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Coital bleeding and HIV risks among men and women in Cape Town, South Africa.

BACKGROUND: South Africa has one of the world's fastest growing HIV epidemics. Genital bleeding during sexual intercourse may play a role in facilitating HIV transmission in South Africa. PURPOSE: The purpose of this study was to examine the prevalence and sources of coital bleeding among men and women living in a Cape Town South Africa township. METHODS: A purposive sample of 464 men and 531 women completed anonymous street intercept surveys of HIV risk history and sexual behaviors. RESULTS: Thirty-one percent of men and 26% of women had a lifetime history of engaging in sexual intercourse that involved genital bleeding, and 21% of men and 16% of women reported coital bleeding in the previous 3 months. Over 75% of coital bleeding was attributed to menses. Across genders and controlling for demographic, sexual behavior, and life history factors, coital bleeding in the previous 3 months was associated with being an indigenous African, having multiple sexual partners, and higher rates of unprotected intercourse during that time period. People who reported coital bleeding were over 3 times more likely to have been diagnosed with a sexually transmitted infection even after controlling for having had genital ulcers. CONCLUSIONS: Coital bleeding may be common in South Africa. Prevention messages that promote condom use or refraining from sex when there is genital bleeding are therefore needed.

Adolescent↗

Long-term mortality of patients admitted to the intensive care unit for gastrointestinal bleeding.

OBJECTIVES: Long-term mortality data for gastrointestinal (GI) bleeders is scarce in the literature. The aim of this prospective study was to determine the long-term mortality of patients admitted to two intensive care units with a primary diagnosis of GI bleeding. METHODS: The charts of patients admitted to the medical intensive care unit (MICU) with GI bleeding were reviewed and the data of the patients' first day in the MICU was used to calculate APACHE III and Charlson scores. A GI bleeding score was computed by combining endoscopic findings and units of blood transfused during patients' MICU stay. Mortality data was obtained from the Vital Statistics Department of Montgomery County, Dayton, OH. Survival data and predictability of mortality based on these scores were assessed. RESULTS: Mean age of the 66 patient cohort was 58.6 years. Twenty-six of 51 patients with upper GI bleeding, five of seven patients with lower GI bleeding, and four of eight patients with unknown site of bleeding died within 7 years. Charlson score correlated significantly with the mortality prediction, whereas the APACHE III and bleeding scores did not. CONCLUSIONS: All-cause and GI bleeding-related 7-year mortality for patients admitted to the MICU with GI bleeding was lower than the rates cited in the literature. The Charlson score was helpful in predicting mortality.

APACHE↗

Menstrual bleeding patterns in pre- and perimenopausal women: a population-based prospective diary study.

BACKGROUND: To investigate natural menstrual bleeding patterns in pre- and perimenopausal women, a prospective observational population study was carried out. METHODS: A total of 1616 (80.8%) of a population-based sample of 2000 Danish women aged 45-54 years answered an initial questionnaire. Of 1059 women with natural gynecological functions, 951 (89.8%) completed 1 year of daily recording of bleeding. Of these women, 592 were pre- or perimenopausal and were included in this study. MAIN OUTCOME MEASURES: Length and heaviness of bleeding episodes, including frequency of spotting, flooding and prolonged bleeding, according to regularity of cycles. RESULTS: The proportion of women with irregular cycles increased from 58.3% at age 45-46 years to 100% at age 53-54 years (P < 0.001). Irregularity of cycles was accompanied by increased variation in both length and subjective assessment of heaviness of bleeding episodes in the individual woman and between women (P < 0.001). Episodes of spotting (P < 0.001) and prolonged bleeding (10 days or more) (P < 0.001) were more common in women with irregular cycles. Subjective assessment of heaviness of bleeding episodes, however, was higher in women with regular cycles (P < 0.001). One or more episodes of flooding were recorded by 24.0% of all women irrespective of regularity of cycles (P = 0.40) but more frequently in younger women (P < 0.001). CONCLUSIONS: Irregularity of cycle lengths at the end of the fertile period is common, and is accompanied by an increased inter- and intraindividual variation in the length and heaviness of bleeding episodes, including increased frequency of prolonged bleeding and spotting.

Case-Control Studies↗

Helicobacter pylori stool antigen test in patients with bleeding peptic ulcers.

