Bleeding from Upper Gastrointestinal Tract and Fibrinolysis

[摘要] About 30,000 people are admitted to hospital in the United Kingdom each year with upper gastrointestinal tract (GIT) bleeding and about 3,000 of those will die. Rebleeding after admission to hospital is one of the major factors contributing to this mortality. One factor which may cause rebleeding is lysis of the fibrin haemostatic plug which seals a leaking vessel. Previous studies have shown that fibrinolytic activity in the stomach and duodenum was increased in patients with peptic ulcer, was localised around the ulcer, and could be released by trauma to the stomach. The serum concentration of fibrin degradation products (FDP) was also increased in patients with recent GIT bleeding. The main aim of this thesis was to measure systemic fibrinolytic activity in a series of patients with acute upper GIT bleeding, and to relate this to clinical outcome, in order to assess its possible role in pathogenesis of bleeding. In this prospective study, 122 patients were studied on the morning after admission to hospital. All had routine endoscopy to establish the likely site of bleeding and the pathological cause of bleeding. Patients were divided into three groups: (1) no transfusion or surgery required; (2) transfusion required; (3) those who required surgery and/or who died. Blood was taken from an arm vein for measurement of serum FDP, as well as the fibrinolytic activity of the euglobulin fraction of plasma (fibrin plate lysis area FPLA). The latter test is a global measurement of plasminogen activators and their inhibitors in the euglobulin fraction. Neither test was significantly related to site of bleeding, or to the pathology of the lesion. The FPLA test showed no correlation with outcome. However serum FDP was significantly higher in patients who required transfusion (Group 2) than in patients who did not (Group 1), and patients who died or required surgery (Group 3) had significantly higher levels compared to Group 2 (p <0.001). Thus the serum FDP level was shown, for the first time, to be of prognostic significance in acute upper GIT bleeding. Multivariate analysis confirmed independent prognostic value. A rapid screening test for raised serum FDP (latex agglutination test) was then evaluated in 36 samples from the study. Of the 7 patients with a positive test, 5 required surgery or died. Hence this test may be clinically useful in assessment of severe or recurrent bleeding. Further investigations were performed to clarify the relationship of serum FDP to outcome of acute GIT bleeding. To evaluate the possibility that blood transfusion may itself raise serum FDP, these were measured before and after blood transfusion in 10 patients: no significant change in levels was observed. Because the serum FDP assay does not distinguish degradation products of fibrinogen from those of cross-linked fibrin, an assay for plasma levels of cross-linked fibrin degradation products (ELISA assay using monoclonal antibodies) was performed in 65 samples from the study. Mean levels were similar in Groups 1 and 2, but significantly elevated in Group 3 (p< 0.05). This confirms the association of poor outcome with lysis of cross-linked fibrin, e g. in haemostatic plugs. It was concluded that the association of lysis of fibrin with poor outcome after GIT bleeding is consistent with the hypothesis that fibrinolysis may play a role in promoting continued or recurrent bleeding. Further evidence for this comes from encouraging results of clinical trials of fibrinolytic inhibitor drugs, e.g. tranexamic acid. The second aim of this thesis was to measure systemic fibrinolytic activity in patients with portal hypertension due to liver cirrhosis. In 10 patients with acute bleeding varices elevated serum FDP were again seen in patients who died or required surgery. In 54 patients without acute bleeding varices who attended for elective sclerotherapy, elevated levels of both serum FDP and FPLA were observed, being most marked in Child's Grade C patients, although this was not statistically significant for FPLA. The results of this study suggest that increased fibrinolysis, related to the severity of cirrhosis, may play a role in bleeding from oesophageal varices, and suggests evaluation of fibrinolytic inhibitor drugs in such patients.

[发布机构] University:University of Glasgow

[关键词] Medicine