|Year : 2007 | Volume
| Issue : 1 | Page : 13-19
Transfusion support in liver transplantation
M.D., P.D.C.C. SeniorAdviser,Anaesthesilogy Presently ClinicalFellow, Institute of Liver Studies, Kings College Hospital, Denmark Hill, London, India
|Date of Acceptance||15-Jan-2007|
|Date of Web Publication||20-Mar-2010|
Department of Anaesthesia and Intensive Care, Army Hospital, R&R Delhi Cantt-110010
Source of Support: None, Conflict of Interest: None
Solid-organ transplantation continues to grow as a treatment modality. Transfusion support remains an integral part of solid-organ transplantation, imparting demands on the transfusion service not only quantitatively in terms of blood product support, but also due to the unique requirements for specialized blood components, the complex serologic problems, and the immunologic effects of transfusion on both the allograft and the recipient.
Keywords: Liver transplantation, Blood products, Transfusion.
|How to cite this article:|
Murthy T. Transfusion support in liver transplantation. Indian J Anaesth 2007;51:13-9
| Introduction|| |
Liver transplant procedures require the most blood components despite the fact that blood use in liver transplantation has declined dramatically over the last decade. Liver transplantation since its introduction by Strazl way back in 1967, has over the period of time emerged as a successful treatment for patients with end-stage liver disease (ESLD). The surgical procedure requires precise skill and expertise and is time consuming. The liver being an highly vascular organ extensive bleeding should be anticipated especially so in patients with portal hypertension due to ESLD.  However over the years it is seen in the reduction of blood product transfusion during liver transplantation  and also in the requirements of transfusion between cadaveric and living donation in relation to Model of End stage liver Disease score (MELD) and baseline coagulation status. 
Intraoperative blood losses and transfusion requirements during adult transplantation remain difficult to predict and several studies have shown no firm conclusion in this regard. 
Liver transplantation is associated with considerable blood product requirement, yet bloodless transplantation has been achieved in Jehovah's Witness patients.  Liver transplantation has been traditionally managed not only, with large autologous transfusions of blood, blood components and blood products, but with other drugs that assisted in restoring balance to metabolic and coagulation abnormalities. In view of the significant problems associated with multiple or massive transfusion therapy alternative therapies are being tried upon. ,, Transfusion-related complications include infection, transfusion reaction, drug overdose, graft rejection or graft death, and patient death.
Studies have observed that increased blood requirements are associated with a higher incidence of sepsis, a prolonged stay in the intensive care unit, a higher rate of severe cytomegalovirus infection, and higher rates of graft failure and patient mortality.  However, whether these differences in outcome are related to the transfusion as an independent risk factor or whether the transfusion is a marker for a technically more difficult surgery remains unclear.
Many factors have contributed to improvements in the mortality rates since the introduction of liver transplantation, which included improved operative techniques, experience, improved preoperative and postoperative care. Specific advances, including autologous transfusion with cell saver-washed erythrocytes, venovenous bypass, and argon-beam coagulation, have contributed to liver transplantation success.  The factors responsible can be classified into the events that occur in the Pre, Intra and Post operative periods. 
| (A) Preoperative period|| |
These are basically related to the underlying disease process - liver failure, cirrhosis, cholestasis, coagulopathies associated and splenomegaly. Failure to synthesize factors II,VII, IX and X results in coagulopathy identified by prolonged Prothrombin time and activated thromboplastin time.  Decreased synthesis of Vit K associated with cholestasis caused abnormal bleeding not correctable with Vit K.  Thrombocytopenia is an invariable accompaniment in cirrhotics the cause of which is multifactorial. The liver is the primary site of thrombopoietin synthesis, and thrombopoietin deficiency due to cirrhosis leads to low platelet production. In addition to the decreased formation of platelets, splenomegaly caused by portal hypertension leads to platelet sequestration and destruction. Thrombocytopenia is sometimes reversed in patients who undergo OLT, although occasional patients have severe, persistent thrombocytopenia after OLT and require splenectomy. , Low levels of coagulation factors and qualitative platelet abnormalities in this subset of patients may exhibit fibrinolytic activity and disseminated coagulation.
| (B) Intraoperative Period|| |
The events in the intraoperative period can be broadly categorized into stage I - the preanhepatic phase - which begins with the dissection of the vascular structures till the removal of the diseased liver. The stage II starts with the implantation of the donor liver till the time reperfusion is started and stage III from the time of reperfusion till the completion of the surgery.
