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Acute management of bleeding oesophageal varices.

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

Acute Disease

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

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

Adrenergic beta-Antagonists

Template bleeding time and clinical hemorrhage in myeloproliferative disease.

In 32 patients with myeloproliferative disorders (MPD), correlations were made among clinical observations of hemorrhagic tendency, template Ivy bleeding time, and platelet aggregation studies. Bleeding time was commonly prolonged, particularly in myelofibrosis. In two cases, this prolongation appeared to reflect a defect in platelet function, which resulted in clinical bleeding. Prolongation of bleeding time did not correlate with degree of thrombocytosis. Two patients with thrombocytosis had serious clinical bleeding at a time when bleeding time was normal. Of the patients, 35% had abnormal findings from aggregation studies, but there was no correlation between aggregation studies and prolongation of bleeding time or clinical hemorrhage. We conclude that bleeding in MPD arises either from a defect in platelet function, which is reflected in a prolonged bleeding time, or from thrombocytosis.

Blood Cell Count

Clopidogrel Versus Dual-Antiplatelet Therapy for Long-Term Maintenance After Coronary Stenting in Ischemic and Bleeding Birisk Patients With Acute Coronary Syndromes and Diabetes: A Prespecified Subgroup Analysis of the OPT-BIRISK Trial.

BACKGROUND: Among patients with acute coronary syndromes at both high bleeding and ischemic risk (birisk), extended clopidogrel monotherapy after 9 to 12 months of dual-antiplatelet therapy reduces bleeding without increasing ischemia. Whether this benefit extends to birisk patients with diabetes is unknown. METHODS: This prespecified subgroup analysis of the OPT-BIRISK (Optimal Antiplatelet Therapy for High Bleeding and Ischemic Risk Patients) trial included birisk patients with acute coronary syndrome who had completed 9 to 12 months of dual-antiplatelet therapy after percutaneous coronary intervention. Patients were then randomized 1:1 to 9 months of clopidogrel plus placebo versus clopidogrel plus aspirin. Outcomes were compared by diabetes status. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding at 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events, defined as a composite outcome of all-cause death, myocardial infarction, stroke, or clinically driven revascularization. RESULTS: Of 7758 patients, 4072 (52.5%) had diabetes. Clopidogrel monotherapy decreased Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (2.1% versus 3.2%; hazard ratio [HR], 0.66 [95% CI, 0.45-0.97]) with no increase in major adverse cardiac and cerebral events (2.9% versus 3.6%; HR, 0.79 [95% CI, 0.56-1.12]) compared with clopidogrel plus aspirin in patients with diabetes. Outcomes were consistent in patients without diabetes, with no significant interactions by diabetes status. CONCLUSIONS: In birisk patients with acute coronary syndrome who were stable on dual-antiplatelet therapy with clopidogrel plus aspirin for 9 to 12 months after percutaneous coronary intervention, clopidogrel monotherapy for an additional 9 months reduced clinically relevant bleeding without increasing ischemic events compared with continued dual-antiplatelet therapy, irrespective of diabetes status. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03431142.

Aged

Upper gastro-intestinal tract bleeding in cirrhotic children candidates for liver transplantation.

Signs of portal hypertension, history of upper gastro-intestinal tract bleeding episodes and outcome of the latter were recorded in 76 cirrhotic children evaluated for liver transplantation. Fifty-three (70%) had varices and 22 (29%) had experienced upper gastro-intestinal tract bleeding. Of these 22, 19 bled from varices and 3 from ulcers. Non bleeding ulcers were also found in five patients bleeding from varices. Iterative sclerotherapy controlled acute variceal bleeding in all but one patient in whom emergency transplantation was performed. Six of the eight patients with ulcers were successfully treated by the H2 histamine receptor antagonist ranitidine. We conclude that iterative sclerotherapy is efficient to control acute variceal bleeding and prevents recurrent bleeding in children with end-stage liver diseases awaiting liver replacement. Bleeding asymptomatic ulcers are frequent and respond to H2 histamine receptor antagonists.

