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Pérez-Calatayud, A.A.; Hofmann, A.; Pérez-Ferrer, A.; Escorza-Molina, C.; Torres-Pérez, B.; Zaccarias-Ezzat, J.R.; Sanchez-Cedillo, A.; Manuel Paez-Zayas, V.; Carrillo-Esper, R.; Görlinger, K. Patient Blood Management in Liver Transplant. Encyclopedia. Available online: https://encyclopedia.pub/entry/42985 (accessed on 04 May 2024).
Pérez-Calatayud AA, Hofmann A, Pérez-Ferrer A, Escorza-Molina C, Torres-Pérez B, Zaccarias-Ezzat JR, et al. Patient Blood Management in Liver Transplant. Encyclopedia. Available at: https://encyclopedia.pub/entry/42985. Accessed May 04, 2024.
Pérez-Calatayud, Angel Augusto, Axel Hofmann, Antonio Pérez-Ferrer, Carla Escorza-Molina, Bettina Torres-Pérez, Jed Raful Zaccarias-Ezzat, Aczel Sanchez-Cedillo, Victor Manuel Paez-Zayas, Raul Carrillo-Esper, Klaus Görlinger. "Patient Blood Management in Liver Transplant" Encyclopedia, https://encyclopedia.pub/entry/42985 (accessed May 04, 2024).
Pérez-Calatayud, A.A., Hofmann, A., Pérez-Ferrer, A., Escorza-Molina, C., Torres-Pérez, B., Zaccarias-Ezzat, J.R., Sanchez-Cedillo, A., Manuel Paez-Zayas, V., Carrillo-Esper, R., & Görlinger, K. (2023, April 12). Patient Blood Management in Liver Transplant. In Encyclopedia. https://encyclopedia.pub/entry/42985
Pérez-Calatayud, Angel Augusto, et al. "Patient Blood Management in Liver Transplant." Encyclopedia. Web. 12 April, 2023.
Patient Blood Management in Liver Transplant
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This entry is adapted from the peer-reviewed paper 10.3390/biomedicines11041093

Transfusion of blood products in orthotopic liver transplantation (OLT) significantly increases post-transplant morbidity and mortality and is associated with reduced graft survival. Based on these results, an active effort to prevent and minimize blood transfusion is required. Patient blood management is a revolutionary approach defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient’s own blood while promoting patient safety and empowerment. This approach is based on three pillars of treatment: (1) detecting and correcting anemia and thrombocytopenia, (2) minimizing iatrogenic blood loss, detecting, and correcting coagulopathy, and (3) harnessing and increasing anemia tolerance.

patient blood management adult and pediatric liver transplant coagulation

1. Introduction

Orthotopic liver transplantation (OLT) is the standard of care for patients with non-reversible liver disease. It is a challenging procedure encompassing multidisciplinary and coordinated efforts to achieve the best results. Surgical procedures involve significant vessel manipulation in a complex scenario and impaired coagulation due to several factors, including temperature changes, hemodilution, calcium and acid-base imbalance, and other phenomena that may promote bleeding, often leading to the administration of red blood cells to restore oxygen delivery. Nevertheless, the transfusion of blood products in OLT significantly increases post-transplant morbidity and mortality [1][2][3][4] and is associated with reduced graft and patient survival [5][6]. Based on these results, an active effort is required to prevent and minimize blood transfusions and yellow blood products [7][8].
Patient blood management (PBM) is a revolutionary approach, defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient’s own blood while promoting patient safety and empowerment [8].
This approach is based on three pillars of treatment: (1) detecting and correcting anemia and thrombocytopenia, (2) minimizing iatrogenic blood loss and detecting and correcting coagulopathy, and (3) harnessing and increasing anemia tolerance [9][10][11][12]. The World Health Organization (WHO) recently published a policy brief regarding the urgent need to implement PBM [13].

