Successful,liver,transplantation,from,a,donor,with,immune,thrombocytopenia

Wen-Tao Yang, Jing-Sheng Ma, Hong-Fei Zhu, Lin Zhong, Qi-Gen Li

Department of Organ Transplantation, The Second Affiliated Hospital of Nanchang University, Nanchang 330 0 0 0, China

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disease, which results from a combination of humoral and cell-mediated attacks on platelets and megakaryocytes [1–3] . ITP patients are always presented as heterogeneous clinical bleeding manifestations. Fatal bleeding such as intracranial hemorrhage is the main cause of death, which turns the patients into potential organ donors. Several studies indicated that the donor lymphocytes secreting autoantibody may be transferred to recipients after transplantation [ 4 , 5 ]. Transplantation-mediated alloimmune thrombocytopenia (TMAT) was donor-derived thrombocytopenia after solidorgan transplantation [6] . TMAT is a rare complication after transplantation, and the recipients of TMAT may present more severe bleeding events than the donors. A total of 6 recipients with TMAT after liver transplantation from ITP donors have been reported internationally [6–11] , among which 3 recipients died and 3 survived. Thus, liver transplantation from ITP donors is relatively risky,and as a marginal donor organ, the use of ITP donor liver is controversial. There are no relevant guidelines for the safety assessment and treatment of ITP donor liver transplantation up to now. Here we reported a successful case with TMAT in liver transplant recipient from ITP donor in purpose of improving our understanding of TMAT.

The donor was a 16-year-old Chinese girl with blood type A,a height of 153 cm, and a weight of 50 kg, who died of a fatal spontaneous intracranial hemorrhage resulting from ITP. She was diagnosed with ITP two years ago, with frequent nosebleeds and bleeding gums, and increased menstrual flow. Although she received steroid therapy, the medication was not taken regularly, resulting in poor quality of treatment. At the time of donating organ,her peripheral platelet (PLT) count was 10 × 109/L, and the other laboratory results were within the normal range. One liver and two kidneys were donated for transplantation.

The liver recipient was a 64-year-old male patient with cirrhosis secondary to hepatitis B virus (HBV). Past medical history included diabetes mellitus type II, chronic cholecystitis, and chronic renal failure. Past surgical history included appendectomy twenty years ago and transjugular intrahepatic portosystemic shunt (TIPS)one year ago. After TIPS, the recipient still suffered from several complications of cirrhosis, including intractable ascites, hypoproteinemia and hepatorenal syndrome. The recipient has no history of drinking, but has a twenty-year history of cigarette smoking,which had been quitted for ten years. At transplantation, the PLT of recipient was 90 × 109/L.

The liver transplant surgery was uneventful. The cold ischemia time was 370 min and the warm ischemia was 40 min. The estimated total blood loss during the operation was 1200 mL. Transfusion requirements were 8 units of A-type red blood cell suspension and 10 0 0 mL of fresh frozen plasma. The recipient’s condition remained stable throughout the procedure, and no surgical complications occurred.

Postoperatively, the patient received methylprednisolone and tacrolimus as immunosuppressive medications. The PLT showed a gradual decreasing trend after surgery, dropping to 13 × 109/L on postoperative day (POD) 4 ( Fig. 1 A). He received one unit of PLT concentrates on POD4, and recombinant thrombopoietin (rhTPO)(15,0 0 0 U daily, subcutaneous injection). In the following 3 days,the PLT remained extremely low (6 × 109/L on POD 7). To prevent serious bleeding complications, one unit of PLT concentrate was transfused on POD 7. Considering the history of ITP in the donor and the possibility of transmission of autoantibodies, intravenous immunoglobulins (IVIg) was administered to reverse ITP on POD 7. The PLT gradually increased and maintained at the normal level for one week. But on POD 21, the PLT dropped to 32 × 109/L again,and one unit of PLT concentrate was transfused with the administration of IVIg and dexamethasone. On POD 23, the PLT increased to 56 × 109/L, but it then began to decline again. Two units of PLT concentrate were transfused and rituximab (200 mg, intravenous drip) was administered on POD 25. The rhTPO was administered from POD 28 to POD 31. The PLT increased since POD 34, and gradually returned to normal levels. The detail treatment regimens and time frame were shown in Fig. 1 B.