Acute Disease

Continuous combined conjugated equine estrogen-progestogen therapy: effects of medroxyprogesterone acetate and norethindrone acetate on bleeding patterns and endometrial histologic diagnosis.

OBJECTIVES: This study was designed to assess the incidence of amenorrhea with continuous combined therapy by using two different progestogens and to determine whether early bleeding predicts subsequent bleeding and endometrial response. STUDY DESIGN: Seventy-nine postmenopausal women on sequential estrogen-progestogen treatment were switched to continuous combined estrogen-progestogen therapy comprising conjugated equine estrogens 0.625 mg daily with either norethindrone acetate 0.35 mg twice daily or medroxyprogesterone acetate 2.5 mg twice daily added continuously for 78 weeks. All bleeding was recorded, and endometrial biopsies were performed at 26 and 78 weeks. RESULTS: Only one third of the women who starting the study had amenorrhea by week 78, but 46 (62%) of these women had withdrawn, mainly because of chronic irregular bleeding. Endometrial atrophy was observed in the majority of biopsy specimens. The two progestogens had similar effects. Bleeding patterns were useful predictors of subsequent bleeding, but not of endometrial response. CONCLUSIONS: Persistent irregular bleeding is common with continuous combined estrogen-progestogen therapy. Women with persistent early bleeding should probably revert to sequential treatment. Regular endometrial sampling is advised.

Amenorrhea

Perinatal outcome of pregnancies complicated by vaginal bleeding.

OBJECTIVE: To examine the effect of first and/or second trimester vaginal bleeding on pregnancy outcome. DESIGN: A prospective one-year birth cohort. SETTING: Two northernmost administrative districts of Finland. PATIENTS: 8718 singleton pregnancies, of whom 807 (9.3%) reported bleeding during the first (601) and/or second trimester (206); light bleeding in 595 cases and heavy bleeding in 212. The remaining 7911 women served as a reference group. MAIN OUTCOME MEASURES: Low birth weight rate (LBW), preterm birth rate, congenital malformations and perinatal mortality rate. RESULTS: Bleeding was most frequent in women of more advanced age (> or = 35 years old), with previous miscarriages, with infertility problems or using an IUCD prior to the pregnancy. Parity, smoking and social status were not associated with bleeding. Caesarean section rate and placental complications during the third trimester and at delivery were more common among the bleeders than in the reference group. The LBW rate was three-fold among the bleeders and the preterm birth rate two-fold. The risk (OR) of a LBW infant among second trimester bleeders was 4.1 (95% CI 2.6-6.4), that of preterm birth 2.9 (95% CI 1.9-4.6), and that of congenital malformations 2.9 (95% CI 1.7-4.7). No association existed between bleeding and perinatal mortality. CONCLUSIONS: Bleeding during the second trimester indicates a poor pregnancy outcome and an increased risk of LBW, and preterm birth and/or congenital malformation.

Adult

Shortening of the bleeding time in rabbits by hydrocortisone caused by inhibition of prostacyclin generation by the vessel wall.