2. Coagulopathy in Liver Disease

Patients with advanced liver disease have a hemostatic profile that typically includes thrombocytopenia and reduced coagulation factors; however, these alterations are counteracted by fibrinolysis inhibition, decreased protein C, and increased endothelial-derived von Willebrand factor (vWF) and factor VIII (FVIII). Therefore, this system is considered rebalanced in a precarious equilibrium vulnerable to extrahepatic variables such as infection, renal impairment, and volume status [14][15]. Thrombocytopenia is attributed to splenic sequestration and decreased thrombopoietin; however, this situation is offset by an increase in vWF. In fact, platelet procoagulant activity is fully preserved in patients with cirrhosis, and it has been demonstrated that thrombin generation in patients with liver disease and thrombocytopenia remained normal down to platelet counts of 60 × 109/dL. In addition, platelet transfusion failed to significantly ameliorate clot firmness in adult patients with platelet counts of 50 × 109/dL, assessed using viscoelastic tests [16][17][18]. Although platelet function defects may be present in vitro, the clinical significance of these defects has been debated [19].
Although there are evident defects in the synthesis of vitamin K-dependent coagulation factors and fibrinogen, the synthesis-derived anticoagulant factors, especially protein C, are also reduced. Elevated endothelial-derived FVIII coupled with low protein C contributes to a hypercoagulable state [20][21][22]. In this setting, PT and APTT suggest defective coagulation. However, these tests are not sensitive to deficiencies of anticoagulants or endothelial-derived procoagulant factors and do not represent the balance seen in LT between the pro-and anticoagulant proteins [23].
The fibrinolytic and antifibrinolytic systems may also be imbalanced in patients with cirrhosis. All liver-dependent factors (such as plasminogen) decrease, but tissue plasminogen activator levels are elevated due to decreased liver clearance. Plasminogen is activated by tissue plasminogen activator (tPA) to form plasmin and fibrin degradation products (FDPs). In some populations, this relationship is responsible for a profibrinolytic state. However, evidence suggests that the plasminogen activator inhibitor (PAI) is augmented in some patients with etiologies, such as cholestatic conditions and nonalcoholic steatosis hepatitis, which makes them prone to hypofibrinolysis and a hypercoagulable state [24][25].
Elevated platelet activation markers, thrombin, fibrin generation, and fibrinolysis are expected in patients with liver diseases. Although elevated levels may indicate defective clearance rather than ongoing activation of platelets, coagulation, and fibrinolysis because the liver clears these proteins [26], elevated plasma levels reflect ongoing low-grade disseminated intravascular coagulation with fibrinolysis activation [27].
Coagulopathy in acute liver failure differs from that in chronic liver failure. In patients with acute liver failure, thrombocytopenia is less common than in patients with cirrhosis; coagulation factors decrease in plasma, and fibrinolysis is particularly inhibited, whereas normal or hyperfibrinolysis is present in cirrhosis [28][29]. This phenomenon explains why thromboembolic events increase with greater liver function decompensation. Thus, patients with compensated cirrhosis have a 1% incidence of portal vein thrombosis, whereas patients with decompensated cirrhosis have an 8–25% incidence [30].
However, hemorrhagic events are common, often explained by reduced platelet count, decreased levels of coagulation factors, and fibrinolysis inhibitors [30]. Bleeding is divided into portal pressure-driven, mucosal, or prolonged puncture wound bleeding caused by premature clot dissolution [14].
In the perioperative context of liver transplantation, this rebalanced hemostasis is quickly vulnerable; therefore, decisions must be made to maintain hemodynamic stability and oxygen delivery to the tissues, avoiding futile overcorrections that promote prothrombotic environments, among other catastrophic complications.

3. Hemostatic Drugs

3.1. Antifibrinolytics

While performing a LT, systemic fibrinolysis is not a significant predictor of mortality and is often transient in the anhepatic and reperfusion phases [31]. In the late anhepatic stage and postreperfusion period, fibrinolysis is caused by tPA being released from vessels but not being cleared by the liver. Clinical evidence for the use of antifibrinolytics during LT supports this practice [31][32].
Aprotinin was the first antifibrinolytic agent used during OLT [33]. There is a strong association between increased transfusion due to intraoperative fibrinolysis and bleeding during OLT [34]. The clinical use of aprotinin was suspended in 2007 after serious safety concerns in high-risk cardiac surgery patients were raised [33][35][36]. Suspension was lifted in Canada and Europe after the health authorities concluded that the respective studies suffered from significant flaws.
However, tranexamic acid (TXA) has become the most used antifibrinolytic agent worldwide. A meta-analysis [37] demonstrated that TXA infusion (10 mg/kg/h) reduces RBC and FFP transfusions compared with placebo. Additionally, the prophylactic use of TXA (bolus: 30 mg/kg plus infusion at 16 mg/kg/h) has been documented. Nowadays, antifibrinolytic therapy is restrictively used due to the potential risk of arteria hepatic thrombosis in most liver transplant centers [38]. EACA-treated patients have received more significant amounts of RBC, plasma, platelets, and cryoprecipitate with repeated bolus injections or prolonged infusion (EACA, from 5–10 to >10 g). The results did not show a difference in thromboembolic events between the EACA and non-EACA groups. Badenoch et al. [39], in patients treated with TXA (n = 367), reported a decrease in RBC and plasma requirements versus matched non-treated cohorts without increased HAT, portal vein, and other venous thromboses. The HALT-IT RCT showed an increased risk of thromboembolic events in patients with gastrointestinal bleeding treated with TXA [40].
Potentially fatal complications in OLT are intracardiac thrombosis (ICT) and pulmonary thromboembolism (PE), occurring in 0.36–4.0% of cases. Intraoperative mortality rates are as high as 30–55%, and overall mortality is as high as 45–68%. Antifibrinolytic therapy and ICT/PE association have not been established; however, TXA or EACA can hinder attempts at clotting dissolution by intravenously administered tPA [41][42]. ICT/PE occurs within 30 min of the reperfusion phase [43][44]. Transesophageal echocardiogram can be used for early diagnosis, and antifibrinolytics should be withheld in high-risk OLT cases during this phase.

