attomol^® Factor II+V Duplex Realtime LT

In the coagulation cascade, factor V together with activated factor X, phospholipids, and calcium ions forms a complex (prothrombin activator) capable of converting prothrombin (factor II) into thrombin, which ultimately causes fibrin polymerization. The mutation 20210G>A is located in the 3'-UTR from the prothrombin gene and
results in increased expression [2]. This mutation causes an increased level of plasma prothrombin. The resulting accumulation of thrombin in the blood leads to an increased tendency to clot, resulting in a higher risk of thrombosis in affected patients [1]. The risk of VTE (venous thromboembolism) is increased 2- to 4-fold in heterozygous carriers of the allele (20210G>A) [1][3][4] and 5-fold in homozygous carriers compared with carriers of the wild-type allele [4].
The inactivation of factor V occurs through the activated protein C (APC). The substitution of guanine (G) for adenine (A) at position 1691 of the factor V gene results in an amino exchange in the binding site for APC. This amino exchange leads to the fact that factor V can only be insufficiently cleaved and thus inactivated [5]. The resulting accumulation of factor V in the blood leads to an increased coagulation tendency, which results in a higher risk of thrombosis in the affected patients. Homozygous mutations in the factor V gene lead to a significantly higher risk than heterozygous defects [6]. The risk of VTE (venous thromboembolism) is increased 3-5-fold in heterozygous carriers of the allele (1691G>A) and 10-80-fold in homozygous carriers, compared to carriers of the wild-type allele [7].
Prothrombin testing is recommended in the following cases: first VTE at a young age (<50 years), recurrent VTE, VTE at unusual sites such as cerebral, mesenteric, portal or hepatic veins, VTE during pregnancy, VTE associated with oestrogen-containing oral contraceptives or hormone replacement therapy, VTE in patients with first-degree relatives who have developed VTE at an age <50 years [9].
Genetic testing for the prothrombin mutation is not recommended as screening and the Society of Angiology does not recommend testing in healthy individuals [8]. The guidelines "Diagnosis of venous thrombosis and pulmonary embolism" of the Society of Angiology consider genetic diagnosis to be useful if it can change the therapeutic approach or prevent a recurrence of the thromboembolic disease [8].
The AWMF guidelines of 2023 recommend the determination of the factor V Leiden mutation (FVL mutation) in patients younger than 50 years with an accumulation of thromboembolism in first-degree relatives. Testing of healthy individuals is not recommended, but is still under discussion [8].

[1] Poort S.R. et al.: A common genetic variation in the 3´-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996, 88:3698-3703.
[2] Ceelie H. et al.: G20210A is a functional mutation in the prothrombin gene; effect on protein levels and 3’-end formation. J Thromb Haemost. 2004, 2(1):119-27.
[3] Brown K. et al.: Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3´-untranslated region of the prothrombin gene. Br J Haematol 1997, 98:907-909.
[4] Shemesh et. al: Clinical significance of prothrombin G20210A mutation in homozygous patients. Am J Hematol 2017, 92, 10:618-620.
[5] Bertina R. et al.: Mutation in blood coagulation factor V associates with resistance to activated protein C. Letters to Nature, 1994, 3697, 64-67.
[6] Zöller B. et al.: Thrombophilia as a multigenic disease. Haematologica, 1999, 84, 59-70.
[7] Kujovich J. L.: Factor V Leiden thrombophilia. Genet Med, 2011, 13, 1-16.
[8] Gesellschaft für Angiologie - Gesellschaft für Gefäßmedizin: Diagnostik und Therapie der Venenthrombose und der Lungenembolie. AWMF, 2023, Leitlinien-Register Nr. 065/002, Klasse S2k.
[9] Kujovich: Prothrombin Thrombophilia. 2006 [updated 2021]. In: Adam M. P. et al., editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.

• Oligomix Factor II+V Duplex LT
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