BACKGROUND: Helicobacter pylori has been linked to chronic gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Invasive tests are less sensitive than noninvasive tests in diagnosing H. pylori infection in patients with bleeding peptic ulcers. The H. pylori stool antigen test has been useful in diagnosing H. pylori in patients with peptic ulcers before and after eradication of H. pylori. The aim of this study was to evaluate the H. pylori stool antigen test in patients with bleeding peptic ulcers. METHODS: Patients with bleeding and nonbleeding peptic ulcers underwent a rapid urease test, histology, bacterial culture and H. pylori stool antigen test. Positive H. pylori infection was defined as a positive culture or both a positive histology and a positive rapid urease test. Helicobacter pylori stool antigen was assessed with a commercial kit (Diagnostec H. pylori antigen EIA Kit, Hong Kong). RESULTS: Between October 2000 and April 2002, 93 patients with bleeding peptic ulcers (men/women: 78/15, gastric ulcer/duodenal ulcer: 58/35) and 59 patients with nonbleeding peptic ulcers (men/women: 47/12, gastric ulcer/duodenal ulcer: 30/29) were enrolled in this study. Forty-seven (50.5%) patients with bleeding peptic ulcers and 30 (50.8%) patients with nonbleeding peptic ulcers, were found to be infected with H. pylori (p > .1). Helicobacter pylori stool antigen tests were positive in 54 (58.1%) and 30 (50.8%) patients with bleeding peptic ulcers and nonbleeding peptic ulcers, respectively (p > .1). The sensitivity (82% vs. 93%), specificity (68% vs. 93%), positive predictive value (74% vs. 93%), negative predictive value (77% vs. 93%) and diagnostic accuracy (75% vs. 93%) were all lower in patients with bleeding vs. nonbleeding peptic ulcers. The specificity, positive predictive value, and diagnostic accuracy of the H. pylori stool antigen test in patients with bleeding peptic ulcers were significantly lower than those in patients with nonbleeding peptic ulcers (p = .01, p = .02 and p = .003, respectively). CONCLUSION: The H. pylori stool antigen test is not reliable for diagnosing H. pylori infection in patients with bleeding peptic ulcers.

Aged↗

Review article: aspirin and gastrointestinal bleeding.

Many animal and human studies have shown aspirin to cause gastric mucosal erosions and enhanced spontaneous microbleeding. Chronic use is associated with uncomplicated gastric ulcer (but not clearly with uncomplicated duodenal ulcer) and with presentation with haematemesis and melaena. Sub-group analysis suggests that the risks of bleeding duodenal ulcer as well as bleeding gastric ulcer (and possibly non-ulcer bleeding) are increased. These data imply that an anti-haemostatic as well as an ulcerogenic effect contributes to such presentation and acute data support this proposition. A broken mucosa and inhibition of thromboxane synthesis both appear to be necessary for bleeding to occur. Aspirin enhances the bleeding associated with mucosal biopsy analogous to its prolongation of the skin bleeding time. Anti-haemostatic properties could account for the apparent increase in presentation with haematemesis and melaena in patients taking low doses of aspirin for cardiovascular prophylaxis. However, acute studies also show aspirin 300 mg to cause a level of mucosal injury which is substantial, though significantly less than with aspirin 600 mg q.d.s. The risk attached to aspirin consumption needs to be kept in perspective. It can be calculated that aspirin use is associated with approximately 700 bleeds per annum in the UK. The relative risk for upper gastrointestinal bleeding is roughly similar to that for non-aspirin non-steroidal anti-inflammatory drugs but those affected are generally younger, in an age group where death from upper gastrointestinal bleeding is very uncommon. In keeping with this and in contrast to non-aspirin non-steroidal anti-inflammatory drugs, no study has shown increased mortality from aspirin-related upper gastrointestinal complications.

Anemia, Hypochromic↗

Wireless capsule endoscopy in patients with obscure gastrointestinal bleeding: a comparative study with push enteroscopy.

