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Development of a contemporary bleeding risk model for elderly warfarin recipients.

BACKGROUND AND PURPOSE: Develop and validate a contemporary bleeding risk model to guide the clinical use of warfarin in the elderly atrial fibrillation (AF) population. METHODS: Chart-abstracted data from the National Registry of Atrial Fibrillation was combined with Medicare part A claims to identify major bleeding events requiring hospitalization. Using a split-sample technique, candidate variables that provided statistically stable relationships with major bleeding events were selected for model development. Three risk categories were created and validated. The new model was compared to existing bleeding risk models using c-statistics and Kaplan-Meier curves. RESULTS: Model development and validation was conducted on 26,345 AF patients who were > 65 years of age and had been discharged from the hospital while receiving warfarin therapy. The following eight variables were included in the final risk score model: age > or = 70 years; gender; remote bleeding; recent (ie, during index hospitalization) bleeding; alcohol/drug abuse; diabetes; anemia; and antiplatelet use. Bleeding rates were 0.9%, 2.0%, and 5.4%, respectively, for the groups with low, moderate, and high risk, compared to the bleeding rates for groups with moderate risk (1.5% and 1.0%) and high risk (1.8% and 2.5%) from other models. CONCLUSIONS: Using a nationally derived data set, we developed a model based on contemporary practice standards for determining major bleeding risk among AF patients receiving warfarin therapy. The larger sample size afforded the opportunity to incorporate additional risk factors. In addition, since the majority of our population was > 65 years of age, we had greater ability to stratify risk among the elderly.

Age Factors↗

Selective serotonin re-uptake inhibitors and the risk of bleeding.

Despite their safety, selective serotonin re-uptake inhibitors (SSRIs) are associated with bleeding. The authors critically reviewed the medical literature on SSRIs to identify subgroups of patients at risk of bleeding complications. The authors performed a literature search using MEDLINE from 1966 to 1st September 2004 using; 'haemorrhage, serotonin uptake inhibitors and antidepressive agents' as search terms and followed up on citations in each paper that was relevant to SSRI associated bleeding. The authors reviewed 7 retrospective analytical studies and 24 case reports of bleeding in 43 different people. Analytical studies support an association between SSRI consumption and upper gastrointestinal (GI) bleeding and perioperative bleeding. Little evidence links SSRI use with intracerebral haemorrhage. The risk of GI bleeding appeared to be highest among patients consuming SSRIs with NSAIDs. Combining aspirin or NSAIDs with SSRIs may further increase the risk of bleeding. Clinicians should caution patients about combining SSRIs with aspirin or NSAIDs. Pharmacotherapy to reduce the risk of GI bleeding should be considered in high risk patients.

Adult↗

Pharmacist-provided anticoagulation management in United States hospitals: death rates, length of stay, Medicare charges, bleeding complications, and transfusions.

We explored the associations between pharmacist-provided anticoagulation management in hospitalized Medicare patients and several major heath care outcomes: death rate, length of stay, Medicare charges, bleeding complications, and transfusions. Using the 1995 National Clinical Pharmacy Services database and the 1995 Medicare database for hospitals, data were retrieved for 717,396 Medicare patients treated in 955 hospitals for conditions requiring anticoagulant therapy. In hospitals without pharmacist-provided heparin management, death rates were 11.41% higher (chi2 (1) = 122.84, p<0.0001), length of stay was 10.05% higher (Mann-Whitney U test = 40039529342, p<0.0001), Medicare charges were 6.60% higher (U = 41004749266, p<0.0001), bleeding complications were 3.1% higher (chi2 (1) = 10.996, p=0.0009) and the transfusion rate for bleeding complications was 5.47% higher (chi2 (1) = 11.24, p=0.0008) than in hospitals with pharmacist-provided heparin management. In hospitals without pharmacist-provided warfarin management, death rates were 6.20% higher (chi2 (1) = 19.20, p<0.0001), length of stay was 5.86% higher (U = 25730993838, p<0.0001), Medicare charges were 2.16% higher (U = 259955112970, p<0.0001), bleeding complications were 8.09% higher (chi2 (1) = 49.259, p<0.0001), and the transfusion rate for bleeding complications was 22.49% higher (chi2 (1) = 78.68, p<0.0001). Study hospitals without pharmacist-provided heparin management had 4664 more deaths, 494,855 more patient-days, 145 more patients with bleeding complications, and $651,274,844 more in patient charges; 9784 more units of whole blood were used in patients requiring transfusions for bleeding complications. Hospitals without pharmacist-provided warfarin management had 2786 more deaths, 316,589 more patient-days, 429 more patients with bleeding complications, and $234,275,490 more in patient charges; 8991 more units of whole blood were used in patients requiring transfusions for bleeding complications. The implications of these findings are significant for the health care system, especially considering that the study population represents 28.25% of hospitalized Medicare patients who should receive anticoagulants, and that total Medicare admissions represent 35.02% of total admissions to United States hospitals.

