Blood Component and Blood Product Provision during Solid Organ Transplantation - Guideline for

Publication: 14/04/2014  --
Last review: 10/04/2019  
Next review: 04/04/2022  
Clinical Guideline
CURRENT 
ID: 3834 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2019  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for Blood Component and Blood Product Provision during Solid Organ Transplantation

  1. Introduction
  2. Graft Rejection in Incompatible Transplants
  3. Haemolytic Reactions
  4. Rationale
  5. ABO Incompatibility 
    5.1 Major ABO Incompatibility
    5.2 Minor ABO Incompatibility
    5.3 Bidirectional ABO Incompatibility
    5.4 Red Blood Cell
    5.5 Components
    5.6 Management
  6. Rhesus D (RhD) Incompatibility
    6.1 Major RhD incompatibility exists where a donor is RhD positive and the recipient is RhD negative
    6.2 Minor Rhesus D incompatibility exists where a donor is RhD negative and the recipient is positive
    6.3 Choice of Rhesus Blood Groups for Transfusion
    6.4 Rhesus Prophylaxis
  7. Other RBC blood group systems
  8. Special Products

Summary of Guideline

A key factor in organ selection for solid organ transplantation is ABO compatibility between the donor and the recipient. Currently the number of patients on the transplant waiting list exceeds the number of available organs.  Due to this, selection of ABO incompatible organs are being more readily used for extremely ill patients but this in itself carries risks which must be closely monitored and managedThese risks include graft rejection and haemolytic complications. This guideline describes the diagnostic tests required to determine if a transplant is under threat of rejection due to haemolytic complications.  This guideline also details scenarios of differing patient and graft blood groups and the recommended transfusion support in each case.

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Background

The ABO histo-blood grouping system belongs to the minor HLA antigens and is the most important transplantation Antigen system in solid organ transplantation1.  ABO blood group antigens are expressed on the red blood cells, cells of solid tissues and on platelets and lymphocytes2.  Pre-existing antibodies in the recipient patient against the ABO antigens of the donor organ have the potential to induce graft rejection.  Ten years ago ABO incompatibility was an absolute barrier for the majority of solid organ transplants.  However recent advances in immunosuppressive treatments and available techniques to reduce anti-A and anti-B alloantibodies in recipient’s serum both pre and post-transplant1allow transplants across the ABO groups.

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Treatment / Management

1. Introduction

Current practice in transplantation is to match the donor and the recipient by their ABO blood group compatibility.  However due to the increase in the number of patients on the organ transplant wait list exceeding the number of available organs the ability to safely use ABO incompatible organs is becoming more common practice1.  The provision of the correct blood components and products play a key role in ensuring that ABO incompatible solid organ transplants are successful.  However there are still associated risks.

The ABO histo-blood grouping system belongs to the minor HLA antigens and is the most important transplantation Antigen system in solid organ transplantation1.  ABO blood group antigens are expressed on the red blood cells, cells of solid tissues and on platelets and lymphocytes2.  Pre-existing antibodies in the recipient against the ABO antigens of the donor organ have the potential to induce graft rejection.  Over ten years ago ABO incompatibility was an absolute barrier for the majority of solid organ transplants.  However recent advances in immunosuppressive treatments and available techniques to reduce anti-A and anti-B alloantibodies in the recipient’s serum both pre and post-transplant1 allow ABO incompatible transplants. 

Therefore, these transplants are high risk for:

  • Graft rejection
  • Haemolytic complications.

2. Graft Rejection in Incompatible Transplants

Anti-A and Anti-B antibodies directed against the ABO antigens of the donor graft may cause hyper acute, acute and chronic rejection.   The preformed recipient antibodies are responsible for hyper acute and acute rejection whereas the persistence of Anti-A and Anti-B antibodies and the production of new antibodies are responsible for chronic graft rejection.  Currently immunosuppressive drugs 11 can be administered to effectively reduce the formation of antibodies while plasmapheresis or immunoadsorption pre and post-transplant may be useful to reduce the recipient’s titres.

Studies suggest that other Red Blood Cell (RBC) antigenic groups including Duffy and Kidd3,4 may represent minor histocompatibility antigens therefore antibodies against these systems may shorten the life span of the graft and  result in graft rejection.

3. Haemolytic Reactions

The majority of haemolytic reactions post ABO incompatible transplants are due to “Passenger Lymphocyte Syndrome” (PLS).  PLS is due to the production of antibodies by the donor B lymphocytes, donor derived antibodies (DDAb) 12.  PLS is a primary or secondary response against the recipient's RBC antigens5 and often is referred to as graft versus host reaction.

There are documented cases of PLS in solid organ transplants due to the presence of donor anti-A and anti-B lymphocytes5 and reported cases of PLS induced haemolysis involving  other RBC blood group systems including Rhesus13.

PLS can develop abruptly and can vary from minor to severe.  Severity is mediated by the quantity of transplanted lymphoid tissue, donor titres of isoagglutinins and a rapid rise in antibody titres in the recipient after transplantation.  Onset of PLS is usually 1-3 weeks post-transplant.  It is a self-limiting process which usually resolves 3 months after the transplant, but may continue for much longer (anecdotally over 2 years for an Rh(D) based one)16  since the lymphocytes transferred with the organ do not proliferate indefinitely and do not engraft15.  Patients are supported by RBC transfusions and rarely require RBC exchanges.  As yet it is unknown if the survival of the graft is affected by transfusion therapy.

4. Rationale

The purpose for this document is to provide guidance:

  • For clinical staff and Blood Bank Staff as to what RBC and blood components should be requested and issued throughout ABO Incompatible Solid Organ Transplant.
  • On any reactions that may be observed during the procedure thought to be caused by blood components or products.
  • On Transfusion Management in the event of haemolysis post transplantation.

5. ABO Incompatibility

Three different groups of ABO incompatibility can be distinguished in transplantation: major, minor and bidirectional ABO incompatibility (Table 1).

5.1 Major ABO Incompatibility

Definition:  the presence of anti-A, anti-B or anti-AB antibodies within the recipient’s plasma that is reactive with the donor’s red cell antigens on the graft/donated organ.

The associated risks of Major ABO Incompatibility include graft rejection and limited haemolysis of residual RBC’s in the graft.

5.2 Minor ABO Incompatibility

Definition:  the presence of anti-A, anti-B, or anti-AB antibodies in the donor plasma that are reactive with the recipient’s RBC antigens.

The associated risks of Minor ABO Incompatibility are haemolysis due to PLS.  PLS is most often observed in solid organ transplantation with a Minor ABO incompatibility.

5.3 Bidirectional ABO Incompatibility

Definition: The presence within both the donor and the recipient’s plasma of anti-A or anti-B antibodies which are reactive with recipient and donor red cell antigens respectively.

The associated risks are as for both major and minor incompatibility.

Table 1: Major, Minor and Bi-Directional ABO Incompatibility.

RECIPIENT Blood Group

DONOR Blood Group

MAJOR ABO INCOMPATIBLE

 

O

A

O

B

A

AB

B

AB

O

AB

MINOR ABO INCOMPATIBLE

 

A

O

B

O

AB

O

AB

A

AB

B

BI-DIRECTIONAL INCOMPATIBLE.

 

A

B

B

A

5.4 Red Blood Cell Transfusion

RBC components for transfusion must be ABO-identical or compatible with the recipient’s serum regardless of the organ donor’s blood group7 .

5.5 Blood Components (platelets, FFP, cryoprecipitate)

When the donor and the recipient are of different ABO blood groups, special attention must be given to the selection of plasma and platelet preparations.

Major ABO incompatibility
Platelets, FFP and cryoprecipitate should be compatible with the ABO group of the graft to reduce the risk of rejection (Table 2)

Minor ABO incompatibility
Platelets, FFP and cryoprecipitate should be ABO-compatible with both the recipient RBCs and the donor organ tissue cells to avoid transfusing any antibodies that may contribute to RBC haemolysis.  Although platelets exhibit low antigenic expression, substantial quantities of antibodies may be found in platelet preparations2.

