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Bleeding Complications to Long-Term Oral Anticoagulant Therapy.

Objective: To evaluate the incidence of bleeding complications in recent randomized trials on oral anticoagetlant treatment for prevention of arterial thromboembolism. Data sources: International publications on studies of prevention. of arterial thromboembolism by oral anticoagulant therapy. Study selection and data extraction: Randomized trials an oral anticoagulant therapy in patients with atrial fibrillation, recent myocardial infarction, and prosthetic heart valves were selected. For comparison older nonrandomized studies were studied. Background: Oral anticoagulant drugs are recommended for primary prevention of thromboembolic events in patients with chronic atrial fibrillation, recent myocardial infarction, and prosthetic heart valves. Still many physicians hesitate to prescribe anticoagulant drugs, presumably for fear of bleeding complications. Results: In six recent trials of warfarin in patients with atrial fibrillation, the highest annual incidence of fatal and major bleeding was 0.8% and 2.0%, respectively. In patients treated with warfarin after a recent myocardial infarction, the incidence of fatal and major bleeding was 0.2% and 0.5% per year, respectively. The annual incidence of fatal and major bleeding in patients with prosthetic heart valves on warfarin treatment was found to be 1.4% and 5.2%, respectively. The mean incidence of fatal and major bleeding in patients on warfarin in these eight trials was 0.5% and 1.7% per year, respectively. The mean incidence of fatal and major bleeds in patients on placebo was 0.1% and 0.7% per year, respectively. In three randomized trials evaluating aspirin versus warfarin, the respective mean incidences of fatal and major bleeding during aspirin treatment were 0.2% and 0.8% per year. A remarkable decrease in the incidence of major bleeding complications to oral anticoagulant therapy is revealed by these trials as compared to previous studies. Reasons for this decline may be less intensive anticoagulant regimes, better control of anticoagulant therapy due to the introduction of the international normalized ratio, and careful pretreatment evaluation of risk factors for bleeding. In alI prospective trials of oral anticoagulation, the risk of bleeding was more than over-weighed by the beneficial effect on the incidence of stroke and peripheral thromboemboli.

Journal Article↗

Regional blood flow in brain and peripheral tissues during acute experimental arterial subdural bleeding.

The effects of a large intracranial arterial subdural bleeding on regional blood flow in the brain (rCBF) and in other body organs were studied, using a porcine model. The bleeding was produced by leading blood through a catheter from the abdominal aorta via an electronic drop recorder into the subdural compartment (SDC) over the left cerebral hemisphere. Pressures in the right lateral cerebral ventricle and in the cisterna magna were recorded along with 15 other vital parameters. Measurements of rCBF were carried out using radioactive microspheres 1) before the start of bleeding, 2) during the early bleeding phase, and 3) during the late bleeding phase. When the bleeding was initiated, the intracranial pressures rose within one minute to a level approximately 40 mmHg below the systemic arterial pressure, whilst the latter usually decreased 30-40 mmHg. In the subsequent early bleeding phase the cerebral perfusion pressure and the bleeding pressure fluctuated at a level of approximately 40 mmHg for several minutes. In the late bleeding phase, the perfusion pressure decreased maximally, even when a Cushing reaction was activated. During the early bleeding phase the changes in rCBF varied between the cerebral regions. However, the mean flow remained largely constant in the presence of a decreasing cerebrovascular resistance, indicating that autoregulation of CBF was intact. Concomitantly, cardiac output and heart rate decreased, whilst regional blood flow in extracerebral organs tended to increase, possibly due to an intracranial effect on the autonomic nervous system. In the late bleeding phase, rCBF was critically reduced in all regions, in spite of a marked rise in systemic arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Hormonal changes associated with bleeding during low dose progestogen contraception delivered by Norplant subdermal implants.

