Background: An elevated plasma level of factor VIII:C (FVIII:C) is a strong and dose-dependent risk factor for venous thromboembolism (VTE). The cause of elevated FVIII:C in patients with thrombophilia is as yet unknown. FVIII:C increases significantly after infusion of epinephrine, vasopressin or physical exercise. The aim of the present study was to investigate whether beta-receptor blockade will lower sustained elevated FVIII:C in patients with VTE.
Methods and results: Two cohorts of patients with documented deep vein thrombosis and an elevated FVIII:C (>175 IU dL(-1)) and healthy volunteers, were studied. One cohort was treated with the beta-receptor blocker, whereas the other cohort served as non-treatment controls. The patient treatment group and healthy volunteers were given 40 mg propranolol, thrice daily, for 14 days. The mean baseline level of FVIII:C was 220 IU dL(-1) and 102 IU dL(-1) in patients and healthy volunteers, respectively. After 2 weeks of propranolol a significant 23% reduction of FVIII:C (- 52 IU dL(-1); 95%CI:[-65; -39]) compared with no change over time in the patient no- treatment group (-1.8 IU dL(-1); 95%CI:[-34; 30]). After discontinuation of propranolol FVIII:C returned to its initial high level. In healthy volunteers propranolol had no effect on the plasma concentration of FVIII:C.
Conclusion: This study demonstrates that in patients with VTE a sustained elevated FVIII:C concentration can be decreased with the use of propranolol. This observation may be of potential clinical relevance, since it has been shown that each increase of 10 IU dL(-1) in FVIII:C concentration enhanced the risk of a recurrent VTE by 24%.