HOMOZYGOUS FACTOR V-DEFICIENT PATIENTS SHOW RESISTANCE TO ACTIVATED PROTEIN-C WHEREAS HETEROZYGOTES DO NOT

Resistance to activated protein C (APC resistance) was assessed in plasma from patients with heterozygous and homozygous factor V (FV) deficiency. Because of the identity of the new APC cofactor with non-activated FV, it was expected that the lower the FV level the higher the APC resistance in plasma. Heterozygotes for the FV defect (both antigen and activity levels around 40%) did not show APC resistance in plasma. In contrast, homozygous patients for the same defect (less than 1% antigen and activity levels), had obvious APC resistance. Whether this finding was consistent with a spurious APC resistance or whether it truly reflected the lack of the APC cofactor activity in congenital FV deficiency remains to be clarified. Mixing (1:1) plasma from patients with a homozygous FV defect with pooled normal plasma (PNP) corrected both procoagulant and anticoagulant FV activities. Whenever severely APC-resistant plasma was used in place of PNP, only procoagulant activity was corrected and APC resistance was not affected. This suggests that homozygous FV-deficient plasma completely lacks the cofactor, i.e. the second APC cofactor, which can correct APC resistance in plasma. This indirectly confirms that the second APC cofactor is related to FV.