3.2. Fibrinogen Concentrates

The use of fibrinogen concentrate (FC) overcomes the limitations of cryoprecipitates. Furthermore, it avoids an increase in factor VIII and von Willebrand factor, a prothrombotic factor in patients with cirrhosis [42][43][44][45]. All products are indicated to actively treat bleeding in patients with congenital fibrinogen deficiency. Stolt [41] reported on in vitro samples with fibrinogen concentrate supplementation the effectiveness of correcting coagulation testing resulting in higher plasma fibrinogen concentrations and improved clot strength. However, the selected dose for restoring clot strength in cardiac surgery patients differed among the three groups, and these results have implications for the choice of concentration and dosing [42].
FC has been shown to increase fibrin polymerization in viscoelastic testing with less variability than cryoprecipitate. This results in an increase in fibrinogen levels in plasma in a more predictable manner [41][45]. The manufacturing of FC mitigates pathogen transmissions [46] and minimizes allergic and other transfusion-related reactions [47].
During any hemostatic intervention, the risk of thromboembolic complications must be considered. HAT is the most feared event in the OLT population, with an incidence of 3–9% [48], a re-transplantation rate prevalence of 53%, and a mortality rate between 27% and 58% [49][50]. A review of 634 consecutive patients found that cytomegalovirus (CMV) infection and accessory hepatic artery reconstruction were significant predictors of HAT [47]. Evidence also showed that the patient’s age, indication for OLT, cold ischemic time, surgical time, and blood transfusion volume were not risk factors for HAT [48]. The incidence of HAT was 4.5% in OLT patients receiving FC and PCC compared with 3.6% in those who did not receive these concentrates [51]. Fibrinogen administration to correct hypofibrinogenemia has a positive effect on surgical bleeding. Fibrinogen concentrates effects on increasing plasma fibrinogen by 0.5 g/L has not been determined in OLT patients, and the administration should be adjusted to replace plasma fibrinogen levels in the range of expected values; it is highly recommended that it be guided by thromboelastometry [52].

3.3. Prothrombin Complex Concentrate

PCC has a higher concentration of factors than FFP (a difference of 0.8 to 1.2 IU/mL), allowing a rapid recovery of vitamin K-dependent factors in warfarin-treated patients without circulatory overload [51][53]. ESLD has reduced production of FII, FV, FVII, FIX, and FX [54][55][56]; four-factor PCC may help restore deficient factors, except for FV [56].
In contrast to modern four-factor PCCs containing significant amounts of proteins C and S, rFVIIa does not contain anticoagulants and is associated with increased thromboembolic events, particularly arterial thrombosis in liver transplantation, and should therefore be avoided [57]. In patients with severe liver damage due to active bleeding or invasive procedures, similar recoveries (1.3–1.4 IU/kg) have been observed among FII, FIX, and FX. The median dose of PCC in this case series was 25.7 IU/kg (1500 [1000–4000] IU). No adverse events, including thrombosis, were observed [54]. A dose of 25 IU/kg of PCC was used if EXTEM-CT above 80 seconds for active hemorrhage in 266 LT cases after restoring fibrinogen levels. PCC was used in 34.9% (n = 93) of the patients compared with 14.7% (n = 39) [55].

3.4. Thrombopoietin Receptors Agonist (TPO)

TPO has been approved in chronic liver disease (CLD) patients programmed for invasive procedures. The published studies demonstrated a reduction in the need for platelet transfusions by enhancing the TPO receptor activation, increasing megakaryocyte progenitor proliferation, and ultimately increasing platelet production [58][59]. The effects of TPO agonist have not been studied in patients programmed for a liver transplant, and the main controversy is the risk of thromboembolic events. The safety profile for OLT has yet to be established. There is no recommendation for their use in this setting.

