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April, 2001

Transfusion Support in Solid-Organ Transplantation

Darrell J. Triulzi, M.D.

                                                                                                           

INTRODUCTION

Solid-organ transplantation continues to grow as a treatment modality. Currently more than 74,000 patients are waiting for an organ transplant. However in 1999 only 21,990 transplants were performed, limited primarily by the availability of organs. 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.

BLOOD COMPONENT UTILIZATION

The typical requirements for blood components for each type of organ transplant in adults are shown in Table 1.  Liver transplant procedures require the most blood components despite the fact that blood use in liver transplantation has declined dramatically over the last decade.  The multiple factors contributing to the reduction in blood usage include: improved surgical technique, organ preservation, and anesthetic management, as well as better intraoperative monitoring of coagulation status and pharmacologic treatment of fibrinolysis. Heart transplantation is associated with lower blood requirements that approximate blood usage observed in complex cardiopulmonary bypass procedures.  Blood usage in lung transplantation varies by the type of lung transplant procedure. More than 2/3 of single-lung transplant recipients do not require any transfusions.  Double-lung transplant procedures typically require more red cells than heart transplant procedures.  The majority of patients receiving kidney transplants do not require blood.

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.  Usually at least 8-10 units of antigen compatible blood can be found for surgery.  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 (Table 2)

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. Published data indicate that although the overall rate of CMV transmission by transfusion is low (5-15%), the morbidity associated with this complication would support the use of methods to prevent CMV transmission from blood components.  Historically, this was accomplished by using blood components from donors who lack antibodies to CMV. Published data suggest that leukocyte reduction by filtration is equally effective in reducing the risk of CMV transmission from blood.1 It appears that this method would also be effective in solid-organ transplant recipients.2

Irradiated Blood Components
Graft vs host disease (GVHD) is a rare complication of organ transplantation (59 cases) reported most frequently in liver recipients and is almost always due to the donor organ. Transfusion associated GVHD is very rare in solid organ transplant recipients with only 4 published cases. Only two of these had convincing supportive evidence, and one of these had an under-lying hematologic abnormality.  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.  A sensitized patient presents problems in identifying a crossmatch-compatible donor and, for some organs, the outcome of transplantation is inferior.  However, white cells in blood components may be beneficial in inducing tolerance and prolonging allograft survival.  Thus, the decision to provide leukocyte-reduced components must weigh the risks and benefits of these opposing effects.  HLA alloimmunization has clearly been shown to be associated with decreased graft survival in renal transplantation and more recently in heart and/or lung transplantation.  However, liver allograft survival is not adversely impacted by HLA alloimmunization. Thus, leukoreduction to prevent alloimmunization provides benefit to kidney, heart, and lung recipients.  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
Transplantation across ABO lines will typically cause hyperacute rejection of kidney and heart transplants, although exceptions do exist.  Successful transplantation of kidneys and hearts across ABO lines has been accomplished by removing ABO antibodies in the recipient or by taking advantage of the variable expression of ABO antigens such as in A2 individuals or neonates.  In general, ABO-incompatible organs are avoided in kidney and heart transplantation. ABO major mismatch liver allografts are used in 6.9% of pediatric and 2.4% of adult liver recipients due to organ shortages.  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 ABO-compatible organ is not available.  ABO compatible but non-identical (minor mismatch) liver transplants are associated with modest reductions in 1- and 3-yr survival.

Immunohematologic complications
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.
 

REFERENCES

1.        Bowden RA, et al. Blood 1995; 86:3598-3603.

2.        Lopez-plaza I, et al. Transfusion 1999;39:S385.

3.       Triulzi DJ et al. Transfusion 2001;41:419-26.

                                                                                                          

Table 1
Median Blood Use (Units) in Organ Transplantation
Organ Red cells Plasma Platelets
Liver (n=118)    12  13  10
Heart (n=51) 4 5   10
Lung
  Single (n=46) 0-2 - -
  Double (n=30) 7 2 8
Kidney 0-2  - -

                                                                  

Table 2
Recommendations for use of specialized blood components in CMV seronegative solid-organ transplant recipients
Type  CMV neg/safe Filtered Irradiated
Kidney Yes* Yes  No
Heart Yes* Yes  No
Lung Yes* Yes No
Liver Yes* No No
*CMV-negative pairs only.  Components rendered CMV-safe by filtration are a reasonable substitute.

                                          

Copyright 2001, The Institute For Transfusion Medicine

                                                                                                             


For questions or further information regarding Transfusion Support in Solid Organ Transplantation, please contact Darrell J. Triulzi at The Institute For Transfusion Medicine: 412-209-7304

Copies of previous Transfusion Medicine Update issues can be obtained from our web page: www.itxm.org.  To be placed on our mailing list for a hard copy, please contact Deborah Small by e-mail: dsmall@itxm.org or by phone: (412) 209-7320.