Predictive value of factor VIII levels for recurrent venous thrombosis: results from the MEGA follow-up study.
BACKGROUND
Prediction of recurrent venous thrombosis remains a challenge in the clinic.


OBJECTIVE
To investigate the predictive value of coagulation factor VIII (FVIII) levels for recurrent venous thrombosis.


METHODS
Patients, aged 18-70 years with a first venous thrombosis, were followed from discontinuation of anticoagulant treatment (1999-2010 MEGA follow-up study). The levels of FVIII activity, FVIII antigen and von Willebrand factor (VWF) antigen were measured at least 3 months after cessation of anticoagulant treatment.


RESULTS
Of 2242 patients followed for a median of 6.9 years, 343 developed recurrent thrombosis (incidence rate 2.7/100 patient-years; 95% confidence interval [CI] 2.5-3.1). Recurrence rates steadily increased with higher FVIII activity levels, from 1.4 (95% CI 1.0-1.9), 2.3 (95% CI 1.8-2.9), 3.0 (95% CI 2.4-3.7), 3.2 (95% CI 2.5-4.1), 3.9 (95% CI 2.8-5.3) to 5.1 (95% CI 3.8-6.8) per 100 patient-years, for levels ranging from < 100 IU dL(-1) to > 200 IU dL(-1) . Patients in the highest category of FVIII (> 200 IU dL(-1) ) had a three-fold higher recurrence rate than patients in the lowest category (≤ 100 IU dL(-1) ) (hazard ratio 3.4; 95% CI 2.2-5.3). Results were similar for FVIII antigen and VWF antigen levels, in several sensitivity analyses, and FVIII predicted recurrence rates over a long time period. Within subgroups of patients currently assumed to have low recurrence risks, a high level of FVIII was still predictive for recurrences. Adding FVIII to an existing prediction model (DASH score) improved its predictive value, and, after replacement of D-dimer with FVIII, the model performed equally well, if not better.


CONCLUSIONS
FVIII predicted recurrence in a dose-response fashion, overall and in several subgroups, and is a strong candidate component of recurrence prediction tools.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
J F
JF
Timp
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.|Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
W M
WM
Lijfering
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
L E
LE
Flinterman
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
A
A
van Hylckama Vlieg
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.|Department of Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands.
S
S
le Cessie
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.|Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
F R
FR
Rosendaal
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
S C
SC
Cannegieter
D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011237:Predictive Value of Tests; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D055815:Young Adult
D000925:Anticoagulants; D015415:Biomarkers; C078147:F8 protein, human; D005169:Factor VIII
epidemiology; factor VIII; recurrence; risk assessment; venous thrombosis