Paroxysmal nocturnal hemoglobinuria – first treatment experience with eculizumab in Slovenian patients

Abstract

Background: Paroxysmal nocturnal hemoglobinuria is a serious form of acquired haemolytic anaemia characterized by a defect in the membrane of red blood cells and also platelets and neutrophils. Clinically, it is typified by the classical triad of (1) intravascular haemolysis, (2) venous thrombosis and (3) bone marrow failure with cytopenia. As an advanced life threatening disease, it leads to end-organ failure and premature death. Until recently, the only treatment options were allogeneic stem-cell transplantation or supportive care with transfusions of packed red blood cells, glucocorticoids and anticoagulant terapy. Case presentation: The first patient developed aplastic anemia at the age of 17 years (y. 2000). She received immunosuppressive therapy including anti-lymphocyte globulin, methylprednisolone and oral cyclosporine A. Some years after this treatment, increasing PNH clone up to 92 % evolved. Haemolysis parameters were very high (LDH to 82 μkat/L, increased indirect bilirubin, reticulocyte count > 300 x 109/L). She became dependent on red blood transfusions. Regular prophylaxis with warfarin and folic acid was introduced. In June 2011, we started eculizumab treatment by standard protocol. The parameters of haemolysis sharply decreased; the need for blood transfusions has decreased, though not completely. The second patient presented with severe pancytopenia in August 2011. Bone marrow showed evidence of hemolysis. PNH clone was 65 %. He was not prone to infections or bleeding, but monthly he needed blood transfusions. Hemolysis parameters were moderately increased (LDH to 13.5 μkat /L, bilirubin increased marginally, reticulocyte 95 x 109/L). In October 2011, he started receiving eculizumab treatment. Pancytopenia persisted, he was still blood-transfusion dependent, and so we decided to start immunosuppressive therapy. At this time we await the effect of immunosuppressive therapy and continue the treatment with eculizumab. Conclusions: In recent years, major progress has been made in PNH treatment with the development of monoclonal antibody directed against C5 protein of the complement system–eculizumab. Blockade of C5 effectively prevents intravascular haemolysis, development of anemia and reduces the need for blood transfusions. It significantly reduces complications such as haemolysis, renal impairment and pulmonary hypertension, reduces thrombosis-related complications and prolongs patients’ survival.