Thrombophilia and pregnancy: What do we need to know?

Ioannis Chrysanthopoulos, Reproductive-Molecular Biologist, BSc, MSc, PhDc

Miscarriage is the most common complication during a pregnancy, as about 15% of pregnancies will result in fetal loss, while 5% of women of childbearing age will experience spontaneous miscarriages (three or more miscarriages). Thrombophilia is a predisposition to clot formation and is caused either by hereditary factors (genetic mutation) or acquired factors diagnosed during a person’s lifetime. Thrombus formation may be due to the modulation of one or more factors of hemostasis, such as clotting factors, plasma proteins, blood flow and various cellular elements. Normally, pregnancy changes the hemostatic system towards a hypercoagulable state, which increases during pregnancy and especially towards the birth of the fetus. Thromboses can cause serious complications for both mother and fetus. For the mother, the risk starts from the point of conception up to the period after the birth of the fetus, with recent data suggesting that the risk is mainly concentrated in the first trimester of pregnancy. For the fetus, the main risks include placental abruption, limited fetal growth, premature fetal birth, late and early miscarriage and intrauterine death.

Hereditary thrombophilia involves mutations in major genes encoding protein C, S and APC, antithrombin III (AT III), Leiden factor, prothrombin, factors VIII, IX, XI, plasminogen inhibitor PAI-1 & PAI-2, MTHFR and homocysteine. Multiple studies have highlighted and associated various mutations in these genes with an increased risk of thrombosis during pregnancy that can lead to miscarriage.

The best-known forms of acquired thrombophilia are antiphospholipid syndrome (APS) and hyperhomocysteinemia, where the concentration of prothrombotic factors increases while anticoagulant factors decrease. In APS, women display antibodies to cardiolipin (aCL), lupus anticoagulant (LA), and β2-glycoprotein I (aβ2-GPI), which can be detected through appropriate and specific diagnostic tests. These antiphospholipid antibodies have been found in 3%-5% of cases with the presence of thrombosis and in 10%-20% of women with spontaneous abortions. In addition, the presence of these antibodies in late pregnancy complications has been associated with vascular complications in the placenta, leading to preeclampsia, fetal growth restriction and preterm delivery.

During the medical evaluation for thrombophilia, an accurate family and personal history of thrombosis, past clinical symptoms, associated pathologies and interpretation of existing risk factors are initially recorded. Subsequently, it is very important to perform a complete and detailed laboratory test. In particular, it is necessary to carry out molecular testing (PCR) in order to identify any mutations in those important genes mentioned above that are associated with hereditary thrombophilia, as well as biochemical testing of blood coagulation and total blood factors, in order to check for both hereditary and acquired factors. It is considered necessary to screen for thrombophilia in persons who have had a thrombotic episode in the past or in women with a known history of pre-eclampsia, recurrent miscarriage, restriction of fetal growth, first trimester miscarriage, mid-trimester miscarriage, placental abruption or intrauterine death.

After the identification of both hereditary and acquired thrombophilia, in an upcoming pregnancy, the management of the case by the attending doctor is adjusted accordingly, as it is possible that anticoagulant agents may be administered, such as low-molecular-weight heparin (LMWH), low-dose aspirin and unfractionated heparin (UFH), in order to prevent thrombotic events that may occur during pregnancy.

In conclusion, the causes of spontaneous abortions are multifactorial. It is necessary and essential to carry out specific and representative laboratory tests, such as molecular tests for mutations in specific genes and biochemical tests for associated factors, in order to identify the exact causes, so that an appropriate therapeutic approach can be followed. An important condition is the two-way cooperation between the treating doctor and the specialized diagnostic laboratory, in order to achieve a personalized approach to the tests according to the indications and then to make appropriate decisions for the expectant mother and the couple as a whole, so that they can have a healthy offspring.

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