Hereditary thrombophilias (hereditary thrombophilias), ie coagulation disorders, are some diseases in which the blood tends to clot with a simple definition. In these diseases, problems such as vascular occlusion due to blood clotting (thromboembolism), formation of clots in organs such as the heart, lungs and brain, pregnancies resulting in miscarriage or stillbirth or intrauterine growth retardation are experienced. Here, the problems caused by hereditary thrombophilias related to pregnancy will be explained. An increase in pregnancy losses is observed in patients with hereditary thrombophilia, but an increase in pregnancy losses is not observed in people with thrombophilia “carriers”.
Hereditary thrombophilias are hereditary, that is, congenital acquired diseases that can be passed from generation to generation depending on genetic disorders. There are also non-congenital and acquired types of thrombophilias (such as antiphospholipid antibody syndrome).
In these patients, the risk of developing obstruction due to clot formation in the veins increases in cases such as trauma, immobility, surgery, use of birth control pills, pregnancy, and cancer. It is absolutely inconvenient for patients with thrombophilia to use birth control pills.
Hereditary thrombophilias:
- Antithrombin III deficiency
- Protein C deficiency
- Protein S deficiency
- Factor V Leiden mutation
- Activated protein C resistance (usually due to Factor V Leiden mutation)
- Prothrombin (Factor II) gene mutation
- MTHFR gene mutation (Methylene tetrahydrofolate reductase)
- Hyperhomocysteinemia
- Thrombomodulin mutation
- Factor 12 deficiency
Antithrombin III deficiency is the most thrombogenic of the hereditary thrombophilic diseases, and patients are at a lifetime risk of more than 50% thromboembolic events (vascular occlusion).
There is no clear information that prothrombin gene mutation or thrombomodulin gene mutation is responsible for poor pregnancy outcomes.
Diagnosis:
Some tests are performed on the suspicion of thrombophilic disease in those who have had vascular occlusion at an early age, those with a family history of vascular occlusion, those with recurrent miscarriages or stillbirths, and those with preeclampsia or growth retardation whose pregnancies started in early months.
These tests are:
- Antithrombin III,
- Protein C,
- Protein S,
- Activated protein C resistance (if positive, Factor V Leiden mutation search),
- Lupus anticoagulant,
- Anticardiolipin antibodies.
While total protein S level does not change during pregnancy, free protein S level decreases. It should be noted that Activated protein C resistance (falsely suggestive of factor V Leiden mutation) increases during pregnancy. These tests should be done during the non-pregnancy period. Functional and antigenic protein C levels do not change during pregnancy.
Treatment:
Since the risk of developing thromboembolism is highest in those with antithrombin III deficiency, they are always treated with a full dose of heparin (anticoagulant drug) throughout their pregnancy. If there is a history of thromboembolic events before pregnancy or if there is a history of bad pregnancy such as miscarriage, prophylactic (preventive) heparin therapy can be given to other hereditary thrombophilia patients during pregnancy. Aspirin therapy is often added to heparin therapy. Treatment is continued orally for 6 weeks after delivery.
Considering that 70% of women with Antithrombin III (AT III) deficiency will experience thrombosis during pregnancy, it seems reasonable to treat these women with heparin throughout their pregnancy. When compared to antithrombin deficiency, prophylactic treatment with heparin during pregnancy is controversial in women with protein C and Protein S deficiency, Factor V Leiden and Prothrombin gene mutation, unless there is a history of thromboembolic events or bad pregnancy, and there are no clear results on the subject. If there is a history of recurrent miscarriage in women with hereditary thrombophilia, empiric treatment with heparin and aspirin is recommended during pregnancy, but it is reported that more studies are needed to clarify this situation because the relationship between hereditary thrombophilias and recurrent miscarriages has not been clearly proven by studies to date. Therefore, the treatments given are not evidence-based, but empirical.
Patients with thrombophilia are treated with heparin if a condition such as vascular occlusion develops at any time other than pregnancy. In cases where the risk of developing vascular occlusion will increase, such as pregnancy, surgery or inactivity, proflactive heparin treatment is started beforehand.