Bleeding during stage I is primarily due to the surgery over the collateral vessels which develop as a result of portal hypertension and from the raw surface of the liver. This can get compounded by the preexisting coagulopathy.  Aggressive correction of the (International Normalized Ratio) INR and platelet must be undertaken so as to avoid any bleeding catastrophe intraoperatively and it is prudent to remember that degrading factors of V and VIII add to the complexity of the issue.  Once the healthy functional graft takes over it restores the clotting function. In few patients however there may be temporary nonfunction before the graft improves and recovers.  In cases with severe rejection the graft remains nonfunctional and requires to be retransplanted. Coagulation should be monitored by studying the PT, INR and the Platelet Counts. The thromboelastogram is a useful to monitor and identify the responsible factor causative of this bleeding and can be corrected appropriately. 
Bleeding in the anhepatic or post anhepatic phase is basically following fibrinolysis due to diminished tissue plasminogen activator (t-PA) uptake and decrease in the alpha - 2 antiplasmin. The bleeding in this phase may also be due to disseminated intravascular coagulation and trapping of platelet, which can be identified by simultaneous measuring of arterial and venous platelet counts. Disseminated intravascular coagulation has been correlated with ischemic damage of the graft liver. Other potential causes of bleeding after reperfusion include the release of heparin like factors from the allograft, release of preservative solution into the systemic circulation, and dysfunction of the graft. 
| (C) Postoperative Period|| |
Postoperative bleeding is usually due to a technical failure such as leaks form suture lines and anastomotic sites. Coagulopathy following a graft failure could be an important cause in this phase, and requires to be investigated and managed. Graft versus host disease (GVHD) is usually seen in the first four to six weeks period following transplant, which can manifest as haemolysis and requires ruling out and managing it with transfusion of donor specific RBC. Thrombocytopenia following liver transplantation causes bleeding, and this is associated with platelet consumption, platelet-associated immunoglobulin M and immunoglobulin A (IgA) antibody production, sequestration, and thrombin generation. Other causes of thrombocytopenia include viral infection, cytomegalovirus-induced hematophagic histiocytosis, treatment with antiviral therapy, and ABO-incompatible GVHD. ,
| Transfusion predictors|| |
The most reliable variables affecting transfusion requirements include the severity of disease or Child classification, preoperative PT, history of abdominal operations, and factor V levels. Other include the preoperative haematocrit value, use of the piggyback transplantation method, and operative time. 
The Child classification is a measure of disease severity that includes assessments of ascites, encephalopathy, and muscle wasting and measurements of serum bilirubin and albumin. Portal vein hypoplasia and decreased donor liver size were predictive of blood loss as its presence is a technical challenge for the surgeons and a correlate of coexisting congenital abnormalities (eg, polysplenia syndrome). 1 Use of a partial liver graft, as in living-donor liver transplantation, creates a graft with a raw surface that can bleed after reperfusion. Because of the great variability of transfusion requirements, the preoperative factors were not helpful in predicting large-volume loss and large transfusion requirements; however, large transfusion requirements were predictive of outcome. 
Established and innovative surgical techniques to minimize blood loss include the use of venovenous bypass, autologous blood transfusion, volume expansion, and a cell saver.
There are many technical details to which surgeons can attend in order to minimize blood loss during OLT. The use of split or reduced-size liver grafts results in the successful transplantation of partial adult livers into infants, and, at times, expands the number of recipients who can receive cadaveric grafts. The experience of the surgical team impacts blood loss, transfusion requirements, and the morbidity of patients undergoing liver transplantation. Additionally, modifications in surgical technique, including the use of cautery, and medical therapy have reduced morbidity. 
OLT involves the explantation of the native liver and replacement with the donor liver. This requires either the use of bypass or clamping of the inferior vena cava and portal vein. A variation of this technique is called piggyback transplantation, whereby the inferior vena cava is preserved and venovenous bypass can be avoided. Porto systemic shunting has been used in patients with liver failure in order to decrease preoperative complications associated with portal hypertension (eg, bleeding varices, ascites, sepsis). Traditionally, surgery was the only option to create a shunt, but a transhepatic intraoperative portosystemic shunt is now available. This procedure is designed to decompress the portal system in order to decrease the risk of variceal rebleeding and minimize ascites. 
