How is hemophilia A (a genetic disorder caused by deficiency of factor VIII, a clotting factor in the blood) managed during pregnancy?

Management of Hemophilia A in Pregnancy

Women with hemophilia A during pregnancy require multidisciplinary care with factor VIII monitoring and replacement therapy, targeting factor VIII levels >50 IU/dL for delivery and neuraxial anesthesia, with desmopressin or recombinant factor VIII concentrate as primary treatment options.

Preconception and Early Pregnancy Management

Preconception counseling is essential for all women with hemophilia A or carriers, including genetic counseling regarding inheritance patterns and prenatal testing options 1, 2. Women should be informed that:

• Factor VIII levels typically rise during pregnancy due to physiological changes, though the degree of rise varies 3
• Baseline factor VIII levels, bleeding phenotype, and genetic mutation should be documented before conception 2
• Prenatal testing uptake is high (97% in one series), with most opting for non-invasive fetal sex determination initially 3

Antenatal Care and Monitoring

Regular factor VIII monitoring throughout pregnancy is critical:

• Measure factor VIII levels at baseline, each trimester, and at 34-36 weeks gestation 1, 2
• Target factor VIII levels should be maintained based on bleeding phenotype and obstetric history 2
• Women with severe hemophilia A (factor VIII <1%) may require prophylactic factor replacement throughout pregnancy 4, 1

Avoid invasive procedures unless absolutely necessary, and only with adequate factor VIII coverage:

• Chorionic villus sampling or amniocentesis should only be performed with factor VIII levels >50 IU/dL 1, 2
• Consider non-invasive prenatal testing as first-line for fetal sex determination 3

Labor and Delivery Management

Target factor VIII levels for delivery:

• Maintain factor VIII >50 IU/dL (0.5 IU/mL) for vaginal delivery 1, 2
• Maintain factor VIII >80 IU/dL (0.8 IU/mL) for cesarean section 1, 2
• Factor VIII >50 IU/dL is required for neuraxial anesthesia (epidural or spinal) 2, 5

Treatment options for factor VIII replacement:

• Desmopressin (DDAVP) 0.3 mcg/kg IV over 15-30 minutes can be used in mild hemophilia A (factor VIII >5%) to transiently increase factor VIII levels 2-4 fold 6
• Recombinant factor VIII concentrate is the treatment of choice for moderate to severe hemophilia A, with dosing calculated to achieve target levels 4, 2
• Administer factor replacement 30 minutes prior to delivery if planned, or immediately upon presentation in labor 6, 4

Delivery considerations:

• Avoid instrumental deliveries (forceps, vacuum extraction) in pregnancies where the fetus may be affected, as these carry highest risk of intracranial hemorrhage (3-4% risk in affected infants) 1, 3
• Avoid fetal scalp electrodes and fetal blood sampling in at-risk pregnancies 1, 2, 3
• Avoid prolonged second stage of labor (>2 hours), as this increases neonatal bleeding risk 1, 3
• Cesarean section rates are higher (47-56%) in this population, often due to obstetric indications or to avoid prolonged labor in at-risk fetuses 3, 5

Postpartum Management

Postpartum hemorrhage (PPH) risk is significantly elevated:

• Primary PPH occurs in approximately 19% of deliveries in hemophilia carriers 3
• Monitor closely for 72 hours postpartum with clinical observation and factor VIII level checks 1, 2
• Maintain factor VIII >50 IU/dL for at least 3-5 days post-vaginal delivery and 5-7 days post-cesarean section 1, 2

Treatment of postpartum hemorrhage:

• Tranexamic acid 1g IV/PO three times daily is highly effective as adjunctive therapy and should be initiated early 1, 2
• Factor VIII replacement should be administered immediately if PPH occurs 4, 2
• Standard obstetric measures (uterotonic agents, uterine massage) should be employed concurrently 1

Neonatal Management

For infants at risk of hemophilia A:

• Avoid intramuscular injections (including vitamin K) until hemophilia status is determined; give vitamin K orally or subcutaneously instead 1, 2
• Delay circumcision until factor VIII levels are confirmed normal 1, 2
• Obtain cord blood for factor VIII level testing at delivery 2, 3
• Cranial ultrasound should be performed if there was prolonged labor, instrumental delivery, or any signs of neurological compromise 1, 3

Critical Pitfalls to Avoid

Common errors that increase morbidity:

• Failing to check factor VIII levels before neuraxial anesthesia—this can result in spinal hematoma 2, 5
• Using instrumental delivery in at-risk fetuses—associated with highest rate of intracranial hemorrhage 1, 3
• Inadequate postpartum monitoring duration—secondary PPH can occur up to 6 weeks postpartum 1, 3
• Administering intramuscular vitamin K to potentially affected neonates—use oral or subcutaneous routes 1, 2

Note on desmopressin use: While desmopressin is effective and safe in pregnancy for mild hemophilia A, it can cause hyponatremia and fluid retention 6. Fluid restriction should be implemented during treatment, and serum sodium should be monitored, particularly with repeated dosing 6.