Perinatal Intraventricular Hemorrhage Related to Maternal Warfarin Use

Abstract

Warfarin is an essential anticoagulant for long term prophylaxis of mechanical valve replacement. However, it can have harmful effects on the fetus including warfarin embryopathy and fetal hemorrhage. A 35-week-gestational age male infant was born to a mother with rheumatic heart disease presenting a history of mitral valve replacement requiring life-long warfarin therapy. The infant was delivered by emergency cesarean section due to fetal distress. He required initial resuscitation and respiratory assistance due to severe anemia. A computed tomography scan of the brain showed a 4.3x5.7x4.9 cm intraventricular hemorrhage, an intracerebral hemorrhage with subfalcine and descending transtentorial brain herniation. Multiple doses of blood products were transfused to correct the patient’s coagulopathy. Genetic polymorphism analysis of the mother and infant revealed the CYP2C9 *1/*1 (wild-type) alleles and two polymorphisms on the VKORC1 gene (-1639 GG>AA and 1173 CC>TT). Individuals exhibiting these polymorphisms affect lower vitamin K epoxide reductase enzyme activity, resulting in lowering levels of active vitamin K and vitamin K-dependent coagulation factors. These findings possibly explain the cause of the infant’s coagulopathy. To prevent serious bleeding consequences in the fetus, pregnant women requiring warfarin use should undergo pharmacogenomic studies testing both themselves and their fetus. This will yield recommended individualized dosing and monitoring of the fetus’s well-being using sequential ultrasonography.