The incidence of recurrent venous thromboembolism in carriers of factor V Leiden is related to concomitant thrombophilic disorders.
The duration of anticoagulant treatment after a first episode of venous thromboembolism primarily depends on the risk of recurrence. Variability of recurrence rates in factor (F) V Leiden carriers may be due to concomitant thrombophilic disorders. A retrospective study was performed in 329 FV Leiden carriers with a history of venous thromboembolism (262 probands, 67 relatives). The annual rate of first recurrence was estimated in relatives. The contribution of concomitant thrombophilic disorders to the recurrence rate was evaluated in probands and relatives by a nested case--control analysis in 105 matched pairs of carriers either with or without recurrence. The overall annual recurrence rate was 2.3 per 100 patient-years. The adjusted risk of recurrence for concomitant thrombophilic disorders was: 9.1 (1.3-62.8) for the FII mutation; 1.0 (0.2-4.9) for homozygosity for FV Leiden; 1.5 (0.2-9.5) for inherited deficiencies of protein C or S; 1.8 (0.7-4.9) for FVIII coagulant activity (FVIII:C) levels >122%; 5.4 (1.6-18.6) for fasting homocysteine levels >15.2 micromol/l; and 4.4 (1.0-18.7) for loading homocysteine levels >45.8 micromol/l. Of these disorders, only the FII mutation and hyperhomocysteinaemia significantly increased the risk of recurrence in FV Leiden carriers. The estimated recurrence rate ranged from 0.45 per 100 patient--years after a secondary first event in the absence of concomitant disorders to 4.8 per 100 patient-years when a spontaneous first event was combined with concomitant disorders. Our study provides supportive evidence that the incidence of recurrent venous thromboembolism in heterozygous FV Leiden carriers depends on the concomitance of other thrombophilic disorders, in addition to whether the first thrombotic event occurred spontaneously.
Meinardi
Johan R
JR
Division of Haemostasis, Thrombosis and Rheology, University Hospital, Groningen, The Netherlands. j.r.meinardi@mzh.nl
Middeldorp
Saskia
S
de Kam
Pieter J
PJ
Koopman
Maria M W
MM
van Pampus
Elisabeth C M
EC
Hamulyák
Karly
K
Prins
Martin H
MH
Büller
Harry R
HR
van der Meer
Jan
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002648:Child; D005165:Factor V / Q000032:analysis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013923:Thromboembolism / Q000209:etiology* / Q000235:genetics; D019851:Thrombophilia / Q000150:complications*; D020246:Venous Thrombosis / Q000209:etiology* / Q000235:genetics
C095381:factor V Leiden; D005165:Factor V