Liver Transplantation for Homozygous Protein C Deficiency?

Liver Transplantation for Homozygous Protein C Deficiency? Is liver transplantation a treatment for homozygous protein C deficiency in a child? profAskTheExpert transplantation Ashokkumar Jain, MD, Assistant Professor in the Department of Surgery in the Division of Transplant Surgery at the Thomas E. Starzl Transplantation Institute and an Adjunct Assistant Professor in the School of Pharmacy, Division of Pharmaceutical Sciences at the University of Pittsburgh in Pittsburgh, Pennsylvania. Medscape Medscape Transplantation 07/12/2001 2 2 <h3>Question</h3> Is liver transplantation a treatment for homozygous protein C deficiency in a child? <H3>Response</H3> from , 07/12/2001 Protein C is a vitamin K-dependent anticoagulant glycoprotein. Once activated by thrombin, it inhibits activated factors V and VII and stimulates fibrinolysis. The deficiency of protein C results in a hypercoagulable state and presents as purpura fulminate, retinal hemorrhage, central nervous system hemorrhage, and renal vein thrombosis in the neonatal period, and results in major vessel thrombosis. It is inherited as an autosomal codominant trait. Patients with heterozygous protein C deficiency have approximately 50% of normal protein C activity and those with the homozygous condition have less than 1% of normal protein C activity. Homozygous protein C deficiency is fatal if not treated. The initial treatment is medical management by replacement with fresh frozen plasma, factor IX and protein C concentrate, procoagulant reductase (vitamin K antagonist), and Coumadin or low-molecular-weight heparin, as anticoagulation.[1-3] Because the liver is the major site of protein C synthesis, liver transplantation, either orthotopic[4] or heterotopic,[5] is useful to restore the deficiency of protein and has been reported to be successful. This restoration eliminates the need for anticoagulants and frequent infusions of plasma products. Continuation of anticoagulation after liver transplantation until the protein C activity is greater than 70% has been recommended, particularly because normalization of protein C activity and other clotting factors (II, V, X) fall after liver transplantation and may take up to 1 week after transplantation to return to normal.[1] Thrombosis of splanchnic vessels can result in infarction of the entire small bowel. A series of 17 cases with hypercoagulable states from a combination of protein C, protein S, and antithrombin III deficiency and factor V mutation has been reported.[6] Eight patients received isolated intestine and 9 received composite liver-intestine transplantation. Two of the 9 patients who received composite liver-intestine grafts experienced recurrent episodes of venous thrombosis of the native vessels and required reinstitution of anticoagulation. The authors postulated the coexistence of an extrahepatic hereditary defect at the endothelial level and recommended anticoagulation therapy for 6 months postoperatively. In conclusion, hepatic replacement corrects the protein C deficiency and eliminates the need for lifelong anticoagulation. After liver transplantation, anticoagulation therapy should be continued until protein C activity is greater than 70%, which usually takes approximately 1-2 weeks. <OL><LI> Harper PL, Edgar PF, Luddington RJ, et al. Protein C deficiency and portal thrombosis in liver transplantation in children. Lancet. 1988;2:924-927. <LI> Stringer MD, Melissari E, Kakkar VV, Tan KC. Protein C deficiency and thrombotic complications after liver transplantation in children. Lancet. 1989;1:102-103. <LI> Marlar RA, Montgomery RR, Broekmans AW. Report on the diagnosis and treatment of homozygous protein C deficiency. Report of the Working Party on Homozygous Protein C Deficiency of the ICTH-Subcommittee on Protein C and Protein S. Thromb Haemost. 1989;61:529-531. <LI> Casella JF, Lewis JH, Bontempo FA, Zitelli BJ, Markel H, Starzl TE. Successful treatment of homozygous protein C deficiency by hepatic transplantation. Lancet. 1988;1:435-438. <LI> Angelis M, Pegelow CH, Khan FA, Verzaro R, Tzakis AG. En bloc heterotopic auxiliary liver and bilateral renal transplant in a patient with homozygous protein C deficiency. J Pediatr. 2001;138:120-122. <LI> Giraldo M, Martin D, Colangelo J, et al. Intestinal transplantation for patients with short gut syndrome and hypercoagulable states. Transplant Proc. 2000;32:1223-1224. </OL>