Central venous pressure (CVP) monitoring is an important aspect of OLT. Patients frequently undergo volume expansion prior to hepatic resection to prevent bleeding complications, but expansion increases CVP. Deliberate lowering of the CVP during liver resection assists in bleeding control by decreasing the blood pressure gradient over which bleeding occurs during dissection. ,
A study investigated recombinant factor VIIa (rFVIIa) during OLT. Significant decreases in transfused red cells, fresh frozen plasma (FFP), and platelets were noted in subjects who received the rFVIIa treatment. The results of this study indicate that rFVIIa may be an innovative therapy, but further investigation is required to confirm this for routine use. 
Autologous blood transfusion can be performed during many surgical procedures to reduce the risks associated with heterologous transfusion. In patients with advanced cirrhosis, the RBC mass may be adequate to use for the replacement of RBCs, but platelets and clotting factor levels are usually so low that avoidance of FFP and platelet transfusion may not be possible.
| Drugs that minimize blood loss|| |
Increased fibrinolytic activity is observed in some patients with ESLD. The mechanisms include increased t-PA activity and reduced synthesis of fibrinolysis inhibitors. In addition, enhanced fibrinolysis is noted in the anhepatic phase of OLT. This may result from a lack of t-PA activity clearance. A subgroup of patients develops a further increase of t-PA activity after reperfusion. The resulting fibrinolysis is one of the chief causes of excessive bleeding during OLT. Various antifibrinolytic agents have been used to counter this accelerated fibrinolysis in the second and third phases of OLT. These include aprotinin, epsilon amino caproic acid (epsilon-ACA), and tranexamic acid. ,,
| Aprotinin|| |
Aprotinin is a serine protease inhibitor that prevents the lysis of fibrinogen by inhibiting plasmin, kallikrein, and leukocyte elastase, which are 3 proteases involved in fibrinolysis. This serves to decrease platelet aggregation and increase both the aPTT and activated clotting time. 
A large dose of aprotinin, ie, 2 million kallikrein inhibitor units (KIU), is usually administered as the initial dose and additional smaller doses of 500,000 KIU/h were administered during surgery.  The precise role of aprotinin remains undefined.
| Epsilon-aminocaproic acid|| |
Epsilon-ACA has been used intraoperatively to inhibit fibrinolysis. It was found to be effective for decreasing blood requirements in some studies but not in others. 
| Tranexamic acid|| |
Tranexamic acid is another synthetic drug that inhibits fibrinolysis. Both high-and low-dose tranexamic acid has significantly reduced the use of intraoperative red cells in several studies. Tranexamic acid also decreases transfusion requirements in some but not all studies. In a double-blinded, randomized, controlled study, high-dose (20 g) tranexamic acid significantly reduced intraoperative blood loss and transfusion requirements for 45 consecutive liver transplantation subjects. Smaller doses were shown to reduce fibrinolysis without affecting transfusion requirements. Mechanisms of action are hypothesized to include decreased platelet aggregation inhibition and inhibition of plasmininduced platelet dysfunction. 
| Others|| |
(a) Clonidine- a centrally acting alpha 2-adrenergic receptor agonist, significantly decreased transfusion and fluid requirements in a small prospective, randomized controlled trial. It was hypothesized that excessive sympathetic stimulation occurred in patients with cirrhosis because of a spillover of excess epinephrine and norepinephrine. Clonidine acted to decrease sympathetic activity on the splanchnic circulation and, thus, decreased flow and pressure in the portal circulation. 
(b) Conjugated estrogen- administered just prior to surgery and just after graft reperfusion has been shown to decrease blood loss and transfusion requirements. Hypothesized mechanisms of action include an increased platelet count secondary to an increase in thromboxane B2 and beta-thromboglobulin. Because actual mechanisms, halflife, optimal dosing, and morbid effects are not well understood, estrogen is not in mainstream use, nor is it the standard of care. 
