Oral contraceptive use in women with poor anticoagulant response to activated protein C but not carrying the factor V Leiden mutation increases the risk of venous thrombosis.
The factor V Leiden mutation (FVL), associated with reduced sensitivity to activated Protein C (APC), is a risk factor for venous thromboembolism (VTE) and displays a strong interaction with oral contraceptives (OC). The aim of this study was to evaluate the risk of VTE in OC users with reduced APC sensitivity unrelated to the FVL. APC sensitivity was measured by an original aPTT-based test (without sample pre-dilution in factor V-deficient plasma) in 195 women who suffered from VTE in reproductive age and in 487 healthy women with results being expressed as normalized ratio. Subjects with currently known clinically relevant thrombophilic alterations were excluded. APC normalized ratios were stratified into quartiles. The adjusted ORs of subjects in the lower quartile (>/= 0.90) was 2.46 (95%CI: 1.02-5.95). Of the 195 patients, 89 had suffered VTE during OC. The 181 healthy women who had used OC for at least 6 months in the two year period before presentation but who had stopped OC at least 3 months before blood sampling were considered OC users. The risk of VTE in subjects using OC with APC normalized ratio in the lower quartile was increased 4.9-fold (95% CI: 1.92-12.6). In conclusion, our results showed that altered APC resistance in women not carrying the FVL significantly increased the VTE risk, albeit to a lesser extent than in women also carrying the FVL. Our data also showed that OC use in women with altered APC resistance further increased the risk of VTE in a way that exceeded the additive expectation.
Legnani
Cristina
C
Dept. Angiology and Blood Coagulation, University Hospital S. Orsola-Malpighi, Via Massarenti, 9, 40138, Bologna, Italy. legnanic@tin.it
Cini
Michela
M
Cosmi
Benilde
B
Mattarozzi
Silvia
S
Lo Manto
Giuseppa
G
Palareti
Gualtiero
G
D020016:Activated Protein C Resistance / Q000150:complications* / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000009:adverse effects*; D005165:Factor V; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk; D020246:Venous Thrombosis / Q000139:chemically induced / Q000209:etiology*
D000925:Anticoagulants; D003276:Contraceptives, Oral; C095381:factor V Leiden; D005165:Factor V