Anticoagulants↗

Problems in localization of bleeding sites and the incidence of varicose rupture in emergency endoscopy.

An investigation was made for problems involved in identification of bleeding sites and the incidences of bleeding from esophageal and gastric varices in emergency endoscopy within 24 hr after overt gastrointestinal bleeding. Varices or ulcers are not always the source of bleeding, and endoscopic examinations should be performed early after the onset of bleeding to make correct identification of the bleeding site. For such purposes, aspiration using endoscopy, washing under direct observation using a teflon tube and changing of body posture were found effective. During the 6 years from 1977, bleeding from the esophageal or gastric varices was detected in 4 cases out of 30 cases of esophageal or gastric varices which had undergone emergency endoscopy for overt bleeding. After June, 1979, when hemostatic measure using pure ethanol was applied actively, bleeding from esophageal or gastric varices was observed in 4 cases (2.5%) out of 160 cases. Results of the present emergency endoscopy revealed that the incidence of rupture of varices was not so high as had been expected conventionally.

Emergencies↗

Longitudinal evaluation of health plan cost per venous thromboembolism or bleed event in patients with a prior venous thromboembolism event during hospitalization.

OBJECTIVE: To measure the per-event health plan costs for acute and follow-up treatment not directed by a clinical study protocol in a group of commercially insured patients in 2 managed care organizations following an incident hospitalization that included a diagnosis for a venous thromboembolism (VTE) event. METHODS: A cohort of patients with an incident in-hospital VTE event, consisting of deep vein thrombosis (DVT), or pulmonary embolism (PE), or both DVT + PE, was retrospectively identified from the administrative claims databases of 2 large U.S. health care plans. Inclusion criteria were (a) an inpatient VTE event between January 1, 1998, and December 31, 2000, (b) no VTE diagnosis or anticoagulation therapy 3 months prior to the incident VTE in-hospital event, (c) at least 1 anticoagulation pharmacy fill following the incident hospital VTE, and (d) continuous health plan enrollment 3 months prior to and 6 months following the incident hospital VTE event. Total costs were reported on a per-event basis and consisted of the aggregated amount paid by the health plan to the provider after subtraction of member cost-share. Costs were collected separately, first for the incident VTE event for all patients identified and second for patients who had at least 1 of the following events in the follow-up period: bleed requiring or not requiring hospitalization, a recurrent VTE event requiring hospitalization, or a recurrent VTE and bleed (VTE + bleed) event requiring hospitalization. Costs were compared between incident diagnosis groups using multivariate generalized linear model techniques. RESULTS: A total of 2,147 patients (DVT=1,499 [69.8%], PE=373 [17.4%], DVT+PE= 275 [12.8%]) were identified (mean age=61.6standard deviation [SD] 16 years; 46.3% male) and were followed for an average of 21.3 (median, 19.2) months. Disease severity was high in these patients, including 59.2% with a history of or active malignancy. The prevalence of VTE was 2.04 per 100,000 study-eligible health plan members. For the incident VTE events, average costs were 7,712+/-18,339 US dollars (median, 3,131 US dollars) per incident DVT event; 9,566+/-13,512 US dollars (median, 6,424 US dollars) per PE incident event; and 12,200+/-24,038 US dollars (median, 6,678 US dollars) per incident DVT+PE event. Warfarin treatment following the incident VTE event was administered to 97.3% of patients for an average of 6.7 (median, 5.0) months at an average cost of 19.40 US dollars per patient per month. During the average period of 21.3 months, 534 patients (24.9%) experienced an average of 1.24 bleed or recurrent VTE events per patient that required hospitalization at a mean cost of 14,975 US dollars per event or 2,101 US dollars per patient per year. For patients with a bleed in the follow-up period that required hospitalization, average costs were 12,326+/-24,448 US dollars (median, 5,736 US dollars) per recurrent VTE; 15,339+/-52,029 US dollars (median, 4,999 US dollars) per bleed; or 24,085+/-65,411 US dollars (median, 10,185 US dollars) per recurrent VTE + bleed event. During the follow-up period, a total of 612 patients (28.5%) experienced 1,489 recurrent bleed events that did not require hospitalization, at an average cost of 239+/-386 US dollars (median, 95 US dollars) per event. There were no significant differences in mean total costs for all pair-wise comparisons between the 3 incident diagnosis groups. CONCLUSIONS: Of patients who experienced a VTE event during the incident hospital stay for any diagnosis, 1 in 4 experienced an average of 1.24 bleed or recurrent VTE events that required hospitalization in the 21 months of follow-up and incurred an average health plan cost of 14,957 US dollars per event. These data may be of interest to managed care decision makers when evaluating the cost impact of new therapies or providing more comprehensive anticoagulation management services for existing therapies.

