Gastro-Intestinal Tract Complications During Antithrombotic Therapy
https://doi.org/10.15360/1813-9779-2018-3-15-26
Abstract
Use of antithrombotic aids (ATA) significantly impact the prevention of life-threatening cardiovascular complications. ATA applications, however, are associated with a wide range of adverse digestive system responses. Due to, continuously growing clinical use of ATA this problem has become a current challenge of contemporary medicine.
Purpose of the study was to evaluate the patterns of digestive system damage in patients receiving ATA.
Materials and Methods. 672 patients were examined, 91.0% males, 46.7±17.4 years of age, who had digestive system changes that occurred due to ATA intake. 71 patients were admitted for treatment after gastrointestinal (GI) bleeding; other patients were hospitalized because of disorders of the digestive system or erosive and ulcerous changes of the digestive system detected by endoscopy. The following parameters were evaluated: GI bleeding sources, character of complaints, the endoscopic patterns due to intake of different ATAs (low doses of aspirin, warfarin, clopidogrel, dabigatran, rivaroxaban, low-molecular heparin, combined therapy), and of risk factors for GI complications.
Results. The sources of GI bleeding (n=71) included gastric ulcers and/or erosions (39.4%), duodenum ulcers and/or erosions (21.1%), colon ulcers and/or erosions (28.2%), unknown (11.3%). The majority of 672 patients noticed various complaints: sensation of heaviness in epigastrium (62.8%), gastralgia (46.7%), burning sensation (34.3%). Endoscopy found erosive esophagitis (13.2%), ulcers in stomach and/or duodenum (11.6%), multiple ( 10) erosions of stomach or duodenum (17.1%), sporadic erosions of stomach or duodenum (24.4%). In 32.3% cases no erosive or ulcerous alterations were found. H. pylori was identified in 57.9% of patients. There was no significant difference in character of alterations in the upper digestive system between patients who received different ATA treatment, except of frequent erosive esophagitis in those patients who received dabigatran (16.8%). The elderly age ( 65 years), ulcer history, concomitant intake of NSAIDS, H. pylori presence, and smoking habit were associated with a higher occurrence of pathological alterations of digestive system. Presence of gastralgia did not correlate with the development of erosive and ulcerous alterations.
Conclusion. In majority of patients who received ATA, the commonly observed erosive and ulcerous alterations in the digestive system might become a source of bleeding.
About the Authors
E. V. MorozRussian Federation
3 Gospitalnaya Square, 105229 Moscow
E. N. Artemkin
Russian Federation
3 Gospitalnaya Square, 105229 Moscow
E. V. Kryukov
Russian Federation
3 Gospitalnaya Square, 105229 Moscow
V. A. Chernetsov
Russian Federation
3 Gospitalnaya Square, 105229 Moscow
References
1. Moroz E.V., Karateyev A.E., Kryukov E.V., Chernetsov V.A. Gastrointestinal bleeding with the use of new oral anticoagulants: epidemiology, risk factors, treatment, and prevention. Rheumatology Science and Practice. 2017; 55 (6): 675-684. DOI: 10.14412/1995-4484-2017-675-684. [InRuss.]
