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Hereditary telangiectasia manifested as gastrointestinal bleeding without external visible telangiectasia.

Gastrointestinal bleeding is one of the most common problems confronting the physician. In most instances, the source of the bleeding is easily identified, e.g., peptic ulcer disease, bleeding esophageal varices or a colonic lesion. Recurrent gastrointestinal bleeding, however, represents one of the major enigmas confronting the practicing physician. The patient experiences intermittent episodes of weakness, easy fatigability and anemia with occult blood in the stool. Multiple barium radiographic examinations and often endoscopy and exploratory laparotomy are unrevealing as to the etiology of the bleeding. We have had occasion to investigate three such patients. Multiple evaluations of these individuals did not reveal the source of the bleeding until many years later--Rendu-Osler-Weber Disease (ROW). At the time of their evaluations these patients did not reveal the usual telangiectatic areas present on the skin and oral mucous membrane. The diagnosis was suggested by the presence of multiple gastric mucosal telangiectasia identified by gastroscopic examination. This report emphasizes the need for thorough endoscopic evaluation of patients with gastrointestinal bleeding and describes the gastroscopic findings that indicated hereditary telangiectasia as the probable source of bleeding from the gastrointestinal tract.

Aged↗

Cytohistologic correlation in patients with clinical symptoms of postmenopausal bleeding.

Today, the life expectancy for women is longer; therefore, many will likely experience the postmenopausal period (termination of fertility and menstrual bleeding). Uterine bleeding after this period is a sign of pathologic condition. The specific objective of this project was to evaluate the cytohistologic findings in women with postmenopausal bleeding (PMB) and to determine the presence of any significant pathologic lesions. Cytohistologic correlations from 66 patients attained in 1993 from the University of Mississippi Medical Center were evaluated. The population evaluated were divided into three groups: (control group 1) dysfunctional uterine bleeding (DUB), (control group 2) postmenopausal (PMP), and (test group 3) the group of women with postmenopausal bleeding. The DUB and PMP age-matched controls (n = 12, mean age 51 +/- 5 and 57 +/- 5 years) were randomly selected, and correlated with the actual group being tested (54 PMB, mean age 57 years). The distribution among the 54 PMB women evaluated were 69% (37/54) black, and 31% (17/54) white. The DUB and PMP control groups consisted of 50% (6/12) black and 50% (6/12) white, respectively. Histopathological confirmation (62/66--94%) revealed 47/66 as negative, 5/66 as endometrial hyperplasia and 10/66 as squamous cell carcinoma or adenocarcinoma. A significant lesion with endometrial pathology was found in 23% of the patients. These findings suggest that the majority of women in this study with clinical symptoms of postmenopausal bleeding were negative for malignancies. While these results lean more towards a normal cytologic evaluation, postmenopausal bleeding should not be taken lightly. Postmenopausal bleeding could represent signs of more serious lesion such as squamous cell carcinoma or endometrial adenocarcinoma if not detected and managed early.

Blood Cells↗

Bleeding patterns after early abortion with mifepristone and misoprostol or manual vacuum aspiration.

OBJECTIVE: To prospectively determine patterns and predictors of bleeding after early abortion with mifepristone and misoprostol or manual vacuum aspiration (MVA). METHODS: Women fewer than 63 days from the last menstrual period and desiring termination of pregnancy were offered medical abortion with 200 mg oral mifepristone and 800 micrograms oral misoprostol or MVA under local anesthesia. Women completed a bleeding diary during the six weeks after abortion. Telephone calls were used to encourage diary completion and determine contraception use. RESULTS: 212 women were enrolled, 80% of whom completed diaries. Mean days of bleeding was higher in the medical (14 days) than MVA (9 days) group, but days of spotting (about 10) was similar in both groups. Increasing gestational age predicted more bleeding or spotting days after medical, but not MVA, abortion. Prolonged bleeding was not rare and was more common in the medical than the surgical abortion group. Combined oral contraceptive (COC) users and non-COC users had similar bleeding patterns after medical or surgical abortion. CONCLUSION: Bleeding after early medical abortion persists longer than after MVA and continues longer than previously appreciated regardless of method. Oral contraceptive use does not decrease bleeding after early medical or surgical abortion.

Abortion, Induced↗

Acute gastrointestinal bleeding: clinical essentials for the initial evaluation and risk assessment by the primary care physician.