Throughout the course of postoperative treatment, no obvious clinical manifestations of bleeding were present except persistent bloody ascites. Human leukocyte antigen was not detected. Since no serum sample of donor was available before transplantation,no anti-PLT antibodies were detected. But antibody against human platelet antigens (HPA) of the recipient on POD 6 and POD 26 was negative. The parameters of liver function such as prothrombin time (PT), total bilirubin (TBil), aspartate aminotransferase (AST)and alanine aminotransferase (ALT) quickly returned to normal levels after liver transplantation surgery, and the creatinine (Cr) maintained at the preoperative level ( Fig. 2 ).

Fig. 1. Clinical treatment of the recipient. A: Postoperative daily platelet counts with the important clinical interventions noted below the graph. B: Therapeutic medications used in the postoperative days. IVIg: intravenous immunoglobulin; rhTPO: recombinant thrombopoietin.

Fig. 2. Postoperative daily prothrombin time (PT), total bilirubin (TBil), creatinine (Cr), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are showed.

The ITP patients dying from spontaneous intracranial hemorrhage become potential donors, but the use of their livers for transplantation is controversial [12] . This type of donor is usually young and the quality of the grafts is higher, but severe postoperative ITP possibly threatens the lives of recipients, thus it needs to strike a balance between risk and benefit. TMAT as a kind of rare complication after liver transplantation, may lead to severe graft dysfunction, liver loss and even death. The risk of TMAT in a recipient who receives an organ from an ITP donor is unknown. And there are no relevant treatment and informative assessment guidance for the application of livers from ITP donors [13] .

A total of 7 cases (including our present case) have been reported (3 recipients died and 4 survived) in the global until now.The detailed information of TMAT cases in the published literature was shown in Table 1 . The clinical manifestations, therapeutic response, and severity of each recipient might vary. Conventional treatments including the IVIg, glucocorticoid, PLT transfusion, plasma exchange and rituximab were commonly proven to be effective in the short term. However, one case reported by Friend et al. [6] who had even received those treatments failed to recover and had to be retransplanted. For the management of liver transplantation from ITP donors, we need to be alert to the occurrence of TMAT in recipients. Due to the limited cases, the understanding of TMAT is still inadequate, and the relative experience needs further accumulation. To some extents, our case report contributes to this rare clinical subject.

Table 1 Clinical characteristics of liver transplant recipients from deceased organ donors with immune thrombocytopenia (ITP).

The exact mechanism of TMAT remains unclear. The current researchers suggested that the possible pathogenesis of TMAT in ITP donor liver transplantation is as follows. (1) Anti-PLT autoantibodies are transferred from the ITP donor to the recipient via liver transplantation, sensitizing the recipient’s PLTs, and being splenic reticuloendothelial destroyed by phagocytes in the tissue system [14] . (2) In the ITP donor liver contains a certain number of B-lymphocytes that produce anti-PLT antibodies. After the recipient receives a transplanted liver, the lymphocytes in the donor liver continue to produce anti-PLT antibodies, sensitizing the recipient PLTs to be destructed. But with the gradual consumption of the lymphocytes, the number of the recipient PLTs will be finally recovered, and transplant-acquired ITP could be self-limiting [ 3 , 5 ].(3) The liver is one of the places destroying PLTs, especially in the liver recipient from an ITP donor after splenectomy, and the mononuclear-phagocytic system may be highly activated, which can remove the antibody-coated PLTs in the recipient more effectively [15] .

Because of the shortage of donors, liver transplant recipients have a certain mortality rate during the waiting period, especially in cases of liver failure with high MELD scores. The previous results showed that the incidence of severe ITP after preconditioning is relatively low. Even if life-threatening ITP occurs, a salvage liver re-transplantation becomes an emergent alternative. The successful treatment of our liver recipient with IVIg, dexamethasone, and rituximab provides a further evidence for the use of organ from ITP donors. We believe that ITP donor livers should be undoubtedly adopted, especially when allocated to those recipients with emergent status. In additional, we suggest that transplant physicians must be alert to the possibility of ITP in the recipients and a prompt therapeutic regimen should be always available.

Acknowledgments

None.

CRediT authorship contribution statement

Wen-Tao Yang: Data curation, Formal analysis, Writing – original draft. Jing-Sheng Ma: Methodology, Writing – original draft.Hong-Fei Zhu: Methodology, Writing – original draft. Lin Zhong:Supervision. Qi-Gen Li: Conceptualization, Writing – review & editing.

Funding

None.

Ethical approval

This study was approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University (2010-0050). Written informed consent was obtained from all participants.

Competing interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.