The effect of hydrocortisone on thrombocytopenic bleeding has been studied in rabbits using a jugular vein bleeding-time technique and a microvascular bleeding-time technique. An inverse relationship was found between the bleeding time and platelet count with both techniques in rabbits made thrombocytopenic by either X-irradiation or injection of heterologous platelet antiserum. Hydrocortisone shortened both bleeding times in thrombocytopenic animals when given in single large doses intravenously (25-100 mg/kg), in daily doses (6 mg/kg) intramuscularly, and shortened the jugular bleeding time when applied to the outside of the jugular vein or instilled intraluminally into the vein. This effect was also noted in normal animals. The effect on thrombocytopenic bleeding was dose related. When given daily, the effect was greater when hydrocortisone was given for 10 d than for 5 d. Both indomethacin and tranylcypromine also reduced the jugular vein bleeding time when instilled intraluminally into the jugular vein, whereas exogenously provided arachidonic acid reversed the effect of hydrocortisone but did not reverse the effect of indomethacin or tranylcypromine. Exogenously provided linoleic acid did not have any effect. Perfusion of the vessel segment with prostacyclin (PGI(2)) reversed the effect of intraluminally administered hydrocortisone, indomethacin, and tranylcypromine. Similarly, hydrocortisone, indomethacin, and tranylcypromine all reduced the rate of loss of fluid from a standard wound in isolated vessels emptied of blood and perfused with saline under constant pressure. PGI(2) reversed the action of these three agents, however, arachidonic acid reversed only the effect of hydrocortisone and did not reverse the effect of indomethacin and tranylcypromine. The generation of PGI(2)-like material and 6-keto-prostaglandinF(1) alpha from jugular vein strips was prevented by prior exposure of the animals or vessel wall to hydrocortisone. These results are compatible with the hypothesis that the vessel wall releases smooth muscle-relaxing prostaglandins when injured and that inhibition of prostaglandin formation by hydrocortisone enhances hemostasis by allowing vasoconstriction to be maintained.

Animals

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

A prospective evaluation of injection sclerotherapy in the treatment of acute bleeding from esophageal varices.

In a 25 month study of massive upper-gastrointestinal hemorrhage, 64 patients were shown to have esophageal varices on emergency endoscopy. Twenty-four patients were actively bleeding from varices and were treated with a Sengstaken tube, and in 22 this was followed by emergency injection sclerotherapy using a rigid esophagoscope and general anesthesia. These 22 patients were followed prospectively and had 51 episodes of endoscopically proven active bleeding from esophageal varices which required Sengstaken tube control of hemorrhage during 36 separate admissions. This group included our total experience of injection sclerotherapy in acute variceal bleeding. The majority (14 of 22 patients) had alcoholic cirrhosis. Definitive control of variceal bleeding during the period of hospitalization was achieved in 33 hospital admissions (92%), usually with a single injection (27 hospital admissions: 75%). The results were satisfactory in 26 hospital admissions (72%). There were nine deaths (41% overall patient mortality rate), but no patient died primarily of variceal bleeding, and exsanguinating variceal bleeding was no longer a problem. The mortality rate per injection was 18%, and the mortality rate per hospital admission was 25%. Injection sclerotherapy is proposed as the emergency treatment of choice for patients with proven bleeding esophageal varices who do not stop bleeding on initial conservative treatment.

Acute Disease

Sustained correction of the bleeding time in an afibrinogenaemic patient after infusion of fresh frozen plasma.

We have evaluated the duration of the effect of replacement therapy with two different doses of fibrinogen on the prolonged bleeding time of an afibrinogenaemic patient and the relationship between changes in bleeding time and plasma and platelet fibrinogen concentrations. The infusion of 40 mg/kg fibrinogen, as fresh frozen plasma (FFP), corrected the prolonged bleeding time of the patient from longer that 30 min to 8 min. The bleeding time was still normal 9 d after infusion, at a time when the plasma and platelet fibrinogen levels were low (0.13 g/l and 27 micrograms/10(9) platelets; normal ranges 1.6-4.0 and 60-190). Two months later, the infusion of a smaller dose of fibrinogen (4 mg/kg) also corrected the bleeding time, which remained normal until the second day after infusion, despite the fact that plasma and platelet fibrinogen were very low (0.02 g/l and 3.4 micrograms/10(9) platelets). The bleeding time returned to the prolonged baseline values only by day 6 post-infusion, when plasma and platelet fibrinogen levels were 4 x 10(-4) g/l and 1.4 micrograms/10(9) platelets. Therefore, sustained correction of the prolonged bleeding time may be obtained in afibrinogenaemic patients with a single infusion of fibrinogen at lower doses than usually recommended.