Acute gastrointestinal bleeding is a common medical emergency that frequently results in hospitalization. Rapid initial assessment of clinical parameters such as estimated volume of blood lost, appearance of expelled blood, hypotension, mental status changes, and coagulopathy should all be evaluated as part of the outcomes prediction equation. For upper gastrointestinal bleeding, early endoscopy of the upper gastrointestinal tract will also provide important information to aid in efforts to predict risk. Endoscopic evidence of ongoing rapid bleeding or the presence of a "visible vessel" or adherent clot on the ulcer base are findings that are associated with a high likelihood of continued bleeding or recurrent bleeding. Endoscopic therapy can reduce the rates of recurrent bleeding, surgery, and length of hospital stay in patient with these "stigmata of recent bleeding." Other endoscopic ulcer appearances such as brown or black pigment in the ulcer base or a clean ulcer base do not require endoscopic therapy, as rates of recurrent bleeding are very low for these lesions. Use of these clinical and endoscopic outcome predictors can also be useful in refining triage decisions as to which patients need to be in the intensive care unit, which need to be admitted to the hospital, and which can have early oral feeding and expedited hospital discharge or outpatient care.

Acute Disease↗

Oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and risk of bleeding. A Multicenter Inception Cohort Study.

Oral anticoagulants (OA) are the drug of choice for stroke prevention in patients with non-rheumatic atrial fibrillation (NRAF). This clear benefit/risk ratio comes from several randomized clinical trials (RCT) in which highly selected patients were strictly monitored. The aim of this study was to ascertain whether the safety of OA was also obtained outside the setting of clinical trials in consecutive patients starting treatment and routinely followed at Italian anticoagulation clinics. A total of 433 patients with NRAF were enrolled in the ISCOAT study and followed up for a mean of 1.4 years. Two patients (0.3% per year) suffered from a complete non-fatal ischemic stroke, 8 patients (1.3% per year) died of thrombosis-related vascular death, and 11 patients (11 events, 1.8% per year) suffered from major bleedings (2 fatal). Major bleeding occurred more frequently in patients >75 years of age (6 events, 5.1% per year) than in younger patients (5 events, 1.0% per year). The cumulative incidence of major bleeding in patients over 75 years of age (10.8%; 95% CI, 1.8-19.8) was significantly higher than in younger patients (2.8%; 95% CI, 0.3-5.3, p = 0.006). Major primary bleeding unrelated to organic lesions (7 patients, 1 male and 6 females) occurred in 5 elderly patients (>75 years old) with a cumulative incidence (9.6%; 95% CI 0.8-18.4) significantly higher than in younger patients (1.2%; 95% CI, 0-3.0, p = 0.0003). Univariate analysis revealed a higher frequency of major primary bleeding in females, in diabetic patients and in in those who had suffered a previous thromboembolic event. Multivariate analysis revealed that only age grater than 75 years was independently related to major primary bleedings (RR 6.6; 95% CI 1.2-37, p = 0.032). Minor bleedings (n = 27) were not more frequent in elderly patients (6% vs 4% per year, p = ns). Patients were kept at optimal intensity of treatment for 63% of the time. These data confirm the efficacy of OA but identify elderly patients as a high risk group of major bleeding.

Administration, Oral↗

[The diagnostic value of hysteroscopy on postmenopausal bleeding].

The objectives of this study were to investigate the causes of postmenopausal bleeding and evaluate the diagnostic value of hysterscopy. Using the diagnostic technique of hysteroscopy and directed biopsies, the authors analysed the causes of postmenopausal bleeding of 234 patients undergoing hysteroscopy. The results showed that atrophic endometrium was the most common cause of postmenopausal bleeding and that endometrial hyperplasia, endometrial carcinoma/precancerous lesion, and submucous leiomyoma/endometrial polyp were also common in the patients with postmenopausal bleeding. The agreement rate between hysteroscopy and directed biopsies was 74.61%. In 234 cases of postmenopausal bleeding, the benign and malignant pathological changes were found in 76 and 27 cases respectively. In terms of age and menopause time, there were significant differences (chi 2 = 3.36, P < 0.01; chi 2 = 3.92, P < 0.01 respectively)between the patients with postmenopausal bleeding in the benign changes group and those in the malignant changes group. So the combined use of hysteroscopical technique and directed biopsies is of great significance in finding out the causes of postmenopausal bleeding, making a definite diagnosis of endometrial carcinoma and precancerous lesion, and further preventing the occurrence of endometrial carcinoma. The examination of hysteroscopy is an effective and valuable method for diagnosing postmenopausal bleeding.

