Pregnancy outcome after maternal intoxication with phenprocoumon

Abstract

Vitamin K antagonists (VKA) like phenprocoumon may be prescribed for certain indications despite pregnancy [1]. These drugs are able to cross the placenta, to reach the foetal blood circulation and to harm the foetus [2]. Case reports of VKA embryopathy describe mental retardation, optic atrophy, cleft lip and palate, nasal hypoplasia and stippling of bone. In addition there is the risk of spontaneous abortion, stillbirth and bleeding complications in the neonate [3, 4]. If there is nevertheless an indication requiring ingestion of VKAs during pregnancy, switching to another anticoagulant treatment is definitely necessary not later than in the 36th week to avoid neonatal intracranial haemorrhage under spontaneous delivery [5, 6]. However, occasionally the obstetrician may be faced with pregnant women who turn out to be severely poisoned by VKAs shortly before the appointed day of delivery. Recently, we were involved in the care of such a rare case of a pregnant woman with massive VKA intoxication. A 26-year-old pregnant woman came to our hospital in the 38th week of pregnancy because of back pain. A routine screening test detected the international normalized ratio (INR), a derived measure of the prothrombin time, as being unmeasurable (i.e. >10) and the activated partial thromboplastin time (aPTT) exceeded 180 s (normal range 26–34 s). The patient denied any anticoagulant treatment. Detailed analysis of clotting factors showed the following results: factor II 3% (normal range 65–130%), factor VII 3% (normal range 70–140%), factor IX 6% (normal range 60–160%), and factor X 2% (normal range 65–125%). A potent inhibitor of these factors was ruled out. A toxicological examination by liquid chromatography-mass spectrometry detected a phenprocoumon concentration of 5913 ng ml−1. For comparison, the therapeutic concentration ranges between 1000 and 3500 ng ml−1[7]. Immediately, 2000 IE prothrombin complex concentrate and 500 IE antithrombin were administered. From day 1 to day 3, the patient received up to 30 mg vitamin K orally per day, thereafter 10 mg until day 16 after admission when she delivered a female baby by Caesarean section without bleeding complications. The coagulation parameters of the mother had already normalized 7 days earlier. Coagulation tests from cord blood showed an INR of 1.23, an aPTT of 58.2 s (normal range for newborn [8] 37.1–48.7 s), a factor II of 44%, a factor VII of 41%, a factor IX of 29% and a factor X of 50%. The phenprocoumon concentration was 297 ng ml−1. The child showed no sign of foetal VKA syndrome, received vitamin K, and was able to leave the hospital after 5 days in good general condition. The almost complete lack of data on the haemostatic capacity in unborn children of mothers suffering from VKA poisoning is a difficult clinical challenge. Of course, it is ethically completely unacceptable to generate such data by periodic cordocentesis. Therefore, it is vital to report cases, pre-partum laboratory findings in mothers and post-partum laboratory findings in newborn children in this regard to clarify the optimal treatment of the mother and the optimal day and route of delivery, if VKA intoxication has been detected shortly before the appointed day of delivery. Our measurements suggest that a spontaneous delivery should not be risked earlier than 1 to 2 weeks after normalization of the mother's coagulation parameters.