The main side effect associated with the use of Norplant contraceptive implants is a disruption of the menstrual bleeding pattern. To explore the relationship between bleeding and hormonal changes, we analyzed the estradiol (E2) and progesterone (P) patterns that preceded bleeding episodes or that corresponded to periods of amenorrhea in 103 cycles observed among 82 women using Norplant subdermal implants. Five different bleeding patterns were defined: 'normal' (24-45 day cycles), oligomenorrhea (46-90 day cycles), amenorrhea (over 90 day cycles), irregular/frequent bleeding (less than 25 day cycles), and prolonged bleeding (continuous bleeding/spotting for more than 10 days). All 'normal' cycles were associated with a rise followed by a fall in E2 levels preceding bleeding. In half of the 'normal' cycles (28/54), a rise and fall of P was also observed. The same pattern was found in oligomenorrheic cycles, but only two of 12 cycles had a rise and fall of both E2 and P. None of the subjects with amenorrhea had luteal activity. Six of the nine amenorrheic cycles displayed persistently low E2 levels (below 75 pg/ml). The remaining three had a moderate elevation in E2 levels during the sampling period. Sixty percent of the subjects who showed irregular/frequent bleeding (15/25) had low E2 levels (less than 75 pg/ml), without luteal activity, and bleeding occurred without clear evidence of a further drop in E2 levels. In the remaining 40%, bleeding was preceded by a rise and drop of E2 without luteal activity, with the exception of one women, who exhibited a rise and fall of both E2 and P. Samples were obtained in only three subjects during continuous bleeding. One had low E2 levels, and the remaining two bled continuously, in spite of having E2 levels in the normal range. We conclude that ovarian hormones continue to influence endometrial shedding during the use of Norplant contraceptive implants.

Amenorrhea↗

Vaginal bleeding and early pregnancy outcome in an infertile population.

OBJECTIVE: Our purpose was to determine the prognostic value of vaginal bleeding in early pregnancy outcome as well as to analyze the role of cardiac activity in predicting pregnancy viability in the presence of vaginal bleeding. STUDY DESIGN: This was a cohort study of pregnancies obtained using either assisted reproductive technology (ART) or routine infertility treatment (RIT). Two hundred twenty-eight pregnant women were divided into two groups based on the presence or absence of vaginal bleeding. Successive measurements of beta-hCG levels were obtained every 2 days, starting on day 14 after ovulation or embryo transfer. All pregnancies underwent weekly transvaginal ultrasound (UTZ) examinations beginning on day 21. The occurrence of vaginal bleeding was monitored weekly. RESULTS: Seventy of the 228 patients (31%) had bleeding in early pregnancy, resulting in 31 (44%) pregnancy losses. Only 22 pregnancy losses (14%) were observed in 158 patients who did not have bleeding (P < 0.001). The abortion rate for the bleeding versus nonbleeding groups was 35 and 9%, respectively (P < 0.001). Vaginal bleeding was associated with a higher abortion rate in pregnancies following RIT than ART (51 vs 8%; P < 0.001). Fetal cardiac activity was noted by vaginal ultrasound in 189 patients. In this subpopulation, bleeding was also associated with a higher abortion rate than that in the nonbleeding group (17 vs 4%; P < 0.001). However this higher incidence was observed only in pregnancies following RIT, not ART (28 vs 5%; P < 0.001). CONCLUSIONS: Although bleeding significantly decreased the chance of a normal pregnancy outcome, more than 50% of the pregnancies did progress to term. The presence of cardiac activity in this population as a sign of fetal viability offered a better pregnancy prognosis. However, the predictive value of fetal cardiac activity was reduced in the presence of vaginal bleeding in an infertile population treated with RIT.

Abortion, Spontaneous↗

Acute gastrointestinal bleeding: detection of source and etiology with multi-detector-row CT.