Adult↗

Short-term clinical study comparing supragingival plaque removal and gingival bleeding reduction of the Philips Jordan HP735 to a manual toothbrush in periodontal patients in a maintenance program.

The Philips Jordan HP735 was compared to a manual brush for plaque removal efficacy and reduction of gingival bleeding. Subjects in a periodontal maintenance program were randomly divided into two groups; Group I (n = 27), average age 36.9 years, brushed with the manual brush; and Group II (n = 22), average age 32.9 years, brushed with the Philips Jordan HP735 electric brush. A dichotomous plaque and bleeding index was used at six sites on all teeth at baseline, three, six and nine weeks. The subjects did not use any other cleaning devices during the study. No significant statistical difference in plaque score or bleeding score was found between the two groups at baseline. Plaque scores did not statistically significantly decrease over time in either group, and there was no significant difference in plaque removal between groups during the study. The bleeding index decreased significantly in the electric toothbrushing group; however, due to the large variation in bleeding scores between subjects, the difference in the number of bleeding sites was not statistically significant between the two groups. In conclusion, in a group of periodontal patients in a maintenance phase, using an electric toothbrush did not significantly enhance plaque removal, but did decrease bleeding compared to baseline. The difference in bleeding percentages was not statistically significant compared to a manual brush.

Adolescent↗

[Anti-bleeding effect of nafamostat mesilate for the surgery of thoracic ascending aorta].

UNLABELLED: During extracorporeal cardiopulmonary bypass (ECB), the activated coagulation and fibrinogenolysis system causes bleeding and postoperative multiple organ failures. We studied the effect of an anti-bleeding agent, nafamostat mesilate (NM) during the surgery of thoracic ascending aorta to decrease a side effect of bleeding. From March 1980 to January 1998, for thoracic ascending aorta operations in our department (true aneurysm, 16-, psudoaneurysm, 2-, and dissection, 11 cases, in 29 cases, respectively), age from 16 to 79 (mean 62.9 +/- 9.5 year of age), we classified the objects in two groups, NM group (intraoperative infusion with NM of 60 mg/hr and with heparin 300 IU/kg) and C group (only with heparin treated, 500 IU/kg). We investigated the preoperative factors (age and aneurysmal diameter), the intraoperative factors (ACT, hematcrit, platelet, aorta clamping time, operative time, ECB time, bleeding volume, and blood transfusion), and the postoperative factors (bleeding and blood transfusion) after the administration of NM. RESULTS: There was no significance for the protection effect of NM infusion on the preoperative and the postoperative factors. However, intraoperative bleeding and blood transfusion volume in NM group were significantly lesser than those in group C. CONCLUSIONS: It might be useful for NM infusion during the surgery of thoracic ascending aorta due to the decrease of volume of intraoperative bleeding and blood transfusion amount with the remarkable anti-bleeding effect.

Adolescent↗

Clinical value of sequential subtraction scintigraphy with 99mTc-RBC for gastrointestinal bleeding.

OBJECTIVE: To evaluate the clinical value of sequential subtraction scintigraphy (SSS) with 99mTc red blood cell (RBC) for the early detection of gastrointestinal (GI) bleeding. METHODS: Ninety patients referred with clinical evidence of GI bleeding underwent 99mTc-RBC scintigraphy with digital gamma camera after labeling of 99mTc-RBC in vivo. Sequential 12 conventional non-subtraction (CNS) images of abdomen were taken at 5 min intervals for 60 min. Then 5-min images were subsequently subtracted from each other using a computer and 11 subtracted images were obtained. Delayed images up to 24 hr were obtained when early results were negative and/or recurrent bleeding was suspected. RESULTS: 62 of 90 patients with suspected GI bleeding were conformed to have active hemorrhage up to 24 hr. The scintigrams were divided into the following three sets: within 30 min, 60 min, and 24 hr. The sensitivity of SSS was 87% (54/62, 30 min) and 91.9% (57/62, 60 min) respectively, which were significantly higher (P < 0.05) than that of CNS (56.4%, 35/62 and 62.9%, 39/62). 24 hr delayed image of CNS increased the sensitivity to 85.4%. No significant difference in specificity between the two methods was noted. Of the 62 patients with definite active hemorrhage, the bleeding sites were identified by surgical operation in 42. The concordant rate with surgical operation in SSS was 92.8% (39/42), higher than that of CNS (73.8%, 31/42). CONCLUSIONS: Sequential subtraction scintigraphy with 99mTc-RBC, compared with conventional non-subtraction scintigraphy, is an effective technique for the early detection of GI bleeding. It increases the diagnostic sensitivity, detecting a small amount of bleeding earlier than CNS; SSS reduces background activity, more accurtely localizing bleeding sites. It also shortens the examination time, making this approach more suitable for pediatric, elderly and critically ill patients.