It is essential that staff within the Blood Transfusion department are made aware of the blood group of the donor organ so that this information can be uploaded onto the Blood Bank IT system therefore any transfusion requirements 4 weeks 17 post transplantation can be managed accordingly.

5.6 Management

Anticipation of PLS is important.  Unfortunately, the titre of antibody within the donor organ is not reliable as a means of prediction of the occurrence of antibody or haemolysis post transplantation.

Anaemia induced by PLS is usually abrupt in onset and associated with a positive Direct Antiglobulin Test (DAT) as well as the presence of serum antibodies in addition to evidence of haemolysis13.  Haemolysis is usually apparent between days 3-24 post- transplant and the timing does not appear to be dependent on antibody specificity.  If the patient develops anaemia post- transplant a haemolysis screen should be requested in the investigation of anaemia.  A haemolysis screen includes tests for DAT and antibody screen (Transfusion Laboratory), Full Blood Count and Reticulocyte (Haematology), Lactate Dehydrogenase and Total Bilirubin (Biochemistry) and Haptoglobin (Immunology). Advice on sample collection can be accessed at www.pathology.leedsth.nhs.uk/Testandtubes

Haemolysis can generally be managed by transfusion of blood group O RBCs (Table 2), avoidance of ABO -incompatible plasma products (platelets, FFP, cryoprecipitate), and maintenance of adequate renal perfusion7.  In patients with more severe haemolysis, plasma exchange may be used to decrease the antibody titre.

Table 2:  Platelet, FFP and cryoprecipitate Selection for Recipients of ABO Mismatched Organs7.17

RECIPIENT Blood Group

DONOR Blood Group

Platelets:
recommended group

FFP/Cryoprecipitate:
recommended
group

MAJOR ABO INCOMPATIBLE

 

 

 

O

A

A

A,AB

O

B

B

B,AB

A

AB

AB

AB

B

AB

AB

AB

O

AB

AB

AB

MINOR ABO INCOMPATIBLE

 

 

 

A

O

A

A

B

O

B

B

AB

O

AB or A (HT Neg)

AB

AB

A

AB or A (HT Neg)

AB

AB

B

AB or B (HT Neg)

AB

BI-DIRECTIONAL INCOMPATIBLE.

 

 

 

A

B

B (HT Neg)

AB

B

A

A (HT Neg)

AB

 

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6. RhD Incompatibility

6.1 Major RhD incompatibility exists where a donor is RhD positive and the recipient is RhD negative.

In these circumstances the recipient may be at risk of developing alloantibodies against the RhD antigen post-transplant.  There is a paucity of data within the literature that highlights the incidence of immunisation of recipients of solid organ transplants against RBC antigens.    Studies suggest that long term immunosuppression may reduce the rate of alloimmunisation to RBCs antigens; however immunosuppression is less effective against secondary immune responses than primary immune responses.  In a review of 1000 liver transplants 6% formed antibodies against RBC antigens post-transplant, as the majority of these cases developed within 5 weeks it suggests a secondary immune response9

A primary immune response was detected in only 0.9% of the cases in the study with antibodies against the RBC antigens not being detected up to 6 months post-transplant.  Studies of liver, heart and lung transplants of RhD positive grafts to RhD negative patients showed a very low incidence of RhD immunisation13

It is unknown whether alloantibodies formed by the recipient post-transplant affect the graft survival.

6.2 Minor Rh D incompatibility exists where a donor is RhD negative and the recipient is positive.

The risk in these cases is the occurrence of delayed haemolysis due to donor lymphocyte derived anti-D. The risks are increased if the donor has been previously sensitised to the RhD antigen through pregnancy or transfusions.

6.3 Choice of Rh Blood Groups for Transfusion.

Major RhD incompatibility: RhD Negative Red Cells and Platelets must be given. 

Minor RhD incompatibility: Give RhD positive Red Cells and platelets post- transplantation.  However, if there are any indications of haemolysis due to donor lymphocyte syndrome then RhD negative blood and platelets should be given until haemolysis is no longer detected. 