4. Pediatric Considerations

Sufficient differences between pediatric and adult patients needing OLT require independent yet complementary documents. Children have distinct diseases, clinical susceptibilities, and physiological responses that distinguish them from those of adults. Significant differences among newborns, infants, children, and adolescents have been found [60]. A multidisciplinary pediatric OLT evaluation team should be skilled in pediatric conditions and adequately communicate LT’s processes, risks, and benefits to the family and the child. Indications for LT in the pediatric population include biliary atresia, metabolic/genetic conditions, acute liver failure, cirrhosis, liver tumor, immune-mediated liver, biliary injury, and other conditions. Acute liver failure (ALF) or acute decompensation may rapidly progress to death or irreversible neurological damage [61].
Despite coagulopathy for liver disease, pediatric patients also acquire coagulopathy due to the dilution of clotting factors. This complication depends on the type of fluid therapy and volume of transfused RBC. Anesthetic challenges during this stage include the maintenance of hemodynamic stability by adequate fluid and blood product administration and correcting coagulation abnormalities. Acquired fibrinogen deficiency should be treated with the substitution of cryoprecipitates or the intraoperative administration of FC (50 mg/kg) to treat hypofibrinogenemia (ROTEM FIBTEM maximum clot firmness < 7 mm) during major pediatric surgery. Substitution with other coagulation factors (FXIII levels > 60%) should be indicated with laboratory or viscoelastic testing results. FFP might help treat severe hemorrhage as an adjunct to primary treatment with coagulation factors. However, it has been shown that FFP does not adequately increase plasma fibrinogen concentration. A 20–30 mL/kg volume dose should be administered to increase fibrinogen concentration. Moreover, it should only be considered after excluding other factors influencing hemostasis (fibrinogen deficiency, hyperfibrinolysis, acidosis, hypothermia, and low platelet count or impaired platelet function).
Cardiac surgery results showed that fibrinogen concentrate is as efficient and safe as cryoprecipitate. Unfortunately, no study has assessed the response to fibrinogen concentration after FFP administration in children with liver transplants [61].
Thrombocytopenia, secondary to hypersplenism, has a high prevalence and impairs coagulation. Platelet administration must always be weighed against the risk of hepatic artery thrombosis in the new graft in the pediatric population [62].
Perioperative treatment with an antifibrinolytic agent reduces bleeding and transfusion requirements in pediatric LT and hepatectomy, with high bleeding risk [63]. Bleeding prevention should be considered a patient-based multimodal approach. Antifibrinolytic agents may play a central role in perioperative bleeding prophylaxis in the pediatric population [64].
Tranexamic acid should be administrated at a loading dose of 10 mg/kg over 15 min, followed by a 5 mg/kg maintenance infusion, to maintain adequate plasma concentrations. Tranexamic acid is necessary for all children undergoing surgery with a significant bleeding risk to treat fibrinolysis but not for routine prophylaxis. Post-reperfusion fibrinolysis is common in marginal grafts (e.g., donation after cardiac death) and should be considered in patients with cirrhosis undergoing liver resection [61][65].
The reference ranges for the ROTEM parameters in children are age dependent. Children aged 0–3 months exhibited accelerated coagulation and firm clot firmness despite showing prolonged standard plasma coagulation test results. In addition, platelet count and FXIII contribute to clot firmness in children’s fibrinogen concentration, as measured with the ROTEM assay. In addition, children aged 4–24 months showed 2.5% percentiles for clot strength, indicating a low reserve when exposed to hemodilution and blood [64][65][66]. Viscoelastic tests during pediatric LT are well-established. The main objective of perioperative coagulation management is to prevent severe coagulopathy and avoid thromboembolic complications and graft thrombosis in pediatric OLT.
In 2008, the NHS Quality Improvement Scotland released a report based on health technology assessment that integrated evidence such as clinical effectiveness, cost and benefits, organizational aspects, and more about patients. Viscoelastic testing is recommended instead of standard coagulation tests during cardiac surgery, and (National Institute for Health and Care Excellence, UK) guidelines recommend viscoelastic tests to monitor coagulation during and after surgery. It is associated with lower mortality risks, reduced complications, and lower transfusion rates and hospitalization time [66][67].

5. Blood Conservation Technics in Liver Transplantation

Several blood conservation strategies should be used for live-donor liver transplantation (LDLT). Postoperative blood conservation involves limited blood sampling and pediatric drainage tubes. Intraoperative techniques include Acute Normovolemic Hemodilution (ANH), cell salvage, and specialized surgical techniques. Combining preoperative blood augmentation with ANH can be especially effective in OLT, allowing the removal of greater quantities of whole blood without causing significant perioperative anemia. Surgical techniques to control portal hypertension and blood loss during OLT in recipients are also essential for blood conservation. Hepatic congestion is unique to OLT and is associated with impaired function of the transplanted lobe. With refining surgical techniques, blood transfusions in OLT have been significantly reduced. Strategies that aim to minimize blood loss and transfusion should be developed. Intraoperative blood salvage autotransfusion (IBSA) reduces the need for allogeneic blood transfusions [68]. A study of 150 consecutive OLT patients showed that IBSA reduced the need for blood transfusion [69]. The risk of bacterial infection in the operative field seems plausible; however, this has not been demonstrated [70].
Cell salvage is globally used in liver transplants as a blood conservation technique. A recent systematic review reported that no data were found indicating whether cell salvage usage resulted in a reduction of transfusion requirements. The use of cell salvage did not increase HCC recurrence and did not affect mortality. Moreover, they found no data for other measures, including perioperative complications. All studies included in this systematic review were observational and had a small sample size; despite the insufficient evidence to state a recommendation, the authors’ conclusion favors its use to reduce blood transfusion in this setting [71].

6. Patient Blood Management Consideration for Acute Liver Failure

In patients with acute liver failure (ALF), the principles of pillar one from the PBM program should be focused on avoiding iatrogenic blood loss; anemia treatment to normalize laboratory parameters is often tricky secondary to the acute illness and timing of presentation, and based on the current evidence, the hemostasis in ALF indicates a “rebalanced” state [72]. Prophylactic transfusion of blood products is undesirable and unwarranted [72]. Without a clear benefit, it may expose patients to complications such as volume overload and transfusion reaction, immunomodulation, and graft rejection [72]. Viscoelastic tests have also gained more recognition as potential tools in evaluating coagulopathy in patients with liver disease [72].
The recommendations for treating coagulation abnormalities and blood loss in patients with CLD have been ported to patients with ALF. The treatment should be coagulation support in the evidence of bleeding with the same objectives as patients with CLD. However, specific research for subgroups of patients with ALF and ACLF must be conducted to provide more personalized and precise treatments.