This study was conducted to determine the ability of multi-detector-row computed tomography (CT) to identify the source and etiology of acute gastrointestinal bleeding. Eighteen patients with acute upper (n = 10) and lower (n = 8) gastrointestinal bleeding underwent 4-detector-row CT (n = 6), 16-detector-row CT (n = 11), and 64-slice CT (n = 1) with an arterial and portal venous phase of contrast enhancement. Unenhanced scans were performed in nine patients. CT scans were reviewed to determine conspicuity of bleeding source, underlying etiology, and for potential causes of false-negative prospective interpretations. Bleeding sources were prospectively identified with CT in 15 (83%) patients, and three (17%) bleeding sources were visualized in retrospect, allowing the characterization of all sources of bleeding with CT. Contrast extravasation was demonstrated with CT in all 11 patients with severe bleeding, but only in 1 of 7 patients with mild bleeding. The etiology could not be identified on unenhanced CT scans in any patient, whereas arterial-phase and portal venous-phase CT depicted etiology in 15 (83%) patients. Underlying etiology was correctly identified in all eight patients with mild GI bleeding. Multi-detector-row CT enables the identification of bleeding source and precise etiology in patients with acute gastrointestinal bleeding.

Acute Disease↗

Endoscopic versus operative treatment in high-risk ulcer bleeding patients - results of a randomised study.

BACKGROUND AND AIMS: The treatment of peptic ulcer bleeding is still a matter of controversy in high-risk patients with arterial bleeding or a visible vessel. Patients with recurrent bleeding during hospital stay carry an increased risk of death. Therapeutic concepts using early elective operation compete with solitary endoscopic treatment. Numerous prospective studies have contrasted comparable improvements for the different therapeutic regimens but there is still a lack of a randomised comparison. PATIENTS AND METHODS: We initiated a multicentre randomised clinical trial comparing endoscopic fibrin glue injection with early elective operation in peptic ulcer patients with arterial bleeding or a visible vessel > or =2 mm. After initial endoscopic control of bleeding, patients were randomised to repeated fibrin glue injection or early elective operation. Outcome criteria were recurrent bleeding and death. The study was terminated after a planned interim analysis. RESULTS: Due to strict inclusion and exclusion criteria 61 patients were randomised and 55 patients could be included in the per-protocol analysis, 23 in the early elective operation group and 32 in the patient group with endoscopic therapy. The type of surgery in the early elective operation group was usually gastric resection (79%). Recurrent bleeding occurred in 50% of the endoscopically treated patient group, and in the operative group in one patient (relative risk: 11.5; 95% CI: 1.6 to 80.7). There were no statistically significant differences between the two treatment groups with respect to mortality (relative risk: 0.7, 95% CI: 0.1 to 4.8). CONCLUSION: Early elective surgery is an effective procedure in bleeding peptic ulcer patients at high risk for re-bleeding. Fibrin glue injection carries a risk for re-bleeding, however, the majority of these re-bleeding episodes can be controlled by re-endoscopic treatment, but a subgroup will need an emergency operation with a fatal outcome in individual patients.

Adult↗

Variceal Bleeding.

Primary prophylaxis: Patients with cirrhosis who have esophageal varices but who have never had a bleeding episode may be treated medically or endoscopically. Without treatment, approximately 30% of cirrhotic patients with varices bleed and this risk is reduced by approximately 50% with therapy. Medical therapy includes nonselective beta blockers with or without nitrates. Compliance and side effects limit efficacy. Primary prophylaxis with endoscopic sclerotherapy is not warranted because of evidence suggesting that complications outweigh benefits. Studies of endoscopic therapy with ligation (endoscopic banding) demonstrate that in select patients (those with large varices), endoscopic banding may reduce the risk of first bleeding episode when compared with propranolol. Patients with large varices may benefit from a combination of banding with nonselective beta blockers. Secondary prophylaxis: After an initial variceal bleed, the risk of a second bleed is high and therapy is warranted to reduce the risk of rebleeding. The options are similar to those for primary prophylaxis, and in addition to medical and endoscopic therapy, transjugular intrahepatic portosystemic shunts (TIPS) and surgical shunts are therapeutic options. The combination of endoscopic therapy with medical therapy is the initial approach to prevent variceal rebleeding. Endoscopic banding is preferred to sclerotherapy because banding is associated with lower bleeding rates and fewer complications. TIPS is useful in cases refractory to endoscopic therapy or in uncontrolled variceal hemorrhage. Surgical shunts are typically reserved for patients in whom TIPS cannot be performed for technical reasons or for well-compensated cirrhotic patients. Acute variceal bleeding: Acute bleeding from esophageal varices requires an endoscopic evaluation and therapeutic intervention. Technically, endoscopic banding may not be possible because of limited visualization from bleeding and sclerotherapy is used because it is easier to perform in this setting. A continuous intravenous drip of octreotide should be initiated if variceal bleeding is suspected. If variceal bleeding cannot be controlled, then a Minnesota tube or Sengstaken-Blakemore tube should be placed by someone with experience. TIPS is effective rescue therapy for controlling acute variceal hemorrhage in circumstances when other methods fail.

