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Factor V Leiden: an additional risk factor for thrombosis in protein S deficient families?
B P Koeleman1, D van Rumpt, K Hamulyák
1Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital, Leiden.
Insights
The Factor V Leiden mutation significantly increases thrombosis risk in individuals with protein S deficiency. Combining both genetic factors leads to an 80% thrombosis rate in affected families.
Area of Science:
- Genetics
- Hematology
- Thrombosis Research
Background:
- Protein S deficiency is a known risk factor for thrombosis.
- The Factor V Leiden mutation (FVL) causes Activated Protein C resistance, another thrombophilia risk factor.
Purpose of the Study:
- To investigate the prevalence of the Factor V Leiden mutation in protein S deficient individuals.
- To assess the combined risk of FVL and protein S deficiency for thrombosis.
Main Methods:
- Study included 16 symptomatic protein S deficient probands.
- Genetic analysis for Factor V Leiden mutation.
- Family segregation analysis of FVL and protein S deficiency.
Main Results:
- Prevalence of FVL in protein S deficient probands was 38%, significantly higher than in the general population.
- In families with both FVL and protein S deficiency, 80% of symptomatic individuals had both abnormalities.
- Individuals with only FVL or only protein S deficiency also showed a notable incidence of thrombosis.
Conclusions:
- The combination of Factor V Leiden mutation and protein S deficiency is associated with a substantially elevated risk of thrombosis.
- The study highlights the importance of genetic screening for thrombophilia risk assessment.
Abstract:
We recently reported a high prevalence of the FV Leiden mutation (R506Q, responsible for Activated Protein C resistance) among symptomatic protein C deficient probands (19%), and the involvement of the FV Leiden mutation in the expression of thrombophilia in six protein C deficient families. Here, we report the results of a similar study in protein S deficient probands and families. Among 16 symptomatic protein S deficient probands the prevalence of the FV Leiden mutation was high (38%). This high prevalence is significantly different from that in the normal population, and is probably caused by the selection of probands for familial thrombosis and protein S deficiency. In 4 families, the segregation of the FV Leiden mutation and the protein S deficiency could be studied. In sibships where both abnormalities were segregating, the percentage of symptomatic individuals with both abnormalities was 80%. Three of the seven subjects with only the FV Leiden mutation, and two out of the three subjects with only protein S deficiency had developed thrombosis. These results indicate that in the families presented here the combination of the FV Leiden mutation and the protein S deficiency is associated with a high risk for thrombosis. A reliable estimate of the penetrance of the single defects is not possible, because the number of individuals with a single defect is too low.