Age Distribution↗

Acute management of bleeding oesophageal varices.

The goals of therapy in acute variceal bleeding are to arrest haemorrhage and to prevent deterioration of liver function and complications related to bleeding. The measures used to stop acute bleeding should, ideally, also prevent the very early rebleeding that is frequently seen with bleeding varices. Variceal bleeding should be managed by a gastrointestinal bleeding team with intensive nursing care. Diagnostic endoscopy is mandatory once initial resuscitation has been achieved, and allows immediate injection sclerotherapy of varices. Drug therapy can be used as the first treatment in patients admitted with variceal bleeding since it can be given immediately. Of the available drugs, somatostatin has the least side effects and is as effective as vasopressin, terlipressin and the combination of vasopressin and an organic nitrate vasodilator. The role of drugs needs to be studied in combination with sclerotherapy. Sclerotherapy remains the mainstay of management as it achieves the twin goals of stopping active bleeding and preventing early rebleeding. Injection of tissue adhesive and endoscopic ligation or 'banding' are new endoscopic techniques that have shown promise in preliminary trials and are currently being assessed more widely. Balloon tamponade is a temporary measure used to prevent exsanguination. Surgery should be reserved for those patients in whom sclerotherapy is unsuccessful or cannot be carried out. Oesophageal staple transection is the most used operation. The new interventional radiological technique of transjugular intrahepatic portosystemic shunting will probably replace surgery in the future, but its role in acute variceal bleeding has yet to be fully defined.

Acute Disease↗

99mTc RBC scintigraphy: correlation of gastrointestinal bleeding rates with scintigraphic findings.

In 62 consecutive patients, 99mTc RBC studies were reviewed and the scintigraphic findings were characterized to determine the ability of 99mTc RBC scintigraphy to estimate bleeding rates in patients with active gastrointestinal hemorrhage. Of the 62 scans, 10 showed early positivity (less than 1 hr) with a strongly intense bleeding focus relative to hepatic activity (group 1), four showed delayed positivity (greater than 1 hr) with a strong focus (group 2), five showed early positivity with a weak focus (group 3), 12 showed delayed positivity with a weak focus (group 4), and 31 studies were negative (group 5). The mean bleeding rates were then calculated by dividing the blood transfusion volume requirements by the duration of active bleeding for each patient, as recorded in the patients' charts. The mean bleeding rates for these groups were 0.4, 0.3, 0.2, 0.15, and 0.1 ml/min, respectively. Group 1 patients had the greatest mean blood-volume loss, longest duration of active bleeding, and highest mean bleeding rate, and they required more aggressive therapy than the other groups. The minimum mean bleeding rate detectable by scintigraphy was 0.1 ml/min. Our results suggest that 99mTc RBC scintigraphy can estimate bleeding rates and identify those patients who are at higher risk for developing massive gastrointestinal hemorrhage requiring more aggressive therapy.

