Inherited thrombophilic risk factors and venous thromboembolism: distinct role in peripheral deep venous thrombosis and pulmonary embolism.
OBJECTIVE
To investigate whether the FII A(20210) mutation is associated with isolated pulmonary embolism (PE).


METHODS
Case-control study.


METHODS
Five thrombosis centers in southern Italy.


METHODS
Six hundred forty-seven consecutive referred patients with objectively documented venous thrombosis and 1,329 control subjects.


RESULTS
Medical histories were collected. The G-to-A transition at nucleotide 1691 within the factor V gene (FV Leiden) and the G-to-A transition at nucleotide position 20210 within the prothrombin gene locus (FII A(20210)), levels of anticoagulant factors, and levels of antiphospholipid antibodies were determined by standard techniques. Patients with deep venous thrombosis (DVT) of the lower extremities (n = 346) or with additional PEs (n = 175) showed similar prevalences of FV Leiden mutation (24.3% and 16.6%, respectively) and FII A(20210) mutation (14.2% and 12.6%, respectively), and similar deficiencies of natural anticoagulants (4.9% and 2.3%, respectively). In both groups, the frequencies of FV Leiden and/or FII A(20210) mutation were higher than those observed among 1,329 apparently healthy control subjects (4.8% and 4.4%, respectively; p < 0.0001). Among patients with isolated PE (n = 126), prevalences of FV Leiden (7.1%) and FII A(20210) mutation (8.7%) were similar to those of control subjects. Inherited thrombophilic abnormalities were less frequent among patients with PE only (15.6%) than among those with DVT only (37.0%; p < 0.001) or whose conditions were complicated by PE (28. 0%; p = 0.020). Adjusting for age and sex, FV Leiden mutation, FII A(20210) mutation, or both mutations were associated with DVT with PE (FV Leiden mutation: odds ratio [OR], 3.0; 95% confidence interval [CI], 1.6 to 5.5; FII A(20210) mutation: OR, 2.6; 95% CI, 1. 3 to 5.2; and both mutations: OR, 82.1; 95% CI, 7.5 to 901.2) or without PE (FV Leiden mutation: OR, 6.1; 95% CI, 4.0 to 9.3; FII A(20210) mutation: OR, 2.8; 95% CI, 1.7 to 4.8; and both mutations: OR, 167.5; 95% CI, 21.6 to 1,297.7), but not with isolated PE (FV Leiden mutation: OR, 1.2; 95% CI, 0.5 to 2.8; FII A(20210) mutation: OR, 1.2; 95% CI, 0.5 to 3.1; and both mutations: OR, 22.1; 95% CI, 1. 3 to 370.2).


CONCLUSIONS
FII A(20210) mutation is associated with DVT in the lower extremities alone or when complicated by PE, but it is not associated with isolated PE.
Margaglione
M
M
Unita' di Aterosclerosi e Trombos, Istituto di Ricovera e Cura a Carattere Scientifico "Casa Sollievo della Sofferenza," S. Giovanni Rotondo, Italy. ate.tro@operapadrepio.it
Brancaccio
V
V
De Lucia
D
D
Martinelli
I
I
Ciampa
A
A
Grandone
E
E
Di Minno
G
G
D020016:Activated Protein C Resistance / Q000235:genetics; D000225:Adenine; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D017152:Antibodies, Antiphospholipid / Q000032:analysis; D000925:Anticoagulants / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D016001:Confidence Intervals; D005165:Factor V / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006147:Guanine; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D017354:Point Mutation / Q000235:genetics; D011516:Prothrombin / Q000235:genetics; D011655:Pulmonary Embolism / Q000209:etiology*; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D013923:Thromboembolism / Q000209:etiology*; D019851:Thrombophilia / Q000235:genetics*; D020246:Venous Thrombosis / Q000209:etiology*
D017152:Antibodies, Antiphospholipid; D000925:Anticoagulants; C095381:factor V Leiden; D006147:Guanine; D005165:Factor V; D011516:Prothrombin; D000225:Adenine