Effect of Rivaroxaban on hemostasis in patients with alcoholic cirrhosis of the liver in combination with obesity
PDF (Українська)

Keywords

alcoholic liver disease
liver cirrhosis
obesity
hemostasis

How to Cite

Virstiuk, N., Matkovska, N., & Vatseba, B. (2020). Effect of Rivaroxaban on hemostasis in patients with alcoholic cirrhosis of the liver in combination with obesity. Medicine Today and Tomorrow, 87(2), 26-35. https://doi.org/10.35339/msz.2020.87.02.03

Abstract

The effect of rivaroxaban on hemostasis was investigated in patients with alcoholic liver cirrhosis (ALC) in combination with obesity and non-valvular atrial fibrillation (NVAF). The study included 48 obese patients with ALC of class A (according to the Child-Pugh score) with NVAF, who were not previously treated with direct oral anticoagulants. There are 43 men and 5 women aged 35 to 64 years, mean age is (54.2±4.8) years. Depending on the treatment, patients were divided into two groups: group I included 22 patients who received oral anticoagulant rivaroxaban at a dose of 10 mg/day for 12 months, group II included 26 patients who received basic therapy without rivaroxaban for 12 months. Assessment of the patients’ condition was performed before treatment, 12, 24 and 48 weeks after treatment onset. The severity of LC was assessed according to the Child-Pugh and the MELD scores. Stratification of the risk of bleeding was performed according to the HAS-BLED score. It is shown, that in obese patients with ALC of class A according to the Child-Pugh score in the presence of NVAF, the use of rivaroxaban in combination therapy for 48 weeks contributed to the positive dynamics of hemostasis: decreased factor VIII activity, von Willebrand factor activity, reduced plasminogen activator inhibitor-1, D-dimer levels (p<0.05) and an increase in the activity of protein C (p<0.05), which was accompanied by a moderate decrease in the Child-Pugh and the MELD scores, and this was not observed in the comparison group. The use of rivaroxaban in this cohort of patients for 48 weeks did not increase the risk of major bleeding according to the clinical course and the HAS-BLED score. It is proved that the use of rivaroxaban in the complex treatment of patients with ALC of class A (according to the Child-Pugh score) in combination with obesity and NVAF, contributes to the positive dynamics of hemostasis with a reduced risk of hypercoagulation. Such therapy does not increase the risk of major bleeding at the stage of compensation of ALC in combination with obesity and NVAF.

https://doi.org/10.35339/msz.2020.87.02.03
PDF (Українська)

References

Nakaz MOZ Ukrainy vid 06.11.14 № 826. Pro zatverdzhennia ta vprovadzhennia medyko- tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry khronichnykh neinfektsiinykh hepatytakh: Unifikovanyi klinichnyi protokol pervynnoi, vtorynnoi (spetsializovanoi) medychnoi dopomohy «Alkoholnyi hepatyt»; Alkoholna khvoroba pechinky. Adaptovana klinichna nastanova, zasnovana na dokazakh [Order of the Ministry of Health of Ukraine dated November 6, 2014 № 826. On approval and implementation of medical and technological documents on standardization of medical care at chronic non-infectious hepatitis: Unified clinical protocol of primary, secondary (specialized) medical care «Alcoholic hepatitis»; Adapted clinical guidelines based on the evidence «Alcoholic liver disease»]. (2014). Retrieved from https://ukrgastro.com.ua/illnesses/ [in Ukrainian],

Nakaz MOZ Ukrainy № 597 vid 15.06.16. Pro zatverdzhennia ta vprovadzhennia medyko- tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry fibryliatsii peredserd: Unifikovanyi klinichnyi protokol pervynnoi, vtorynnoi (spetsializovanoi) ta tretynnoi (vysoko- spetsializovanoi) medychnoi dopomohy «Fibryliatsiia peredserd» [Order of the Ministry of Health of Ukraine № 597 of 15.06.16. On approval and implementation of medical and technological documents for standardization of medical care for atrial fibrillation: Unified clinical protocol of primary, secondary (specialized) and tertiary (highly specialized) medical care «Atrial fibrillation»]. (2016). Retrieved from https://www.dec.gov.ua/wpcontent/uploads/2019/ll/2016_597_ykpmd_fibrpreds.pdf [in Ukrainian],