Adult

Terlipressin vs. somatostatin in bleeding esophageal varices: a controlled, double-blind study.

Fifty episodes of bleeding from esophageal or gastric varices in 33 patients with cirrhosis were randomized to treatment with either intravenous terlipressin (2 mg initially and 1 mg every 4 hr for 24 hr together with bolus injection and continuous infusion of placebo) or with somatostatin (250 micrograms as a bolus and continuous infusion of 250 micrograms/hr somatostatin for 24 hr and placebo injections). Standard therapy with transfusions, fluid and electrolyte correction and lactulose was administered in both groups. In the terlipressin group, 22 of 25 bleeding episodes (88%) were initially stopped by the vasoactive drugs, and in the somatostatin group 19 of 25 bleeding episodes (76%) were initially stopped by the vasoactive drugs. Two of the three bleeding episodes not arrested by terlipressin and five of the six bleeding episodes not arrested by somatostatin were controlled by balloon tamponade. In one patient in each group variceal bleeding initially could not be stopped, and the patients died. The failure rate of the vasoactive treatment alone, including rebleeding episodes within the study period, was 20% in the terlipressin group and 32% in the somatostatin group. The control rate, including balloon tamponade, was 96% in both groups. The hospital mortality rate was 16% (4 of 25) in the terlipressin group and 24% (6 of 25) in the somatostatin group. Blood transfusions, use of balloon tamponade and duration of bleeding did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Peptic ulcer bleeding: medical and surgical point of view. Results of a prospective interdisciplinary multicenter observational study. DUSUK Study Group.

Various treatment policies and clinical disciplines compete for the treatment of bleeding peptic ulcer. In a prospective multicenter and interdisciplinary study performed during a 1-year period at ten hospitals in Düsseldorf, all patients admitted for peptic ulcer bleeding were recorded. The characteristics of patients admitted to surgical and to medical departments, the distribution of endoscopic treatment, indications for surgery, type of surgical procedures, and outcome were investigated. In the study period 387 bleeding peptic ulcers were recorded. Of these patients 82% were primarily admitted to medical and 18% to surgical departments. No differences in terms of severity of ulcer disease or bleeding activity were noted between the groups of medical and surgical patients. However, accompanying or underlying diseases were detected more often in patients admitted to medical departments. Endoscopy treatment was performed in the majority of patients with arterial spurting bleeding (88%) or a visible vessel (80%). Injection therapy with epinephrine or polidocanol was mainly used (78%). In 16% of cases the patients underwent operation; 44% of the patients primarily admitted to a surgical department were operated (medical departments, 10%). About half of the operated patients underwent emergency surgery; in the majority of cases resections were performed (gastric ulcer, 76%; duodenal ulcer, 56%). Overall mortality was 11%, with no difference between surgical and medical patients. A high mortality was observed in the subgroup of patients with late recurrent bleeding (27%). It is concluded that for optimal treatment of peptic ulcer bleeding intensive cooperation between physicians and surgeons is necessary, and that agreed and evaluated treatment policies are needed.

Aged

Gastrointestinal bleeding in cases of ruptured cerebral aneurysms.

Among 1,000 cases of patients undergoing direct surgery on cerebral aneurysms, two, showed clear signs of preoperative, and 19 cases showed postoperative gastrointestinal bleeding. We have made a clinical analysis of various aspects of the 19 cases in which the bleeding developed postoperatively. 1. Gastrointestinal bleeding was most frequent postoperatively in cases of AComA aneurysms (4.3%) and ICA aneurysms (2.0%), and less common in MCA and ACA aneurysm cases. 2. Gastrointestinal bleeding was most frequently seen in those cases operated on between the third and seventh days after the last subarachnoid haemorrhage (8.9%) and was more common in cases with a relatively poor preoperative grade. 3. The development of such bleeding in cases with a good preoperative grade was due to problems with the surgical operation in most cases, although the influence of vasospasm must not be ignored. The development of bleeding in cases with a poor preoperative grade is thought to be due primarily to vasospasm and transitory brain damage to the hypothalamus and the orbital portion of the anterior lobe due to a haematoma caused by aneurysm rupture. 4. First, the location of gastrointestinal bleeding should be determined endoscopically and, if haemostasis is not achieved by coagulation, then the desirability of surgery should be considered early. Abdominal surgery may be performed.