Adolescent↗

Abnormal uterine bleeding associated with hormonal contraception.

Millions of women in the United States use some type of hormonal contraception: combination oral contraceptive pills (OCPs), progestin-only pills, medroxyprogesterone acetate injections, or subdermal levonorgestrel implants. Abnormal uterine bleeding is a common but rarely dangerous side effect of hormonal contraception. It is, however, a major cause for the discontinuation of hormonal contraception and the resultant occurrence of unplanned pregnancy. The evaluation of abnormal uterine bleeding in women who are using hormonal contraception includes an assessment of compliance, a thorough history and complete physical examination to exclude organic causes of bleeding, and a targeted laboratory evaluation. Pregnancy and the misuse of OCPs are frequent causes of abnormal uterine bleeding. Bleeding is common during the first three months of OCP use; counseling and reassurance are adequate during this time period. If bleeding persists beyond three months, it can be treated with supplemental estrogen and/or a nonsteroidal anti-inflammatory drug (NSAID). Other options are to change to an OCP with a higher estrogen content or to a different formulation (i.e., a low-dose OCP containing a different progestin). Management strategies for women with abnormal uterine bleeding who are using progestin-only contraceptive methods include counseling and reassurance, as well as the administration of supplemental estrogen and/or an NSAID during bleeding episodes.

Contraceptive Agents, Female↗

[Utility of the clinical history, physical examination and radiography in the localization of bleeding in patients with hemoptysis].

OBJECTIVE: We examined the medical history, physical examination and chest radiography utility to accurately identifying the site of pulmonary bleeding in patients with hemoptysis. METHODS: We prospectively reviewed and compared the suspected site of bleeding obtained with the medical history, physical examination and chest radiography (right or left) in 466 patients with hemoptysis after the confirmation with a bronchoscopy, computed chest tomography (CT) or bronchial arteriography, and separately analysing the more common etiologies and the volume of bleeding. RESULTS: Age 62.6 years (DS 14), 85% males, 80% smokers with a volume of bleeding of 42.5 ml/day (DS 86) and > or = 100 ml/day in 13.5%. Medical history localized the site of bleeding in 1-13% (p < 0.0001), clinical responses in 8-29% (p < 0.0001), physical examination in 13-47.5% (p < 0.0001) and chest radiography in 14.5-88% (p = 0.04), with a more frequent accurately location findings (p < 0.01) that gradually increased as the previous results with the lung carcinomas and decreased with bronchiectasis or chronic bronchitis. When the volume of bleeding was > or = 100 ml/day, clinical responses utility improved (p = 0.04) as when it was < 100 ml/day with the radiography (p = 0.0001). Specificity, sensitivity and predictive values were variable and better with the radiography than with the medical history or physical examination. CONCLUSIONS: We concluded that chest radiography was most useful than the medical history or physical examination to localize the site of bleeding in patients with hemoptysis. Almost all of the findings that suggests the site of bleeding were accurate and they increased with the radiography or decreased with the physical examination and specially with the medical history in patients with bronchiectasis or chronic bronchitis.

Adolescent↗

[IT IS USEFULL THE UREA/CREATININE RATE FORDIFFERENTIATION OF UPPER FROM LOWER GASTROINTESTINAL BLEEDING?]

Gastrointestinal bleeding constitutes a third part of the hospitalizations in our service. Some times is difficult to clinically distinguish the site of bleeding. It was pointed that the urea/creatinine ratio can help to define the site of bleeding, but there is a lot of superposition in the results. We studied prospectively 154 patients with gastrointestinal bleeding. 123 (79.9%) patients had upper gastrointestinal bleeding with an urea/creatinine ratio of 62.27 +/- 29.13 and 31(20.1%) patients had lower gastrointestinal bleeding with an urea/creatinine ratio of 39.49 +/- 13.83. This difference is statistically significant but has a lot of overlap results. Defining gastrointestinal bleeding as an urea/creatinine ratio greater than 60, we found a great specificity (96.77%) but a low sensibility (51.22). In addition, when we only took hematochezia cases, that usually is a diagnostic problem, the specificity was 96.42% and the sensitivity 46.15%. In conclusion, an urea/creatinine ratio greater than 60 usually indicate us an upper gastrointestinal bleeding, but values below of 60 isn't of diagnostic value.