Blood Transfusion↗

Incidence and pattern of peptic ulcer bleeding in a defined geographical area. DUSUK Study Group.

Despite the introduction of effective medical treatment for peptic ulcer disease, no decrease in the incidence of bleeding has been observed. Unfortunately, most incidence studies rely on a questionable case ascertainment and poor data. We therefore conducted a prospective study, to achieve an unbiased estimate of incidence and pattern of peptic ulcer bleeding in Düsseldorf (Germany). In a 1-year period all patients with endoscopically verified peptic ulcer bleeding who were admitted to the departments of internal medicine or surgery in nine hospitals or seen by nine general practitioners offering endoscopic service were included in the study. Incidence rates were calculated in accordance with sociodemographic variables and expressed per 100,000 person-years of observation. The overall incidence of peptic ulcer bleeding was 51.4, with almost even rates for gastric (26.5) and duodenal (24.9) ulcer. Age was associated with an increased likelihood of bleeding in gastric ulcer patients of 19 per decade from about 40 years onwards (duodenal ulcer, 15). The incidence was about twice as high in men as in women (relative risk = 1.9). The pattern of peptic ulcer bleeding was similar in gastric and duodenal ulcers with regard to ulcer size, multiple lesions, and bleeding activity at endoscopy. However, patients with gastric ulcer bleeding had significantly more often accompanying or underlying diseases. No significant differences were observed between gastric and duodenal ulcer bleeding with regard to nonsteroidal antiinflammatory drug intake and ulcer history. The incidence rates in our study are in the upper range of the literature and comparable to rates from the USA and UK both before and after the introduction of H2 blockers. We hypothesize that the persistently high incidence rate is a superposition of two trends: higher incidences due to a more elderly and diseased population and more NSAID intake, and lower incidences due to effective medical treatment.

Adult↗

Which peptic ulcers bleed? Results of a case-control study. DUSUK Study Group.

BACKGROUND: The incidence of ulcer bleeding has not decrease despite effective medical treatment of peptic ulcer disease. Numerous studies have been performed on risk factors for ulcer bleeding, but only a few studies have related the risk of developing ulcer bleeding to the risk of developing uncomplicated ulcer disease. METHODS: This study was performed as a multicenter interdisciplinary case-control study and was based on diagnosis by endoscopy, prospective data collection, and multivariate analysis. To every study patient with ulcer bleeding (case) one patient with uncomplicated peptic ulcer proven at endoscopy (control) was assigned with regard to sex, ulcer localization, and age (+/-5 years). The controls were randomly taken from three sources: inpatients, outpatients, and patients treated by a private physician. RESULTS: Owing to strict inclusion and exclusion criteria, 209 matched pairs were available for evaluation out of 401 patients with peptic ulcer bleeding. In univariate analysis the duration of ulcer pain and the number of previous ulcer treatments proved to be protective factors for ulcer bleeding. The intake of non-steroidal anti-inflammatory drugs (NSAID) as a whole, acetylsalicylic acid (aspirin), and paracetamol gave an increased risk for ulcer bleeding. Multivariate analysis identified four risk factors for peptic ulcer bleeding: lung disease, NSAID intake, no pretreatment with H2 blockers, and acetylsalicylic acid intake. CONCLUSIONS: The following patient groups represent a risk for peptic ulcer bleeding: multimorbid patients, receiving NSAID and/or aspirin, and patients with no previous ulcer history.

Aged↗

Abnormal uterine bleeding: a management algorithm.