(c ) Factor VIIa : Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve haemostasis in a variety of disorders , however there has been a limited amount of research into its use in OLT. It has a role to facilitate liver transplantation in a Jehovah's Witness. 
| Transplantation without transfusion|| |
The literature includes cases of OLT performed without transfusion of any blood products and OLT performed safely without additional blood products if blood loss is limited to about less than 3 liters, and institution of the various techniques for intraoperative blood salvage and sparing as discussed. Liver transplantation may be challenging in terms of bleeding and transfusion requirements in - IgA-deficient patients, hemophiliac patients, alloimmunized patients, children, and obese recipients. 
| Pediatric patients|| |
Children undergo OLT for biliary cirrhosis secondary to congenital or acquired neonatal biliary atresia. Pediatric liver recipients are frequently poorly matched for size with the donor liver because of a lack of availability. In this circumstance, graft reduction is necessary, although this technique often contributes to increased blood loss from the raw liver surface after reperfusion. 
| Obese patients|| |
Obese patients undergoing OLT who have a body mass index greater than 30 kg/m 2 may experience higher intraoperative and postoperative complications, including infection. 
| Transfusion-related infection|| |
Many infectious complications arise from the transfusion of blood; these complications make matters worse for the critical condition of liver transplantation patients. Well-described infectious complications include hepatitis, HIV infection, and cytomegalovirus infection. More rare transmissions, which are described herein, include endotoxin effects and malaria transmission.
In addition, latently infected patients may experience a resurgence of infection because of immunosuppression.
| Transfusion reactions|| |
Transfusion reactions are well described in the literature, such as acute intravascular immune hemolytic reactions from ABO incompatibility, delayed immune hemolytic reactions, and febrile reactions. Febrile reactions, believed to be cytokine-mediated, are also similar to transfusion-related lung injury, which can manifest as adult respiratory distress syndrome. 
| Metabolic derangements|| |
Metabolic complications associated with blood transfusion during OLT include benzodiazepine-associated encephalopathy, metabolic alkalosis, hypercalcemia, and hypomagnesaemia. 
Metabolic alkalosis is reported in patients who received large-volume transfusions. The alkalosis is not by sodium bicarbonate administration during the anhepatic phase, but it correlated with a rise in serum citrate levels. 
Blood is treated with citrate to bind ionized calcium (Ca 2 +) and prevent its action as a cofactor in the coagulation cascade. Massive infusion of citrated blood products may cause hypocalcaemia and hypomagnesaemia, particularly in patients with poor hepatic function, neonates, and patients with hypothermia. During OLT, patients are at increased risk of citrate toxicity and subsequent hypocalcemia because aconitase, a citrate-metabolizing enzyme, is not produced. Hypocalcemia is treated with intraoperative calcium as needed to prevent ventricular hypocontractility and decrease peripheral vascular resistance.
Citrate can cause important hypomagnesaemia can result in loss of electrolyte pump control and intracellular hypercalcemia. These complications could result in dysarrhythmias and end in a fatality. 
| Cost Effectiveness|| |
Liver transplantation is a very expensive undertaking, of which blood products may represent a variable portion. The analysis concludes that when larger volumes of blood loss are encountered, cell-saver use is economical.  A recent study concluded that intraoperative red blood cell salvage and autologous transfusion is cost-effective in adult liver transplantation, especially where optimum resource utilization and financial constraints are key issues in health care. 
| Transfusion alternatives|| |
While minimizing transfusion requirements is the goal of any good surgeon, many situations necessitate blood products. In these instances, planning for anticipated needs can minimize transfusion-associated complications. These include the following:
| Plasma|| |
Coagulopathy remains a serious complication of liver disease and transplantation. FFP is used to correct deficiencies in plasma coagulation factors, but it carries a risk of viral transmission. When FFP is needed, it can be treated with solvent-detergent to inactivate viral particles. Treated plasma has lower factor VIII and alpha-2 antiplasmin activity, but patients who receive treated FFP demonstrate a similar correction of the international normalized ratio, aPTT, and transfusion requirements compared with patients who receive untreated FFP. Patients who receive treated FFP also have a decreased risk of viral infection.
| Erythropoietin|| |
Erythropoietin is a safe and effective drug for acute blood-loss anemia, although it requires time to work. It can be used preoperatively in patients who are scheduled to undergo surgery, and it can be used postoperatively to stimulate bone marrow stem cells to produce erythrocytes more quickly. Used in conjunction with intravenous iron, erythropoietin can effectively enhance erythropoiesis. 
