Summary
Factor VIII activity (factor VIII:C) levels ≥150 IU/dl are associated with a 5- to
6-fold increased risk of venous thrombosis compared to levels <100 IU/dl, and fibrinogen
levels ≥5.0 g/l increase the thrombosis risk 4-fold. These high levels are present
in 25% resp. 3% of the patients with a first episode of venous thrombosis. These findings
were based on measurements after the thrombotic event, so the factor VIII and fibrinogen
levels in thrombosis patients may have been influenced by acute phase reactions or
ongoing inflammatory responses. In the present study we measured plasma C-reactive
protein (CRP) as a sensitive marker of an acute phase reaction in 474 thrombosis patients
and 474 age- and sex-matched healthy controls, that were part of the Leiden Thrombophilia
Study (LETS). Mean and median CRP levels were higher in thrombosis patients than in
the controls, suggesting inflammation in some patients. CRP affected both factor VIII
and fibrinogen levels, in patients and controls alike. After adjustment for the effect
of CRP, high factor VIII:C levels still increased the thrombosis risk 6-fold and high
fibrinogen levels 4-fold, which is for both very similar to the risk before correction
for CRP levels. These results show that although systemic inflammation may be present
in some of the patients, elevated levels of factor VIII:C and fibrinogen were in general
not caused by acute phase reactions. This further supports a causal relationship between
both high factor VIII:C and fibrinogen levels and venous thrombosis.