Journal Article↗

[Summary of the standard "Vaginal bleeding" (first revision) of the Dutch College of General Practitioners].

In the first revised version of the Dutch College of General Practitioners' practice guideline 'Vaginal bleeding' a distinction is made between excessive (cyclical), irregular, breakthrough and postmenopausal bleeding. The diagnostic guidelines are aimed at identifying possible causes. However, in a considerable number of patients no underlying cause is found and the bleeding is assumed to be caused by hormonal fluctuations, for instance shortly after the menarche or premenopausal. Other causes can be: myomas, an intra-uterine device (IUD), medication, or endometrial carcinoma. Furthermore, lesions of the perineum, vulva or vagina, a pelvic inflammatory disease, Chlamydia infection, cervical carcinoma, imminent abortion or ectopic pregnancy also have to be excluded. In this practice guideline, the management guidelines are limited to the treatment of bleeding from the endometrium. In most cases bleeding caused by hormonal fluctuations is self-limiting. However, symptomatic treatment with progestogens or sub-50 oral contraceptives is possible. NSAIDs taken during the first three days of menstruation are the second-choice treatment in women with excessive bleeding. Tranexamic acid or a levonorgestrel-releasing IUD are other possibilities. Postmenopausal women with vaginal bleeding, first of all have to be examined by means of a cervical smear and transvaginal ultrasonography, to exclude an endometrial carcinoma. They can initially be reassured if the ultrasonography reveals an endometrial thickness of 4 mm or less. In the case of persistent or recurrent vaginal bleeding, they should still be referred to a gynaecologist.

Female↗

Relationship between progesterone receptor level in endometrium and bleeding pattern in depot medroxyprogesterone acetate users.

Bleeding disturbance is the major reason for discontinuation among depot medroxyprogesterone acetate (DMPA) users. However, the causes of progestin-induced bleeding are not well understood. The aim of the study was to examine the correlation between the occurrence of uterine bleeding and progesterone receptor (PR) levels in the endometrium. Forty-five matched pairs of age and body mass index in DMPA users with bleeding and amenorrhea were studied. The endometrial PR levels were evaluated. The PR score was assessed semi-quantitatively. Forty-two subject pairs met the criteria. There was no difference in serum estradiol and progesterone levels between the groups. No correlation between the number of bleeding days and PR score nor between the number of bleeding days and serum estradiol and progesterone level was detected. The stromal PR score in DMPA subjects with amenorrhea was significantly higher than those with bleeding (p < 0.05). By contrast, the PR score in glandular endometrium was not significantly different between the groups (p > 0.05). In conclusion, after a second dose of DMPA, subjects with amenorrhea had a higher stromal PR score than those with uterine bleeding.

Adult↗

[Factors associated with failure of endoscopic therapy in gastric ulcer bleeding].

INTRODUCTION: Endoscopic therapy is an effective technique in the control of bleeding due to peptic ulcer. However, bleeding persists or recurs in as many as 10-30% of patients. Gastric and duodenal ulcers present different clinical and endoscopic features and consequently the efficacy of endoscopic therapy and the factors associated with its failure should be studied separately. OBJECTIVES: To analyze the efficacy of endoscopic therapy in patients at high risk of persistent or recurrent bleeding due to gastric ulcer and to identify the factors associated with the failure of this technique. PATIENTS AND METHODS: We performed a retrospective study based on a clinical intervention protocol. Two hundred eight patients admitted for bleeding secondary to gastric ulcer with active bleeding or stigmas of recent bleeding who received endoscopic therapy between January 1992 and December 2001 were analyzed. Clinical, laboratory and endoscopic variables on admission, as well as the medical treatment and endoscopic procedure applied, were registered. Endoscopy was performed within 12 hours of admission. Patients were classified according to their response to endoscopic therapy: a) patients with limited bleeding, and b) patients with persistent or recurrent bleeding due to therapeutic failure. Intervention in patients with therapeutic failure was performed according to a previously established protocol. Variables that were statistically significant in the univariate analysis were included in a logistic regression model to identify those with an independent predictive value for failure of endoscopic therapy. RESULTS: Definitive hemostasis was achieved after initial therapy in 181 patients (87%). The efficacy of a second procedure increased the percentage of hemostasis to 91% of the patients. In the logistic regression model, the only variables that were independently associated with initial therapeutic failure were: hemodynamic status on admission (p = 0.016; OR = 3.99), the need for transfusion of blood products prior to endoscopy (p = 0.025; OR = 3.48), upper localization of the gastric ulcer (p = 0.050; OR = 3.08) and unsatisfactory endoscopic therapy (p = 0.009; OR = 17.39). CONCLUSION: These variables could contribute to the early identification of a subgroup of patients, which would enable us to increase medical-surgical surveillance and offer them other therapeutic alternatives.

