Factsheet
Condition:
Thrombophilias
Inheritance:
Genetically heterogeneous; most common autosomal dominant (with more severe manifestations in homozygote)
Genetic Etiology:
Thrombophilias result from mutation in genes involved in limiting the extent of the blood clotting reaction. The most common form is due to mutation in the F5 gene that encodes factor V, rendering the protein resistant to cleavage by activated protein C. The most common F5 mutation is a G to AAC change at nucleotide 1691, referred to as Factor V Leiden. The second most common is a G to A change at position 20210 in the F2 gene (encoding prothrombin). Less common causes involve mutations in genes for protein C or protein S.
Frequency:
Factor V Leiden : heterozygosity in 3-8% of individuals in Europe and USA ; factor II: heterozygosity in 2-5%
Clinical features:
Thrombophilias present most often with venous thromboembolism, particularly in settings of prolonged inactivity, such as post-surgery. Heterozygotes for Factor V Leiden face a 4-8 increased relative risk of thrombosis, whereas homozygote risk is increased up to 80 fold. Risk is also increased in the presence of heterozygosity for mutations in F5 and F2.
Management:
Avoidance of situations that would increase risk of thrombosis, if possible; anti-coagulation for thrombotic episodes.
Genetic counseling:
Transmitted as dominant traits with incomplete penetrance; both genetic and hematological testing available.