Erythropoietin also was used in a Jehovah's Witness patient who underwent OLT for biliary cirrhosis. Preoperative total hemoglobin levels increased from 11.1 mg/dL to 14 mg/dL within 5 weeks of erythropoietin treatment (2000 IU/d for 5 or 7 d). In lieu of PRBC transfusion, the patient was treated with meticulous haemostasis, argon-beam coagulation, continuous auto transfusion of salvaged blood, tranexamic acid, and transfusion of both platelets and cryoprecipitate.
| Strategies for selection of compatible components|| |
For solid-organ transplant procedures other than liver, transfusion requirements are generally not sufficient to require deviation from traditional selection criteria of ABO identical/compatible red cells. However, in liver transplantation, transfusions frequently exceed the available supply of ABO identical red cells, antigen-negative red cells, or compatible plasma, and thus require blood bank blood group switching protocols to optimally use available blood resources. 
| Patients with clinically significant alloantibodies|| |
Pre-existing potentially clinically significant red cell alloantibodies are found in approx 6% of liver transplant candidates. In order to minimize the risk of hemolysis, these patients are ideally managed by using antigen-negative units for the first 5-10 units, switching to antigen-unscreened units in the middle of the case, and then switching back to antigen-negative units for the last 5-10 U transfused. This strategy requires close communication between the anesthesiologist and blood bank.
| Indications for specialized blood components|| |
CMV-Negative/Safe Blood Components : CMV infection is the most frequent infectious complication following solid organ transplantation. In seropositive solid organ recipients, reactivation of latent virus represents the major risk for CMV infection. Thus, there is no documented benefit to providing blood CMV neg/safe components to patients who are CMV seropositive. In seronegative patients, the major source for primary CMV infection is the seropositive transplanted organ and, to a lesser extent, transfused blood components.
Irradiated Blood Components : Graft vs host disease (GVHD) is a rare complication of organ transplantation reported most frequently in liver recipients and is almost always due to the donor organ. These few cases do not support a policy of routine irradiation of cellular blood components for organ transplant recipients. 
Leukocyte-Reduced Blood Components: Alloimmunization to HLA antigens is of considerable importance in organ transplantation However; liver allograft survival is not adversely impacted by HLA alloimmunization. The beneficial immunomodulatory effect of non-leukoreduced transfusions on allograft survival has only been demonstrated for renal transplant recipients. This effect is only apparent when the blood donor shares an HLA haplotype with the recipient. The magnitude of the effect has become less apparent with currently available immuno-suppressive drugs, and thus transfusions are not routinely used for this indication. 
| Abo blood group system in organ transplantation|| |
The ABO system is clinically important in two aspects of solid-organ transplantation: first, as a transplantation antigen that influences graft survival, and second as an antigen-antibody system implicated in immune hemolytic anemias in ABO non-identical organ transplant recipients.
ABO System as a Transplantation Antigen : Liver allografts are felt to be resistant to hyperacute rejection when transplanted across ABO barriers although reports of hyperacute rejection do exist. ABO-incompatible liver transplants are commonly associated with acute graft failure with a 46% graft failure rate reported within 30 days of the transplant. Plasmapheresis to remove recipient isohemagglutinins and/or splenectomy may be of benefit. Currently, ABO-incompatible liver allografts are reserved for patients with fulminant liver failure in whom death is imminent without transplantation and when an ABOcompatible organ is not available. ABO compatible but nonidentical (minor mismatch) liver transplants are associated with modest reductions in 1- and 3-yr survival.
Immunohematologiccomplications : Passenger lymphocytes transplanted with the donor organ are capable of producing ABO antibodies and hemolysis in ABO mismatched organ recipients. A positive Coombs test +/hemolysis is typically observed 7-10 days after transplantation. Blood Bank protocols for optimal component selection are required to minimize hemolysis.
| Autotransfusion|| |
Use of the cell-saver device is a safe and effective method of salvaging RBCs during OLT. Autotransfusion decreases some of the complications of homologous transfusions, including citrated products, infection transmission, metabolic derangements, benzodiazepine toxicity, and coagulopathy. Additionally, autotransfusion conserves blood bank resources and reduces overall costs. Autotransfusion for living-donor liver transplantation has also been successful in preventing heterologous transfusion. Its use also has been described in a Jehovah's Witness patient undergoing OLT; a continuous circuit was established and maintained.
