Skip to main content
NCBI home page
Gut logoLink to Gut
. 1995 Mar;36(3):358–362. doi: 10.1136/gut.36.3.358

Pharmacological manipulation of gastric juice: thrombelastographic assessment and implications for treatment of gastrointestinal haemorrhage.

S E Patchett 1, D P O'Donoghue 1
PMCID: PMC1382445  PMID: 7535282

Abstract

The impairment of formation and maintenance of a formed fibrin clot contributes to the prolonged bleeding and high incidence of rebleeding in upper gastrointestinal haemorrhage. To investigate the basis for the use of drug therapy in gastric bleeding, this study used thrombelastography to determine the effects of pharmacological manipulation of gastric juice on coagulation and fibrinolysis. The thrombelastograph is a mechanical device that provides a visual assessment of all stages of coagulation and fibrinolysis. The effects of fresh and pharmacologically changed gastric juice was assessed after its addition to fresh whole blood in the thrombelastograph cuvette. Pharmacological manipulation was achieved through alkalisation or through addition of tranexamic acid, aprotinin, or sucralfate. Fresh gastric juice delayed clot formation, decreased maximum clot amplitude, and stimulated clot lysis. Alkalisation inhibited the lytic effects of fresh gastric juice and improved the induced abnormalities in coagulation. Tranexamic acid partially inhibited gastric juice induced clot lysis but did not exhibit a beneficial effect on coagulation. Sucralfate, and to a lesser extent aprotinin significantly inhibited fibrinolysis but exacerbated the detrimental effect of gastric juice on the parameters of coagulation. Alkalisation of gastric juice reduces the adverse effect on coagulation and fibrinolysis. Tranexamic acid, aprotinin, and sucralfate can all reduce or inhibit clot lysis, but the adverse effects on clot formation may outweigh any potential benefit in the treatment of gastrointestinal bleeding.

Full text

PDF
358

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amris C. J. Inhibition of fibrinolytic and thromboplastic activity by Trasylol. Scand J Haematol. 1966;3(1):19–32. doi: 10.1111/j.1600-0609.1966.tb00622.x. [DOI] [PubMed] [Google Scholar]
  2. Astrup T., Egeblad K. Thrombelastographic patterns produced by fibrinolytic agents incorporated in fibrin. Am J Physiol. 1965 Jul;209(1):84–94. doi: 10.1152/ajplegacy.1965.209.1.84. [DOI] [PubMed] [Google Scholar]
  3. Barer D., Ogilvie A., Henry D., Dronfield M., Coggon D., French S., Ellis S., Atkinson M., Langman M. Cimetidine and tranexamic acid in the treatment of acute upper-gastrointestinal-tract bleeding. N Engl J Med. 1983 Jun 30;308(26):1571–1575. doi: 10.1056/NEJM198306303082606. [DOI] [PubMed] [Google Scholar]
  4. Cohen E., Caprini J., Zuckerman L., Vagher P., Robinson B. Evaluation of three methods used to identify accelerated coagulability. Thromb Res. 1977 Apr;10(4):587–604. doi: 10.1016/0049-3848(77)90214-6. [DOI] [PubMed] [Google Scholar]
  5. Collins R., Langman M. Treatment with histamine H2 antagonists in acute upper gastrointestinal hemorrhage. Implications of randomized trials. N Engl J Med. 1985 Sep 12;313(11):660–666. doi: 10.1056/NEJM198509123131104. [DOI] [PubMed] [Google Scholar]
  6. DE NICOLA P., MAZZETTI G. M. Evaluation of thrombelastography. Am J Clin Pathol. 1955 Apr;23(4):447–452. doi: 10.1093/ajcp/25.4_ts.0447. [DOI] [PubMed] [Google Scholar]
  7. Daneshmend T. K., Hawkey C. J., Langman M. J., Logan R. F., Long R. G., Walt R. P. Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial. BMJ. 1992 Jan 18;304(6820):143–147. doi: 10.1136/bmj.304.6820.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldfarb J. P., Czaja M. J. A comparison of cimetidine and sucralfate in the treatment of bleeding peptic ulcers. Am J Gastroenterol. 1985 Jan;80(1):5–7. [PubMed] [Google Scholar]
  9. Green F. W., Jr, Kaplan M. M., Curtis L. E., Levine P. H. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology. 1978 Jan;74(1):38–43. [PubMed] [Google Scholar]
  10. Henry D. A., O'Connell D. L. Effects of fibrinolytic inhibitors on mortality from upper gastrointestinal haemorrhage. BMJ. 1989 Apr 29;298(6681):1142–1146. doi: 10.1136/bmj.298.6681.1142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hollander D. Efficacy of sucralfate for duodenal ulcers: a multicenter, double-blind trial. J Clin Gastroenterol. 1981;3(Suppl 2):153–157. [PubMed] [Google Scholar]
  12. Lam S. K., Lau W. Y., Lai C. L., Lee N. W., Poon G. P., Hui W. M., Lok A. S., Ng M. M., Fok K. H., Yu H. C. Efficacy of sucralfate in corpus, prepyloric, and duodenal ulcer-associated gastric ulcers. A double-blind, placebo-controlled study. Am J Med. 1985 Aug 30;79(2C):24–31. doi: 10.1016/0002-9343(85)90568-6. [DOI] [PubMed] [Google Scholar]
  13. Low J., Dodds A. J., Biggs J. C. Fibrinolytic activity of gastroduodenal secretions--a possible role in upper gastrointestinal haemorrhage. Thromb Res. 1980 Mar 15;17(6):819–830. doi: 10.1016/0049-3848(80)90247-9. [DOI] [PubMed] [Google Scholar]
  14. Nagashima R., Yoshida N., Terao N. Sucralfate, a basic aluminum salt of sucrose sulfate. II. Inhibition of peptic hydrolysis as it results from sucrose sulfate interaction with protein substrate, serum albumins. Arzneimittelforschung. 1980;30(1):73–76. [PubMed] [Google Scholar]
  15. Patchett S. E., Enright H., Afdhal N., O'Connell W., O'Donoghue D. P. Clot lysis by gastric juice: an in vitro study. Gut. 1989 Dec;30(12):1704–1707. doi: 10.1136/gut.30.12.1704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Samloff I. M., O'Dell C. Inhibition of peptic activity by sucralfate. Am J Med. 1985 Aug 30;79(2C):15–18. doi: 10.1016/0002-9343(85)90566-2. [DOI] [PubMed] [Google Scholar]
  17. Terao N., Yoshida N., Nagashima R. Sucralfate, a basic aluminum salt of sucrose sulfate. III. Inhibition of peptic hydrolysis of fibrinogen by sucrose sulfate. Arzneimittelforschung. 1980;30(1):76–78. [PubMed] [Google Scholar]
  18. Thorsen S. Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of omega-aminocarboxylic acids. Biochim Biophys Acta. 1975 May 30;393(1):55–65. doi: 10.1016/0005-2795(75)90216-0. [DOI] [PubMed] [Google Scholar]
  19. VON KAULLA K. N. Continuous automatic recording of fibrin formation and fibrinolysis: a valuable tool for coagulation research. J Lab Clin Med. 1957 Feb;49(2):304–312. [PubMed] [Google Scholar]
  20. al-Mohana J. M., Lowe G. D., Murray G. D., Burns H. G. Association of fibrinolytic tests with outcome of acute upper-gastrointestinal-tract bleeding. Lancet. 1993 Feb 27;341(8844):518–521. doi: 10.1016/0140-6736(93)90278-o. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES