Hereditary Thrombophilia and Pregnancy Complications

Thrombophilia is a predisposition to thrombosis associated with particular inherited or acquired factors. It does not mean that a clot will inevitably form. Risk depends on the specific disorder, personal and family history and accompanying circumstances.

Pregnancy and the postpartum period themselves increase venous thromboembolism risk. Physiological coagulation changes help limit bleeding at delivery, but together with venous stasis and other factors create conditions favoring thrombosis. Previous thrombosis, surgery, prolonged immobility and certain illnesses also matter.

Inherited and Acquired Conditions

Clinically established inherited thrombophilias include factor V Leiden (F5), the prothrombin G20210A variant (F2), and deficiencies of antithrombin, protein C or protein S. Their risks differ; results are interpreted in the clinical context.

Antiphospholipid syndrome (APS) is a distinct acquired autoimmune thrombophilia that can cause thrombosis and certain obstetric complications. Lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I testing is not equivalent to an inherited-polymorphism panel. APS diagnosis requires appropriate clinical findings and persistent laboratory abnormalities.

Pregnancy Loss and Placental Complications

Recurrent pregnancy loss, fetal growth restriction, preeclampsia, placental abruption and IVF failure have different, often multifactorial causes. They cannot automatically be attributed to inherited thrombophilia. Evidence linking individual inherited disorders with these outcomes is inconsistent; the claim that inherited thrombophilia explains at least 60% of pregnancy complications is unsupported.

Routine inherited thrombophilia testing solely because of recurrent pregnancy loss is not recommended. This includes factor V Leiden, F2, antithrombin, proteins C/S, MTHFR and homocysteine. APS testing for justified obstetric indications is considered separately.

Common MTHFR and SERPINE1/PAI-1 variants should not be used as proof of clinically significant thrombophilia or grounds for anticoagulation. Polymorphisms in folate metabolism, the renin–angiotensin system and the kallikrein–kinin system likewise do not replace established assessment of thrombosis or obstetric disease.

When Testing Is Considered

Selective testing may be useful with certain personal histories of venous thrombosis or a known high-risk thrombophilia in the family, if the result will change prevention or treatment. The clinician selects tests and timing: pregnancy, acute thrombosis and anticoagulants can affect some measurements.

Prevention and treatment are determined jointly by the obstetrician and, when needed, a hematologist. A positive genetic result alone does not make aspirin or heparin mandatory or demonstrate that they will improve pregnancy outcomes. Sudden breathlessness, chest pain or painful swelling of one leg requires urgent medical assessment.

See also: clinically significant variants in blood coagulation genes.