Antiphospholipid Syndrome in Pregnancy

Antiphospholipid syndrome in pregnancy is an autoimmune condition with persistent antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti beta 2 glycoprotein I), causing thrombosis or pregnancy morbidity. It is a treatable cause of recurrent miscarriage, stillbirth, severe preeclampsia and placental insufficiency. It matters because aspirin and heparin improve live birth rates.

• Diagnosis needs a clinical event and antibodies positive on 2 occasions at least 12 weeks apart.
• Obstetric events: 3 or more consecutive losses before 10 weeks, a fetal death after 10 weeks, or delivery before 34 weeks for severe preeclampsia or placental insufficiency.
• Thrombotic disease needs full dose anticoagulation.

Women have a history of miscarriages, stillbirth, early severe preeclampsia, growth restriction, or venous or arterial thrombosis. Examine for livedo reticularis, leg swelling and hypertension.

• Thrombosis in unusual sites.
• Often coexists with systemic lupus erythematosus.
• Differential diagnosis: sporadic miscarriage, systemic lupus erythematosus, inherited thrombophilia, preeclampsia from other causes, thrombotic thrombocytopenic purpura, HELLP syndrome.
• Complications: recurrent miscarriage, preeclampsia, fetal growth restriction, placental abruption, stillbirth, preterm birth, venous and arterial thrombosis, catastrophic antiphospholipid syndrome.

The approach is repeated antibody testing with fetal and maternal surveillance.

• Lupus anticoagulant, anticardiolipin IgG and IgM, anti beta 2 glycoprotein I IgG and IgM; repeat at 12 weeks; lupus anticoagulant is tested before starting heparin.
• Full blood count (platelets), creatinine, urine protein to creatinine ratio, blood pressure, antinuclear antibody and anti dsDNA.
• Uterine artery Doppler at 20 to 24 weeks; growth scans every 4 weeks from 24 weeks; umbilical artery Doppler.
• Cardiotocography from 32 weeks if growth is poor.

The principle is aspirin with prophylactic or therapeutic heparin guided by the clinical history, with close surveillance.

• Supportive: stop smoking; control blood pressure; avoid oestrogen containing contraception; early booking; regular scans.
• Pharmacological: obstetric antiphospholipid syndrome only: aspirin 75 to 150 mg oral at night from before conception or booking until 36 weeks, plus enoxaparin 40 mg subcutaneous daily from a positive pregnancy test and for 6 weeks after delivery; previous thrombosis: aspirin 75 to 150 mg oral daily plus enoxaparin 1 mg/kg subcutaneous 12-hourly throughout pregnancy and for 6 weeks postpartum; hydroxychloroquine 200 mg oral 12-hourly (maximum 5 mg/kg daily) for refractory cases or associated lupus; prednisolone 10 to 20 mg oral daily only for lupus flares; labetalol 200 mg oral every 8 to 12 hours (maximum 2.4 g daily) or nifedipine modified release 30 to 60 mg daily for blood pressure above 140/90 mmHg; warfarin 5 mg oral daily after delivery with overlap of enoxaparin for 5 days until the INR is 2 to 3 for 24 hours in women with thrombosis; do not use direct oral anticoagulants; catastrophic syndrome: methylprednisolone 1 g IV daily for 3 days, therapeutic heparin, plasma exchange and immunoglobulin 0.4 g/kg IV daily for 5 days.
• Procedures: induction or caesarean section at 37 to 39 weeks, earlier for growth restriction or preeclampsia; stop therapeutic enoxaparin 24 hours before delivery and prophylactic doses 12 hours before.
• Special groups: warfarin is avoided in pregnancy because of embryopathy; breastfeeding is compatible with warfarin, aspirin and enoxaparin.
• Red flags: leg swelling, breathlessness, chest pain, headache, visual change, blood pressure above 160/110 mmHg, reduced fetal movements, vaginal bleeding.
• Follow-up: review every 2 to 4 weeks; growth scans every 4 weeks from 24 weeks; platelets at 7 to 14 days on heparin; review at 6 weeks postpartum.