BACKGROUND: The identification and treatment of lesions located in the small intestine in obscure gastrointestinal bleeding is always a clinical challenge. AIM: To examine prospectively the diagnostic precision and the clinical efficacy of capsule endoscopy compared with push enteroscopy in obscure gastrointestinal bleeding. METHODS: Forty-two patients (22 men and 20 women) with obscure gastrointestinal bleeding (overt bleeding in 26 cases and occult blood loss with chronic anaemia in 16) and normal oesophagogastroduodenoscopy and colonoscopy were analysed. All patients were instructed to receive the capsule endoscopy and push enteroscopy was performed within the next 7 days. Both techniques were blindly performed by separate examiners. The diagnostic yield for each technique was defined as the frequency of detection of clinically relevant intestinal lesions carrying potential for bleeding. RESULTS: A bleeding site potentially related to gastrointestinal bleeding or evidence of active bleeding was identified in a greater proportion of patients using capsule endoscopy (74%; 31 of 42) than enteroscopy (19%; eight of 42) (P = 0.05). The most frequent capsule endoscopy findings were: angiodysplasia (45%), fresh blood (23%), jejunal ulcers (10%), ileal inflammatory mucosa (6%) and ileal tumour (6%). No additional intestinal diagnoses were made by enteroscopy. In seven patients (22%), the results obtained with capsule endoscopy led to a successful change in the therapeutic approach. CONCLUSIONS: Compared with push enteroscopy, capsule endoscopy increases the diagnosis yield in patients with obscure gastrointestinal bleeding, and allows modification on therapy strategy in a remarkable proportion of patients.

Adolescent↗

Meta-analysis: endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleeding.

BACKGROUND: The treatment effects of primary prophylactic endoscopic variceal ligation are unclear. AIM: To compare the treatment effects of endoscopic variceal ligation and beta-blockers for primary prophylaxis of oesophageal variceal bleeding. In addition, a subgroup analysis was done with the purpose to delineate differences in the effects of intervention that were biologically based. METHODS: We performed a literature search for randomized controlled trials, which compared the treatment effects of endoscopic variceal ligation with beta-blockers for primary prophylaxis of oesophageal variceal bleeding. Of the 955 articles screened, eight randomized-controlled trials including 596 subjects (285 with endoscopic variceal ligation and 311 with beta-blockers) were analysed. Outcomes measures evaluated were first gastrointestinal bleed, first variceal bleed, all-cause deaths, bleed-related deaths and severe adverse events. The measure of association employed was relative risk; with heterogeneity and sensitivity analyses. RESULTS: Variceal obliteration was obtained in 261 (91.6%) patients and target beta-blockers therapy was achieved in 294 (94.5%) patients (P = 0.19). Endoscopic variceal ligation compared with beta-blockers significantly reduced rates of first gastrointestinal bleed by 31% (RR, 0.69; 95% CI: 0.49-0.96; P = 0.03; NNTB = 15) and first variceal bleed by 43% (RR, 0.57; 95% CI: 0.38-0.85; P = 0.0067; NNTB = 11). All-cause deaths and bleed-related deaths were unaffected (RR, 1.03; 95% CI: 0.79-1.36; P = 0.81 and RR, 0.84; 95% CI: 0.44-1.61; P = 0.60 respectively). Severe adverse events were significantly less in endoscopic variceal ligation compared with beta-blockers (RR, 0.34; 95% CI: 0.17-0.69; P = 0.0024; NNTB = 28). Sensitivity analysis of five trials published in peer review journals and four trials with high quality showed results similar to those seen in the primary analysis of all the eight trials, confirming stability of conclusions. Following variceal obliteration with endoscopic variceal ligation, oesophageal varices recurred in 83 (29.1%) patients. Seven (28.1%) patients bled with one fatal outcome. In subgroup analyses, endoscopic variceal ligation had significant advantage compared wtih beta-blockers in trials including < or =30% patients with alcoholic cirrhosis, >30% patients with Child Class C cirrhosis and >50% patients with large varices. CONCLUSIONS: In patients with cirrhosis with moderate to large varices and who have not bled, endoscopic varices ligation compared with beta-blockers significantly reduced bleeding episodes and severe adverse events, but had no effect on mortality.

Adrenergic beta-Antagonists↗

Laboratory issues in bleeding disorders.