Journal Article↗

A multicentred phase III comparative study of two hormonal contraceptive preparations given once-a-month by intramuscular injection. II. The comparison of bleeding patterns. World Health Organization Task Force on Long-Acting Systemic Agents for Fertility Regulation.

A multicentred Phase III clinical trial was conducted in 12 countries to compare HRP112 (depot-medroxyprogesterone acetate, 25 mg and estradiol cypionate, 5 mg) and HRP102 (norethisterone enantate, 50 mg and estradiol valerate, 5 mg) given every 28 days. Contraceptive efficacy and side-effects of both regimens were reported previously. Their effect on vaginal bleeding patterns is the object of this paper. A total of 2320 women were randomly assigned to each drug and 2000 of them provided a menstrual diary. The comparison of the bleeding patterns is made using a 90-day reference period approach and following the guidelines published by WHO. The analysis failed to identify any major difference in the vaginal bleeding patterns induced by both contraceptive preparations. For both drugs, the first bleeding episode following the first injection occurs early. For 70% of users, this is followed by a regular vaginal bleeding pattern similar to an untreated pattern. Others experience irregular bleeding and a few have either infrequent or frequent bleeding. The extremes of amenorrhea and prolonged bleeding are rare. There are no major trends in vaginal bleeding patterns with prolonged use of either preparation. Women with the worst vaginal bleeding patterns discontinue early in the clinical trial and the last three months of experience have the most influence in their decision to stop using the contraceptive method. The analysis suggests how the life-table analysis of discontinuation reasons underestimates the true incidence of vaginal bleeding irregularities in a clinical trial.

Amenorrhea↗

Bleeding events with abciximab in acute coronary syndromes without early revascularization: An analysis of GUSTO IV-ACS.

BACKGROUND: The glycoprotein IIb/IIIa receptor antagonist abciximab reduces the risk of thrombotic complications with percutaneous coronary intervention, but also has been associated with higher bleeding rates. METHODS: In the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO IV-ACS) trial, abciximab (either a 24-hour or 48-hour infusion) was compared with placebo in 7800 patients with an acute coronary syndrome. During study drug administration, 2% of the patients underwent a revascularization procedure. RESULTS: In 1507 patients (19.3%), bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) classification was observed while they were hospitalized or within 7 days. Ninety-eight patients (1.2%) had a major bleed, including 8 with intracranial hemorrhages. In 215 patients (2.8%), a minor bleed was reported, and in 1194 patients (15.3%), an insignificant bleed was reported. Bleeding was more frequent in patients receiving a 48-hour infusion of abciximab. Spontaneous bleeding was seen in 911 patients (11.7%). The other 596 patients had a bleeding event in conjunction with a procedure. The most significant predictors for bleeding with multivariable analysis were: use of low-molecular weight heparin, duration of abciximab infusion, region of hospitalization, performance of coronary artery bypass grafting or percutaneous coronary intervention (PCI), advanced age, and female sex. For major bleeding, the predictors were performance of coronary artery bypass grafting or PCI, long duration of abciximab administration, and advanced age. CONCLUSION: Treatment with abciximab in patients with non-ST-elevation acute coronary syndromes is safe because major bleeding and stroke are rare, and most events are clinically manageable or have few clinical consequences. Guidelines for use of abciximab in combination with other antithrombotic agents developed for PCI should also be respected in acute coronary syndromes. Specific dosing guidelines for combination with low-molecular weight heparin must be developed for patients who subsequently will undergo a PCI.

