VON WILLEBRAND FACTOR DYNAMICS AFTER RELATED LIVER TRANSPLANTATION
Keywords:
liver recipients, hemostasis, coagulopathy, thrombohemorrhagic complications, von Willebrand factor, endothelial dysfunction, MELD, hypercoagulation, coagulogram, plasminogen, protein C, AT3, platelets, liver cirrhosis, transplantation, inflammation, ischemia-reperfusionAbstract
Liver transplant recipients have a high risk of bleeding and thrombosis due to hemostatic dysfunction. Standard coagulation tests are uninformative, key predictors are associated with blood loss and transfusions.
Hypercoagulation is caused by inflammation, ischemia-reperfusion, platelet activation and metabolic disorders. MELD, hypothermia and acidosis increase the risk of bleeding, endothelial dysfunction and hemostatic imbalance - thrombosis and sepsis. New markers and approaches are needed to optimize the hemostatic strategy.
Objective: to study markers of endothelial dysfunction and inflammation in connection with hemostatic parameters in liver transplant recipients with decompensated cirrhosis.
Materials and methods: The study is registered (NCT06169592). Analysis of coagulogram and metabolic panel in 30 recipients (viral hepatitis B, D), average age 39.8±9.1 years. Groups by the presence of thrombohemorrhagic complications (THC). Fatal THC (hepatic artery thrombosis, venous thrombosis, bleeding) – in 5 patients, in 8 (27%) – conservative management.
Results:The decrease in anticoagulants in recipients is more pronounced than in procoagulants: AT3 - 2.5 times, protein C - 1.9, plasminogen - 1.5, INR - 1.4, fibrinogen - 1.2 compared to the control. Endothelial dysfunction with an increase in the antigen and activity of von Willebrand factor was noted. In patients with an unfavorable outcome, the number of platelets was reduced before surgery (p < 0.05), but the liver panel and coagulogram parameters did not differ (p > 0.05). The dynamics of von Willebrand factor differed significantly between the groups, but the threshold value was not established (p > 0.05).
Conclusions:The decrease in anticoagulants (AT3, protein C, plasminogen) in recipients is more pronounced than in procoagulants (INR, fibrinogen). In RTX recipients, coagulation factors (IIa) and anticoagulants (proteins C, S, AT-III) are reduced with a significantly (p<0.05) increased von Willebrand factor (VWF Ag, VWF Act).
References
Бабаджанов А.Х., З.Р. Хайбуллина, Э.К. Тургунбаев, Маткаримов Ш.У. Оценка параметров системы гемостаза у реципиентов после родственной трансплантации правой доли печени // Трансплантология и искусственные органы, 2023.-№4.
Emuakhaagbon V, Philips P, Agopian V Incidence and risk factors for deep venous thrombosis and pulmonary embols after liver transplantation // Am J Surg.-2016; 211:768-771.
Хайбуллина З.Р., А.Х. Бабаджанов, Н.М. Джураева, Э.К. Тургунбаев Особенности системы гемостаза и метаболизма у больных с терминальной стадией болезни печени как предпосылки для развития осложнений при ее трансплантации // Хирургия Узбекистана 2023.-№4(100).-С.56-63.
Bezinover D., Molly F. Deacutis, Priti G. Dalal1, Robert P. Moore, Jonathan G. Stine, Ming Wang,Ethan Reeder, Christopher S. Hollenbeak. Perioperative thrombotic complications associated with pediatric liver transplantation: a UNOS database evaluation // HPB.- 2019, 21, 370–378.
Guerrero A, Campo LD, Piscaglia F, Scheiner B, Han G, Violi F, Ferreira CN., Baveno Cooperation: an EASL consortium Anticoagulation improves survival in patients with cirrhosis and portal vein thrombosis: The IMPORTAL // competing-risk meta-analysis // J Hepatol. 2023 Jul;79(1):69-78. doi: 10.1016/j.jhep.2023.02.023. Epub 2023 Feb 28
Haas T, Fries D, Tanaka KA, Asmis L Usefulness of standard plasma coagulation tests in the management of perioperative coagulopathic bleeding: is there any evidence? // British Journal of Anaesthesia .-2014.-№8.-Р.1-8.
Soltys K, Caroline Lemoine, Xingyu Zhang, Rukhmi Bhat, John Bucuvalas, Sara Rasmussen, Rene Romero, Irini Batsis, Blayne Sayed, John Tunno. Factors associated with thrombotic and hemorrhagic complications in pediatric liver transplant: A multi-center analysis from the Starzl Network for Excellence in Pediatric Transplantation // 2022.-https://doi.org/10.1111/petr.14521
An Rui, Bai R, Zhang S. Blood loss during liver transplantation is a predictor of postoperative thrombosis // Am J Surg.-2021; 231:718-721.
