PB1936: PAROXYSMAL NOCTURNAL HEMOGLOBINURIA AND THROMBOSIS: A MULTICENTRIC RETROSPECTIVE STUDY

Background: INTRODUCTION Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal hematopoietic stem cell disorder, potentially life-threatening, manifesting with chronic hemolytic anemia, thrombosis, and various degrees of bone marrow failure. Thrombosis is the most common cause of death in PNH with 29% - 44% of patients experiencing at least one thromboembolic event during the course of the disease. Although thrombosis can affect any anatomical site, the most frequent sites include intra-abdominal and cerebral veins. The mechanism of thrombosis in PNH is complex and continues to be of great research interest. Aims: OBJECTIVE-PATIENTS The aim of the study is the retrospective analysis of thrombotic episodes of 38 patients with PNH from 13 hematology centers in Greece. Methods: - Results: RESULTS Of the 38 patients, 17 were women (45%) and 21 men (55%) with a median age at diagnosis of 38 years (range 11 - 82 years). Twenty (52.6%) patients were diagnosed with the classic form of PNH while 16 (42.1%) patients developed PNH in the setting of another bone marrow disorder. The main symptoms recorded were weakness, abdominal pain, hemoglobinuria, back pain, headache, dysphagia and erectile dysfunction. Anemia was present in 92.10% at diagnosis with 60.52% requiring red blood cell transfusion, while thrombocytopenia was observed in 25 patients (65.79%) with 15.7% requiring platelet transfusion. In total, 15 (39.47%) patients experienced at least one episode of thrombosis, eight (21.05%) at diagnosis and the rest during the course of the disease. Five patients experienced episodes of thrombosis at multiple sites. The most common vascular sites of thrombosis were hepatic (Budd-Chiari syndrome; n=6 patients), portal (n=2) and mesenteric veins (n=4) and ocular arteries (n=2). Of the eight patients who developed thrombosis at diagnosis, six received eculizumab and to-date they have not had a new thrombotic episode [median time of f/u 22 months (range 12 - 179)]. Of the 15 patients without a thrombotic episode who received eculizumab due to hemolytic anemia, two developed thrombosis during the course of the disease (one 14 months after eculizumab initiation with underlying primary myelofibrosis, and the second after five years without identifying any other factor for thrombosis). The antithrombotic therapy that was used was acenocoumarol following a short course of low molecular weight heparin. In none of the 15 patients the thrombotic event was fatal. Summary/Conclusion: CONCLUSIONS Thrombotic events occur in a significant percentage of patients with PNH, often in unusual anatomical sites. Ongoing treatment with complement inhibitors has significantly contributed to the reduction of thrombotic events and consequently the increase in patient survival.