Evidence of a U-shaped association between factor XII activity and overall survival.
BACKGROUND
The clinical relevance of decreased coagulation factor XII (FXII) plasma activity as a risk factor for both venous and arterial thrombosis is still discussed controversially. The current study evaluated the predictive value of FXII levels for all-cause mortality in a large Viennese patient cohort.


METHODS
Individuals, whose FXII activity levels were determined for suspected coagulation disorders or thrombophilia screening between 1991-2003 were included in this study (n = 8936, 51% male, 49% female, median age 43 years). Death/survival was determined by record linkage with the Austrian Death Registry. The median observation period was 5 years covering a total of 46 400 person years; the death rate was 17.1%. For Cox regression analysis, FXII plasma activity was divided into 11 categories of 10% steps with the category of > 100% FXII serving as a reference category.


RESULTS
With decreasing FXII plasma activity, hazard ratios for all-cause mortality gradually increased linearly from 1.0 in the > 100% category to 1.5 (95% CI: 1.2-1.9) in the 80-90% category to 4.7 (95% CI: 3.4-6.5) in the 10-20% category. Similar results were obtained, when only vascular mortality or death as a result of ischemic heart disease was considered. No significant increase in all-cause mortality (HR: 1.4, 95%CI 0.7-2.8) was observed in the small group of FXII-deficient subjects [0-10% category (n = 58)].


CONCLUSIONS
This study first demonstrates a strong and almost linear association of FXII plasma activity between 90% and 10% with all-cause mortality in a large Viennese patient cohort. Interestingly, mortality rates are not increased when FXII activity is below 10%, resulting in a U-shaped survival curve.
Endler
G
G
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria.
Marsik
C
C
Jilma
B
B
Schickbauer
T
T
Quehenberger
P
P
Mannhalter
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D015982:Bias; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005174:Factor XII / Q000378:metabolism*; D005175:Factor XII Deficiency / Q000097:blood* / Q000401:mortality*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D015996:Survival Rate
D005174:Factor XII