PB1864 MORE THAN 2 YEARS DELAY IN DIAGNOSIS OF PNH DUE TO GASTROINTESTINAL MASK OF BONE MARROW INSUFFICIENCY

Abstract

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is an ultrarare bone marrow insufficiency of childhood consisted of the triad of diagnostic symptoms: hemolytic anemia, thrombosis, and peripheral blood cytopenias. Acute abdominal pain is one of the most important prodrome of PNH mostly due to venous thrombosis of intra-abdominal veins, including hepatic, portal, mesenteric, and splenic blood vessels. Aims: To show how a complicated course of diseases due to “abdominal mask” resulted in more than 2 years delay in diagnosis might be fatal to a PNH patients. Methods: We report a boy of 15th, suffered from PNH, who presented long before the diagnosis with seasonal (spring and autumn only) paroxysmal acute and severe (8-9 VAS score) abdominal pain with cramps and tenderness and no other hematological presentation of disease. There were a couple attacks observed during the season with complete resolution of abdominal symptoms in between. He had been diagnosed as acute appendicitis, peptic ulcer disease, pancreatitis or cholecystitis especially when hyperbilirubinemia emerge, Crohn and atypical celiac disease for more than 2 years. Since a peripheral pancytopenia followed by severe anemia required erythrocyte transfusions during the last 2 attacks occurred, hematologist had been asked for consultation. Due to severe anemia with reticulocytosis, hyperbilirubinemia, highly elevated LDH, meaningful splenomegaly and almost nondetectable concentration of serum haptoglobin and a dark urine with confirmed hemoglobinuria, with a weak bone marrow aplasia, the diagnosis of PNH was feasible. The cytometric results, which revealed no expression of GPI proteins in 93.8% of type III PMNs, confirmed the diagnosis (percentage of RBC lacking GPI was not persuasive, as he has been previously transfused). Up to this point of his disease, except of transient, he had no fixed postembolic lessons in liver and kidney, and a negligible bowel signs revealed for the several time in CT/MR-angiography. He had no other embolic events in other organs as well. Results: As the results of HSCT are questionable in PNH, especially in children, we decided to start eculizumab. The complete clinical remission assessed as complete symptoms resolution had been achieved with the 2nd dose, and complete biochemical remission, based on LDH normalization, was confirmed with the 3rd dose of a MoAb therapy. The presence and percentage of PNH clones tested twice since diagnosis in both PNMs and RBCs did not change till now. We have not observed any complications during a year and half of treatment up to date of publication. Summary/Conclusion: The insidious and hidden course of thrombosis of intra-abdominal veins even accompanied by hemolysis may mask the real reason and significantly prolong the diagnosis of ultrarare disease such as a PNH, especially in children. Eculizumab is a treatment of choice of childhood PNH.