Paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria
Synonyms	paroxysmal nocturnal haemoglobinuria, Marchiafava–Micheli syndrome
Classification and external resources
Specialty	hematology
ICD-10	D59.5
ICD-9-CM	283.2
OMIM	300818
DiseasesDB	9688
MedlinePlus	000534
eMedicine	article/207468
MeSH	D006457
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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's intrinsic immune system. This destructive process is a result of a defect in the formation of surface proteins on the red blood cell, which normally function to inhibit such immune reactions. Since the complement cascade attacks the red blood cells throughout the circulatory system, the hemolysis is considered an intravascular hemolytic anemia. Other key features of the disease, notably the high incidence of thrombosis, are not totally understood.

PNH is the only hemolytic anemia caused by an acquired (rather than inherited) intrinsic defect in the cell membrane (deficiency of glycophosphatidylinositol leading to absence of protective proteins on the membrane). 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 (26%) have the telltale red urine in the morning that originally gave the condition its name.

Allogeneic bone marrow transplantation is the only curative therapy, but has significant rates of both mortality and ongoing morbidity. The monoclonal antibody eculizumab is effective at reducing the need for blood transfusions and improving quality of life. It, however, does not appear to change the risk of death or blood clots and has an extremely high price, with a single year of treatment costing at least $440,000.

The classic sign of PNH is red discoloration of the urine due to the presence of hemoglobin and hemosiderin from the breakdown of red blood cells. As the urine is more concentrated in the morning, this is when the color is most pronounced. This phenomenon mainly occurs in those who have the primary form of PNH, who will notice this at some point in their disease course. The remainder mainly experience the symptoms of anemia, such as tiredness, shortness of breath, and palpitations.

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