Anticoagulation During Pregnancy

Anticoagulation in pregnancy prevents and treats venous thromboembolism and protects mechanical heart valves, while avoiding warfarin embryopathy, direct oral anticoagulant exposure and bleeding at birth. Pregnancy raises thrombosis risk 4 to 6 fold, highest in the first 6 weeks after birth.

Drug of choice. Low molecular weight heparins do not cross the placenta, have predictable effect and low rates of thrombocytopenia and osteoporosis.

Warfarin. Crosses the placenta; embryopathy with exposure at 6 to 12 weeks, central nervous system abnormalities and foetal bleeding later. Retained only for selected mechanical valve patients.

Direct oral anticoagulants. Cross the placenta with limited human data; contraindicated in pregnancy and breastfeeding.

Prophylactic low molecular weight heparin by booking weight (daily dose).

Doses of 60 mg enoxaparin or more are usually split twice daily. Duration: whole of antenatal period for high-risk women, and 10 days to 6 weeks after birth by risk.

Treatment of venous thromboembolism (early pregnancy weight).

• Enoxaparin 1 mg/kg subcutaneously twice daily (1.5 mg/kg once daily is an alternative, though twice daily is preferred in pregnancy).
• Dalteparin 100 units/kg twice daily.
• Tinzaparin 175 units/kg once daily.
• Continue for the rest of pregnancy and at least 6 weeks after birth, with a total of at least 3 months.

Unfractionated heparin. Treatment where bleeding risk or imminent birth favours rapid reversal: 80 units/kg IV bolus, then 18 units/kg/hour, adjusted to aPTT ratio 1.5 to 2.5 (or anti-Xa 0.3 to 0.7 units/mL). Prophylaxis where low molecular weight heparin is unavailable: 5000 units subcutaneously every 12 hours (7500 units in the third trimester or obesity).

Mechanical heart valves (specialist only).

• Option 1: low molecular weight heparin throughout, enoxaparin 1 mg/kg twice daily adjusted to peak anti-Xa 0.8 to 1.2 units/mL (4 to 6 hours after the dose) with trough over 0.6 units/mL.
• Option 2: warfarin throughout if the daily dose is 5 mg or less, with low molecular weight heparin from 6 to 12 weeks; target INR by valve type (usually 2.5 to 3.5 mitral, 2.0 to 3.0 aortic bileaflet).
• Switch to low molecular weight heparin or IV unfractionated heparin by 36 weeks.
• Add aspirin 75 to 100 mg daily in many units.

Antiphospholipid syndrome. Previous thrombosis: treatment-dose low molecular weight heparin plus aspirin 75 to 150 mg daily. Obstetric antiphospholipid syndrome: prophylactic low molecular weight heparin plus aspirin from a positive pregnancy test.

Heparin-induced thrombocytopenia or heparin allergy. Fondaparinux 2.5 mg daily (prophylaxis) or 7.5 mg daily (treatment, 50 to 100 kg) or danaparoid where available.

After birth. Restart low molecular weight heparin, or switch to warfarin from day 5 to 7 when bleeding risk has settled: overlap until INR is 2.0 or more on 2 consecutive days, target 2.0 to 3.0.

Contraindications. Active bleeding, placenta praevia with bleeding, platelets under 75 x 10^9/L, severe uncontrolled hypertension, recent intracranial haemorrhage, and for heparins previous heparin-induced thrombocytopenia.

Adverse effects. Bleeding, injection-site bruising, skin reactions, osteoporosis with long-term unfractionated heparin, heparin-induced thrombocytopenia (much rarer with low molecular weight heparin), hyperkalaemia.

Neuraxial and birth timing. Stop prophylactic low molecular weight heparin at least 12 hours and treatment doses at least 24 hours before planned neuraxial block or birth. Give the first prophylactic dose 4 hours after spinal anaesthesia or epidural catheter removal; treatment doses no sooner than 24 hours after a neuraxial procedure. Remove the epidural catheter no sooner than 12 hours after the last prophylactic dose.

Interactions. NSAIDs, aspirin at analgesic doses and SSRIs raise bleeding risk. Warfarin with antibiotics (metronidazole, macrolides, quinolones, co-trimoxazole), azoles and rifampicin alters INR sharply.

Reversal. Protamine sulphate fully reverses unfractionated heparin (1 mg for each 100 units given in the previous 2 hours or so, maximum 50 mg) and partly reverses low molecular weight heparin (1 mg for each 1 mg enoxaparin given within 8 hours).

Special groups.

• Kidney impairment (creatinine clearance under 30 mL/min): enoxaparin treatment 1 mg/kg once daily, prophylaxis 20 mg daily, with anti-Xa monitoring; or unfractionated heparin.
• Weight extremes: anti-Xa checks under 50 kg or over 130 kg.
• Breastfeeding: low molecular weight heparin, unfractionated heparin and warfarin are compatible; avoid direct oral anticoagulants.
• Regional: low molecular weight heparin cost and supply limit use in parts of East Africa; subcutaneous unfractionated heparin with platelet checks is the usual alternative.

Monitoring. Baseline full blood count, creatinine, liver tests, coagulation screen and weight. Anti-Xa not routine except for mechanical valves, kidney impairment, weight extremes or recurrent thrombosis on treatment: peak 4 to 6 hours after the dose, treatment target 0.5 to 1.0 units/mL (0.8 to 1.2 for valves). Platelets every 2 to 3 days from day 4 to 14 on unfractionated heparin.

Warfarin on conception. Switch to low molecular weight heparin before 6 weeks of gestation; advise early pregnancy testing in anyone on warfarin who could conceive.

Stopping rules. Stop all heparin if platelets fall by 50% or more with thrombosis or skin necrosis from day 5 to 14, and switch to a non-heparin anticoagulant. Hold doses at the onset of labour or bleeding.

Referral and escalation. Refer mechanical valves, antithrombin deficiency, thrombosis on treatment, heparin-induced thrombocytopenia and suspected pulmonary embolism with haemodynamic compromise to a haematology and obstetric medicine team immediately. Massive pulmonary embolism with shock may need thrombolysis despite pregnancy.