The clinical history of the patient and of his/her relatives is the most important tool for making correct diagnosis of inherited or acquired bleeding disorders. Several attempts have been made by clinicians to evaluate the sensitivity and specificity of bleeding symptoms. Specific and detailed questionnaires have been designed to quantify the bleeding tendency of patients with von Willebrand's disease (VWD) and a bleeding score has been calculated. VWD is considered the most frequent inherited bleeding disorder according to population studies: however, due to the complexity of its diagnosis, the number of patients with correct diagnosis of VWD in many developing countries is relatively low and most cases remain still under- or misdiagnosed. Once bleeding history is carefully evaluated by means of a bleeding score, the laboratory workout should be organized to find out the specific defect of haemostasis responsible for bleeding. Since factors involved in haemostasis are many, the correct approach must include first level screening tests with the aim to identify the abnormal phase of haemostasis involved: then, second level tests should be focused on the specific factors within the abnormal step of haemostasis. Among many other acquired bleeding disorders related to clinical conditions or to the use of drugs, the acquired inhibitors of haemostasis are rare but should be immediately characterized by appropriate laboratory tests because they can be often life-threatening for the patients.

Blood Coagulation Disorders↗

Bleeding complications in patients on celecoxib and warfarin.

PURPOSE: Non-selective non-steroidal anti-inflammatory drugs (nNSAIDs) used in combination with warfarin are associated with an approximately 3-fold increased risk of upper gastrointestinal bleeding (UGIB) compared with warfarin alone. Celecoxib, a selective inhibitor of cyclo-oxygenase 2 (COX-2), is associated with less gastric mucosal injury and platelet dysregulation than nNSAIDs. We compared rates of bleeding complications in patients taking celecoxib and warfarin with those taking warfarin alone. SUBJECTS AND METHODS: We performed a retrospective analysis using data from our Protime Clinic and pharmacy databases from January 2001 to April 2004. We identified 123 patients who took celecoxib and warfarin concurrently (overlap group). We compared rates of bleeding complications in this group with 1022 control patients who were taking warfarin alone. Bleeding complications were defined as major if they resulted in hospitalization, blood transfusion or death. RESULTS: During approximately 1063 months of exposure to both celecoxib and warfarin, 10 bleeding complications were identified, only one of which was considered major. No patients had UGIB. In the control group, 116 bleeding complications were identified over approximately 16 520 months of exposure to warfarin alone, with 101 minor and 15 major events, including six episodes of UGIB. The relative risk of all bleeding complications was 1.34 (95% CI: 0.70-2.57) in the overlap vs. control groups, and for major bleeds was 1.04 (95% CI: 0.14-7.85). CONCLUSIONS: There is a mild but non-significant increase in bleeding complications in patients taking celecoxib and warfarin compared with those taking warfarin alone.

Aged↗

Plasma endotoxin concentration and endotoxin binding capacity of plasma acute phase proteins in cirrhotics with variceal bleeding: an analysis by new methods.

Plasma endotoxin levels in 12 cirrhotics with bleeding from oesophageal varices and 50 cirrhotics without bleeding were measured by the chromogenic assay after the pretreatment of sample by perchloric acid (HClO4) and triethylamine. Endotoxin in cirrhotics with bleeding from varices was significantly higher than those without bleeding. In patients with bleeding, endotoxin increased for 3 days after the bleeding, first in the supernatant fraction and then in the precipitate fraction by HClO4 treatment. Peak plasma alpha 1-acid glycoprotein and haptoglobin were observed 3 days after the bleeding. Alpha 1-antitrypsin gradually increased for 14 days. Transferrin did not markedly change. The endotoxin-binding capacity of transferrin and alpha 1-acid glycoprotein increased immediately after bleeding and thereafter decreased, but that of alpha 1-antitrypsin tended to increase in the recovery period. In summary, the plasma endotoxin concentration and endotoxin-binding capacity of alpha 1-acid glycoprotein and transferrin were shown to have increased after bleeding from varices by this new method. There may be a close relationship between endotoxaemia and acute phase reaction in this situation.

Acute-Phase Proteins↗

Bleeding Risk Index in an anticoagulation clinic. Assessment by indication and implications for care.

