Paroxysmal Nocturnal Hemoglobinuria and Pregnancy: The French Experience.

Abstract 1984

Poster Board I-1006

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired stem cell disorder characterized by hemolytic anemia, bone marrow failure and venous thromboembolism. PNH and pregnancy is associated with an increased risk of complications for both mother and foetus with high maternal and foetal mortality rates (around 10%, Fieni et al, Obst and Gynecol survey, 2006). However, the literature about PNH and pregnancy is scarce. We took advantage of the French PNH registry to systematically review all cases of pregnancy between 1978 and 2008. We thus identified 27 pregnancies occurring in 22 patients. The median age was 21 years (17-41) at PNH diagnosis and 27 years (21-38) at pregnancy. Pregnancy occurred mainly in women who were already diagnosed with PNH (n=20) with a median time of 70.4 months (1-192) between PNH diagnosis and pregnancy. The PNH diagnosis was also made during pregnancy for 4 patients (2 cytopenias and 2 hemolytic anemia). For the remaining 3 cases, PNH diagnosis was made after pregnancy with strong evidence of PNH history during pregnancy. Among the 27 pregnancies, 2 ended in therapeutic abortion and one was complicated by severe intrauterine foetal growth restriction leading to foetal death at 27 weeks of amenorrhea. Twenty four pregnancies gave birth to live newborns. The foetal mortality was 4%. Delivery was preterm in 29% of cases and therapeutically induced in 70% (half cases delivered by caesarean section). Birth weight was less than 3 kg in 53% of cases with one case of high prematurity. During pregnancy, minor maternal complications (not requiring hospitalization and/or intensive care) occurred in all but one of the 22 documented cases and consisted mostly in cytopenias requiring transfusions (14/22). Anemia (Hb<10 g/dl) occurred in 18/22 cases (82%) with 10 patients requiring red blood cell transfusions. Thrombocytopenia (<80.000/mm³) was observed in 16/21 cases (76%), with 10 patients requiring platelet transfusions. Arterial hypertension and diabetes occurred in 6/24 and in 1/24 women, respectively. Major maternal complications during pregnancy were observed in 8% of the patients (n=2/25, aplastic anemia). In one case, the onset of aplastic anemia allowed the diagnosis of PNH at 5 months of pregnancy while in the other case, it was a relapse of a previously treated disease. We did not observe any thrombotic events during pregnancy. Most severe complications appeared in the immediate post partum (PP) period with an incidence rate of 32%. Three thrombotic events were recorded (12.5%): 2 cerebral venous thromboses occurred in the first month of PP, one associated with maternal death. One patient experienced a Budd-Chiari syndrome leading to death at one month PP. Maternal mortality rate in post partum was 8.3%. Other maternal major complications during post partum were hemorrhagic delivery (n=2), febrile neutropenia (n=1), HELLP syndrome (n=1) and hemolysis (n=1). After delivery, two patients experienced late major thrombotic events at 7 and 9 months PP (mesenteric venous thrombosis and cerebral thrombotic event). Concerning thrombosis prophylaxis, 13/24 pregnancies (54%) were accompanied by prophylactic anticoagulation with half of them started during the first or second trimester. In all documented cases, anticoagulation was continued during at least 1 month PP. The 3 post partum thrombotic events appeared in 3 patients whom at least 1 was anticoagulated (one without anticoagulation, one unknown). In conclusion, we confirmed that pregnancy during PNH is associated with an increased risk of complications for both mother and foetus with maternal and foetal mortality rates of 8.3% and 4%, respectively. However, those rates are lower than those previously described in the literature probably because of the preferentially report of selective dramatic cases. Thrombotic events are still the main fatal complication in this context, occurring preferentially during the post partum period. Young women patients with PNH must be informed about the high risk of complications during and after pregnancy. Prophylactic anticoagulation should be started from the sixth month and continued at least until six weeks post partum. Anticoagulation is not always enough to prevent thrombotic complications raising the potential role of Eculizumab in this situation.