Hereditary Thrombophilias and Pregnancy
There are only a few conditions associated with an increased hereditary tendency to form blood clots (hereditary thrombophilias). They can be roughly divided into two groups:
1️⃣ Monogenic mutations:
F2 mutation / PGM — mutation in the prothrombin (Factor II) gene G20210A
F5 mutation / FVL — Factor V Leiden mutation (Factor V gene, proaccelerin)
2️⃣ Hereditary deficiencies of natural anticoagulants (serum proteins that prevent clot formation). These are also due to mutations, but are more diverse and harder to detect. The main ones are: antithrombin III, protein C, and protein S.
At present, let’s focus on the first two mutations — F2 and F5. They are relatively easy to detect by molecular methods, and many genetic laboratories offer testing. In addition to these two, labs often include a dozen other so-called “polymorphisms of coagulation genes” in their packages.
❓ Which tests should be done, when, and most importantly — for whom?
❌❗ The test that should not be done is “screening for polymorphisms of coagulation system genes.” These markers are often called mutations, but this is incorrect. True mutations are rare, while polymorphisms are common variants of genes.
Most of us carry one or more polymorphisms in coagulation-related genes. This list often includes, but is not limited to:
MTHFR c.665C>T, MTHFR c.1286A>C
MTR c.2756A>G, MTRR c.66A>G
F13 c.103G>T, FGB c.-467G>A
ITGA2 c.759C>T, PAI-1 (SERPINE1) –675 5G>4G
These genetic markers are not relevant for diagnosing hereditary thrombophilias. ⛔
👉 For example, 10–30% of the population may be homozygous for the so-called “risk” allele of one of these genes, yet thrombotic events occur in less than 1% of cases. This means that the vast majority of “carriers” never experience thrombosis, even when they acquire additional risk factors. ⚠️
Clinical Relevance of F2 and F5
F2 and F5 mutations, especially in homozygous form or in compound heterozygosity, increase the risk of venous thromboembolism (VTE) during pregnancy.
Testing can be performed before, during, or after pregnancy.
❓ Who should be tested for F2 and F5 mutations?
📢 Genetic testing for F2 and F5 mutations is recommended in women planning pregnancy if they have: 🔴 A personal history of thrombosis / thromboembolism, and/or 🔴 A first-degree relative with a high-risk thrombophilia.