EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Thrombocytopenia is common during the early posttransplant period. Most cases are mild and recover in 1 month. Occasionally, severe thrombo-cytopenia may occur in the late posttransplant period. We report a 10-year-old boy with severe thrombocytopenia 3.5 years after liver transplant. We exclude secondary causes of thrombocytopenia. Bone marrow aspiration findings and treatment response were suggestive for immune thrombo-cytopenic purpura. The patient was treated with intravenous immunoglobulin at thrombocytopenia periods successfully. We continued tacrolimus, but preferred a reduced dose. In conclusion, immune thrombocytopenic purpura should be borne in mind as a reason of late onset, severe thrombocytopenia after liver transplant.

Key words : Immune thrombocytopenic purpura, Liver transplant, Thrombocytopenia, Intravenous immuno-globulin

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder and a common cause of isolated thrombocytopenia in childhood. It is characterized by low circulating platelet count, owing to destruction of platelets and disordered thrombopoiesis.¹ Rapid onset of easily bruising and diffuse petechiae are the most common presenting symptoms.1 Immune thrombocytopenic purpura is a diagnosis of exclusion. Vitamin deficiencies, infections, drugs, and autoimmune diseases are common causes of thrombocytopenia. Ample megakaryocytes in bone marrow aspirate and platelet increase in response to corticosteroids or intravenous immunoglobulin (IVIG) treatments are suggestive for ITP. Independent of any treatment strategy, complete remission will be attained in two thirds of all ITP cases.

Thrombocytopenia is common in liver transplant patients, not only candidates, but in the early posttransplant period. Platelet sequestration in the liver graft, immunologic reactions, hypersplenism, heparin-induced thrombocytopenia, excessive consumption of platelets, infections, disseminated intravascular coagulation, sepsis, and impaired thrombopoietin production are causative factors of thrombocytopenia in early posttransplant period.^2-4 Posttransplant lymphoproliferative disease and tacrolimus-related microangiopathic hemolytic anemia may cause thrombocytopenia less commonly.² Most cases are mild and recover in about 1 month.² However, occasionally a marked decrease in the platelet count may persist, and ITP diagnosis verified after liver transplant (LT). Autoimmune hemolytic anemia and Evans syndrome (ITP and autoimmune hemolytic anemia) are reported as autoimmune cytopenias in pediatric LT patients.⁵ We report a child with ITP after having had an LT.

A 10-year-old boy, diagnosed with progressive familial intrahepatic cholestasis underwent a living-related LT on January 2010. Three and half years after surgery, he presented with multiple cutaneous ecchymosis on his legs and arms. He had received nothing but tacrolimus during the previous 2 years. His platelet count was 2.7 × 10⁹/L, and the results of a Coombs’ test were positive. There were no hemolysis findings on peripheral blood smear. Total immunoglobulin G level was 4.5 (range, 6.0-15.7 g/L), lower than expected for his age. The results of his liver function tests were normal (aspartate aminotransferase, 29 U/L; alanine aminotransferase, 25 U/L; gamma glutamyl transferase, 24 U/L; albumin, 36 g/L; total bilirubin, 7.3 μmol/L; prothrombin time 11.3 s; international normalized ratio, 0.97). Serum Ebstein-Barr virus DNA, cytomegalovirus DNA, and parvovirus B19 DNA, varicella zoster DNA, and herpes virus 1 and 2 IgM were negative. Bone marrow aspiration showed increased megakaryocytes. Idiopathic immune thrombocytopenic purpura was considered. The patient was treated with 3 dose IVIG (1 g/kg) and platelets improved 2.7 to 144.7 × 10⁹/L. We continued tacrolimus, but preferred a reduced dose. His platelet count was stable for 3 months. He had 2 relapses after 3 months and 5 months of initial therapy and was treated with IVIG successfully (1 g/kg).

He had been taking tacrolimus continuously after LT surgery. He did not have a recent infection and was not taking any drug different from tacrolimus; there were no blood product transfusions. Vitamin deficiencies and acute or chronic viral infections were excluded. Bone marrow aspiration were compatible with ITP. Increases in platelet count by IVIG therapy also were suggestive of ITP.

We describe a 10-year-old boy with severe thrombocytopenia of more than 3 years duration after LT for progressive familial intrahepatic cholestasis. In contrast to our patient, thrombocytopenia is seen mostly during early posttransplant period in LT patients. A marked decrease in the platelet count occurs during the fourth day after transplant and recovers within 2 to 4 weeks.² Also, Chatzipetrou and associates reported severe thrombocytopenia in the early posttransplant period was 22.1%.²

In the literature, the most persistent severe thrombocytopenia after LT were ITP cases. Taylor and associates reported 8 adult cases of new-onset ITP after LT among 256 patients.⁶ They found an incidence of ITP after LT was 0.7%, median platelet count at presentation was 3.5 × 10⁹/L, and median time from transplant to ITP onset was 53.5 months (range, 1.9-173 mo).⁶ Similar to our patient, ITP occurrs mostly after 1 year.⁶ Miloh and associates reported 2 cases of new-onset ITP after LT with an incidence of 1.3% among 158 pediatric patients.⁵ Additionally, they found 2 isolated autoimmune hemolytic anemia and 1 Evans syndrome cases.⁵ Median time from transplant time to ITP onset was 13 months (range, 1 d-5 y).⁵ Associated cytomegalovirus, Epstein-Barr virus, and parvovirus B19 infections are described with ITP after LT.^5,6 Pre-existing ITP in liver donors, or those with alloimmune thrombocytopenia because of human platelet antigen-1, may cause thrombocytopenia after LT.⁶ Corticosteroids, immunoglobulin infusions, anti-D antibody, rituximab, or splenectomy may be chosen as a treatment.⁷ Long-term remission can be achieved in most patients by these therapies.^5,6 As shown in this patient, immunoglobulin infusion is effective therapy in LT patients with ITP. Also, IVIG can be used successfully for relapses of thrombocytopenia. Another concern is the need to stop taking tacrolimus. Calcineurin inhibitors, cyclosporine, and tacrolimus may cause microangiopathic hemolytic anemia and thrombocytopenia, which is the same as thrombotic thrombocytopenic purpura. The present case showed no clinical signs similar to thrombotic thrombocytopenic purpura. Miloh and associates suggest that tacrolimus may be continued, but reduced immunosuppression may be preferred.⁵ In conclusion, ITP should be borne in mind as a reason of late onset severe thrombocytopenia after LT.

Volume: 12 Issue: 1 March 2014 - Supplement - 1

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