Abnormal uterine bleeding is a common problem, and its management can be complex. Because of this complexity, concise guidelines have been difficult to develop. We constructed a concise but comprehensive algorithm for the management of abnormal uterine bleeding between menarche and menopause that was based on a systematic review of the literature as well as the actual management of patients seen in a gynecology clinic. We started by drafting an algorithm that was based on a MEDLINE search for relevant reviews and original research. We compared this algorithm to the actual care provided to a random sample of 100 women with abnormal bleeding who were seen in a university gynecology clinic. Discrepancies between the algorithm and actual care were discussed during audiotaped meetings among the 4 investigators (2 family physicians and 2 gynecologists). The audiotapes were used to revise the algorithm. After 3 iterations of this process (total of 300 patients), we agreed on a final algorithm that generally followed the practices we observed, while maintaining consistency with the evidence. In clinic, the gynecologists categorized the patient's bleeding pattern into 1 of 4 types: irregular bleeding, heavy but regular bleeding (menorrhagia), severe acute bleeding, and abnormal bleeding associated with a contraceptive method. Subsequent management involved both diagnostic and treatment interventions, which often occurred simultaneously. The algorithm in this article is designed to help primary care physicians manage abnormal uterine bleeding using strategies that are consistent with the evidence as well as the actual practice of gynecologists.

Algorithms↗

Risk factors for bleeding after endoscopic mucosal resection.

AIM: To clarify the risk factors for bleeding after endoscopic mucosal resection (EMR). METHODS: A total of 297 consecutive patients who underwent EMR were enrolled. Some of the patients had multiple lesions. Bleeding requiring endoscopic treatment was defined as bleeding after EMR. Odds ratios (OR) with 95% confidence intervals (CI), calculated by logistic regression with multivariate adjustments for covariates, were the measures of association. RESULTS: Of the 297 patients, 57 (19.2%) patients with bleeding after EMR were confirmed. With multivariate adjustment, the cutting method of EMR, diameter, and endoscopic pattern of the tumor were associated with the risk of bleeding after EMR. The multivariate-adjusted OR for bleeding after EMR using endoscopic aspiration mucosectomy was 3.07 (95%CI, 1.59-5.92) compared with strip biopsy. The multiple-adjusted OR for bleeding after EMR for the highest quartile (16-50 mm) of tumor diameter was 5.63 (95%CI, 1.84-17.23) compared with that for the lowest (4-7 mm). The multiple-adjusted OR for bleeding after EMR for depressed type of tumor was 4.21 (95%CI, 1.75-10.10) compared with elevated type. CONCLUSION: It is important to take tumor characteristics (tumor size and endoscopic pattern) and cutting method of EMR into consideration in predicting bleeding after EMR.

Aged↗

Prevention of first bleeding in cirrhosis. A meta-analysis of randomized trials of nonsurgical treatment.

OBJECTIVE: To assess the effectiveness of beta-blockers and endoscopic sclerotherapy in the prevention of first bleeding and reduction of mortality in patients with cirrhosis and esophagogastric varices. DATA SOURCES: Pertinent studies were selected using MEDLINE (1980 to 1990), reference lists from published articles or reviews, and congress abstract lists. STUDY SELECTION: Randomized trials comparing beta-blockers or sclerotherapy with a nonactive treatment. Nine randomized clinical trials of beta-blockers and 19 trials of sclerotherapy were reviewed. Seven trials of beta-blockers and 15 of sclerotherapy were published as full papers. DATA EXTRACTION: Crude rates of bleeding and death in treated and control groups were extracted from each trial by three independent observers according to the intention-to-treat principle. The quality of published papers was systematically assessed and scored. DATA SYNTHESIS: The Mantel-Haenszel-Peto method was used for statistical evaluation of heterogeneity and for pooling of the results. No substantial heterogeneity was found, and the incidence of bleeding in trials of beta-blockers was significantly reduced (pooled odds ratio, 0.54; 95% CI, 0.39 to 0.74), particularly in patients with large or medium-sized varices or in those with varices and a hepatic vein pressure gradient above 12 mm Hg; however, only a trend toward reduced mortality was obtained. Sclerotherapy trials were highly heterogeneous in the direction of the treatment effects on both bleeding (pooled odds ratio, 0.6; CI, 0.49 to 0.74) and mortality (pooled odds ratio, 0.76; CI, 0.61 to 0.94). The quality of the trials and the rate of bleeding in the untreated groups were the major sources of heterogeneity. The favorable results of sclerotherapy were obtained in trials with high bleeding rates among controls; several of these trials had a low quality score. CONCLUSIONS: Beta-blockers may be recommended for prevention of first bleeding in cirrhotic patients with varices who have a high risk for bleeding. The effectiveness of sclerotherapy remains undetermined. Further trials in high-risk patients may prove useful if improved criteria to predict bleeding risk become available.

