Hereditary thrombophilia, pregnancy and the risk of miscarriages

Thrombophilia is a disorder associated with an increased tendency to develop thrombotic events. A venous or arterial thrombotic event occurs when the blood forms a clot inside a blood vessel , adheres to its wall and obstructs it, preventing normal blood flow; the clot is called a thrombus.

The condition of thrombophilia can be associated with congenital anomalies of one or more blood coagulation factors, hereditary thrombophilia , but it can also be linked to alterations or pathologies that have arisen over time ( acquired thrombophilia ). The diagnostic suspicion of hereditary thrombophilia is based on the presence of certain clinical features , such as recurrent thrombotic events, family history of thrombosis, idiopathic thrombosis (i.e. with no apparent cause) and in unusual locations, thrombosis at a young age or during pregnancy and the puerperium.

The presence of congenital coagulation abnormalities will be confirmed by performing a blood coagulation screening , i.e. a series of specific blood tests.

Among the most important causes of hereditary thrombophilia I mention:

• The V factor Leiden
• The prothrombin G20210A mutation
• The defects of natural anticoagulants (Protein C, protein S and antithrombin III)
• Mutations of methylenetetrahydrofolate reductase (MTHFR C677T, MTHFR 1298C)

The V factor of Leiden

Factor V Leiden is caused by a mutation in the gene that codes for factor V coagulation. This mutation can be in the heterozygous form , involving an approximately 8 times higher risk of developing venous thrombosis, or in the homozygous form, involving an up to 80 times higher risk.

The finding of resistance to activated protein C is usually due to the presence of factor V Leiden.

Prothrombin mutation

The prothrombin gene mutation , also called prothrombin variant G20210A , affects coagulation factor II; in heterozygous form it carries a 3-fold higher risk of developing venous thrombosis, 5-fold higher risk of developing ischemic stroke or myocardial infarction and 10-fold higher cerebral vein thrombosis.

MTHFR mutations

The homozygous form is rare. Antithrombin III deficiency is uncommon but carries a high thrombotic risk. Protein C or protein S deficiency lead to a thrombotic risk of less than 10% in pregnancy and less than 20% in the puerperium. The mutation of methylenetetrahydrofolate reductase (MTHFR C677T or more rarely MTHFR 1298C),in the homozygous form, it can be associated with an increase in homocysteinemia levels, responsible for an increased risk of cardiovascular thrombotic events. The presence of the MTHFR mutation in heterozygosity appears to be less relevant and the presence of the MTHFR mutation in the presence of normal homocysteine ​​levels appears to have no relevant clinical implications. Folic acid and vitamin B supplementation helps reduce homocysteine ​​levels; in addition, pregnancy involves a slight reduction in homocysteine. The association of multiple hereditary thrombophilic defects increases the thrombotic risk ^[1] .

Pregnancy and hypercoagulability

Pregnancy is already in itself characterized by physiological hypercoagulability , induced by an increase in almost all coagulation factors and by a reduction in some anticoagulant and fibrinolytic factors. Furthermore, at the time of delivery, particular substances are released at the tissue level, called thromboplastins, which activate the coagulation cascade; finally, also the cesarean section, due to the increased permanence in bed to which one is subject, increases the risk of thromboembolic events. Therefore, the presence of a hereditary thrombophilic defect further increases the risk of thrombosis during pregnancy; it is estimated that hereditary thrombophilia may be responsible for about 50% of thrombosis in pregnancy and postpartum. Thrombophilic defects may in some cases be associated with an increased risk of adverse pregnancy events such as spontaneous (and sometimes recurrent) abortions, abruptio placentae, pre-eclampsia and HELLP syndrome ^[2] .

Furthermore, other acquired thrombophilic risk factors should not be forgotten , which can be associated with the hereditary thrombophilic factors mentioned above: trauma, antiphospholipid antibody syndrome, hormonal therapies, tumors, inflammatory bowel disease, vasculitis, paroxysmal nocturnal hemoglobinuria and some kidney diseases.

Based on the specific clinical history and the type of any thrombotic risk, your doctor will establish whether some “preventive” measures are necessary ; in some cases the administration of prophylactic doses of low molecular weight heparin and possibly low doses of aspirin may reduce the risk of thrombotic complications or adverse events in pregnancy.