Therapeutic challenges in pregnant women with paroxysmal nocturnal hemoglobinuria

Abstract

Introduction:Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disease, arising from the mutation of clonal hematopoietic stem cells, with an estimated incidence of 1 to 5 cases per million individuals. In pregnant women, adequate information regarding the prevalence of PNH is lacking, and its management has been a challenge because of the significant complications in this group. The condition is diagnosed based on clinical findings and laboratory tests. Eculizumab, the drug of choice for the treatment of PNH, reduces hemolysis and stabilizes hemoglobin levels, thereby decreasing the need for blood transfusions and improving the overall quality of life.Case presentation:A 38-year-old woman was diagnosed with PNH in 2007 and eculizumab therapy was initiated at the end of 2014. She became pregnant in September 2015 and presented various decompensations from forced reductions in therapy due to the nonavailability of eculizumab. The pregnancy was interrupted in week 35, but the well-being of the newborn was not compromised. The patient, however, had to remain hospitalized for resolution of acute kidney insufficiency, anemia, and intense hemolysis, which were reverted by means of intravenous hydration, transfusion of 10 packed red blood cell units, and eculizumab therapy.Conclusion:The rarity of the disease and the lack of protocols for its management during pregnancy hampered the treatment of the patient. However, the symptoms were progressively treated as they appeared, based on laboratory tests since it was necessary to circumvent and handle the lack of eculizumab which was not readily available in Brazil's Public Health System.

Pregnancy with Paroxysmal Nocturnal Hemoglobinuria

“…[ 9 ] In PNH generally, a multinational longitudinal study found that eculizumab effectively stops intravascular hemolysis, thereby reducing risk of thrombosis and improving the quality of life. [ 16 ] However, specifically during pregnancy, its safety remains unclear as reported by Rodríguez-Ferreras and Velasco-Roces[ 23 ] that the Drug's Technical Data Sheet and studies have warned regarding its potential teratogenic risk and discourage its use. This contrasts with the observations of other case series and recent reviews about its safety during pregnancy.…”

“…The eculizumab dosage and frequency usually increased during pregnancy due to the physiological and pathophysiological factors of pregnancy and PNH, respectively, an approach supported by the existing literature. [ 16 ]…”

“…The assessment was based on clinical symptoms and laboratory parameters including hemoglobin, LDH, bilirubin, haptoglobin, reticulocytes and renal function to observe any signs of hemolysis. [ 16 ]…”

“…[ 12 13 ] In the management of PNH, eculizumab therapy has both been shown to be safe and effective as well as reported to potentially have teratogenic effects that may require dosage and frequency adjustments; the effect of ravulizumab on pregnancy outcomes has yet to be reported. [ 5 14 15 16 17 ]…”

A Case of Paroxysmal Nocturnal Hemoglobinuria (PNH) in an Obstetric Patient: A South African Perspective

“…The clinical sequelae of the deficiency of these complement-regulatory proteins renders affected cells susceptible to lysis mediated via complement [3]. C5 protein terminal, which reduces erythrocytic cellular lysis and stabilizes the plasma hemoglobin levels [6]. Eculizumab is the only drug approved for the treatment of PNH in USA, EU, and several other countries.…”