Adrenergic beta-Antagonists↗

A multicomponent intervention to prevent major bleeding complications in older patients receiving warfarin. A randomized, controlled trial.

BACKGROUND: Warfarin is effective in the treatment and prevention of many venous thromboembolic disorders, but it often leads to bleeding. OBJECTIVE: To develop a multicomponent program of management of warfarin therapy and to determine its effect on the frequency of warfarin-related major bleeding in older patients. DESIGN: Randomized, controlled trial. SETTING: University hospital in Cleveland, Ohio. PATIENTS: 325 patients 65 years of age or older who started warfarin therapy during hospitalization. INTERVENTIONS: Patients were stratified according to baseline risk for major bleeding and were randomly assigned to receive the intervention (n = 163) or usual care (n = 162) by their primary physicians for 6 months. The intervention consisted of patient education about warfarin, training to increase patient participation, self-monitoring of prothrombin time, and guideline-based management of warfarin dosing. MEASUREMENTS: Major bleeding, death, recurrent venous thromboembolism, and therapeutic control of anticoagulant therapy at 6 months. RESULTS: In an intention-to-treat analysis, major bleeding was more common at 6 months in the usual care group than in the intervention group (cumulative incidence, 12% vs. 5.6%; P = 0.0498, log-rank test). The most frequent site of major bleeding in both groups was the gastrointestinal tract. Death and recurrent venous thromboembolism occurred with similar frequency in both groups at 6 months. Throughout 6 months, the proportion of total treatment time during which the international normalized ratio was within the therapeutic range was higher in the intervention group than in the usual care group (56% vs. 32%; P < 0.001). After 6 months, major bleeding occurred with similar frequencies in the intervention and usual care groups. CONCLUSIONS: A multicomponent comprehensive program of warfarin management reduced the frequency of major bleeding in older patients. Although the generalizability and cost-effectiveness of this program remain to be demonstrated, these findings support the premise that efforts to reduce the likelihood of major bleeding will lead to safe and effective use of warfarin therapy in older patients.

Aged↗

Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency.

BACKGROUND: Dose adjustment or laboratory monitoring of low-molecular-weight heparin (LMWH) is commonly recommended for patients with severe renal insufficiency (creatinine clearance < or =30 mL/min), but the basis for this recommendation is unclear. PURPOSE: To compare levels of anti-Xa heparin and risk for major bleeding in LMWH-treated patients with a creatinine clearance of 30 mL/min or less versus those with a creatinine clearance greater than 30 mL/min by using standard weight-adjusted therapeutic doses, empirically adjusted doses, or prophylactic doses of LMWH. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, and the Cochrane Library) searched to December 2005 with no language restrictions. The authors also searched reference lists and contacted experts. STUDY SELECTION: Observational or subgroups of randomized studies that included non-dialysis-dependent patients with varying degrees of renal function who were treated with LMWH and reported creatinine clearance and anti-Xa levels or major bleeding. DATA EXTRACTION: Two reviewers independently selected studies and extracted data on patient characteristics, renal function, LMWH treatment, anti-Xa levels, and major bleeding. The pooled odds ratio of major bleeding in patients with a creatinine clearance of 30 mL/min or less was calculated by using the Peto method. DATA SYNTHESIS: Eighteen studies using 3 preparations of LMWH (15 studies using enoxaparin, 2 using tinzaparin, and 1 using dalteparin) were included. Peak anti-Xa levels measured 4 hours after a subcutaneous injection were statistically significantly higher in patients with a creatinine clearance of 30 mL/min or less compared with those with a creatinine clearance greater than 30 mL/min in studies that used a standard therapeutic dose of enoxaparin (4 studies) but not in studies of empirically dose-adjusted enoxaparin (3 studies). Data were insufficient to assess the relationship between anti-Xa and renal function for prophylactic doses of enoxaparin and therapeutic doses of tinzaparin or dalteparin. In 12 studies involving 4971 patients, LMWH was associated with a statistically significant increase in the risk for major bleeding in patients with a creatinine clearance of 30 mL/min or less compared with those with a creatinine clearance greater than 30 mL/min (5.0% vs. 2.4%; odds ratio, 2.25 [95% CI, 1.19 to 4.27]; P = 0.013). When analyzed according to LMWH preparation, major bleeding was increased when a standard therapeutic dose of enoxaparin was used (8.3% vs. 2.4%; odds ratio, 3.88 [CI, 1.78 to 8.45]) but may not be increased when an empirically adjusted dose of enoxaparin is used (0.9% vs. 1.9%; odds ratio, 0.58 [CI, 0.09 to 3.78]; P = 0.23 for heterogeneity). There were insufficient studies to assess the risk for major bleeding with tinzaparin, dalteparin, and prophylactic doses of enoxaparin. LIMITATIONS: The data for tinzaparin and dalteparin were limited. Data are observational, and the potential for confounding cannot be excluded. CONCLUSIONS: Non-dialysis-dependent patients with a creatinine clearance of 30 mL/min or less who are treated with standard therapeutic doses of enoxaparin have elevated levels of anti-Xa and an increased risk for major bleeding. Empirical dose adjustment of enoxaparin may reduce the risk for bleeding and merits additional evaluation. No conclusions can be made regarding other LMWHs.