2. Weitz J.I., Jaffer I.H., Fredenburgh J.C. Recent advances in the treatment of venous thromboembolism in the era of the direct oral anticoagulants. F1000Res. 2017; 6: 985. DOI: 10.12688/f1000research.11174.1. PMID:28713563
3. Deutsch D., Boustière C., Ferrari E., Albaladejo P., Morange P.E., Benamouzig R. Direct oral anticoagulants and digestive bleeding: therapeutic management and preventive measures. Therap. Adv. Gastroenterol. 2017; 10 (6): 495-505. DOI: 10.1177/1756283X17702092. PMID: 28567119
4. Hsu P.I., Tsai T.J. Epidemiology of upper gastrointestinal damage associated with low-dose aspirin. Curr. Pharm. Des. 2015; 21 (35): 5049-5055. DOI: 10.2174/1381612821666150915104800. PMID: 26369688
5. Cheung K.S., Leung W.K. Gastrointestinal bleeding in patients on novel oral anticoagulants: risk, prevention and management. World J. Gastroenterol. 2017; 23 (11): 1954-1963. DOI: 10.3748/wjg.v23.i11.1954. PMID: 28373761
6. Eikelboom J.W., Wallentin L., Connolly S.J., Ezekowitz M., Healey J.S., Oldgren J., Yang S., Alings M., Kaatz S., Hohnloser S.H., Diener H.C., Franzosi M.G., Huber K., Reilly P., Varrone J., Yusuf S. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011; 123 (21): 2363-2372. DOI:10.1161/CIRCULATIONAHA.110.004747. PMID: 21576658
7. Healthcare in Russia. 2017. Statistical collection of Rosstat. Moscow; 2017: 170. [In Russ.]
8. Zagorodny N.V. Some statistical data on hip and knee arthroplasty in
9. the Russian Federation for 2014-2015. Opinion Leader. 2017; 3: 12-18.[In Russ.]
10. Thomopoulos K.C., Mimidis K.P., Theocharis G.J., Gatopoulou A.G., Kartalis G.N., Nikolopoulou V.N. Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: endoscopic findings, clinical management and outcome. World J. Gastroenterol. 2005; 11 (9):1365-1368. DOI: 10.3748/wjg.v11.i9.1365. PMID: 15761977
11. Rubin T.A., Murdoch M., Nelson D.B. Acute GI bleeding in the setting of supratherapeutic international normalized ratio in patients taking warfarin: endoscopic diagnosis, clinical management, and outcomes. Gastrointest. Endosc. 2003; 58 (3): 369-373. DOI: 10.1067/S0016-5107(03)00010-5. PMID: 14528210
12. Karateyev A.E., Nasonova V.A. Development and relapse of gastroduodenal ulcer in patients taking nonsteroid anti-inflammatory drugs: effects of standard risk factors. Terapevtichesky Arkhiv. 2008; 80 (5): 62–66. PMID: 18590118. [In Russ.]
13. Karateyev A.E. Bisphosphonate treatment and esophageal disease. Sovremennaya Revmatologiya. 2010; 3: 73-79. [In Russ.]
14. Wood M., Shaw P. Pradaxa-induced esophageal ulcer. BMJ Case Rep.2015; 2015: pii: bcr2015211371. DOI: 10.1136/bcr-2015-211371. PMID:26452739
15. Singh S., Savage L., Klein M., Thomas C. Severe necrotic oesophageal and gastric ulceration associated with dabigatran. BMJ Case Rep. 2013; 2013: pii: bcr2013009139. DOI: 10.1136/bcr-2013-009139. PMID: 23608859
16. Izumikawa K., Inaba T., Mizukawa S., Kawai Y., Sakakihara I., Ishikawa S., Miyoshi M., Wato M., Kawai K. Two cases of dabigatran-induced esophageal ulcer indicating the usefulness of drug administration guidance. Nihon Shokakibyo Gakkai Zasshi. 2014; 111 (6): 1096-1104. PMID:24898488
17. Scheppach W., Meesmann M. Exfoliative esophagitis while taking dabigatran. Dtsch. Med. Wochenschr. 2015; 140 (7): 515-518. DOI: 10.1055/s-0041-101313. PMID: 25826037
