Frequency of thrombophilia-related genetic variations in patients with idiopathic pulmonary embolism in an urban emergency department.

BACKGROUND The frequency of the thrombophilic genetic variants factor V Leiden (FVL) G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T in acutely symptomatic ambulatory patients with idiopathic pulmonary embolism (PE) has not been measured. METHODS This prospective case-control study included patients presenting to urban emergency departments (EDs) with chest pain or shortness of breath. Cases were classified as idiopathic PE (49 patients with PE, but without overt risk factors for thrombosis). Control groups included (a) patients with nonidiopathic PE (152 patients with PE and risk factors); (b) patients in whom PE was excluded (91 patients who had PE ruled out with a structured protocol, including follow-up); and (c) patients in whom PE was not suspected (193 patients without a workup for PE, who were free of PE on follow-up). Blood DNA extracts were analyzed by PCR and restriction fragment length polymorphism analysis for the FVL, prothrombin, and MTHFR sequence variations. RESULTS Either the FVL or prothrombin variant was found in 10% (95% confidence interval, 3%-22%) of patients with idiopathic PE compared with 13% (8%-20%) of nonidiopathic PE, 2% (5%-14%) of PE excluded, and 9% (5%-14%) of PE not suspected patients. Patients with idiopathic PE tended to have a higher frequency of homozygous MTHFR sequence variants, but mean (SD) plasma homocysteine concentrations were not increased [15.6 (5.4) micromol/L vs 12.8 (4.6) micromol/L for homozygous, and wild-type, respectively; P = 0.40]. CONCLUSIONS The frequency of either the FVL or prothrombin sequence variant was not increased in idiopathic PE patients compared with nonidiopathic PE patients or patients who had PE excluded. These data suggest that genotyping to detect idiopathic PE would have limited clinical utility in the urban ED setting.