Azhie A, Sheth P, Hammad A, Woo M, Bhat M. Metabolic Complications in Liver Transplantation Recipients: How We Can Optimize Long-Term Survival // Liver Transpl. 2021;27(10):1468. Epub 2021 Jul 31
Dunn R, Voleti S, Rowley S, Mackintosh Ch. Risk factors associated with urgent surgical reintervention due to postoperative hemorrhage after orthotopic liver transplantation // Journal of liver transplantation .-2022.-100124
Guerrero A, Campo LD, Piscaglia F, Scheiner B, Han G, Violi F, Ferreira CN., Baveno Cooperation: an EASL consortium Anticoagulation improves survival in patients with cirrhosis and portal vein thrombosis: The IMPORTAL // competing-risk meta-analysis // J Hepatol. 2023 Jul;79(1):69-78. doi: 10.1016/j.jhep.2023.02.023. Epub 2023 Feb 28
Lisman T, Caldwell SH, Burroughs AK, Northup PG, Senzolo M, Stravitz RT, Tripodi A, Trotter JF, Valla DC, Porte RJ; Coagulation in Liver Disease Study Group. Hemostasis and thrombosis in patients with liver disease: the ups and downs // J Hepatol 2010; 53:362-371
Хайбуллина З.Р., А.Х. Бабаджанов, Н.М. Джураева, Э.К. Тургунбаев Особенности системы гемостаза и метаболизма у больных с терминальной стадией болезни печени как предпосылки для развития осложнений при ее трансплантации // Хирургия Узбекистана 2023.-№4(100).-С.56-63.
Готье С.В., Хомяков С.М. Донорство и трансплантация органов в Российской Федерации в 2017 году // Вестник трансплантологии и искусственных органов, 2018. 2:140-143.
Lecchi Anna , Giulia Tosetti , Claudia Ghali , Silvia La Marca, Marigrazia Clerici. Comprehensive investigation of platelet function in patients with cirrhosis // 2024 May:237:64-70. doi: 10.1016/j.thromres.2024.03.017. Epub 2024 Mar 16.
Nghiem B Ha , Srilakshmi Seetharaman, Dorothea S Kent, Frederick Yao , Amy M Shui , Chiung-Yu Huang, Jeremy Walston, Jennifer C Lai. Serum and plasma protein biomarkers associated with frailty in patients with cirrhosis // Liver Transpl - 2023 Oct 1;29(10):1089-1099. doi: 10.1097/LVT.0000000000000128.
Nesci, A.; Ruggieri, V.;Manilla, V.; Spinelli, I.; Santoro, L.; DiGiorgio, A.; Santoliquido, A.; Ponziani, F.R. Endothelial Dysfunction and Liver Cirrhosis: Unraveling of a Complex Relationship // Int. J. Mol. Sci. 2024, 25, 12859. https://doi.org/10.3390/ ijms252312859.
Ladikou EE, Sivaloganathan H, Milne KM et al. Von Willebrand factor (vWF): marker of endothelial damage and thrombotic risk in COVID-19 // Clin Med 2020;20:e178–82.
Lisman T, Caldwell SH, Burroughs AK, Northup PG, Senzolo M, Stravitz RT, Tripodi A, Trotter JF, Valla DC, Porte RJ; Coagulation in Liver Disease Study Group. Hemostasis and thrombosis in patients with liver disease: the ups and downs // J Hepatol 2010; 53:362-371
Haas T, Fries D, Tanaka KA, Asmis L Usefulness of standard plasma coagulation tests in the management of perioperative coagulopathic bleeding: is there any evidence? // British Journal of Anaesthesia .-2014.-№8.-Р.1-8.
Harris, N. S., Pelletier, J. P., Marin, M. J., & Winter, W. E. (2021). Von Willebrand factor and disease: a review for laboratory professionals // Critical Reviews in Clinical Laboratory Sciences, 59(4), 241–256. https://doi.org/10.1080/10408363.2021.2014781 22. Soltys K, Caroline Lemoine, Xingyu Zhang, Rukhmi Bhat, John Bucuvalas, Sara Rasmussen, Rene Romero, Irini Batsis, Blayne Sayed, John Tunno. Factors associated with thrombotic and hemorrhagic complications in pediatric liver transplant: A multi-center analysis from the Starzl Network for Excellence in Pediatric Transplantation // 2022.-https://doi.org/10.1111/petr.14521
Guglielmetti G, Quaglia M, Sainaghi PP et al. ‘War to the knife’against thromboinflammation to protect endothelial function of COVID-19 patients //Crit Care 2020;24:365
Saadalla A, Seheult J, Pruthi RK, Chen D. Von Willebrand Factor Multimer Analysis and Classification: A Comprehensive Review and Updates. // Semin Thromb Hemost.- 2023 Sep;49(6):580-591. doi: 10.1055/s-0042-1757183. Epub 2022 Sep 29. PMID: 36174612
Baronciani L, Peyvandi F. How we make an accurat e diagnosis of von Willebrand disease // Thromb Res. - 2020 Dec;196:579-589. doi: 10.1016/j.thromres.2019.07.010. Epub 2019 Jul 16. PMID: 31353031
Колосков А.В., Мангушло А.А., Беляева Е.Л., Филиппова О.И., Чернова Е.В., Шендеров С.В., Марченко В.Н. Изменения активности металлопротеазы ADAMTS13 и антигена фактора фон Виллебранда у больных острым коронарным синдромом // Гематология и трансфузиология.- 2022; 67(2): 160–170. https://doi.org/10.35754/0234-5730-2022-67-2-160-170
Boender J, Eikenboom J, van der Bom JG, Meijer K, de Meris J, Fijnvandraat K, Cnossen MH, Laros-van Gorkom BAP, van Heerde WL, Mauser-Bunschoten EP, de Maat MPM, Leebeek FWG; WiN Study Group. Clinically relevant differences between assays for von Willebrand factor activity // J Thromb Haemost. 2018 Dec;16(12):2413-2424. doi: 10.1111/jth.14319
Favaloro EJ, Oliver S, Mohammed S, Vong R. Comparative assessment of von Willebrand factor multimers vs activity for von Willebrand disease using modern contemporary methodologies // Haemophilia.- 2020 May;26(3):503-512. doi: 10.1111/hae.13957
