestin use, oral contraceptives, nonsteroidal antiinflammatory drugs, antifibrinolytic agents, danazol, and as a last resort gonadotropin-releasing hormone agonists are part of the therapeutic armamentarium. A combination of two or more of these agents is often required to successfully control the abnormal bleeding. For patients who no longer desire future fertility and have associated pelvic pathologic disorders or for those who fail all medical regimens, surgical therapy may be considered. Either hysterectomy or endometrial ablation has been used. Patients with von Willebrand's disease and excessive menstrual blood loss may be misdiagnosed as having dysfunctional uterine bleeding. van Willebrand's disease is the most common bleeding disorder and is present in approximately 1% of the population. It is much more common than previously recognized. There are improved diagnostic tests to identify this disorder and, most important, there is a high-concentration desmopressin acetate nasal spray available as treatment that does not involve the risk of transmission of hepatitis and human immunodeficiency virus.

Female↗

The characteristics and the prognosis for patients presenting with actively bleeding esophageal varices at endoscopy.

BACKGROUND: It remains unresolved whether the prognosis is worse for patients who present with actively bleeding varices at endoscopy compared with those in whom variceal bleeding has stopped. METHODS: Patients with acute esophageal variceal bleeding were enrolled in this study and were divided into two groups: an active bleeding group and an inactive bleeding group. All patients had band ligation shortly after endoscopic examination and underwent elective ligation procedures until the varices were obliterated. Patients were followed for 1 year or until death. Short- and long-term prognoses were compared. RESULTS: The active bleeding group included 54 patients and the inactive bleeding included 251 patients. Initial hemostasis was achieved in 93% in the active group and 99% in the inactive group ( p = not significant). The rate of recurrent variceal bleeding within 30 days was 24% in the active bleeding group vs. 12% in the inactive bleeding group ( p = 0.01); the mortality rates were 18% and 8%, respectively ( p = 0.03 in a single statistical test; however, Bonferroni correction for the multiple testing of data removed this significance). The rate of recurrent variceal bleeding within 1 year was 37% in the active bleeding group and 27% in the inactive bleeding group ( p = 0.06); the mortality rates were 22% and 21%, respectively ( p = not significant). CONCLUSIONS: Whether variceal bleeding is active or inactive at endoscopy, variceal ligation is equally effective for control of bleeding. The rates of recurrent bleeding and mortality at 1 month were significantly higher among patients with active bleeding. However, the mortality rate was similar for both groups at 1 year.

Endoscopy, Gastrointestinal↗

Bleeding and surgery in children with Glanzmann thrombasthenia with and without the use of recombinant factor VII a.

BACKGROUND: An inherited deficiency of platelet glycoprotein II b/III a (GP II b/III a), Glanzmann thrombasthenia, can lead to excessive bleeding and require platelet transfusion to secure hemostasis. Antibodies to GP II b/III a or HLA may platelet transfusion render ineffective to stop bleeding or to cover surgery. Recombinant factor VII a has been introduced as therapeutic alternative and has been suggested to be effective. PATIENTS AND AIMS OF THE STUDY: In a retrospective evaluation, bleeding episodes and surgery in six patients treated with antifibrinolytics and with and without the additional use of rFVII a were analysed to achieve informations for treatment indication and efficacy. RESULTS: Nineteen mucosal and subcutaneous bleeding episodes, two dental surgeries and seven joint bleeds occurred. In 11 mild to moderate mucocutaneous bleeds treated without rFVII a, seven stopped within 48 hours, three stopped until the fourth day; one showed recurrence. Three bleeds were treated with rFVII a and responded within 24 hours. One severe bleed treated without rFVII a did not stop until the 8 (th) day after cautery. In 4 severe bleeds treated with rFVII a, one stopped within 24 hours, one showed recurrence, one was treated with platelet transfusion concurrently and one did not respond to rFVII a. Clinical signs persisted in one conservatively treated elbow joint bleed, whereas in two episodes treated with rFVII a, the bleeding responded within 5 and 7 days and in four episodes in at least 4 days. Two dental surgeries showed no recurrence after rFVII a over 18 or 36 hours. CONCLUSIONS: In severe mucocutaneous bleeding episodes or joint bleeding rFVII a is of some benefit whereas in surgeries like teeth extraction, prophylactically administered rFVII a seems effective to avoid bleeding. In mild to moderate mucocutaneous bleeding events, antifibrinolytics and local measures were sufficient in most cases and the additional use of rFVII a does not seem to be necessary. Further information is needed to elaborate clear indications for the rational use of rFVII a in bleeding episodes in patients with Glanzmann thrombasthenia compared to standardized baseline treatment. This information may generate a prospective multicenter study to provide clear advice with respect to bleeding site, severity and duration.