Abciximab↗

Bleeding complications with the tension-free vaginal tape operation.

OBJECTIVE: This study was undertaken to analyze bleeding problems with tension-free vaginal tape (TVT) operations in a national registry. STUDY DESIGN: We studied patients for whom increased intraoperative bleeding or reoperation for bleeding/hematoma with TVT operation were reported to the registry. RESULTS: Bleeding problems were reported for 151 of 5578 (2.7%) TVT operations. Increased intraoperative bleeding was reported for 106 (1.9%) and reoperation (or conversion) in 45 (0.8%) patients (both in 5 patients). Increased intraoperative bleeding was managed conservatively in 103 patients (95%). Overall, 45 (0.8%) patients required reintervention for bleeding or hematoma. The reinterventions comprised 34 laparotomies, 4 transvaginal evacuations of hematomas, 3 revisions for bleeding from a suprapubic catheter site, and 2 revisions of the vaginal incision (details unclear in 1 patient). Bleeding was considered arterial in 12% (including 1 external iliac artery injury and 1 obturator artery injury) and venous or unknown in 88%. Of reoperated patients, 39% were reoperated within 24 hours, 20% within 2 to 10 days, and 41% within 11 to 56 days after TVT placement. Overall, 19 patients received blood transfusions (range, 1-10 units). There were no deaths from bleeding complications. CONCLUSION: Bleeding complications were reported with less than 3% of 5578 TVT operations. Most cases of increased intraoperative bleeding were managed conservatively; 0.8% of patients required conversion or reoperation.

Austria↗

Differential diagnosis of abnormal uterine bleeding.

The causes of abnormal uterine bleeding include a wide spectrum of diseases of the reproductive system and nongynecologic causes as well. The differential diagnosis of abnormal excessive uterine bleeding includes organic causes that may be subdivided into reproductive tract disease, iatrogenic causes, and systemic disease. Reproductive tract disease that may result in abnormal uterine bleeding comprises the complications of pregnancy (threatened, incomplete, or missed abortion, ectopic pregnancy, trophoblastic disease, placental polyp, and subinvolution of the placental site), malignant tumors (endometrial, cervical, vaginal, vulvar, and oviduct malignancies and granulosa theca cell ovarian tumors), infection (endometritis, salpingitis), and other benign pelvic disorders (traumatic lesions of the vagina, severe vaginal infections, foreign bodies, cervical polyps, cervical erosion, cervicitis, submucous uterine leiomyomas, adenomyosis, endometriosis, and endometrial polyps). Iatrogenic causes of abnormal uterine bleeding include sex steroids, hypothalamic depressants, digitalis, phenytoin, anticoagulants, and intrauterine contraceptive devices. Systemic diseases that may cause abnormal uterine bleeding include hypothyroidism, cirrhosis, and coagulation disorders. Abnormal uterine bleeding that occurs in a woman of reproductive age should be considered the result of complication of pregnancy until proved otherwise. Abnormal uterine bleeding occurring in a woman of perimenopausal or postmenopausal age should be considered the result of a malignancy until proved otherwise. Menorrhagia occurring in an adolescent should be attributed to a coagulopathy until proved otherwise. When an organic cause of abnormal uterine bleeding cannot be found, then by exclusion the diagnosis of dysfunctional uterine bleeding is assumed. Coagulation disorders, particularly von Willebrand disease, are more common than many physicians realize. Women with a history of high-risk factors, all adolescents with menorrhagia, women with anovulatory dysfunctional uterine bleeding who fail medical or surgical therapy, and women with ovulatory dysfunctional uterine bleeding without an anatomic uterine lesion should be screened for a coagulopathy.

Diagnosis, Differential↗

Endometrial ablation for refractory postmenopausal bleeding with continuous hormone replacement therapy.