References

  1. Rana, A.; Petrowsky, H.; Hong, J.C.; Agopian, V.G.; Kaldas, F.M.; Farmer, D.; Yersiz, H.; Hiatt, J.R.; Busuttil, R.W. Blood transfusion requirement during liver transplantation is an important risk factor for mortality. J. Am. Coll. Surg. 2013, 216, 902–907.
  2. McCluskey, S.A.; Karkouti, K.; Wijeysundera, D.N.; Kakizawa, K.; Ghannam, M.; Hamdy, A.; Grant, D.; Levy, G. Derivation of a risk index for the prediction of massive blood transfusion in liver transplantation. Liver Transpl. 2006, 12, 1584–1593.
  3. Massicotte, L.; Lenis, S.; Thibeault, L.; Sassine, M.P.; Seal, R.F.; Roy, A. Effect of low central venous pressure and phlebotomy on blood product transfusion requirements during liver transplantations. Liver Transpl. 2006, 12, 117–123.
  4. Cleland, S.; Corredor, C.; Ye, J.J.; Srinivas, C.; McCluskey, S.A. Massive haemorrhage in liver transplantation: Consequences, prediction and management. World J. Transplant. 2016, 6, 291e305.
  5. Holt, S.; Donaldson, H.; Hazlehurst, G.; Varghese, Z.; Contreras, M.; Kingdon, E.; Sweny, P.; Burns, A. Acute transplant rejection induced by blood transfusion reaction to the Kidd blood group system. Nephrol. Dial. Transplant. 2004, 19, 2403–2406.
  6. Han, S.; Kwon, J.H.; Jung, S.H.; Seo, J.Y.; Jo, Y.J.; Jang, J.S.; Yeon, S.M.; Jung, S.H.; Ko, J.S.; Gwak, M.S.; et al. Perioperative Fresh Red Blood Cell Transfusion May Negatively Affect Recipient Survival After Liver Transplantation. Ann. Surg. 2018, 267, 346–351.
  7. Görlinger, K.; Saner, F.H. Prophylactic Plasma and Platelet Transfusion in the Critically Ill Patient: Just Useless and Expensive or even Harmful? BMC Anesthesiol. 2015, 15, 86.
  8. Steinbicker, A.U.; Wittenmeier, E.; Goobie, S.M. Pediatric Non-Red Cell Blood Product Transfusion Practices: What’s the Evidence to Guide Transfusion of the ‘Yellow’ Blood Products? Curr. Opin. Anaesthesiol. 2020, 33, 259–267.
  9. Shander, A.; Hardy, J.F.; Ozawa, S.; Farmer, S.L.; Hofmann, A.; Frank, S.M.; Kor, D.J.; Faraoni, D.; Freedman, J. A Global Definition of Patient Blood Management. Anesth Analg. 2022, 135, 476–488.
  10. Isbister, J. The three-pillar matrix of patient blood management. ISBT Sci. Series 2015, 10, 286–294.
  11. Hofmann, A.; Friedman, D.; Farmer, S. Western Australian Patient Blood Management Project 2008–2012: Analysis, Strategy, Implementation and Financial Projections; Western Australia Department of Health: Perth, Australia, 2007; pp. 1–154.
  12. Hofmann, A.; Farmer, S.; Shander, A. Five drivers shifting the paradigm from product-focused transfusion practice to patient blood management. Oncologist 2011, 16 (Suppl. 3), 3–11.
  13. World Health Organization. The Urgent Need to Implement Patient Blood Management: Policy Brief; World Health Organization: Geneva, Switzerland, 2021; ISBN 9789240035744. Available online: https://apps.who.int/iris/handle/10665/346655 (accessed on 12 March 2023).
  14. Parker, A.; Karvellas, C.J. Coagulation Defects in the Cirrhotic Patient Undergoing Liver Transplantation. Transplantation 2018, 102, 1453–1458.
  15. Mrzljak, A.; Franusic, L.; Pavicic-Saric, J.; Kelava, T.; Jurekovic, Z.; Kocman, B.; Mikulic, D.; Budimir-Bekan, I.; Knotek, M. Pre- and intraoperative Predictors of Acute Kidney Injury after Liver Transplantation. World J. Clin. Cases 2020, 8, 4034–4042.
  16. Lisman, T.; Adelmeijer, J.; de Groot, P.G.; Janssen, H.L.; Leebeek, F.W. No evidence for an intrinsic platelet defect in patients with liver cirrhosis studies under flow conditions. J. Thromb. Haemost. 2006, 4, 2070–2072.
  17. Tripodi, A.; Primignani, M.; Chantarangkul, V.; Clerici, M.; Dell’Era, A.; Fabris, F.; Salerno, F.; Mannucci, P.M. Thrombin generation in patients with cirrhosis: The role of platelets. Hepatology 2006, 44, 440–445.
  18. Blanchard, R.A.; Furie, B.C.; Jorgensen, M.; Kruger, S.F.; Furie, B. Acquired vitamin K-dependent carboxylation deficiency in liver disease. N. Engl. J. Med. 1981, 305, 242–248.
  19. Martinez, J.; MacDonald, K.A.; Palascak, J.E. The role of sialic acid in the dysfibrinogenemia associated with liver disease: Distribution of sialic acid on the constituent chains. Blood 1983, 61, 1196–1202.