BACKGROUND: The Outpatient Bleeding Risk Index (BRI) prospectively classified patients who were at high, intermediate, or low risk for warfarin-related major bleeding. However, there are only 2 published validation studies of the index and neither included veterans. OBJECTIVE: To determine the accuracy of the BRI in patients attending a Veterans Affairs (VA) anticoagulation clinic and to specifically evaluate the accuracy of the BRI in patients with atrial fibrillation. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Using the BRI, all patients managed by the Anticoagulation Clinic between January 1, 2001 and December 31, 2002 were classified as high, intermediate, or low risk for major bleeding. Bleeds were identified via quality-assurance reports. Poisson regression was used to determine whether there was an association between the index and the development of bleeding. RESULTS: The rate of major bleeding was 10.6%, 2.5%, and 0.8% per patient-year of warfarin in the high-, intermediate-, and low-risk groups, respectively. Patients in the high-risk category had 14 times the rate of major bleeding of those in the low-risk group (incidence rate ratio (IRR) 14; 95% confidence interval (CI), 1.9 to 104.7). The rate of major bleeding was significantly different between the high- and intermediate-risk categories (P<.001). Among those with atrial fibrillation, patients in the high-risk category had 6 times the major bleeding rate of those in the intermediate- and low-risk groups combined (IRR=6; 95% CI, 2.4 to 15.3). CONCLUSIONS: The BRI discriminates between high- and intermediate-risk patients in a VA anticoagulation clinic, including those with atrial fibrillation.

Aged↗

Methods for the analysis of bleeding outcomes in randomized trials of PLT transfusion triggers.

BACKGROUND: A number of methodologic challenges arise in the analysis of bleeding data from clinical trials of PLT transfusion triggers. It is important to understand the assumptions and role of the various methods of analysis to interpret published trials and to design future studies appropriately. STUDY DESIGN AND METHODS: The methods of analysis used for testing the effectiveness and safety of transfusion strategies are reviewed from several recent PLT transfusion trigger trials. The underlying assumptions of these methods are discussed, as well as the clinical interpretations of the resulting summary statistics. Four methods of analysis were applied to data from a large PLT transfusion trigger study to illustrate the differences in the interpretations that can arise from various approaches. RESULTS: PLT transfusion trigger trials of patients with leukemia have based their primary analyses on 1) simple dichotomous classifications of whether or not at least 1 day of clinically important bleeding was experienced; 2) the time to the first day of clinically important bleeding; and 3) the proportion of days at risk with clinically important bleeding. Recurrent event methods provide a robust alternative approach to the analysis of this kind of data and should be considered if interest is in capturing the overall burden of bleeding over time. These four methods differ in the extent to which they utilize information on the number of days with bleeding and the temporal variation in bleeding patterns. Inferences drawn regarding the relative safety and efficacy of different transfusion triggers can vary depending on the method of analysis. CONCLUSION: To rigorously design and analyze future PLT transfusion studies based on bleeding outcomes, it is important to have a clear understanding of the interpretation of the different ways of analyzing bleeding outcomes. The analysis strategy should be selected based on the clinical question being addressed.

Hemorrhage↗

Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review.

BACKGROUND: The literature was systematically reviewed to determine whether a prolonged prothrombin time or elevated international normalized ratio predicts bleeding during invasive diagnostic procedures. STUDY DESIGN AND METHODS: MEDLINE and CENTRAL were searched through August 2004, with no language restriction, and reference lists were reviewed. For inclusion, articles must have reported on bleeding in more than five patients with abnormal test results undergoing diagnostic procedures. RESULTS: One trial and 24 observational studies were included. In 2 studies of bronchoscopy, the bleeding rates were similar among those with normal and abnormal tests, with wide confidence intervals (CIs) around the risk differences. During central vein cannulation (3 studies), bleeding rates among those with abnormal tests was unlikely to exceed 2.3 percent. The largest of 3 studies of arteriography found equivalent bleeding rates in patients with and without abnormal tests (risk difference, 0%; 95% CI, -3% to 2%). In the 3 studies of liver biopsy with plugging, bleeding rates were 0, 4, and 5 percent with the upper bounds of the CI as high as 17 percent. In the largest study of transjugular biopsy, the bleeding rate was 1.5 percent (95% CI, 0.3%-4%) in patients with abnormal tests. The highest bleeding rate in the 3 studies of percutaneous liver biopsy was 5.3 percent (95% CI, 1%-13%), similar to the rate in patients with normal test results. CONCLUSION: There is insufficient evidence to conclude that abnormal test results predict bleeding. Randomized controlled trials should be performed to provide stronger evidence for clinical decision making regarding preprocedure transfusion.

