CD55 protein/Decay Accelerating Factor structure CD59 protein/Protectin structure All cells have proteins attached to their membranes, often serving as a mode of communication or signaling between the cell and the surrounding environment. These signaling proteins are physically attached to the cell membrane in various ways, commonly anchored by glycolipids such as glycosyl phosphatidylinositols (GPI).<unk>  occurs as a result of a defect in the assembling of these glycolipid-protein structures on the surface of blood cells. The most common defective enzyme in<unk>  is phosphatidylinositol glycan A (PIGA), one of several enzymes needed to make GPI. The gene that codes for PIGA is located on the X chromosome, which means that only one active copy of the gene for PIGA is present in each cell (initially, females have two copies, but one is silenced through X-inactivation). A mutation in the PIGA gene can lead to the absence of GPI anchors expressed on the cell membrane. When this mutation occurs in a hematopoietic stem cell in the bone marrow, all of the cells it produces will also have the defect. Several of the proteins that anchor to GPI on the cell membrane are used to protect the cell from destruction by the complement system, and, without these anchors, the cells are more easily targeted by the complement proteins. Although red blood cells, white blood cells, and platelets are targeted by complement, red blood cells are particularly vulnerable to lysis. The complement system is part of the innate immune system and has a variety of functions, from destroying invading microorganisms by opsonization to direct destabilization by the membrane attack complex. The main proteins that protect blood cells from destruction are decay-accelerating factor (DAF/CD55), which disrupts formation of C3-convertase, and protectin (CD59/MIRL/MAC-IP), which binds the membrane attack complex and prevents C9 from binding to the cell. The symptoms of esophageal spasm, erectile dysfunction, and abdominal pain are attributed to the fact that hemoglobin released during hemolysis binds with circulating nitric oxide, a substance that is needed to relax smooth muscle. This theory is supported by the fact that these symptoms improve on administration of nitrates or sildenafil (Viagra), which improves the effect of nitric oxide on muscle cells. There is a suspicion that chronic hemolysis causing chronically depleted nitric oxide may lead to the development of pulmonary hypertension (increased pressure in the blood vessels supplying the lung), which in turn puts strain on the heart and causes heart failure. Historically, the role of sleep and night in this disease (the<unk> " component of the name) has been attributed to acidification of the blood at night due to relative hypoventilation and accumulation of carbon dioxide in the blood during sleep. This hypothesis has been questioned by researchers who note that not all those with<unk>  have increased hemolysis during sleep, so it is uncertain how important a role sleep actually plays in this disease.
Paroxysmal nocturnal hemoglobinuria
Paroxysmal cold hemoglobinuria
Hereditary spherocytosis
Beta thalassemia
Congenital hemolytic anemia
Hemoglobinemia
Alpha-thalassemia
Congenital dyserythropoietic anemia type II