Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal Nocturnal Hemoglobinuria, or PNH, is a rare, chronic, debilitating, acquired blood disorder most frequently diagnosed in early adulthood that usually continues throughout the life of the patient. Some of the prominent symptoms of PNH include severe anemia, a condition resulting from having too few healthy red blood cells, severe abdominal pain, severe headaches, back pain, excessive weakness, fatigue, and recurrent infections. If not treated, PNH results in the death of approximately 35% of affected individuals within five years of diagnosis, and 50% of affected individuals within 10 years of diagnosis, primarily due to the formation of life-threatening blood clots inside the blood vessels, or thrombosis. It is estimated there are approximately 16,000 PNH patients worldwide. Eculizumab is the only drug currently approved to treat PNH.
PNH patients acquire a genetic mutation that prevents the normal attachment of complement regulatory proteins to the membranes of blood cells. On normal cells, these proteins are critical inhibitors of complement activity and provide one means of distinguishing host cells from invading pathogens. The absence of these proteins results in deposition of the MAC on essentially all blood cells, including red blood cells and platelets. Red blood cells are particularly susceptible to lysis by MAC, resulting in release of hemoglobin and destruction of red blood cells, leading to anemia. Uncontrolled activation of complement on platelets can promote thrombosis, which is the most common cause of death in PNH patients. Other serious and potentially life-threatening complications of PNH include high blood pressure in the lungs and damage to the kidneys.