Adult

BUN/Cr ratio as an index of gastrointestinal bleeding mass in children.

Determining the site and severity of blood loss is important in the management of children with gastrointestinal (GI) bleeding. Blood urea nitrogen (BUN) and serum creatinine (Cr) were measured on the day of hospitalization and the ratio of BUN/Cr was calculated in 11 children with 16 episodes of upper GI bleeding and 49 with lower GI bleeding. There was a significant difference between the two GI bleeding groups with regard to BUN/Cr ratio (p less than 0.001). When the ratio was 30 or above, the specificity of upper GI bleeding was 98% with a sensitivity of 68.8%. A linear relationship was found between the BUN/Cr ratio and delta Hb (delta Hb = 0.08 x BUN/Cr +/- 0.8 g/dl) for bleeding originating from the upper GI tract. This study confirms that measurement of the BUN/Cr ratio is useful for localizing the source of bleeding to the upper GI tract and also demonstrates its usefulness as an estimation of the severity of blood loss from the upper GI tract.

Adolescent

Multiple bleeds in haemophilia A.

One hundred and eighty-one bleeding episodes involving two sites simultaneously were noted during a survey of 4935 bleeding episodes, an incidence of 3.7%. Elbows, knees and ankles were the commonest sites involved in double bleeds, while the thigh, upper arm and elbow were the commonest sites involved in the double bleeds needing most transfusions. The overall transfusion requirements were less than for single bleeds. The frequency of multiple bleeds correlated significantly with the overall bleeding frequency, but not with the number of days under observation.

Ankle

Emergency arteriography in acute gastrointestinal bleeding.

Emergency arteriography was carried out on 35 patients with acute gastrointestinal bleeding, in 31 of them within two hours of active bleeding (a haematemisis; a diagnostic change in central venous pressure, pulse rate, or blood pressure; or gastric aspiration of fresh blood). A definite site of bleeding was identified in 27 patients (77%)-this being a small-intestinal vascular abnormality in three--and a probable site in three. Confirmation of the bleeding site was obtained in 20 out of 23 patients treated surgically. An intra-arterial vasoconstrictor infusion was given as a temporary measure before surgery in seven patients, only one of whom showed active bleeding at operation. An intra-arterial vasoconstrictor infusion was tried as definitive treatment in an additional 10 patients, but in four out of seven with a chronic ulcer bleeding recurred after 5-68 hours and was therefore treated surgically. We recommend the diagnostic use of arteriography in patients with reliable evidence of active bleeding if its site cannot be determined by endoscopy. We do not recommend its therapeutic use in those with a chronic ulcer, except to facilitate resuscitation before surgery; further studies are needed to define its role in those with an acute lesion.

Aged

Patterns of bleeding in adolescents with severe haemophilia A.

Eighty-two boys with severe haemophilia A who spent some time at Lord Mayor Treloar College during 1973-7 were studied. All episodes of bleeding that occurred during term time were recorded, along with the number of transfusions. The bleeding frequency among these boys, most of them aged 10-17 years, increased steadily from 8,31 episodes/100 days in 1973 to 12,63 episodes/100 days in 1977. At the same time there was a steady fall in bleeding frequency with age. Altogether 24% of bleeding episodes were into the elbow joint, 22% into the knee, and 15% into the ankle. As the boys grew older the proportion of bleeding episodes in the legs declined and that in the arms increased. The overall results reflect the fact that special schools now see only the severest cases of haemophilia. The pattern of bleeding during adolescence suggests that concepts of management of arm bleeding need modifying.

Adolescent