Canterbury DHB


Physiological Anticoagulants

Natural Anticoagulants

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.

Molecular Defect

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.

Laboratory Tests

The Leiden abnormality can be detected either by a relatively simple clotting test (APC resistance), or by direct analysis of the Factor V gene.

Thrombotic Risk

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



At 5 years - 40%

At 10 years - 55%

Factor V Leiden

Prothrombin 20210A




At 5 years - 11%

At 10 years - 25%

About this Canterbury DHB document (5196):

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Last Reviewed:

August 2016

Next Review:

August 2018


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Topic Code: 5196