Associations between high factor VIII and low free protein S levels with traditional arterial thrombotic risk factors and their risk on arterial thrombosis: results from a retrospective family cohort study.
BACKGROUND
Whether high factor (F)VIII and low free protein S levels are risk factors for arterial thrombosis is unclarified.


METHODS
In a post-hoc analysis of a single-centre retrospective family cohort, we determined if these two proteins could increase the risk of arterial thrombosis. In total, 1399 relatives were analysed.


RESULTS
Annual incidence in relatives with high FVIII levels was 0.29% (95%CI, 0.22-0.38) compared to 0.13% (95%CI, 0.09-0.19) in relatives with normal FVIII levels. In relatives with low free protein S levels, this risk was 0.26% (95%CI, 0.16-0.40), compared to 0.14% (95%CI, 0.10-0.20) in relatives with normal free protein S levels. Mean FVIII levels adjusted for age and sex were 11 IU/dL, 18 IU/dL, and 21 IU/dL higher in relatives with hypertension, diabetes mellitus, and obesity as compared to relatives without these arterial thrombotic risk factors. Moreover, a dose response relation between increasing FVIII and body mass index was found. None of these associations were shown for free protein S.


CONCLUSIONS
High FVIII and low free protein S levels seemed to be mild risk factors for arterial thrombosis. High FVIII levels were particularly observed in relatives with traditional arterial thrombotic risk factors. Free protein S levels were not influenced by these thrombotic risk factors. This assumes that low free protein S levels were genetically determined.
Mulder
René
R
Division of Haemostasis and Thrombosis, Department of Haematology, University Medical Centre Groningen, Groningen, The Netherlands. r.mulder@lc.umcg.nl
van Schouwenburg
Inge M
IM
Mahmoodi
Bakhtawar K
BK
Veeger
Nic J G M
NJ
Mulder
André B
AB
Middeldorp
Saskia
S
Kluin-Nelemans
Hanneke C
HC
Lijfering
Willem M
WM
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017293:Protein S / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology*
D017293:Protein S; D005169:Factor VIII