  20. Hughes, R.D.; Lane, D.A.; Ireland, H.; Langley, P.G.; Gimson, A.E.; Williams, R. Fibrinogen derivatives and platelet activation products in acute and chronic liver disease. Clin. Sci. 1985, 68, 701–707.
  21. McMurry, H.S.; Jou, J.; Shatzel, J. The Hemostatic and Thrombotic Complications of Liver Disease. Eur. J. Haematol. 2021, 107, 383–392.
  22. Gunetilleke, B.; Welikala, N.D.; Görlinger, K. Viscoelastic Haemostatic Test Based Management of Coagulopathy in Liver Transplantation for Cirrhosis. Sri Lanka J. Haematol. 2021, 13, 1–9.
  23. Lisman, T.; Leebeek, F.W.; Mosnier, L.O.; Bouma, B.N.; Meijers, J.C.; Janssen, H.L.; Nieuwenhuis, H.K.; De Groot, P.G. Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology 2001, 121, 131–139.
  24. Pihusch, R.; Rank, A.; Gohring, P.; Pihusch, M.; Hiller, E.; Beuers, U. Platelet function rather than plasmatic coagulation explains hypercoagulable state in cholestatic liver disease. J. Hepatol. 2002, 37, 548–555.
  25. Ben-Ari, Z.; Panagou, M.; Patch, D.; Bates, S.; Osman, E.; Pasi, J.; Burroughs, A. hypercoagulability in patients with primary biliary cirrhosis and primary sclerosing cholangitis evaluated by thrombelastography. J. Hepatol. 1997, 26, 554–559.
  26. Lisman, T.; Porte, R.J. Rebalanced hemostasis in patients with liver disease: Evidence and clinical consequences. Blood 2010, 116, 878–885.
  27. Lisman, T.; Bongers, T.N.; Adelmeijer, J.; Janssen, H.L.; de Maat, M.P.; de Groot, P.G.; Leebeek, F.W. Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology 2006, 44, 53–61.
  28. Mannucci, P.M.; Canciani, M.T.; Forza, I.; Lussana, F.; Lattuada, A.; Rossi, E. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood 2001, 98, 2730–2735.
  29. Stravitz, R.T.; Fontana, R.J.; Meinzer, C.; Durkalski-Mauldin, V.; Hanje, A.J.; Olson, J.; Koch, D.; Hamid, B.; Schilsky, M.L.; McGuire, B.; et al. ALF Study Group. Coagulopathy, Bleeding Events and Outcome According to Rotational Thromboelastometry in Patients with Acute Liver Injury/Failure. Hepatology 2021, 72, 937–949.
  30. Colucci, M.; Binetti, B.M.; Branca, M.G.; Clerici, C.; Morelli, A.; Semeraro, N.; Gresele, P. Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis. Hepatology 2003, 38, 230–237.
  31. Boylan, J.F.; Klinck, J.R.; Sandler, A.N.; Arellano, R.; Greig, P.D.; Nierenberg, H.; Roger, S.L.; Glynn, M.F. Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation. Anesthesiology 1996, 85, 1043–1048.
  32. Dalmau, A.; Sabaté, A.; Acosta, F.; Garcia-Huete, L.; Koo, M.; Sansano, T.; Rafecas, A.; Figueras, J.; Jaurrieta, E.; Parrilla, P. Tranexamic acid reduces red cell transfusion better than epsilon-aminocaproic acid or placebo in liver transplantation. Anesth. Analg. 2000, 91, 29–34.
  33. Neuhaus, P.; Bechstein, W.O.; Lefbre, B.; Blumhardt, G.; Slama, K. Effect of aprotinin on intraoperative bleeding and fibrinolysis in liver transplantation. Lancet 1989, 2, 924–925.
  34. Hawkins, R.B.; Raymond, S.L.; Hartjes, T.; Efron, P.A.; Larson, S.D.; Andreoni, K.A.; Thomas, E.M. Review: The Perioperative Use of Thromboelastography for Liver Transplant Patients. Transplant. Proc. 2018, 50, 3552–3558.
  35. Lentschener, C.; Roche, K.; Ozier, Y. A review of aprotinin in orthotopic liver transplantation: Can its harmful effects offset its beneficial effects? Anesth. Analg. 2005, 100, 1248–1255.
  36. Dalmau, A.; Sabaté, A.; Koo, M.; Bartolomé, C.; Rafecas, A.; Figueras, J.; Jaurrieta, E. The prophylactic use of tranexamic acid and aprotinin in orthotopic liver transplantation: A comparative study. Liver Transpl. 2004, 10, 279–284.
  37. Molenaar, I.Q.; Warnaar, N.; Groen, H.; TenVergert, E.M.; Slooff, M.J.H.; Porte, R.J. Efficacy and safety of antifibrinolytic drugs in liver transplantation: A systematic review and meta-analysis. Am. J. Transplant. 2007, 7, 185–194.
  38. Hartmann, M.; Walde, C.; Dirkmann, D.; Saner, F.H. Safety of Coagulation Factor Concentrates guided by ROTEM-Analyses in Liver Transplantation: Results from 372 Procedures. BMC Anesthesiol. 2019, 19, 97.