Nakaz MOZ Ukrainy vid 06.08.14 № 826. Pro zatverdzhennia ta vprovadzhennia medyko- tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry khronichnykh neinfektsiinykh hepatytakh: Unifikovanyi klinichnyi protokol «Alkoholnyi steatohepatyt» [Order ofthe Ministry of Health of Ukraine dated 06.08.14 № 826. On approval and implementation of medical and technological documents on standardization of medical care at chronic non-infectious hepatitis: Unified clinical protocol «Alcoholic steatohepatitis»]. (2014). Retrieved from https://ukrgastro.com.ua/illnesses/ [in Ukrainian],

Nakaz MOZ Ukrainy vid 06.11.14 № 826. Pro zatverdzhennia ta vprovadzhennia medyko- tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry khronichnykh neinfektsiinykh hepatytakh: Unifikovanyi klinichnyi protokol «Nealkoholnyi steatohepatyt» [Order of the Ministry of Health of Ukraine dated November 6, 2014 № 826. On approval and implementation of medical and technological documents on standardization of medical care at chronic non-infectious hepatitis: Unified clinical protocol «Non-alcoholic steatohepatitis»]. (2014). Retrieved from https://ukrgastro.com.ua/illnesses/ [in Ukrainian],

Ambrosino R, Tarantino L., Di Minno G., Paternoster M., Graziano V., Petitto M. et. al. (2017). The risk of venous thromboembolism in patients with cirrhosis. Thrombosis and Haemostasis, vol. 26, issue 1, pp. 139-148. DOI: 10.1160/TH16-06-0450, PMID: 27761574.

European Association for the Study of the Liver. (2018). EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. Journal of Hepatology, vol. 69, issue 2, pp. 406-460. DOI: https://doi.org/10.1016/jjhep.2018.03.024.

Bos S., van den Boom B., Kamphuisen P.W., Adelmeijer X, Blokzijl H., Schreuder T., Lisman T. (2019). Haemostatic profiles are similar across all aetiologies of cirrhosis. Thrombosis and Haemostasis, vol. 119, issue 2, pp. 246-253. DOI: 10.1055/s-0038-1676954, PMID: 30609442.

Cagin Y.F., Bilgic Y., Berber X, Yildirim O., Erdogan M.A., Firat F. et al. (2019). The risk factors of portal vein thrombosis in patients with liver cirrhosis. Experimental and Therapeutic Medicine, vol. 17, issue 4, pp. 3189-3194. DOI: 10.3892/etm.2019.7300, PMID: 30936992, PMCID: PMC6434378.

Chiang D.J., McCullough A. J. (2014). The impact of obesity and metabolic syndrome on alcoholic liver disease. Clinics in Liver Disease, vol. 18, issue 1, pp. 157-163. DOI: 10.1016/j.cld.2013.09.006, PMID: 24274871, PMCID: PMC6130318.

Dirkmann D. (2019). The hemostatic system in patients with cirrhosis, monitoring of coagulation and management of bleeding. Critical Care for Potential Liver Transplant Candidates (pp. 101-118). Springer, Cham. DOI: 10.1007/978-3-319-92934-7 7.

European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). (2016). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol., vol. 64, issue 6, pp. 1388-1402. DOI: 10.1016/j.jhep.2015.11.004, Epub 2016 Apr 7, PMID: 27062661.

European Association for the Study of the Liver. (2018). EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. Journal of Hepatology, vol. 69, issue 1, pp. 154-181. DOI: https://doi.org/10.1016/jjhep.2018.03.018.