| Conclusion|| |
OLT, hepatic resection, and living-donor liver transplantation are operations associated with large losses of blood volume. Historically, patient support has required large volumes of transfused red cells, platelets, FFP, and cryoprecipitate and the administration of albumin and crystalloid. Transfusion is associated with many risks and complications, and efforts to minimize blood loss and transfusion volume have been described. Technological advances, drug therapy, and transfusion alternatives have contributed to an overall increase in survival and a decreased in morbidity and transfusion requirements during OLT.
| References|| |
|1.||Julie Maurer, Richard K Spence. Transfusion requirements in Liver transplantation, e-Medicine specialities, Transplantation; Sept 2004. |
|2.||Massicotte et al. Reduction of blood product transfusions during liver transplantation, Can J Anaesth 2005; 52:545-46. |
|3.||Frasco et al. A Comparison of Transfusion Requirements Between Living Donation and Cadaveric Donation Liver Transplantation: Relationship to Model of End-Stage Liver Disease Score and Baseline Coagulation Status, Anesth Analg 2005; 101: 30-37. |
|4.||Massicotte et al. Transfusion Predictors in Liver Transplant, Anesth Analg 2004; 98: 1245-51. |
|5.||Jabbour et al. Liver Transplantation Without Blood Products: Strategies Developed for Jehovah's Witnesses Offer Broad Application. Annals of Surgery 2004; 240(2): 350-57. |
|6.||Belghiti J, Noun R, Malafosse R et al. Continuous versus intermittent portal triad clamping for liver resection: a controlled study. Ann Surg 1999; 229(3): 369-75. |
|7.||Chen CL, Chen YS, de Villa VH et al. Minimal blood loss living donor hepatectomy. Transplantation 2000; 69(12):2580-86. |
|8.||Davidson BR, Burnett S, Javed MS et al. Experimental study of a novel fibrin sealant for achieving haemostasis following partial hepatectomy. Br J Surg 2000; 87(6): 790-95. |
|9.||Palomo Sanchez JC, Jimenez C, Moreno Gonzalez E et al. Effects of intraoperative blood transfusion on postoperative complications and survival after orthotopic liver transplantation. Hepatogastroenterology 1998; 45(22): 1026-33. |
|10.||Chen H, Merchant NB, Didolkar MS. Hepatic resection using intermittent vascular inflow occlusion and low central venous pressure anesthesia improves morbidity and mortality. J Gastrointest Surg 2000; 4(2): 162-67. |
|11.||Gerlach H, Gosse F, Rossaint R et al. [The relevance of perioperative coagulation parameters to indications for blood transfusion. A retrospective analysis of 300 liver transplantations]. Anaesthesist 1994; 43(3): 168-77. |
|12.||Deakin M, Gunson BK, Dunn JA et al. Factors influencing blood transfusion during adult liver transplantation. Ann R Coll Surg Engl 1993; 75(5): 339-44. |
|13.||Candinas D, Decurtins M, Kunz M et al. [Thrombopenia after liver transplantation]. Helv Chir Acta 1993; 59(4): 617-21. |
|14.||Cheema SP, Webster NR, Dunn F, Bellamy MC: Mediators of fibrinolysis in orthotopic liver transplantation. Clin Transplant 1996; 10(1 Pt 1): 24-27. |
|15.||Freeman JW, Williamson LM, Llewelyn C et al. A randomized trial of solvent/detergent and standard fresh frozen plasma in the treatment of the coagulopathy seen during Orthotopic Liver Transplantation. Vox Sang 1998; 74 Suppl 1: 225-29. |
|16.||Federici AB, Mannucci PM, Stabile F et al. Orthotopic liver transplantation in a patient with severe hemophilia A: a lifesaving treatment for the first Italian case. Int J Clin Lab Res 1995; 25(1): 44-46 |
|17.||Goulis J, Chau TN, Jordan S et al. Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation. Gut 1999; 44(5): 754-58. |
|18.||Farid H, O'Connell T. Hepatic resections: changing mortality and morbidity. Am Surg 1994; 60(10): 748-52. |