Anticoagulants↗

Rectal bleeding in general practice patients.

OBJECTIVE: To determine the prevalence of observed rectal bleeding in general practice patients, the health seeking behaviour of those with rectal bleeding, and what rectal bleeding 'means' to patients in terms of perceived health risk. METHOD: Self administered questionnaire survey of general practice patients aged 50 years and over in northern Tasmania recruited as they visited their general practitioner (GP). RESULTS: The reported lifetime prevalence of rectal bleeding in our sample was 33% (299 of 903 respondents). It was more common in younger people, becoming less common with increasing age. Many respondents do not examine for bleeding. Only 45% of respondents with rectal bleeding consulted their GP about the most recent bleed. Patients were more likely to consult if they reported blood in the toilet pan and if they sought advice from a family member. There were significant differences between the meaning of bleeding for GP consulters and non consulters. This may have important implications for health education. CONCLUSION: Colorectal cancer (CRC) is a common problem managed by a combination of screening and case finding. With the high prevalence of rectal bleeding and low consultation rates for this problem there is potential to enhance the effectiveness of early detection of CRC through general practice based public health and education campaigns.

Adult↗

Short-term crystalloid fluid resuscitation in uncontrolled intra-abdominal bleeding in swine.

INTRODUCTION: Fluid therapy in uncontrolled bleeding is controversial. In a previously used experimental animal model of aortic injury, the outcome often was impaired by re-bleeding that began at least 20 minutes after crystalloid fluid resuscitation was initiated. Therefore, it was hypothesized that re-bleeding might be avoided if volume loading is carried out for 20 minutes and then discontinued. METHODS: Ten minutes after a 5 mm laceration was produced in the infra-renal aorta on eight anesthetized pigs, they received a 20-minute intravenous infusion of Ringer's solution in the ratio of 1:1 to the expected blood loss. Hemodynamics were studied for 120 minutes using arterial and pulmonary artery catheters and blood flow probes placed proximal and distal to the aortic lesion and around the left renal artery and portal vein. RESULTS: The bleeding stopped between three and four minutes after the onset of bleeding. The blood flow rate dropped to 38% (mean) of baseline in the splanchnic region, to 31% in the upper aorta, and to 13% in the kidney. The flow rates and the oxygen consumption increased transiently during fluid resuscitation, but never reached baseline levels. Re-bleeding amounted to about 15% of the initial bleeding and occurred in only three of the animals. Four of the pigs died of shock within 90 minutes (range 47-85 minutes) after the aortic injury. CONCLUSION: Short-term crystalloid fluid therapy in uncontrolled aortic hemorrhage transiently improved the hemodynamic status and the oxygen consumption following the initial bleeding. Furthermore, the infusion did not cause re-bleeding of more than 100 ml, which occurred in previously conducted experiments when the infusion was continued for more than 20 minutes.