6.4 Rh Prophylaxis and the use of anti-D injection.

Immunoprophylaxis using anti-D Immunoglobulin should be considered for female patients who are potentially child-bearing to prevent Haemolytic Disease of the Newborn (HDN) in the future.  HDN can be a severe condition causing profound anaemia in the foetus and occasionally severe morbidity and fatalities.

Anti-D immunoglobulin should be considered post solid organ transplant where:

  • Female recipient aged 0-50 years of childbearing age potential and
  • Donor grouped as RhD positive or RhD weak and
  • Recipient grouped RhD negative.
  • Graft expecting to contain residual RBC.

An initial dose of 500iu of Anti-D is recommended. Prior to administration of anti-D a sample should also be sent to the Red Cell Immunohaematology (RCI) laboratory for quantification of the volume of circulating RhD positive cells . Further anti D administration should be discussed with Transfusion Lab based on the RCI results.


Patients Informed Consent should be obtained and recorded in the patient’s case notes.  Anti-D must be ordered from the Blood Transfusion Laboratory using the request form found on the Hospital Transfusion Team website:
http://lthweb/sites/hospital-transfusion-team/how-to-order-blood-and-blood-products/Anti-D%20Order%20form%20Apr%2011.pdf

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7. Other RBC blood group systems

If a transplant recipient has other clinically significant red cell alloantibodies at the time of transplantation the donor should be phenotyped for the relevant blood group antigen.  If the recipient and the donor are incompatible methods should be used to reduce antibody titres similar to those for the reduction of anti-A and anti-B antibodies.

Advice should be taken from a red cell Immunohaemotology Consultant if the significance of an alloantibody is uncertain.

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8. Special Transfusion requirements

Hepatitis E Virus (HEV) Negative products-HEV may be acquired in the UK17 both through the diet and through receiving blood components, tissues and organs from viraemic donors.   The Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) has recommended that Solid Organ Transplant patients receive HEV negative screened blood and components.
Solid Organ Transplant patients should receive HEV negative blood and blood components 3 months prior to the elective transplant and remain on HEV negative blood and components for life.

Cytomegalovirus (CMV) Negative products- current guidelines state that children up to 6 months and pregnant women require CMV negative products.

Irradiated – If a transplant patient requires Irradiated components, this and the reason why must be communicated to the Transfusion Laboratory as early as possible so laboratory staff can update the blood bank records on the laboratory IT system to ensure the provision of correct components. For further information on who requires CMV negative and/or irradiated blood components see: the guidelines on the Hospital Transfusion website.

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Provenance

Record: 3834
Objective:

Aims
To improve the diagnosis and management of patients who may receive an ABO incompatible solid organ transplant.

Objectives
To provide evidence-based recommendations for appropriate diagnosis, investigation and management of compatible blood and blood components during and post ABO incompatible solid organ transplantation. To guide clinicians on the correct procedures to establish which blood group should be given in transfusion depending upon the severity of ABO incompatibility.

Clinical condition:

Patients with organ failure that may require a Solid Organ Transplant.

Target patient group: Liver, Renal and Cardiac Transplant Teams
Target professional group(s): Allied Health Professionals
Secondary Care Nurses
Adapted from:

Evidence base

 

