PHENOTYPIC CORRECTION OF ACTIVATED PROTEIN-C RESISTANCE FOLLOWING ORTHOTOPIC LIVER-TRANSPLANTATION

A 43-year-old white female underwent orthotopic liver transplantation in 1992 for cirrhosis related to primary sclerosing cholangitis. Pre-t ransplantation protein S (PS) studies revealed a discrepancy between P S activity and free PS antigen consistent with type LI PS deficiency. Since the presence of activated protein C (APC) resistance has been re ported to interfere with PS activity assays resulting in an apparent t ype II PS deficiency, we retrospectively tested a pre-transplantation frozen plasma sample for APC resistance. The sample was found to have an abnormal APC resistance ratio (APCR-R) of 1.71. Follow up testing 2 1/2 years post-transplantation revealed correction of the APC resistan ce phenotype (normalization of the APCR-R to 2.79). Analysis of DNA ex tracted from lymphocytes revealed the patient to be heterozygous for t he FV mutation associated with APC resistance (FV Leiden). Hereditary APC resistance was confirmed by family studies which revealed the pres ence of APC resistance and heterozygous FV Leiden in her son. Although the patient's post-transplantation plasma FV is normal, her platelet FV remains heterozygous for FV Leiden. To what extent, if any, platele t FV Leiden in the absence of plasma FV Leiden may contribute to a pre disposition to thrombosis is unknown.