Vol 5, No 3 (2014)
Review paper
Published online: 2014-11-20

open access

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Laboratory and genetic evaluation of antithrombin, protein C and protein S deficiency in patients following thrombotic events

Magdalena Szymańska, Ewa Wypasek, Anetta Undas
Hematologia 2014;5(3):213-227.

Abstract

Inherited deficiencies of natural anticoagulants such as antithrombin (AT), protein C (PC) and protein S (PS), with the prevalence of 0.02–0.17%, 0.2–0.3% and 0.5%, respectively, in the general population of Europe, are associated with an increased risk of venous thromboembolism (VTE), both spontaneous and induced by transient risk factor such as surgery. The frequency of these abnormalities — inherited in most cases in an autosomal dominant pattern — is estimated at 0.5–4.9%, 3%, 2–12% of patients after the first incident of VTE. The activity assay as the initial screening test of AT, PC or PS deficiencies is recommended. Beside the acquired causes of the deficiencies such as liver disease or pregnancy (in the case of PS deficiency), activity tests can be modified by anticoagulant treatments with heparin in case of AT and vitamin K antagonists in case of PC and PS. It is also not recommended to perform the laboratory investigation during the acute phase of thrombotic event. The laboratory investigation of congenital deficiency of anticoagulant proteins should include analysis of both functional activity and measurement of plasma concentration of AT, PC as well as PS with immunological methods. To confirm the inherited defect and identify mutations in the genes SERPINC1, PROC and PROS1 encoding the naturalanticoagulants — respectively, AT, PC and PS — direct gene sequencing is used and in some cases multiplex ligation-dependent probe amplification, which allows to detect large deletions and duplications. Testing for deficiency of AT, PC and PS are recommended by most experts in patients with unprovoked episode of VTE at a young age, especially with positive family history of thrombosis, recurrent VTE and thrombosis at unusual sites. AT deficiency with 50% risk of developing VTE during lifetime as a severe thrombophilia is an indication for life-long anticoagulant therapy. Deficiencies of PC and PS in adults after the first VTE episode are not in most cases the indication for chronic anticoagulation, unless other thrombophilias for example factor V Leiden or prothrombin G20210A mutation coexist.




Hematology in Clinical Practice