Paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria
Other names	Paroxysmal nocturnal haemoglobinuria, Marchiafava–Micheli syndrome
Intravascular hemolytic anemia
Specialty	Hematology

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired,^[1] life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. There is ongoing research into other key features of the disease, such as the high incidence of venous blood clot formation.^[2] Research suggests that PNH thrombosis (a blood clot) is caused by both the absence of GPI-anchored complement regulatory proteins (CD55 and CD59) on PNH platelets and the excessive consumption of nitric oxide (NO).^[3]

PNH is the only hemolytic anemia caused by an acquired (rather than inherited) intrinsic defect in the cell membrane (deficiency of glycophosphatidylinositol or GPI) leading to the absence of protective exterior surface proteins that normally attach via a GPI anchor.^[4] It may develop on its own ("primary PNH") or in the context of other bone marrow disorders such as aplastic anemia ("secondary PNH"). Only a minority of affected people have the telltale red urine in the morning that originally gave the condition its name.^[5]

Allogeneic bone marrow transplantation is the only cure, but has significant rates of additional medical problems and death.^[6] The monoclonal antibody eculizumab reduces the need for blood transfusions and improves quality of life for those affected by PNH.^[6] Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to the extent that it may be equivalent to that of the general population.^[7] Eculizumab costs at least US$440,000 for a single year of treatment and has been reported as one of the world's most expensive drugs.^[8][9][10]