Animals↗

Octreotide in acute bleeding esophageal varices: a prospective randomized study.

BACKGROUND/AIMS: To assess the value of octreotide in the control of acute bleeding esophageal varices, in a prospective randomized study. METHODOLOGY: One hundred and ninety-seven patients admitted for variceal bleeding confirmed at endoscopy were recruited and divided into two groups: group I (n = 111) with endoscopic stigmata of recent bleeding; and group II (n = 86) with active bleeding at emergency endoscopy. Patients in group I were randomized to receive a continuous infusion of octreotide (n = 58) or emergency sclerotherapy (n = 53). Patients in group II were assigned to sclerotherapy (n = 42) or to sclerotherapy plus octreotide (n = 44). At the end of the period of study (48 hours), patients were submitted to sclerotherapy or band ligation until variceal obliteration was achieved. RESULTS: In group I, octreotide was found to be as effective as sclerotherapy regarding hemostasis at 48 hours and on day 7 after the index bleeding episode. Transfusion needs were not significantly different for the two treatment modalities. In group II, the association of octreotide with sclerotherapy was significantly better than sclerotherapy alone either in controlling acute active bleeding (P < 0.001) or in achieving hemostasis at 48 hours (P < 0.01). Transfusion needs were significantly fewer in patients treated with this therapeutic association as compared to sclerotherapy alone. CONCLUSIONS: These results suggest that octreotide infusion is effective in the treatment of variceal bleeding. In patients with recent bleeding, octreotide infusion is as effective as emergency sclerotherapy. In active variceal bleeding, it is a valuable adjuvant treatment in association with emergency sclerotherapy.

Acute Disease↗

Upper gastrointestinal bleeding in Kuala Lumpur Hospital, Malaysia.

Despite advancements in endoscopy and pharmacology in the treatment of peptic ulcer disease the overall mortality has remained constant at 10% for the past four decades. The aim of this study was to determine the age, gender, racial distribution, incidence and causes of endoscopically diagnosed cases of upper gastrointestinal (UGI) bleeding to summarise treatments undertaken and to report their outcome. A prospective study of UGI bleeding in 128 patients was performed in two surgical wards of Kuala Lumpur Hospital, involving both elective and emergency admissions. The study group comprised of 113 (88.2%) males and 15 (11.7%) females. The mean age was 51.9 years (range 14 to 85 years) and 37.5% (48 of 128 patients) were older than 60 years. The Indian race was over-represented in all disease categories. Smoking (50.1%), alcohol consumption (37.5%), non-steroidal anti-inflammatory drugs (NSAIDs) (17.2%), traditional remedies (5.5%), anti-coagulants (2.3%) and steroids (0.8%) were among the risk factors reported. Common presenting symptoms and signs included malaena (68.8%), haematemesis (59.4%) and fresh per rectal bleeding (33.6%). The commonest causes of UGI bleeding were duodenal ulcer (32%), gastric ulcer (29.7%), erosions (duodenal and gastric) (21.9%), oesophageal varices (10.9%) and malignancy (3.9%). UGI bleeding was treated non-surgically in 90.6% of cases. Blood transfusions were required in 62.6% (67/107) of peptic ulcer disease patients. Surgical intervention for bleeding peptic ulcer occurred in around 10% of cases and involved under-running of the bleeding vessel in most high risk duodenal and gastric ulcer patients. The overall mortality from bleeding peptic ulcer disease was 4.7%. Six patients died from torrential UGI haemorrhage soon after presentation, without the establishment of a cause. Active resuscitative protocols, early endoscopy, more aggressive interventional therapy, early surgery by more senior surgeons, increasing intensive care unit beds and more active participation of multidisciplinary teams in co-ordinating management are among remedial measures advocated. Broader educational preventive strategies should target the causes of UGI bleeding.

Adolescent↗