Adolescent↗

Efficacy and safety of transjugular intrahepatic portosystemic shunt in the treatment of nongastric extraesophageal variceal bleeding.

OBJECTIVES: Although esophageal varices are the most common site of variceal bleeding, extraesophageal varices cause up to 30% of variceal bleeding. Unlike esophageal variceal bleeding, the experience in management of extraesophageal variceal bleeding, especially nongastric extraesophageal variceal bleeding is limited, and there are no established guidelines for treatment of nongastric extraesophageal variceal bleeding. This study aims to provide experience in treatment of nongastric extraesophageal variceal bleeding with transjugular intrahepatic portosystemic shunt in a tertiary medical center. METHODS: We retrospectively reviewed all cases, admitted or transferred to Emory University Hospital, with extraesophageal variceal bleeding who had transjugular intrahepatic portosystemic shunt as the final resolution to control bleeding over a period of 4 years, from January 1999 to January 2003. We also compared the outcomes after transjugular intrahepatic portosystemic shunt for bleeding from gastric varices and nongastric extraesophageal varices. RESULTS: Forty-one patients (33 gastric varices and 8 nongastric extraesophageal varices) with extraesophageal variceal bleeding who had transjugular intrahepatic portosystemic shunt performed were identified in this study period. Bleeding was controlled immediately in 90% (37/41) of those patients. The mortality was 7% (3/41). The rebleeding rate was 10% (4/41). Encephalopathy occurred in 24% (10/41) of the patients. Patients with gastric varices bleeding appeared to have more advanced liver disease than patients with nongastric extraesophageal varices bleeding. The outcomes after transjugular intrahepatic portosystemic shunt for bleeding from gastric varices and nongastric extraesophageal varices were similar. CONCLUSIONS: Transjugular intrahepatic portosystemic shunt is an effective and safe treatment of extraesophageal variceal bleeding, including bleeding from gastric varices and nongastric extraesophageal varices.

Esophageal Diseases↗

The significance of corpus anterior wall ulcers on morbidity and mortality of patients with upper gastrointestinal bleeding.

BACKGROUND/AIMS: Acute upper gastrointestinal bleeding is a common and potentially life-threatening medical emergency. Various factors modulating morbidity and mortality on upper gastrointestinal bleeding have been reported. However, there are no reports on the prognosis of bleeding ulcers on the anterior wall of corpus (on fundus-corpus junction, 10-15 mm from the lesser curvature) bleeding ulcers on the anterior wall of the corpus. Thus, in this trial we tried to investigate the role of bleeding ulcers on the anterior wall of the corpus on acute upper gastrointestinal bleeding mortality and morbidity. METHODS: One hundred seventy-seven (63 women and 114 men, mean age 52 years) patients with a clinical diagnosis of upper gastrointestinal bleeding were endoscoped between August 1999 and December 2002. All patients were treated endoscopically, medically or with surgery. The site of the bleeding was noted and compared regarding rebleeding and mortality rates. RESULTS: 50% (3/6) of the patients with bleeding ulcers on the anterior wall of the corpus required further surgical procedure or were associated with mortality, but only 7% (12/171) of the patients with bleeding sites other than bleeding ulcers on the anterior wall of the corpus had mortality or required further surgical intervention (p<0.05). Recurrent bleeding occurred in 50% (3/6) of our patients with bleeding ulcers on the anterior wall of the corpus during their hospitalization compared to 7.60% (13/171) (p<0.05) of patients with bleeding sites other than bleeding ulcers on the anterior wall of the corpus. CONCLUSIONS: Bleeding ulcers on the anterior wall of the corpus is indicative of recurrence or persistence of the hemorrhage and of greater mortality. Bleeding from this site needs more aggressive and diligent care.

Endoscopy, Gastrointestinal↗

Massive upper gastrointestinal bleeding after acid-corrosive injury.