Hoolwerf E.W., KraaijpoelN., Buller H.R., van EsN. (2018). Direct oral anticoagulants inpatients with liver cirrhosis: a systematic review. Thrombosis Research, vol. 170, pp. 102-108. DOI: 10.1016/ j.thromres.2018.08.011, Epub 2018 Aug 17, PMID: 30153564.

IntagliataN.M., Maitland H., Northup P.G., Caldwell S.H. (2015). Treating thrombosis in cirrhosis patients with new oral agents: ready or not? Hepatology, vol. 61, issue 2, pp. 738-739. DOI: 10.1002/ hep.27225, PMID: 24829112.

Jones K., Pham C., Aguilar C., Sheth S. (2020). Retrospective review on the safety and efficacy of direct oral anticoagulants compared with warfarin in patients with cirrhosis. Federal Practitioner, vol. 37, issue 10, pp. 479-485. DOI: 10.12788/fp.0058, PMID: 33132687, PMCID: PMC7592895.

Kalambokis G.N., Oikonomou A., Christou L., Kolaitis N.I., Tsianos E.V., Christodoulou D., Baltayiannis G. (2016). Von Willebrand factor and procoagulant imbalance predict outcome in patients with cirrhosis and thrombocytopenia. Journal of Hepatology, vol. 65, issue 5, pp. 921-928. DOI: 10.1016/ j.jhep.2016.06.002, PMID: 27297911.

Kirchhoff P, Benussi S., Kotecha D., Ahlsson A., Atar D., Casadei B. et al. (2016). 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Heart J., vol. 37, issue 38, pp. 2893-2962. DOI: 10.1093/eurheartj/ehw210, PMID: 27567408.

LapumnuaypolK.,DiMariaC.,ChiasakulT. (2019). Safety of direct oral anticoagulants inpatients with cirrhosis: a systematic review and meta-analysis. QJM: An International Journal of Medicine, vol. 112, issue 8, pp. 605-610. DOI: 10.1093/qjmed/hczl27.

Lip G.Y., Halperin J.L. (2010). Improving stroke risk stratification in atrial fibrillation. The American Journal of Medicine, vol. 123, issue 6, pp. 484-488. DOI: 10.1016/j.amjmed.2010.05.007.

Raja K., Jacob M., Asthana S. (2014). Portal vein thrombosis in cirrhosis. Journal of Clinical and Experimental Hepatology, vol. 4, issue 4, pp. 320-331. DOI: 10.1016/j.jceh.2013.12.003.

Saner F.H., Bezinover D. (2019). Assessment and management of coagulopathy in critically-ill patients with liver failure. Current Opinion in Critical Care, vol. 25, issue 2, pp. 179-186. DOI: 10.1097/ MCC.0000000000000591, PMID: 30855324.

SingalA.K.,BatallerR., Ahn J.,KamathP.S., ShahV.H. (2018). ACGclinicalguideline: alcoholic liver disease. The American Journal of Gastroenterology, vol. 113, issue 2, pp. 175-194. DOI: 10.1038/ ajg.2017.469, PMID: 29336434, PMCID: PMC6524956.

Turco L., de Raucourt E., Valla D.C., Villa E. (2019). Anticoagulation in the cirrhotic patient. JHEPReports, vol 1, issue 3,pp. 227-239. DOI: 10.1016/j.jhepr.2019.02.006, PMID: 32039373, PMCID: PMC7001584.

Madden L., Damme W.V., Put W.V.D., Button Ricarte, Affun-Adegbulu C., Belle S.V., Pas R.V.D. (2019). World Health Organization. (2018). Primary health care and health emergencies. World Health Organization WHO. DOI: 10.13140/RG.2.2.16223.20640.

Verbeek T.A., Stine J.G., Saner F.H., Bezinover D. (2018). Hypercoagulability in end-stage liver disease: Review of epidemiology, etiology, and management. Transplantation Direct, vol. 4, issue 11, e403. DOI: 10.1097/TXD.0000000000000843, PMID: 30534594, PMCID: PMC6233657.