  39. Badenoch, A.; Sharma, A.; Gower, S.; Selzner, M.; Srinivas, C.; Wąsowicz, M.; McCluskey, S.A. The effectiveness and safety of tranexamic acid in orthotopic liver transplantation clinical practice: A propensity score matched cohort study. Transplantation 2017, 101, 1658–1665.
  40. HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): An international randomised, double-blind, placebo-controlled trial. Lancet 2020, 395, 1927–1936.
  41. Stolt, H.; Shams Hakimi, C.; Singh, S.; Jeppsson, A.; Karlsson, M. A comparison of the in vitro effects of three Fibrinogen Concentrates on clot strength in blood samples from cardiac surgery patients. Acta Anaesthesiol. Scand. 2021, 65, 1439–1446.
  42. Colin-Bracamontes, I.; Pérez-Calatayud, Á.A.; Carrillo-Esper, R.; Rodríguez-Ayala, E.; Padilla-Molina, M.; Posadas-Nava, A.; Olvera-Vázquez, S.; Hernández-Salgado, L. Observational Safety Study of Clottafact® Fibrinogen Concentrate: Real-World Data in Mexico. Clin. Drug Investig. 2020, 40, 485–491.
  43. Zermatten, M.G.; Fraga, M.; Moradpour, D.; Bertaggia Calderara, D.; Aliotta, A.; Stirnimann, G.; De Gottardi, A.; Alberio, L. Hemostatic Alterations in Patients With Cirrhosis: From Primary Hemostasis to Fibrinolysis. Hepatology 2020, 71, 2135–2148.
  44. Hensley, N.B.; Mazzeffi, M.A. Pro-Con Debate: Fibrinogen Concentrate or Cryoprecipitate for Treatment of Acquired Hypofibrinogenemia in Cardiac Surgical Patients. Anesth. Analg. 2021, 133, 19–28.
  45. Neisser-Svae, A.; Hegener, O.; Görlinger, K. Differences in the Biochemical Composition of Three Plasma Derived Human Fibrinogen Concentrates. Thromb. Res. 2021, 205, 44–46.
  46. Groeneveld, D.J.; Adelmeijer, J.; Hugenholtz, G.C.G.; Arins, R.A.S.; Porte, R.J.; Lisman, T. Ex vivo addition of fibrinogen concentrate improves the fibrin network structure in plasma samples taken during liver transplantation. J. Thromb. Haemost. 2015, 13, 2192–2201.
  47. Sabate, A.; Gutierrez, R.; Beltran, J.; Mellado, P.; Blasi, A.; Acosta, F.; Costa, M.; Reyes, R.; Torres, F. Impact of preemptive fiFibrinogenoncentrate on transfusion requirements in liver transplantation: A multicenter, randomized, double-blind, placebo- controlled trial. Am. J. Transplant. 2016, 16, 2421–2429.
  48. Stange, B.J.; Glanemann, M.; Nuessler, N.C.; Settmacher, U.; Steinmüller, T.; Neuhaus, P. Hepatic artery thrombosis after adult liver transplantation. Liver Transpl. 2003, 9, 612–620.
  49. Bekker, J.; Ploem, S.; de Jong, K.P. Early hepatic artery thrombosis after liver transplantation: A systematic review of the incidence, outcome and risk factors. Am. J. Transplant. 2009, 9, 746–757.
  50. Gunsar, F.; Rolando, N.; Pastacaldi, S.; Patch, D.; Raimondo, M.L.; Davidson, B.; Rolles, K.; Burroughs, A.K. Late hepatic artery thrombosis after orthotopic liver transplantation. Liver Transpl. 2003, 9, 605–611.
  51. Kirchner, C.; Dirkmann, D.; Treckmann, J.W.; Paul, A.; Hartmann, M.; Saner, F.H.; Görlinger, K. Coagulation management with factor concentrates in liver transplantation: A single-center experience: Factor concentrates in liver transplant. Transfusion 2014, 54, 2760–2768.
  52. Görlinger, K.; Pérez-Ferrer, A.; Dirkmann, D.; Saner, F.; Maegele, M.; Calatayud, Á.A.P.; Kim, T.Y. The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management. Korean J. Anesthesiol. 2019, 72, 297–322.
  53. Goldstein, J.N.; Refaai, M.A.; Milling TJJr Lewis, B.; Goldberg-Alberts, R.; Hug, B.A.; Sarode, R. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: A phase 3b, open-label, non-inferiority, randomized trial. Lancet 2015, 385, 2077–2087.
  54. Refaai, M.A.; Goldstein, J.N.; Lee, M.L.; Durn, B.L.; Milling, T.J.; Sarode, R. Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal. Transfusion 2015, 55, 2722–2729.
  55. Kelly, D.A.; O’Brien, F.J.; Hutton, R.A.; Tuddenham, E.G.; Summerfield, J.A.; Sherlock, S. The Effect of liver disease on factors V, VIII and protein C. Br. J. Haematol. 1985, 61, 541–548.
  56. Lorenz, R.; Kienast, J.; Otto, U.; Egger, K.; Kiehl, M.; Schreiter, D.; Kwasny, H.; Haertel, S.; Barthels, M. Efficacy and safety of a prothrombin complex concentrate with two virus-inactivation steps in patients with severe liver damage. Eur. J. Gastroenterol. Hepatol. 2003, 15, 15–20.