Our purpose was to delineate the characteristics and outcome of massive upper gastrointestinal bleeding (UGI) caused by acid-corrosive injury and to determine its management protocol. From June 1988 to June 2000, all patients with the history of acid-corrosive injury at our institution were reviewed. Patients with massive UGI bleeding (hematocrit level <25% or transfusion of three or more units of whole blood required to restore normal vital sign) were enrolled into this study. Altogether, 12 (3.2%) of 378 patients with acid-corrosive injury developed massive bleeding: 8 gastric bleeding, 2 duodenal bleeding, and 2 first gastric and then duodenal bleeding. Gastric bleedings started an average of 12.1 days after the initial injury (range 9-21 days). Duodenal bleeding usually occurred later, at 10.1 days (range 6-18 days) after a gastric or esophagogastric operation. Nine of the ten patients with gastric bleeding underwent surgery during the subacute stage: three esophagogastrectomy, three gastric mucosectomy with gastrostomy and jejunostomy, and three total or subtotal gastrectomy. Operative findings were hemorrhagic gastritis with diffuse mucosal bleeding. Two of four patients with duodenal bleeding underwent duodenotomy with suture-ligation of bleeding vessels, and the other two had conservative treatment. Nine patients (75%) had postoperative complications. One patient (8%) died from complications of surgery performed to stop duodenal bleeding. Massive UGI bleeding rarely occurs after acid-corrosive injury; but when it does, it occurs during the subacute stage. Aggressive surgical treatment is mandatory for gastric bleeding. How duodenal bleeding can be better managed requires further study.

Adult↗

Clinical and economic consequences of bleeding following major orthopedic surgery.

BACKGROUND: Major orthopedic surgery patients who receive antithrombotics as prophylaxis against VTE may be at higher risk of bleeding. The clinical and economic consequences of this complication may be relevant to therapeutic decision-making. OBJECTIVE: To assess the impact of major bleeding following major orthopedic surgery on length of stay (LOS) and inpatient charges. METHODS: Using a database with information on approximately 750,000 admissions annually to 100+ US acute-care hospitals, we identified all patients who underwent major orthopedic surgery between January 1, 1998 and December 13, 2000. Patients were stratified according to whether or not they experienced major postoperative bleeding prior to hospital discharge, defined as (a) fatal bleeding; (b) nonfatal bleeding at critical site; (c) re-operation due to bleeding; and (d) overt bleeding with bleeding index (BI)>or=2, where BI=number of blood units transfused plus pre-bleeding minus post-bleeding hemoglobin (g/dL) values. LOS and total inpatient charges were compared between patients with and without major bleeding. RESULTS: The incidence of major bleeding among 23,518 patients who underwent major orthopedic surgery was 2.6%. In multivariate analyses controlling for differences in baseline characteristics between patients with and without major bleeds, adjusted mean LOS was 1.8 days longer among those with major bleeding (95% CI: 1.5, 2.0) (6.1 days vs. 4.3 days for those without bleeds); adjusted mean total inpatient charges were 7,593 dollars higher (95% CI: 6,622 dollars, 8,646 dollars) (25,669 dollars vs. 18,076 dollars). CONCLUSION: Bleeding following major orthopedic surgery may increase length of stay and total hospital charges and should be an important consideration in choice of VTE prophylaxis.

Aged↗

Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remediable lesions.

PURPOSE: To determine the relation of bleeding to prothrombin times and important remediable lesions in outpatients treated with warfarin. PATIENTS AND METHODS: An inception cohort of 565 patients starting outpatient therapy with warfarin on discharge from a university hospital was assembled. Detailed records of outpatient prothrombin times were obtained for 103 of 130 case subjects with major or minor bleeding and for 117 control patients without bleeding. A nested case-control design was used to evaluate the association of bleeding with temporally related prothrombin times; odds ratios were estimated using multivariate logistic regression analysis to control for known predictors of major bleeding. The relation of bleeding to important remediable lesions was determined in all 130 cases of bleeding. RESULTS: For each 1.0 increase in the prothrombin time-to-control ratio, the odds ratio for major bleeding during the week after a prothrombin time measurement increased 80%; the odds ratio for minor bleeding increased 50%. These odds ratios were lower during the first month of therapy and higher thereafter. Bleeding was related to important remediable lesions in 49 of 130 cases (38%), but these lesions were unknown before bleeding in only 22 cases (17%). The mean prothrombin time rose sharply at the time of bleeding in patients without important remediable lesions, but not in patients with lesions. New, previously unknown lesions (including nine malignancies) were discovered in 20 of 59 case subjects (34%) with gastrointestinal bleeding or hematuria, but in only two of 71 case subjects (3%) with other bleeding (p less than 0.001). CONCLUSION: Our results provide a valid quantitative basis for estimating the odds of bleeding in relation to the prothrombin time and the yield of diagnostic evaluation in patients with bleeding.

