Chronic Hemolysis Is the Underlying Cause of Progressive Morbidities and Mortality in PNH1
Chronic hemolysis is the underlying cause of progressive morbidities and mortality in PNH, resulting in systemic threats including thrombosis and end organ damage or failure including brain, liver, GI system, kidney, and lung. Symptoms and severity vary widely between patients, yet all share the destructive consequences of ongoing hemolysis. Hemolysis is subtle, but the progressive consequences can be unpredictable, sudden, and devastating.1
During chronic hemolysis, excess free hemoglobin depletes plasma nitric oxide (NO), which may play an important role in normal platelet function. It is believed that nitric oxide may down-regulate platelet aggregation, adhesion, and regulating molecules in the coagulation cascade. Therefore, nitric oxide depletion may lead to platelet activation and aggregation. Chronic consumption of nitric oxide by free hemoglobin may play a role in thrombotic events that occur in patients with PNH. Other symptoms that may be associated with nitric oxide deficiency include: abdominal pain, dysphagia, erectile dysfunction, and pulmonary hypertension.2-6
Thrombosis and renal failure are two leading causes of death in PNH. In fact, venous or arterial thromboses account for approximately 40% to 67% of PNH-related deaths.7 Renal insufficiency, another leading cause of death, is five times more prevalent in patients with PNH than in the general population.8,9
Patients with PNH also suffer from severe quality-of-life issues, including disabling abdominal pain, fatigue, and dyspnea. Quality-of-life issues are often the first complaint of patients, yet are easy to overlook. It can be beneficial to ask patients directly about the presence or absence of all potential symptoms and diagnostic markers.10
-
Hemolysis is chronic, with consequences that can be sudden and devastating
-
Even in the absence of symptoms, hemolysis is ongoing and destructive
The current availability of an effective PNH treatment option warrants testing appropriate patients.
