A Hematopoietic Stem Cell Disorder with Serious Morbidities and Mortality
PNH is an acquired hematopoietic stem cell disorder in which blood cells lack a key, naturally occurring terminal complement inhibitor on the cell surface, rendering them vulnerable to lysis by the terminal complement complex (TCC), also known as C5b-9 or the membrane attack complex (MAC).1-3
PNH results from the expansion of hematopoietic stem cells that possess a mutation of the phosphatidylinositol glycan class A (PIG-A) gene. This mutation results in a deletion of GPI anchors, which normally tether certain types of proteins to the cell surface. These proteins are unable to attach to the surface of the cell in PNH.1,2
Unprotected erythrocytes are at risk for destruction by complement
The mutation of the PIG-A gene prevents the assembly of a fatty-acid tail, known as a glycosyl-phosphatidylinositol (GPI) anchor, a necessary step in surface attachment of some proteins. When proteins with this GPI anchor are diminished or absent, two of which are crucial in protecting blood cells from inappropriate complement destruction, PNH erythrocytes, in particular, are easily lysed by complement. This can potentially result in thrombosis, end organ damage, and increased mortality.
PNH is frequently associated with other serious diseases, including aplastic anemia (AA), myelodysplastic syndromes (MDS), and other forms of bone marrow failure.4
Associations with bone marrow disorders
PNH is characterized by the continuous destruction of PNH red blood cells; it frequently occurs in conjunction with conditions characterized by diminished production of RBCs, WBCs, and platelets (e.g., AA and MDS).
PNH cells (granulocytes) are common in bone marrow disorders.5,6
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Approximately 70% of patients with AA have PNH clones5*
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As many as 42% of patients with MDS have PNH clones6*
*0.003% PNH cell threshold
