Venous thromboembolism with special focus on genetic and potential acquired risk factors

University dissertation from Lund University, Faculty of Medicine

Abstract: Venous thromboembolism (VTE) is a relatively common cause of morbidity and mortality. It has an annual incidence of around 0.1- 0.3%. It is a multifactorial disease with many known risk factors, both transient and persistent. Among these, several genetic risk factors have been described. The most common genetic risk factor, factor V Leiden mutation in heterozygote form, is found in 5-8% of the Caucasian population. Although much is known about the VTE disease, evaluating the recurrence risk, duration and risk of the anticoagulation therapy remains a challenge and many questions are still unanswered. The aims of this thesis are to evaluate the distribution and clinical impact of the most common inherited risk factors for VTE in a population based total material from southern Sweden as well as estimating heterozygous FVL mutation as a risk factor for VTE recurrence. Furthermore, to look into other potential acquired risk factors for VT, such as inflammation in a male cohort from a screening program and, finally, evaluate the risk for bleeding in relation to renal function within VTE patients on warfarin treatment in a cohort from a Swedish national quality registry for anticoagulation (AuriculA). The prevalence of the FVL mutation in heterozygous form was found in approximately one fourth of the VTE patients and increased the risk for recurrence significantly, by 2-3 fold. The mutation in homozygous form is much less frequent but these patients had a higher average age at first thrombosis than many studies previously described. Furthermore, homozygous women were affected at an earlier age compared to men and female controls and it appeared that thrombi in homozygous FVL were more prone to be in the lower extremity. The odds ratio for thrombosis was lower than previously described. The risk for VTE in relation to the number of raised inflammatory specific proteins (ISPs), i.e. fibrinogen, haptoglobin, ceruloplasmin, alfa-1-antitrypsin and orosomucoid, as well as individual ISPs was not significantly increased. However, age, BMI and diabetes mellitus type 2 were significant risk factors for developing a VTE. On the other hand, factors such as cholesterol, triglycerides, blood pressure and smoking were not. VTE patients on anticoagulation treatment with warfarin seemed to be younger, and hence had a better renal function, than patients with other indications for warfarin therapy. Among those VTE patients there was not significantly increased bleeding with impaired renal function, although a trend could be seen.