Blood Coagulation Tests↗

A descriptive analysis of international transfusion practice and bleeding outcomes in patients with acute leukemia.

BACKGROUND: Recently, bleeding has been used in platelet (PLT) trials rather than surrogate outcomes. The purpose of this study was to provide a descriptive summary of data from PLT studies conducted in four countries and exploratory analyses to determine the relationship between bleeding and PLT count. STUDY DESIGN AND METHODS: A descriptive analysis was performed on original data from the Italian trigger study, the US TRAP study, the Canadian febrile reaction study, and a clinical chart review from one hospital site in the United Kingdom. The relationship between bleeding and PLT count was explored with the Italian data. RESULTS: A total of 897 patients with acute leukemia received 10,506 PLT transfusions. Grade 3 or Grade 4 WHO bleeding frequency was 28.1 percent (252/897) but varied by country: Italy, 10.8 percent (27/250); United States, 36.4 percent (217/598); Canada, 18.9 percent (7/37); and the United Kingdom, 8.3 percent (1/12). Grade 1 or Grade 2 bleeding was reported only in the Italian study (46.4%[116/250] and 11.6%[29/250], respectively). The relative rates of WHO Grade 2, 3, or 4 bleeding for PLT counts in the ranges of 0 to 4, 5 to 9, 10 to 14, and 15 to 19 (x10(9)/L) were 8.8, 1.9, 1.8, and 1.2, respectively, compared to those counts within the range of 20 to 29 (x10(9)/L). CONCLUSION: The study provides descriptive data on PLT use and frequency of bleeding. When PLT counts were 0x10(9) to 4x10(9) per L there was an eightfold increase in bleeding and a twofold risk increase when counts were 5x10(9) to 14x10(9) per L compared to the 20x10(9) to 29x10(9) per L reference range. The increased rate of bleeding at low counts occurred despite PLT therapy.

Acute Disease↗

Clinical outcome of patients with venous thromboembolism and recent major bleeding: findings from a prospective registry (RIETE).

BACKGROUND: Patients who have experienced a recent major bleeding episode are usually excluded from clinical studies of venous thromboembolism (VTE) treatment. Therefore, recommendations based on evidence from clinical trials may not be suitable for these patients. The Registro Informatizado de la Enfermedad TromboEmbolica (RIETE) is a multicenter, observational registry designed to gather and analyze data on VTE treatment practices and clinical outcomes in patients with acute VTE. OBJECTIVES: The aim of this analysis was to study outcomes of patients with VTE who had experienced recent major bleeding (< 30 days prior to VTE diagnosis). METHODS: Patients with objectively confirmed symptomatic acute VTE are consecutively enrolled into the RIETE registry. Patient characteristics, details of antithrombotic therapy, and clinical outcomes at 3 months were recorded. RESULTS: Of 6361 patients enrolled up to January 2004, 170 (2.7%) had experienced recent major bleeding: 69 (40.6%) gastrointestinal tract, 60 (35.3%) intracranial, 41 (24.1%) other. The incidences of major bleeding (4.1%) and recurrent pulmonary embolism (PE) (2.4%) were significantly higher in patients with recent major bleeding. Among them, patients with cancer had an increased incidence of major bleeding [odds ratio (OR) 10.0, 95% confidence interval (CI) 2.3, 50; P < 0.001] and fatal PE (OR 4.1, 95% CI 0.98, 17; P < 0.05). CONCLUSIONS: Patients with VTE and recent major bleeding prior to VTE diagnosis (2.7% of total enrolled patients) had poorer clinical outcomes compared with those who had not experienced recent major bleeding. In patients who had recent major bleeding prior to enrollment, those with cancer had a poorer clinical outcome than those without cancer.

Adult↗

Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von Willebrand disease: an international, multicenter study.