|19.||Busque S, Esquivel CO, Concepcion W, So SK. Experience with the piggyback technique without caval occlusion in adult orthotopic liver transplantation. Transplantation 1998; 65(1): 77-82. |
|20.||Motschman TL, Taswell HF, Brecher ME et al. Intraoperative blood loss and patient and graft survival in orthotopic liver transplantation: their relationship to clinical and laboratory data. Mayo Clin Proc 1989; 64(3): 346-55. |
|21.||Stieber AC. One surgeon's experience with the piggyback versus the standard technique in orthotopic liver transplantation: is one better than the other? Hepatogastroenterology 1995; 42(4): 403-05. |
|22.||Inomata Y, Uemoto S, Asonuma K, Egawa H. Right lobe graft in living donor liver transplantation. Transplantation 2000; 69(2): 258-64. |
|23.||Hendriks HG, Meijer K, de Wolf JT et al: Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation: a pilot study. Transplantation 2001; 71(3): 402-05 |
|24.||Kaspar M, Ramsay MA, Nguyen AT et al. Continuous smalldose tranexamic acid reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation. Anesth Analg 1997; 85(2): 281-85. |
|25.||Llamas P, Cabrera R, Gomez-Arnau J, Fernandez MN: Hemostasis and blood requirements in orthotopic liver transplantation with and without high-dose aprotinin. Haematologica 1998; 83(4): 338-46. |
|26.||Marcel RJ, Stegall WC, Suit CT et al. Continuous small-dose aprotinin controls fibrinolysis during orthotopic liver transplantation. Anesth Analg 1996; 82(6): 1122-25. |
|27.||Dalmau A, Sabate A, Acosta F et al. Tranexamic acid reduces red cell transfusion better than epsilon- aminocaproic acid or placebo in liver transplantation. Anesth Analg 2000; 91(1): 29-34. |
|28.||De Kock M, Laterre PF, Van Obbergh L et al. The effects of intraoperative intravenous clonidine on fluid requirements, hemodynamic variables, and support during liver transplantation: a prospective, randomized study. Anesth Analg 1998; 86(3): 468-76. |
|29.||Frenette L, Cox J, McArdle P et al. Conjugated estrogen reduces transfusion and coagulation factor requirements in orthotopic liver transplantation. Anesth Analg 1998; 86(6): 1183-86. |
|30.||Snook NJ, O'Beirne HA, Enright S et al. Use of recombinant human erythropoietin to facilitate liver transplantation in a Jehovah's Witness. Br J Anaesth 1996; 76(5): 740-43. |
|31.||Ramos HC, Todo S, Kang Y et al. Liver transplantation without the use of blood products. Arch Surg 1994; 129(5): 528-32; discussion 532-33. |
|32.||Ozier YM, Le Cam B, Chatellier G et al. Intraoperative blood loss in pediatric liver transplantation: analysis of preoperative risk factors. Anesth Analg 1995; 81(6): 1142-47. |
|33.||Nair S, Cohen DB, Cohen MP et al. Postoperative morbidity, mortality, costs, and long-term survival in severely obese patients undergoing orthotopic liver transplantation. Am J Gastroenterol 2001; 96(3): 842-45. |
|34.||Miyata T, Yokoyama I, Todo S et al. Endotoxaemia, pulmonary complications, and thrombocytopenia in liver transplantation. Lancet 1989; 2(8656): 189-91. |
|35.||Driscoll DF, Bistrian BR, Jenkins RL et al. Development of metabolic alkalosis after massive transfusion during orthotopic liver transplantation. Crit Care Med 1987; 15(10): 905-08. |
|36.||Bartosh SM, Sprague SM, Nakagawa Y et al. Severe hypercalcemia following neonatal liver transplantation. Miner Electrolyte Metab 1995; 21(6): 428-30. |
|37.||Robson SC, Kahn D, Gordon P, Jacobs P. A cost-to-benefit analysis of blood products used during the initiation of an orthotopic liver transplantation programme. S Afr J Surg 1995; 33(4): 154-58. |
|38.||Simon D, Philips et al. A prospective study investigating the cost effectiveness of intraoperative blood salvage during liver transplantation. Transplantation 2006; 81: 536-40. |
|39.||Darrell J Triulzi. Tansfusion support in solid organ transplant. Transfusion 2001; 41: 419-26. |