OBJECTIVE: To determine the role of endometrial ablation and benign uterine pathology in menopausal women with refractory bleeding who were treated with continuous hormone replacement therapy (HRT). DESIGN: Prospective. SETTING: Health maintenance organization. PATIENTS: One hundred seventy-one menopausal women with an average age of 55 were enrolled in an algorithm of continuous HRT, endometrial biopsy for bleeding with initial therapy, doubling of the progestin dose, hysteroscopy, and endometrial resection-ablation for continued refractory bleeding. INTERVENTION: Endometrial biopsy, hormone manipulation, office hysteroscopy, and hysteroscopic resection-ablation. MAIN OUTCOME MEASURES: Refractory menopausal bleeding and benign uterine pathology. RESULTS: One hundred sixty-two women completed the study. One hundred six (65.4%) remained free of bleeding at the end of the initial 3 months of hormone therapy. Fifty-six (34.6%) had one or more bleeding episodes and required office biopsy and an increase in dosage of progestin. Bleeding ceased in an additional 35 (87%) while 21 (13%) continued to bleed. Those patients underwent endometrial resection-ablation. Surgical specimen demonstrated endometrial polyps, submucous leiomyomas, and adenomyosis in 85.7% of the cases. All patients are now free of bleeding. CONCLUSION: Many women became amenorrheic on the initial dose of continuous HRT; however, if bleeding continues, most stop when the dosage of progestin is doubled. Benign uterine pathology may cause refractory bleeding in a small group of patients but may be eliminated with endometrial resection-ablation.

Adult↗

Argon plasma coagulation for prevention of recurrent bleeding from GI angiodysplasias.

BACKGROUND: Angiodysplasia is a frequent cause of GI bleeding. Argon plasma coagulation has been shown to arrest bleeding, but its efficacy for prevention of recurrent bleeding has not been thoroughly evaluated. This study assessed the effectiveness and the safety of argon plasma coagulation for prevention of recurrent bleeding from GI angiodysplasias. METHODS: A total of 60 patients with GI bleeding caused by angiodysplasia were included. The endoscopic intervention was considered successful if there was no further overt bleeding and if the Hb level stabilized. Recurrent bleeding was defined as any detectable bleeding episode (hematemesis, melena, or hematochezia) or a decrease in Hb level. RESULTS: Overt bleeding was resolved, and the Hb level stabilized without transfusion or supplemental iron therapy in 50 of the 60 patients (83%) at a median follow-up of 18 months (range 6-38 months). In the subgroup of patients with anemia, mean Hb level increased from 8.6 g/dL (range 5.1-12.2 g/dL) to 12 g/dL (range 8.0-15.2 g/dL) ( p < 0.01). The estimated probability of remaining free of recurrent bleeding at 1- and 2-year follow-up was 86%: 95% CI [73%, 93%] and 80%: 95% CI [64%, 89%], respectively. Among 72 procedures, only two were associated with a complication (2.8%). CONCLUSIONS: Endoscopic argon plasma coagulation is both effective and safe for prevention of recurrent bleeding from GI angiodysplasia.

Adolescent↗

Predictors of utilization of early colonoscopy vs. radiography for severe lower intestinal bleeding.

