Hemorrhagic and thrombotic disorders due to factor V deficiencies and abnormalities: an updated classification.

The recent description of a factor V abnormality (factor V Leiden) associated with an increased incidence of thrombosis has considerably increased interest in this clotting factor. The discovery of this new clinical entity indicated the need for an updated classification of factor V defects. These should be divided into hemorrhagic and thrombotic disorders. A proper classification of hemorrhagic disorders should include: 1) homozygous and heterozygous 'true' factor V deficiency; and 2) combined factor V and factor VIII deficiencies. The latter should be subdivided in Type I (association type) and Type II (common defect). A suitable classification of the thrombotic factor V defects should include: 1) homozygous and heterozygous factor V Leiden; and 2) combined heterozygous factor V Leiden and heterozygous 'true' factor V deficiency. The presence of thrombosis in these latter patients, often as severe as those seen in homozygous patients with activated protein C (APC) resistance, allows important considerations on the functions of factor V. It would seem that half the normal level of factor V activity and antigen is unable to protect against thrombosis in patients with heterozygous APC resistance. An accurate evaluation of factor V activity and antigen is indicated in all patients with suspected factor V defects. The first suspicion may be obtained by the presence of a mild prolongation of prothrombin time and of partial thromboplastin time. The suspicion should then be immediately confirmed by specific factor V activity and antigen assays. This approach is of great importance even for the presumptive diagnosis of pseudohomozygosis for APC resistance. In fact, in these cases, factor V activity is about 50% of normal, whereas factor V antigen is 100% of normal. In heterozygous 'true' factor V deficiency both activity and antigen are about 50% of normal.

Population differences in the frequency of the factor V Leiden variant among people with clinically symptomatic protein C deficiency.

The factor V Leiden variant, responsible for the phenomenon of activated protein C resistance, was found to be less frequent among British (0.06) and Swedish/Danish (0.15) protein C deficiency patients than previously reported in a Dutch study (0.19). In the Swedish population, a significantly increased frequency of the factor V Leiden allele was apparent in protein C deficiency patients as compared to healthy controls. However, this was not found in the British population. Coinheritance of the factor V Leiden variant is therefore unlikely to be the sole determinant of whether a person with protein C deficiency will come to clinical attention. Nevertheless, when patient data were analysed by type of protein C deficiency, it was noted that the frequency of the factor V Leiden variant was 2.8-fold higher in type II patients compared to type I patients. A possible explanation of this disparity is discussed.