Clinical Signs and Symptoms In Non-Transfused Patients With Paroxysmal Nocturnal Hemoglobinuria From a Korean Prospective PNH Registry

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and progressive disease driven by chronic complement mediated hemolysis leading to thromboembolism (TE), renal impairment, and death. Transfusion requirement has been one complication that has suggested a more severe case of PNH. Here, we report the prevalence of clinical symptoms, hemolysis, and TE in non-transfused (no transfusions in the past 12 months) PNH patients from the Korean prospective PNH registry.

Korean patients with a diagnosis of PNH are eligible for inclusion in the prospective registry study designed to identify key symptoms in close proximity of the event and support the associations of hemolysis and other risk factors. The study included medical history data from the time of diagnosis and to enrollment. Patient data included in this study were captured using an electronic case report form that collected patient demographics; medical history; PNH-specific information including RBC and granulocyte clone size; and laboratory values. PNH was confirmed at each individual site using a consistent flow cytometry or FLAER protocol based on the expression of CD55, CD59, or CD24. The PNH granulocyte and RBC clone sizes were also evaluated. Chronic kidney disease (CKD) was measured by eGFR and proteinuria.

Data are presented for 106 PNH patients; all of these patients have been actively participating in the study since the first patient enrollment at Dec, 2011. At enrollment patients had a median age of 47 years (range 20 to 84) and 57 (54%) were female. The majority of patients (87.2%) were reported to have ≥10% granulocyte clone size and 74% of patients had LDH levels ≥1.5 x ULN. The most frequently reported clinical symptoms were fatigue (62%), hemoglobinuria (58%), CKD or renal failure (45%), pain (including abdominal pain and backache, 43%), and thrombosis was reported in 16 patients (15%). About half of the patients (43%) had never been transfused for at least 12 months prior to enrollment (non-transfused). Non-transfused patients continue to experience LDH ≥1.5 x ULN and was not different when compared to patients requiring transfusions (P=0.654). Prevalence of abdominal pain, shortness of breath and chest pain, symptoms associated with risk of TE, as well as fatigue and hemoglobinuria were similar between both groups (table). We also note that history of TE prior to entering the registry was similar between both groups (P=0.507). Prevalence of thrombocytopenia and neutropenia was similar between the groups; however, prevalence of anemia (hemoglobin<8g/dL) was lower in non-transfused patients (P=0.002).

Our analyses demonstrate that non-transfused PNH patients can continue to experience hemolysis, a risk factor for thrombosis and organ damage. Indeed, non-transfused patients continue to experience abdominal pain, chest pain and shortness of breath at a similar rate as transfused patients in our patient cohort. We further note that non-transfused patients also experienced a similar history of TE at enrollment. Some PNH patients may compensate for the loss of RBC due to hemolysis as demonstrated by fewer patients with anemia (hemoglobin<8g/dL) in the non-transfused group. However, thrombocytopenia and neutropenia in the non-transfused were similar suggesting marrow function alone maybe not explain why some patients do not need transfusions. Overall these data suggest that transfusion requirement alone is not a measure of risk for poor outcomes. A full clinical work up including history of TE should be followed in newly diagnosed PNH patients and treatment management should be based on presenting risk factors regardless of transfusion requirement. Further investigation on the risk of clinical symptoms, hemolysis, and TE in PNH patients who do not receive blood transfusion is warranted.

Lee:Alexion Pharmaceutical Company: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Jang:Alexion Pharmaceutical Company: Honoraria, Membership on an entity’s Board of Directors or advisory committees.