BACKGROUND: The management of acute lower intestinal bleeding is not standardized. This study assessed factors associated with early (within 24 hours of presentation) colonoscopy vs. radiographic evaluation of patients with severe acute lower intestinal bleeding in routine practice. METHODS: A cohort of 252 patients admitted with acute lower intestinal bleeding to a teaching hospital (August 1996 to June 1999) was studied retrospectively. Severe bleeding was defined as transfusion of two units of packed red blood cells and/or a greater than 20% decrease in hematocrit within 24 hours of presentation. If both colonoscopy and radiography were performed, the initial procedure was analyzed. Multivariable regression was used to identify independent factors related to each of the two initial interventions. RESULTS: A total of 118 patients met criteria for severe bleeding; 33 (28%) underwent an initial, early colonoscopy and 20 (17%) underwent an initial, early radiographic procedure (17 radionuclide scintigraphy, 3 angiography). Independent factors related to early colonoscopy were post-polypectomy bleeding (OR 6.3: 95% CI[1.4, 28.0]), admission on a weekday (OR 3.0: 95% CI[1.0, 8.6]), and admission late in the day (OR 2.7: 95% CI[1.0, 7.0]). Independent factors related to early radiography were tachycardia (OR 5.1: 95% CI[1.7, 14.9]), syncope (OR 3.8: 95% CI[1.1, 13.2]) and bleeding during the first 4 hours after admission (OR 3.1: 95% CI[1.0, 9.0]). Colonoscopy was associated with shorter hospital stay (p=0.025), increased diagnostic yield (p=0.005), and fewer red blood cell transfusions (p=0.024). Rates of therapeutic intervention, surgery, and death did not differ significantly between the two strategies. CONCLUSIONS: Logistical factors and the likelihood of a localized source of bleeding influence the performance of early colonoscopy for the evaluation of acute lower intestinal bleeding, whereas patients with clinical indicators of severe bleeding often undergo radiographic procedures. Because early colonoscopy may improve outcomes, further studies are needed to compare available strategies and to standardize the management of acute lower intestinal bleeding.

Adult↗

Abnormal uterine bleeding.

Concerns about abnormal menstrual bleeding are a common reason for women to consult a primary care physician. The first step in the evaluation is to determine the patient's ovulatory status. Women with heavy bleeding but normal ovulatory cycles should be evaluated for coagulopathies, structural lesions, and hypothyroidism. In the absence of a systemic or structural cause, menorrhagia can be treated with OCPs or NSAIDs. Intermenstrual bleeding in OCP users may be due to noncompliance or the use of low-dose pills. Encouraging patient compliance and adjustment of the estrogen dose can often solve the problem. If the patient is not on OCPs, intermenstrual bleeding is usually due to a structural or inflammatory lesion. The differential diagnosis for anovulatory bleeding is extensive. Pregnancy, systemic illnesses, and structural lesions should be ruled out by history, physical examination, and laboratory evaluation. Endometrial biopsy is indicated in patients over age 35 and younger patients with risk factors for endometrial cancer, such as chronic anovulation and obesity. Dysfunctional uterine bleeding is a nonspecific term for abnormal uterine bleeding in the absence of systemic or structural disease. It is usually associated with anovulation. Adolescents frequently have dysfunctional uterine bleeding owing to immaturity of the hypothalamic-pituitary-ovarian axis. Perimenopausal women have an increased incidence of irregular bleeding secondary to decreased estrogen production by the ovary. Obesity, polycystic ovary syndrome, stress, crash diets, and vigorous exercise can all disrupt normal ovulatory function. Treatment options for dysfunctional uterine bleeding include oral contraceptives, cyclic progesterone, or hormone replacement with estrogen and progesterone. Patients with structural lesions or those who do not resume normal withdrawal bleeding patterns on hormone therapy should be referred to a gynecologist for further evaluation and treatment.

Adolescent↗

Endometrial histology and bleeding patterns in post-menopausal women taking sequential, combined estradiol and dydrogesterone.

