Low Prevalence of Factor V:Q506 in 41 Patients with Isolated Pulmonary Embolism

Abstract

SummaryIn 70-80% of cases, pulmonary embolism is the consequence of lower extremity deep vein thrombosis. It has been demonstrated that the most common coagulation defect predisposing to venous thrombosis, resistance to activated protein C (APC), is not associated with an increased risk for pulmonary embolism, but the evidence was based on a functional assay to diagnose APC resistance and no information about concomitant deep vein thrombosis was provided. The aim of our study was to evaluate the prevalence of factor V:Q506, the gene mutation responsible for APC resistance, in patients with symptomatic non-fatal pulmonary embolism, whether or not associated with deep vein thrombosis. Patients with uncomplicated deep vein thrombosis and healthy controls were investigated as comparison groups. The overall prevalence of factor V:Q506 in 106 patients with pulmonary embolism was 12.3%, lower than that found in 106 patients with deep vein thrombosis (22.6%, OR 0.5, 95% Cl 0.2-1.0) but significantly higher than that found in 212 healthy subjects taken as controls (2.8%, OR 4.8,95% Cl 1.8-13.0). In the 41 patients with isolated pulmonary embolism, i.e., without the presence of deep vein thrombosis, the prevalence was 4.9%, similar to that in controls (OR 1.8,95% Cl 0.3-9.6), while in the remaining 65 patients with pulmonary embolism associated with deep vein thrombosis the prevalence was significantly higher (16.9%, OR 5.5, 95% Cl 2.0-15.8). In conclusion, the prevalence of factor V:Q506 is high in patients with pulmonary embolism associated with deep vein thrombosis, whereas in patients with isolated pulmonary embolism it is similar to that found in control subjects. This intriguing finding is of difficult interpretation and needs confirmation by further studies.

Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected patients with venous thromboembolism

“…Our study confirms and further substantiates most of the earlier findings (Desmarais et al, 1996;Manten et al, 1996;Baglin et al, 1997;Martinelli et al, 1997;Turkstra et al, 1999), indicating that the prevalence of APC resistance or factor V Leiden mutation in patients with isolated PE is about half the prevalence of that in patients with DVT (Table III). The prevalence of factor V Leiden in PE in our study is well within the range observed in these studies.…”

“…For example, the mean age of patients with primary PE (71 years) in the present study is much higher than in the study of Manten et al (1996) (45 years) and in the study of Martinelli et al (1997) (41 years). However, even if there are differences in methodologies and populations, one fact constantly emerges: the prevalence of factor V Leiden is more than doubled in DVT patients over isolated PE patients.…”

“…A search (MEDLINE) was performed to find similar studies with categorization of patients as having primary DVT, primary PE or both, and where DNA analysis was available (Manten et al, 1996;Baglin et al, 1997;Martinelli et al, 1997;Turkstra et al, 1999). Studies with missing data for either primary DVT or both DVT and PE were included, but studies without a group of primary PE were excluded.…”

Different risk of deep vein thrombosis and pulmonary embolism in carriers with factor V Leiden compared with non-carriers, but not in other thrombophilic defects. Results from a large retrospective family cohort study

“…We observed the factor V Leiden paradox which has been described elsewhere [4][5][6][7][8][9][10] in our population as well. As to the suggestion of different clot-structure in persons carrying factor V Leiden, which could be supposed to be due to activated protein C resistance, one would expect to also find it in other thrombophilic defects influencing activated protein C, like protein S deficiency for example.…”

“…4 This differential effect is known as the "factor V Leiden paradox" 5 and has been reported repeatedly. [6][7][8][9][10] A pathophysiological mechanism that can explain the factor V Leiden paradox is not at hand. The hypothesis that presence of factor V Leiden would often lead to fatal pulmonary embolism, resulting in a lower number of factor V Leiden carriers among those surviving pulmonary embolism and thereby explaining this paradox, has been rejected as autopsy studies have shown that among patients with fatal pulmonary embolism, the proportion of subjects with factor V Leiden did not differ from that in pulmonary embolism survivors or from the general population.…”