18. Okada M., Okada K. Exfoliative esophagitis and esophageal ulcer induced by dabigatran. Endoscopy. 2012; 44 Suppl 2 UCTN: E23-E24. DOI: 10.1055/s-0031-1291503. PMID: 22396259
19. Toya Y., Nakamura S., Tomita K., Matsuda N., Abe K., Abiko Y., Orikasa S., Akasaka R., Chiba T., Uesugi N., Sugai T., Matsumoto T. Dabigatraninduced esophagitis: the prevalence and endoscopic characteristics. J. Gastroenterol. Hepatol. 2016; 31 (3): 610-614. DOI: 10.1111/jgh.13024. PMID: 26102078
20. Vicente V., Martín A., Lecumberri R., Coll-Vinent B., Suero C., GonzálezPorras J.R., Marco P., Mateo J., Roldán V., Soulard S., Crespo C., Camats M.; Grupo DECOVER. Clinical perspectives on the management of bleeding in patients on oral anticoagulants: the DECOVER Study (DElphi Consensus on oral COagulation and therapy action reVERsal). Emergencias. 2017; 29 (1): 18-26. PMID: 28825264
21. Lanas-Gimeno A., Lanas A. Risk of gastrointestinal bleeding during anticoagulant treatment. Expert Opin. Drug Saf. 2017; 16 (6): 673-685. DOI: 10.1080/14740338.2017.1325870. PMID: 28467190
22. Albaladejo P., Samama C.M., Sié P., Kauffmann S., Mémier V., Suchon P., Viallon A., David J.S., Gruel Y., Bellamy L., de Maistre E., Romegoux P., Thoret S., Pernod G., Bosson J.L.; GIHP-NACO Study Group. Management of severe bleeding in patients treated with direct oral anticoagulants: an observational registry analysis. Anesthesiology. 2017; 127 (1): 111-120. DOI: 10.1097/ALN.0000000000001631. PMID: 28410272
23. Lauffenburger J.C., Rhoney D.H., Farley J.F., Gehi A.K., Fang G. Predictors of gastrointestinal bleeding among patients with atrial fibrillation after initiating dabigatran therapy. Pharmacotherapy. 2015; 35 (6): 560-568. DOI: 10.1002/phar.1597. PMID: 26044889
24. Karateyev A.E., Tsurgan A.V., Moroz E.V. Helicobacter pylori in patients with rheumatic diseases: the incidence of infection and evaluation of the effectiveness of an alternative regimen of eradication therapy. Russky Meditsinsky Zhurnal. 2017; 25 (17): 1220-1224. [In Russ.]
25. Karateyev A.E., Moroz E.V., Tsurgan A.V., Gontarenko N.V. Is Helicobacter pylori eradication required for non-steroidal anti-inflammatory drug-associated erosions and ulcers? Rossiisky Zhurnal Gastroenterologii, Gepatologii i Koloproktologii. 2016; 26 (6): 5-17. DOI: 10.22416/1382-4376-2016-6-5-17. [In Russ.]
26. Andersen I.B., Jørgensen T., Bonnevie O., Grønbaek M., Sørensen T.I. Smoking and alcohol intake as risk factors for bleeding and perforated peptic ulcers: a population-based cohort study. Epidemiology. 2000; 11 (4): 434-439. DOI: 10.1097/00001648-200007000-00012. PMID: 10874551
27. Kang J.M., Kim N., Lee B.H., Park H.K., Jo H.J., Shin C.M., Lee S.H., Park Y.S., Hwang J.H., Kim J.W., Jeong S.H., Lee D.H., Jung H.C., Song I.S. Risk factors for peptic ulcer bleeding in terms of Helicobacter pylori, NSAIDs, and antiplatelet agents. Scand. J. Gastroenterol. 2011; 46 (11): 1295-1301. DOI: 10.3109/00365521.2011.605468. PMID: 21815866
28. Strate L.L., Singh P., Boylan M.R., Piawah S., Cao Y., Chan A.T. A prospective study of alcohol consumption and smoking and the risk of major gastrointestinal bleeding in men. PLoS One. 2016; 11 (11): e0165278. DOI:10.1371/journal.pone.0165278. PMID: 27824864
Review
For citations:
Moroz E.V., Artemkin E.N., Kryukov E.V., Chernetsov V.A. Gastro-Intestinal Tract Complications During Antithrombotic Therapy. General Reanimatology. 2018;14(3):15-26. https://doi.org/10.15360/1813-9779-2018-3-15-26