OBJECTIVES: To determine the endometrial response and bleeding patterns in post-menopausal women who were given a sequential hormone replacement regimen with estradiol 2 mg and dydrogesterone 10 mg. METHODS: One-hundred-and-eighty-eight (188) post-menopausal women with amenorrhea of 6 months or longer, with FSH/estradiol (E2) levels in the post-menopausal range and normal endometrium were entered in the study. All patients received a daily dose of 2 mg E2 during day 1-14 of each 28 day cycle and 2 mg E2 combined with 10 mg dydrogesterone during cycle day 15-28. The total duration of treatment was 12 months (13 cycles of 28 days). RESULTS: The rate of adequate progestational response (secretory or atrophic) in the 146 patients who remained in the study for at least 356 days with 90% study medication compliance and received an endometrial biopsy after 13 cycles of study medication was 97.2%. Three patients had proliferative endometrium and one simple hyperplasia. Cyclic bleedings in the 153 women who remained on study medication for at least 76 days occurred in over 85% of all cycles; the day of onset occurring regularly on day 13 or 14 of the combined period; the mean duration of bleeding per cycle was approximately 5 days with most patients having (very) slight bleeding. Sixty percent of patients had no intermittent bleedings over the whole 12-month study period. The average incidence of intermittent bleeding in the remaining patients was only 2.7 and generally of very slight quantities and of short duration. Per evaluable cycle the percentage of patients with an intermittent bleeding varies from 4.6 to 9.8%. Only two patients discontinued therapy because of bleeding problems. A clear decrease in the incidence of typical menopausal symptoms, i.e. hot flushes and night sweats was observed by the first visit after 6 weeks of treatment. CONCLUSIONS: The endometrial safety of 2 mg E2 sequentially combined with 10 mg dydrogesterone is very good as determined by the histologic response of the endometrium. The incidence of cyclic bleedings with this combination therapy is very high as is the regularity of day of onset and duration of bleeding. Blood loss during intermittent bleedings was mild and of short duration.

Climacteric↗

Portal hypertensive bleeding.

Portal hypertension bleeding is a common and serious complication of cirrhosis. All patients with cirrhosis should undergo endoscopy and be evaluated for possible causes of current or future portal hypertensive bleeding. Possible causes of bleeding include esophageal varices, gastric varices, and PHG. Patients with esophageal varices at high risk of bleeding should be treated with nonselective beta-blockers for primary prevention of variceal hemorrhage. HVPG measurements represent the optimal way to monitor the success of pharmacologic therapy. EVL may be used in those with high-risk varices who do not tolerate beta-blockers. When active bleeding develops, simultaneous and coordinated attention must be given to hemodynamic resuscitation, prevention and treatment of complications, and active control of bleeding. In cases of acute esophageal variceal (Fig. 5) and PHG bleeding, terlipressin, somatostatin, or octreotide should be started. Endoscopic treatment is provided for those with bleeding esophageal varices. If first-line therapy fails, TIPS or surgery may need to be performed. Unlike esophageal variceal or PHG bleeding, there is no established optimal treatment for gastric variceal bleeding. Individual and specific treatment modalities for acute gastric variceal bleeding must be calculated carefully after considering side effects.

Clinical Protocols↗

Intramuscular bleeding of the tongue in the victims of house fire.

Intramuscular bleeding of the tongue is frequently observed in autopsy cases of house fire victims. The meaning of this finding has not yet been fully discussed. We examined 69 autopsy cases of house fire victims and investigated several factors contributing to intramuscular bleeding of the tongue. Victims comprised 45 males and 24 females, ranging in age from 1 to 95 years old. Sixty-four cases (93%) involved severely charred bodies, while the remaining five bodies displayed slight burns. Factors studied were age, sex, posture of the body at the scene of the fire, degree of burn injury and carboxyhemoglobin (CO-Hb) levels in blood. CO-Hb level proved to be the only factor relevant to intramuscular bleeding of the tongue. Of 69 autopsy cases, 23 (33%) demonstrated intramuscular bleeding of the tongue (13 cases of slight bleeding, ten cases of severe bleeding). Low concentrations of CO-Hb (</=30%) were observed in six of ten cases (60%) with severe intramuscular bleeding. Of 46 cases without intramuscular bleeding, ten (22%) displayed low concentrations of CO-Hb. These results may indicate that severe burn injuries occurring before inhaling air containing high levels of carbon monoxide represent the cause of intramuscular bleeding of the tongue in fire victims. The burned regions of the body in the early stage of the fire process were unclear due to severe charring in most victims. However, asphyxiation due to neck compression is known to often induce intramuscular bleeding of the tongue. Lack of skin elasticity following burns, particularly in the neck, might act in a similar manner to asphyxial neck compression. In conclusion, intramuscular bleeding of the tongue in fire victims may occur as a vital reaction to burns.

Adolescent↗