Correction of Factor XI Deficiency by Liver Transplantation
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《新英格兰医药杂志》
To the Editor: Liver transplantation is considered to be an appropriate therapeutic option for hemophilia complicated by cirrhosis.1 Correction of deficiencies of factor VIII and factor IX by liver transplantation is well known.2 Factor XI deficiency is a less common form of hemophilia that is associated with prolonged bleeding during surgery, rather than with spontaneous hemorrhage, as is seen in patients with hemophilia A or B. Correction of factor XI deficiency by liver transplantation has not been reported, to our knowledge.
Recently, we performed a liver transplantation in a 48-year-old man with hepatitis C virus (HCV) cirrhosis and hepatocellular carcinoma who had previously been found to have factor XI deficiency. His only known risk factor for HCV infection was a blood transfusion he received as treatment for unexpected bleeding after an inguinal hernia repair 28 years earlier. In the intervening years, he was found to have a prolonged partial-thromboplastin time. Investigation revealed an isolated factor XI deficiency (plasma factor XI level, 0.27 U per milliliter; normal range, 0.5 to 1.5). The levels of factors VII, VIII, and IX were normal. The patient was not of Ashkenazi Jewish ancestry.
In 2002, he was given a diagnosis of HCV cirrhosis. Hepatocellular carcinoma was diagnosed during the preparation for liver transplantation. In April 2004, his liver was removed, and the right side of a split-liver graft from a cadaveric donor was orthotopically transplanted. The procedure was complicated by intraoperative bleeding at the cut margin of the liver, which was brought under control by local measures. Fresh-frozen plasma was used to correct his coagulopathy during surgery. Postoperatively, he had a smooth recovery, and he has subsequently remained well. Factor XI levels returned to the normal range by day 7 after transplantation and have remained normal since that time (Table 1).
Table 1. Coagulation Values in a Patient with Factor XI Hemophilia Who Received a Liver Transplant for HCV Cirrhosis and Hepatocellular Carcinoma.
Transfer of factor XI deficiency from a donor to the recipient of an orthotopic liver transplant has been described in the Journal3 and confirmed elsewhere.4 That observation strongly suggests that factor XI production is confined to the liver. However, transfer of a clone of lymphocytes producing factor XI inhibitor with the transplantation was not ruled out.3,4 Such a mechanism was recently shown to explain the development of acquired hemophilia A in a liver-transplant recipient.5 Our observation of the correction of factor XI deficiency by liver transplantation supports the hypothesis that this coagulation factor is produced predominantly in the liver.
Nina Ghosh, B.Sc.
Paul J. Marotta, M.D.
Vivian C. McAlister, M.B.
London Health Sciences Centre
London, ON N6A 5A5, Canada
vmcalist@uwo.ca
References
Punch JD, Merion RM, Turcotte JG. Hemophilia. N Engl J Med 2001;345:1066-1067.
Hoyer LW. Hemophilia A. N Engl J Med 1994;330:38-47.
Dzik WH, Arkin CF, Jenkins RL. Transfer of congenital factor XI deficiency from a donor to a recipient by liver transplantation. N Engl J Med 1987;316:1217-1218.
Clarkson K, Rosenfeld B, Fair J, Klein A, Bell W. Factor XI deficiency acquired by liver transplantation. Ann Intern Med 1991;115:877-879.
Hisatake GM, Chen TW, Renz JF, et al. Acquired hemophilia A after liver transplantation: a case report. Liver Transpl 2003;9:523-526.
Recently, we performed a liver transplantation in a 48-year-old man with hepatitis C virus (HCV) cirrhosis and hepatocellular carcinoma who had previously been found to have factor XI deficiency. His only known risk factor for HCV infection was a blood transfusion he received as treatment for unexpected bleeding after an inguinal hernia repair 28 years earlier. In the intervening years, he was found to have a prolonged partial-thromboplastin time. Investigation revealed an isolated factor XI deficiency (plasma factor XI level, 0.27 U per milliliter; normal range, 0.5 to 1.5). The levels of factors VII, VIII, and IX were normal. The patient was not of Ashkenazi Jewish ancestry.
In 2002, he was given a diagnosis of HCV cirrhosis. Hepatocellular carcinoma was diagnosed during the preparation for liver transplantation. In April 2004, his liver was removed, and the right side of a split-liver graft from a cadaveric donor was orthotopically transplanted. The procedure was complicated by intraoperative bleeding at the cut margin of the liver, which was brought under control by local measures. Fresh-frozen plasma was used to correct his coagulopathy during surgery. Postoperatively, he had a smooth recovery, and he has subsequently remained well. Factor XI levels returned to the normal range by day 7 after transplantation and have remained normal since that time (Table 1).
Table 1. Coagulation Values in a Patient with Factor XI Hemophilia Who Received a Liver Transplant for HCV Cirrhosis and Hepatocellular Carcinoma.
Transfer of factor XI deficiency from a donor to the recipient of an orthotopic liver transplant has been described in the Journal3 and confirmed elsewhere.4 That observation strongly suggests that factor XI production is confined to the liver. However, transfer of a clone of lymphocytes producing factor XI inhibitor with the transplantation was not ruled out.3,4 Such a mechanism was recently shown to explain the development of acquired hemophilia A in a liver-transplant recipient.5 Our observation of the correction of factor XI deficiency by liver transplantation supports the hypothesis that this coagulation factor is produced predominantly in the liver.
Nina Ghosh, B.Sc.
Paul J. Marotta, M.D.
Vivian C. McAlister, M.B.
London Health Sciences Centre
London, ON N6A 5A5, Canada
vmcalist@uwo.ca
References
Punch JD, Merion RM, Turcotte JG. Hemophilia. N Engl J Med 2001;345:1066-1067.
Hoyer LW. Hemophilia A. N Engl J Med 1994;330:38-47.
Dzik WH, Arkin CF, Jenkins RL. Transfer of congenital factor XI deficiency from a donor to a recipient by liver transplantation. N Engl J Med 1987;316:1217-1218.
Clarkson K, Rosenfeld B, Fair J, Klein A, Bell W. Factor XI deficiency acquired by liver transplantation. Ann Intern Med 1991;115:877-879.
Hisatake GM, Chen TW, Renz JF, et al. Acquired hemophilia A after liver transplantation: a case report. Liver Transpl 2003;9:523-526.