  1. Dahlseid A L: Successful ABO Incompatible Organ Transplantation. University of Alberta Health Sciences Journal.  May 2005; Vol 2. Issue 1; 17-21
  2. Foreman C, Gruewald C and West L.  ABO Incompatible Heart Transplantation a Perfusion Strategy. Perfusion 2004:19:69-72
  3. Holt S, Donaldson H, Hazelhurst G, Varghese Z,  Contreas M, Kingdon E et al. Acute Renal Rejection Induced by Blood Transfusion Reaction to the Kidd Blood Group System. Nephrol  Dial Transplant. 2004: 19: 2403-2406.
  4. Roedder Silke, Vitalone M, Khatri P and Sarwal M M: Biomarkers in Solid Organ Transplantation; establishing personalized transplantation medicine. Review. Genome Medicine 2011:3: 37
  5. Audet M, Panaro F, Piardi T, Haung P, Cag M, Cinqualbre J and Wolf P.  Review Article: Passenger Lymphocyte Syndrome and Liver Transplantation. Clinical and Developmental  Immunology. Volume 2008. Article 715796
  6. Achkar R, Chiba AK, Zampieri-Filho J P, Pestana J O.M and Bordin J O.  Haemolytic Anaemia after Kidney Transplantation: A Prospective Analysis.  Transfusion:2011:51:2495-2499.
  7. Petz L D.  Immune Haemolysis Associated with Transplantation.  Semin Hematol 2005 42:145-155.
  8. Abbasoglu O. Liver transplantation: yesterday, today and tomorrow.  World J Gastroenterol. 2008 May 28:14(20):3117-22. Review
  9. Ramsey G, Cornell FW, Hahn LF, Larson P, Issitt LB, Starzl TE.  Red cell antibody problems in 1000 liver transplants.  Transfusion. 1989;29(5):396-400
  10. Grosskreutz C, Gudzowaty O,  Shi P, Rodriguez-Liaz G, Malone A, Isola L. Partial HLA matching and RH incompatilbility resulting in graft versus host reaction and Evans syndrome after liver transplantation.  Am J Haematol. 2008;83:500-601
  11. Darrell J. Triulzi, MD.  Specialized transfusion support for solid organ transplantation. Current Opinion in Hematology 2002,9:527-532
  12. Devi AS. Transfusion practice in orthotopic liver transplantation. Indian J Crit Care Med 2009;13:120-8
  13. Ainsworth CD, Crowther MA, Treleaven D, Evanovitch D, Webert KE, Blajchman MA. Severe hemolytic anemia post-renal transplantation produced by donor anti-D passenger lymphocytes: case report and literature review. Transfus Med Rev. 2009 Apr;23(2):155-9. doi: 10.1016/j.tmrv.2008.12.005. Review.
  14. Lerut E,  Van Damne B, Noizat-Pirenne F, Emonds MP, Rouger P, Vanrenterghem Y, Pirenne J and Ansart-Pirenne H.  Duffy and Kidd blood group antigens: Minor histocompatilility antigens involved in renal allograft rejection?  Transfusion 2007;47:28-40
  15. Hoffman Philip C, Immune hemolytic anemia-selected topics. American Society of Hematology. 2009:80-86
  16. Longster, Haines & Jones, Transfusion medicine supplement 1992 (S1)  p88
  17. Laura Green, Paula Bolton-Maggs, Craig Beattie, Rebecca Cardigan,        Yiannis Kallis, Simon J Stanworth, Jecko Thachil and Sharon Zahra.  British Society of Haematology Guidelines on the spectrum of fresh frozen plasma and cryoprecipitate products: their handling and use in various patient groups in the absence of major bleeding. British Journal of Haematology 2018; 181, 54-67

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Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

Glossary of Terms

Antigen – Substances recognised by the body as foreign, causing the body to produce an antibody to react specifically.

Antibody- Proteins produced by white cells as a result of stimulation by an antigen which can interact specifically with that particular antigen.

Antibody titre- a test that detects the presence and measures the amount of antibodies within a person’s blood.

Blood component- in this guideline refers to: red cells, platelets, FFP and cryoprecipitate.

CMV-Cytomegalovirus

FFP-Fresh Frozen Plasma

Graft Rejection-transplanted tissue is rejected by the recipient’s immune system, which then destroys the transplanted tissue.

Haemolysis-the breakdown of red cells and the release of haemoglobin to the surrounding area.

HLA-Human Leucocyte Antigen     

Issoagglutinins-antibodies produced by an individual that causes agglutination of red blood cells in other individuals.

Phenotype – characteristics of traits expressed by the organism.

PLS-Passenger Lymphocyte Syndrome

Irradiated- Use of X or gamma irradiation to treat cellular products (red cells and/or platelets)

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