What causes the disease and how common is it? Paroxysmal nocturnal hemoglobinuria (PNH), previously Marchiafava–Micheli syndrome, is a very rare (< 1/1,000,000), 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.
What are the most frequent symptoms if I have the disease? The classic sign of PNH is dark discoloration of the urine due to the presence of haemoglobin and haemosiderin 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. A small proportion of patients report attacks of abdominal pain, difficulty swallowing and pain during swallowing, as well as erectile dysfunction in men; this occurs mainly when the breakdown of red blood cells is rapid, and is attributable to spasm of smooth muscle due to red cell breakdown products. 40% of PNH patients develop thrombosis (a blood clot) at some point in their illness. This is the main cause of severe complications and death in PNH. These may develop in unusual sites: the hepatic vein (causing Budd-Chiari syndrome), the portal vein of the liver (causing portal vein thrombosis), the superior or inferior mesenteric vein (causing mesenteric ischemia) and veins of the skin. In PNH patients it is also more common cerebral venous thrombosis, an uncommon form of stroke.
Which treatment must I follow if I have the disease? Transfusion therapy may be needed to correcting significant anemia, this suppresses the production of PNH cells by the bone marrow, and indirectly the severity of the hemolysis. Iron deficiency develops with time, due to losses in urine, and may have to be treated if present. Iron therapy can result in more hemolysis as more PNH cells are produced.. PNH is a chronic condition and given the high risk of thrombosis , preventive treatment with warfarin decreases the risk of thrombosis in those with a large clone. In 2007, the drug eculizumab was approved for the treatment of PNH. It improves quality of life and decreases the need for blood transfusions but does not appear to affect the risk of death. It does not appear to change the risk of blood clots, myelodysplastic syndrome, acute myelogenous leukemia, or aplastic anemia. Eculizumab is controversial due to its high cost as it is among the most expensive pharmaceuticals in the world, with a price of 350,000 Euro per person per year.