Canterbury DHB
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As well as many “clotting” factors (which stimulate the formation of blood clots when activated), there are other proteins in normal blood that have an anticoagulant effect. Key natural anticoagulants are Protein C, protein S, and antithrombin. Protein C becomes functional when activated (Activated Protein C).
The normal role of APC is to cleave the activated forms of Factors VIII and V, thereby impeding the development of excessive clotting. It does this by enzymatically cleaving Factors VIIIa and Va at specific loci.
Factor V Leiden is a Factor V variant with a point mutation at the APC cleavage site. At the amino acid 506, there is a change from arginine to glutamine (FVR506Q) which prevents cleavage by APC. The Prothrombin G20210A mutation enhances mRNA translation, increasing prothrombin levels and thrombotic risk.
The Leiden abnormality can be detected either by a relatively simple clotting test (APC resistance), or by direct analysis of the Factor V gene.
Thrombophillia: grading the risk. M Makris. Blood 2009; 113:5038-9.
Thrombophilic defect |
Annual risk of first DVT |
Relative risk (compared to community controls) |
Risk of recurrence |
Antithrombin deficiency Protein C deficiency Protein S deficiency |
1.52-1.90% |
15-19x |
At 5 years - 40% At 10 years - 55% |
Factor V Leiden Prothrombin 20210A High FVIII |
0.34-0.49% |
3-5x |
At 5 years - 11% At 10 years - 25% |
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Topic Code: 5196
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