  57. Lodge, J.P.; Jonas, S.; Jones, R.M.; Olausson, M.; Mir-Pallardo, J.; Soefelt, S.; Garcia-Valdecasas, J.C.; McAlister, V.; Mirza, D.F. Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation. Liver Transpl. 2005, 11, 973–979.
  58. Terrault, N.; Chen, Y.C.; Izumi, N.; Kayali, Z.; Mitrut, P.; Tak, W.Y.; Allen, L.F.; Hassanein, T. Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia. Gastroenterology 2018, 155, 705–718.
  59. Peck-Radosavljevic, M.; Simon, K.; Iacobellis, A.; Hassanein, T.; Kayali, Z.; Tran, A.; Makara, M.; Ben Ari, Z.; Braun, M.; Mitrut, P.; et al. Lusutrombopag for the treatment of thrombocytopenia in patients with chronic liver disease undergoing invasive procedures (L-Plus 2). Hepatology 2019, 70, 1336–1348.
  60. Pérez-Ferrer, A.; García-Erce, J.A.; Muñóz, M. Medicina Transfusional Patient Blood Management. Edicion 2. El Paciente Pediátrico; Editorial Panamericana: Madrid, Spain, 2018; pp. 161–172.
  61. Squires, R.H.; Ng, V.; Romero, R.; Ekong, U.; Hardikar, W.; Emre, S.; Mazariegos, G.V. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Hepatology 2014, 60, 362–398.
  62. Kozek-Langenecker, S.A.; Ahmed, A.B.; Afshari, A.; Albaladejo, P.; Aldecoa, C.; Barauskas, G.; De Robertis, E.; Faraoni, D.; Filipescu, D.C.; Dietmar, F.; et al. Management of severe perioperative bleeding: Guidelines from the european society of anaesthesiology. Eur. J. Anaesthesiol. 2017, 34, 332–395.
  63. Yudkowitz, F.S.; Chietero, M. Anesthesic issues in pediatric liver transplantation. Pediatric. Transplant. 2005, 9, 1399–3046.
  64. Hass, T.; Mauch, J.; Weis, M.; Schmugge, M. Management of dilutional coagulophaty during pediatric major surgery. Transfus. Med. Hemotheraphy 2012, 39, 114–119.
  65. Faroni, D.; Goobie, S.M. New insights about the use of tranexamic acid in children undergoing cardiac surgery: From pharmacokinetics to pharmacodynamic. Anesth. Analg. 2013, 117, 760–762.
  66. New, H.V.; Berryman, J.; Bolton-Maggs, P.H.; Cantwell, C.; Chalmers, E.A.; Davies, T.; Gottstein, R.; Kelleher, A.; Kumar, S.; Morley, S.L.; et al. Guidelines on transfusion for fetuses, neonates and older children. Br. J. Haematol. 2016, 175, 784–828.
  67. Whiting, P.; Al, M.; Westwood, M.; Ramos, I.C.; Ryder, S.; Armstrong, N.; Misso, K.; Ross, J.; Severens, J.; Kleijnen, J. Viscoelastic point-of-care testing to assist with the diagnosis, management and monitoring of haemostasis: A systematic review and cost-effectiveness analysis. Health Technol. Assess. 2015, 19, 1–228.
  68. Pinto, M.A.; Chedid, M.F.; Sekine, L.; Schmidt, A.P.; Capra, R.P.; Prediger, C.; Prediger, J.E.; Grezzana-Filho, T.J.; Kruel, C.R. Intraoperative cell salvage with autologous transfusion in liver transplantation. World J. Gastrointest. Surg. 2019, 11, 11–18.
  69. Massicotte, L.; Thibeault, L.; Beaulieu, D.; Roy, J.D.; Roy, A. Evaluation of cell salvage autotransfusion utility during liver transplantation. HPB 2007, 9, 52–57.
  70. Feltracco, P.; Michieletto, E.; Barbieri, S.; Serra, E.; Rizzi, S.; Salvaterra, F.; Cillo, U.; Ori, C. Microbiologic contamination of intraoperative blood salvaged during liver transplantation. Transplant. Proc. 2007, 39, 1889–1891.
  71. Yoon, U.; Bartoszko, J.; Bezinover, D.; Biancofiore, G. ERAS4OLT.org Working Group. Intraoperative Transfusion Management, Antifibrinolytic Therapy, Coagulation Monitoring and the Impact on Short-term Outcomes after Liver Transplantation—A Systematic Review of the Literature and Expert Panel Recommendations. Clin. Transplant. 2022, 6, e14637.
  72. O’Leary, J.G.; Greenberg, C.S.; Patton, H.M.; Caldwell, S.H. AGA Clinical Practice Update: Coagulation in Cirrhosis. Gastroenterology 2019, 157, 34–43.e1.
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Subjects: Transplantation
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Angel Augusto Pérez-Calatayud
,
Axel Hofmann
,
Antonio Pérez-Ferrer
,
Carla Escorza-Molina
,
Bettina Torres-Pérez
,
Jed Raful Zaccarias-Ezzat
,
Aczel Sanchez-Cedillo
,
Victor Manuel Paez-Zayas
,
Raul Carrillo-Esper
,
Klaus Görlinger
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Revisions: 2 times (View History)
Update Date: 13 Apr 2023
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