Aged↗

[Dental extraction in patients with bleeding disorders. Proposal of a protocol based on the type of anesthesia used].

INTRODUCTION: The authors propose a protocol to avoid bleeding complications in patients with bleeding disorders. MATERIAL AND METHOD: When a general anesthesia or trunk nerve infiltration is indicated, clotting factor concentrates are to be used in patients with severe bleeding disorders. Desmopressin is to be used in patients with mild bleeding disorders but who are good responders and in patients with thrombopathy. An antifibrinolytic treatment and a fibrin glue are also used. Ninety-six patients underwent 107 extractions with this protocol. RESULTS: Only two patients had bleeding complications requiring an additional treatment. DISCUSSION: In case of bleeding disorders, the treatment depends on disease severity and type of anesthesia. A general treatment (clotting factor concentrates or desmopressin) is indicated with general anesthesia and with local anesthesia in severe bleeding disorders, but not absolutely necessary with local anesthesia in mild bleeding disorders. However, desmopressin can used in all good responders.

Adolescent↗

Efficacy of endoscopic hemoclipping for GI bleeding in relation to severity of shock.

BACKGROUND/AIMS: To examine the efficacy of prospectively performing endoscopic hemoclipping in patients with severe gastrointestinal bleeding by assessing in relation to the severity of the case. METHODOLOGY: Endoscopic hemoclipping was performed in 44 patients in shock caused by severe gastrointestinal bleeding. The level of severity was categorized using two factors. One factor was the presence or absence of severe shock, and the other was the presence or absence of active bleeding at endoscopy. Age, blood transfusion volume, APACHE III score, coagulopathy, initial hemostatic, rebleeding and mortality rate were recorded in relation to those four subsets. If rebleeding occurred, the systolic blood pressure, heart rate and serum hemoglobin concentration were compared between the initial time of bleeding and rebleeding. RESULTS: Initial hemostasis was successfully achieved in all cases. The severe shock group required significantly more blood transfusions. The most severe subset had the highest APACHE III score, and coagulopathy. Rebleeding occurred in seven cases in the severe shock group only. In the rebleeding group, the systolic body pressure was lower, heart rate was higher, and serum hemoglobin concentration was lower than the non-rebleeding group. Four patients, all in subset 1, died, but no patient died due to gastrointestinal bleeding. CONCLUSIONS: The endoscopic hemoclipping method is very effective for severe gastrointestinal bleeding in shock. The severity of shock was a more important risk factor than the presence of active bleeding. Our category of severity is simple, it reflects the patients' clinical condition accurately, and is very useful for patients with gastrointestinal bleeding.

APACHE↗

[Warfarin treatment and bleeding].

BACKGROUND: Warfarin is involved in the majority of fatal adverse drug events in Norway. The aim of this study is to identify risk factors behind the haemorrhagic complications. MATERIAL AND METHODS: We analysed all adverse event reports involving bleeding related to warfarin that were received by the Norwegian Medicines Agency from 1990 to 2000. RESULTS: 713 reports were included; 71% of the patients were above 70 years of age. The most frequent diagnosis was atrial fibrillation (39%). Cerebral bleedings were reported in 57% of the cases, 73% of which were fatal, as were 39 % of gastrointestinal bleedings and 14% of other bleedings. International normalised ratio values (INR values) at the time of bleeding were reported in 83% of the cases; mean INR value was 4.4 (range 1.2 - > 8.0). INR values above recommended limits at the time of bleeding were found in 74% of the patients. In 63%, bleedings occurred during the first month; in 30% during the first five days. Median duration of treatment was shorter in fatal (16 days) than in non-fatal cases (24 days). INTERPRETATION: Our results show that haemorrhagic complications are associated with high INR values and initiation of treatment. Simple strategies for reducing bleedings include better monitoring of patients, careful dose adjustment, and INR values in the lower end of the recommended ranges.

Adult↗