Aged↗

Optimized analysis of recurrent bleeding and death in patients with cirrhosis and esophageal varices. Copenhagen Esophageal Varices Sclerotherapy Project.

The course of cirrhosis after the first episode of variceal bleeding is characterized by recurrent episodes of bleeding and bleeding-free periods, with each new stage being associated with an initially high mortality rate. Analysis of the course of this disease is usually based on traditional survival models measuring observation time from admission to hospital. This approach cannot provide valid answers to the following clinically relevant questions: 1) what is the risk of death while bleeding? 2) what is the risk of continuing bleeding? 3) what is the risk of death after bleeding has stopped? 4) what is the risk of a new bleeding episode among those who remain alive and do not bleed? and 5) do the answers to the former four questions depend on the number of previous bleeding episodes or on the time since the first episode? These questions may be addressed using the multistage, competing risks model presented here. By measuring time from the start of each new bleeding or bleeding-free period, this model synchronizes the patients with respect to disease development and, hence, to level of the rate of new clinical events. This reduces the heterogeneity of risk levels in the patient group at any given time. In an analysis of 94 patients with cirrhosis admitted for their first episode of variceal bleeding, we estimated the mortality rates during bleeding and without current bleeding, the rate of cessation of bleeding and the rate of rebleeding. The influence of number of previous rebleedings and of the time since the first bleeding was examined using a Cox regression model for competing risks.(ABSTRACT TRUNCATED AT 250 WORDS)

Disease Progression↗

Risk of esophageal variceal bleeding based on endoscopic ultrasound evaluation of the sum of esophageal variceal cross-sectional surface area.

OBJECTIVE: The aim of this study was to evaluate the risk of future variceal bleeding, based on the endoscopic ultrasound measurement of the sum of the cross-sectional surface area (CSA) of all of the esophageal varices in the distal esophagus. METHODS: Twenty-eight patients with portal hypertension and esophageal varices, but no prior history of variceal bleeding, were evaluated using endoscopic ultrasound (20-MHz ultrasound probe, Microvasive, Boston, MA; Olympus, Tokyo, Japan). The entire esophagus was imaged, and an image was selected at a point where the varices appeared the largest. This image was digitized, and the sum of the CSA of all of the varices was measured (Image Pro Plus, Silver Springs, MD) by an investigator blinded to the patients' clinical status. The follow-up time for each patient was calculated (time to first bleed, time to liver transplantation, time to death, or time to the end of study). The Cox Proportional Hazards Model was used to determine if there was a significant difference between the sums of the CSA in the patients who bled compared with those who did not bleed. An OR was calculated to determine the risk of future variceal bleeding based on the sum of the CSA as measured in cm(2)/month. Positive and negative predictive values were calculated for future variceal bleeding. RESULTS: Six of 28 patients (21%) experienced esophageal variceal bleeding on follow-up. The mean CSA +/- SEM of the sum of the esophageal varices in these patients was 0.77 cm(2) +/- 0.31 cm(2) (range 0.07-2.09 cm(2)). The mean time to bleeding was 15.5 months +/- 4.95 months (range 1-29 months). Twenty-two of 28 patients (79%) did not experience variceal bleeding. The mean CSA +/- SEM of the sum of the varices in these patients was 0.36 cm(2) +/- 0.08 cm(2) (range 0.02-1.19 cm(2)). The mean time to follow-up was 35.7 months +/- 6.69 months (range 1.2-103.2 months). The sum of the CSA between the patients who bleed and those who did not bleed was significantly different at the p < 0.018 level. The OR for the risk of variceal bleeding for each one cm(2) difference in the sum of the CSA per month was 6.34. Using a cutoff of 0.45 cm(2), the sensitivity and specificity for future variceal bleeding was 83% and 75%, respectively. CONCLUSIONS: There is a significant difference (p < 0.018) in the sum of the esophageal variceal CSA between those patients who will experience future variceal bleeding and those who will not. There is a 76-fold increase per year in the risk of future variceal bleeding for each one cm(2) increase in variceal CSA. Using a cutoff value for the CSA of 0.45 cm(2), the sensitivity and specificity for future variceal bleeding above and below this point is 83% and 75%, respectively.

Adult↗