OBJECTIVES: We undertook an international, multicenter study to describe the clinical picture and to estimate the bleeding risk in a group of obligatory carriers of type 3 von Willebrand disease (VWD). PATIENTS AND METHODS: Obligatory carriers (OC) of type 3 VWD were identified by the presence of offspring with type 3 VWD or by being an offspring of a type 3 patient. Normal controls were age- and sex-matched with the obligatory carriers. A physician-administered standardized questionnaire was used to evaluate hemorrhagic symptoms at presentation. A score system ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion) was used to quantitate bleeding manifestations. Odds ratios were computed for each symptom. RESULTS: Ten centers participated to the study, enrolling a total of 35 type 3 VWD families, with 70 OC. A total of 215 normal controls and 42 OC for type 1 VWD were also included. About 40% of type 3 OC had at least one bleeding symptom compared to 23% of normal controls and 81.8% of type 1 OC (P < 0.0001 by chi-squared test), showing that type 3 OC clearly represent a distinct population from type 1 OC. The clinical situations associated with an increase of bleeding risk in type 3 OC were epistaxis [odds ratio 3.6; 90% confidence intervals (CI) 1.84-21.5], cutaneous bleeding (odds ratio 5.5; 90% CI 2.5-14.1) and postsurgical bleeding (odds ratio 16.3; 90% CI 4.5-59). The severity of bleeding score correlated with the degree of factor (F) VIII reduction in plasma. CONCLUSIONS: OC for type 3 VWD represent a distinctive population from type 1 OC. These patients, however, present with more frequent bleeding symptoms in comparison to normal controls, especially in case of significantly low FVIII. Desmopressin and/or tranexamic acid might be useful to prevent or treat bleeding in these cases.

Adolescent↗

Fatal pulmonary embolism and fatal bleeding in cancer patients with venous thromboembolism: findings from the RIETE registry.

OBJECTIVES: To examine the clinical characteristics and outcomes of cancer patients with venous thromboembolism (VTE) in order to identify factors that place these patients at an increased risk for fatal pulmonary embolism (PE) or fatal bleeding. PATIENTS AND METHODS: Registro Informatizado de la Enfermedad Trombo Embólica (RIETE) is a prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. RESULTS: Up to January 2006, a total of 14 391 patients with symptomatic acute VTE were enrolled in RIETE, of whom 2945 (20%) had cancer. During the 3-month follow-up period the frequency of fatal PE in cancer patients was 2.6%, and that of fatal bleeding 1.0%. These frequencies were significantly higher than in VTE patients without cancer (1.4% and 0.3%, respectively). In patients with cancer, abnormal renal function, metastatic disease, recent major bleeding and recent immobility for >or= 4 days (42% of the 108 patients who died from PE or bleeding had recent immobility) were factors independently associated with an increased risk for both fatal PE and fatal bleeding. In addition, PE diagnosis on admission was an independent risk factor for fatal PE, while body weight < 60 kg was an independent risk factor for fatal bleeding. CONCLUSIONS: Both fatal PE and fatal bleeding are more common in cancer patients with VTE than in those patients without cancer. In cancer patients, abnormal renal function, metastatic disease, recent major bleeding and recent immobility for >or= 4 days are associated with an increased risk for both fatal PE and fatal bleeding.

Aged↗

Predictors of bleeding complications and thrombocytopenia with the use of abciximab during percutaneous coronary intervention.

Abciximab (c7e3; ReoPro; Centocor, Inc., Pennsylvania, USA), a Fab fragment of the chimeric human-murine monoclonal antibody directed against platelet glycoprotein IIb/IIIa receptors, has been shown to reduce acute ischemic complications in patients undergoing percutaneous coronary interventions (PCI). However, its use has been associated with an increased incidence of bleeding events. The aim of this study is to examine the frequency of bleeding complications and to identify clinical variables associated with it in our patients. We prospectively recorded incidence of bleeding complications in 344 consecutive patients who underwent PCI with adjunctive use of abciximab (Ab). Clinical predictors for patients who developed bleeding complications with Ab were compared with the nonbleeders. Major bleeding occurred in six patients (1.7%) one of whom had pulmonary hemorrhage and one had intracranial hemorrhage. Minor bleeding occurred in 20 (5.8%) patients. Thrombocytopenia was seen in 13 (3.9%) patients of which four (1.2%) were mild, four (1.2%) were severe, and five (1.5%) were profound. Multivariate analyses showed that female gender and the "bail-out" use of Ab were risk factors for bleeding complications. The rate of major bleeding complications and thrombocytopenia were low and comparable with published trials. Female patients and those who received Ab as a "bail-out" were at higher risk of developing bleeding complications.

Abciximab↗