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Rhesus Alloimunization Occurs After Rh Incompatible Liver Transplantation in Children

Bolia, Rishi, MD, DM1; Shankar, Sahana, MD1; Herd, Lauren1; Hardikar, Winita, FRACP, PhD1

doi: 10.1097/TP.0000000000001976
In Brief

1 Department of Gastroenterology and Clinical Nutrition, The Royal Children’s Hospital, Melbourne, Australia.

Received 11 August 2017. Revision received 13 September 2017.

Accepted 16 September 2017.

The authors declare no funding or conflicts of interest.

R.B. participated in the drafting the work and final approval of the version to be published. S.S. participated in the conception of the work and writing of the article. L.H. participated in the acquisition of data and final approval of the version to be published. W.H. participated in the conception of the work, revising it critically for important intellectual content, and final approval of the version to be published.

Correspondence: Winita Hardikar, FRACP, PhD, Department of Gastroenterology, Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia. (

Rhesus (Rh) mismatch in liver transplantation is not taken into consideration for organ matching in centers across the world. In theory, RhD-negative recipients of RhD donor livers are at a risk of alloimunization from the small amount of blood transplanted with a liver and subsequent development of anti-RhD antibodies. Patients who develop anti-RhD antibodies may be vulnerable to hemolytic transfusion reactions, which may lead to significant hemolysis and hemolytic disease of the newborn. There is no consensus guidelines regarding the need to administer RhD immunoglobulin (RhDIg) to such patients to prevent these potential complications and although some centers routinely administer it to such patients, others do not.1 The rationale behind the practice in centers where RhDIg is not routinely administered is that immunosuppressant drugs modify the immunosuppressive response and prevent the formation of anti-D antibodies precluding the need to give RhDIg.

However, this practice is not backed by evidence. Available literature on the risk of Rh alloimunization in RhD-negative adult liver transplant recipients of RhD-incompatible blood products is conflicting. Although one study reports a 15.7%2 risk, 2 others report a complete lack of alloimunization.3,4 There is no available pediatric data. Data from adults about the risk and outcome of RhD alloimunization cannot be extrapolated to children who in general have less prior exposure to blood products, no pregnancies, less comorbidities, and an immature immune system.

We carried out a review of medical records of all patients who have undergone a Rh incompatible (RhD-positive donor, RhD-negative recipient) liver transplant (n = 18) at the Royal Children Hospital, Melbourne, between 1995 and 2016. Clinical details and laboratory records (including a posttransplant red cell antibody screen) were recorded.

RhD immunoglobulin was not administered routinely in our unit for Rh-incompatible transplants. There were 9 men, and median age of transplantation was 23 months (interquartile range, 55 months), the commonest etiology being biliary atresia (n = 13). One child (5.5%) developed anti-RhD antibodies 10 days after the transplant. Compliance with immunosuppression was ensured, and tacrolimus levels were within the target range. There was no episode of acute rejection. Moreover, this patient had a hepatoblastoma and had also received chemotherapy in the pretransplant and posttransplant period which would suggest an even heightened state of immunosuppression The remaining 17 patients remained negative for anti-RhD antibodies for a median of 238 days (interquartile range, 578 days) after their transplant. To conclude, even though the risk of Rh alloimunization is low in RhD-negative patients receiving an RhD-positive liver graft, it may occur. Our observations are similar to those of Quan et al5 who also had observed a 5% incidence of RhD alloimmunization in RhD-incompatible kidney transplant recipients.

Rh alloimunization makes one vulnerable to complications in the future. Review of a large multicenter pediatric liver transplant database is necessary to determine if prophylactic administration of RhDIg in RhD-incompatible transplants at the time of transplantation is useful in the prevention of alloimmunization. The optimal timing and dosage of RhDIg needs to be determined.

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2. Ramsey G, Hahn LF, Cornell FW, et al. Low rate of Rhesus immunization from Rh-incompatible blood transfusions during liver and heart transplant surgery. Transplantation. 1989;47:993–995.
3. Casanueva M, Valdes MD, Ribera MC. Lack of alloimmunization to D antigen in D-negative immunosuppressed liver transplant recipients. Transfusion. 1994;34:570–572.
4. Yuan S, Davis R, Lu Q, et al. Low risk of alloimmunization to the D antigen in D-orthotopic liver transplant recipients receiving D+ RBCs perioperatively. Transfusion. 2008;48:2653–2655.
5. Quan VA, Kemp LJ, Payne A, et al. Rhesus immunization after renal transplantation. Transplantation. 1996;61:149–150.
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