The factor V Leiden mutation: spectrum of thrombotic events and laboratory evaluation

This study aims to describe the spectrum of clinical thrombotic events and to compare the methods of laboratory evaluation for the newly described prothrombotic factor V Leiden mutation.

Specimens from 1376 patients with thrombotic events or their relatives were tested for the factor V Leiden mutation by polymerase chain reaction plus restriction digest from Jan. 1, 1995, to Mar. 31, 1996. Activated protein C (APC) resistance test data was available for 554 of these patients. Clinical information was available for 166 patients with the mutation.

Of 1376 patients tested for factor V Leiden mutation, 270 (19.6%) were positive, with 12 homozygotes and 258 heterozygotes. Of 554 patients for whom APC resistance data was available, 221 (39.9%) had low APC resistance ratios (< or = 2.4); of these only 97 (43.9%) were factor V Leiden-positive. Among 333 samples with normal or elevated APC resistance ratios, 19 (5.7%) were later identified with the factor V Leiden mutation, despite the normal screening test. One hundred fourteen of 166 patients (68.7%) with the mutation had at least one thrombotic event, most commonly deep venous thrombosis and pulmonary embolus. Arterial cerebrovascular thrombotic events occurred in 11 patients (10%), and myocardial infarctions in eight (7%). The mean age of all patients with arterial thrombotic events was 45.4 years.

The factor V mutation is a common cause of venous thromboses but may also be associated with the early presentation of arterial thrombotic events. The APC resistance test is a sensitive screening assay but has limitations of its specificity in clinical practice.