What causes PNH?

PNH occurs because of a change (mutation) in the PIG-A gene of a single stem cell in the bone marrow. This gene allows a substance called glycosyl-phosphatidylinositol (GPI) to help certain proteins stick to cells.

Here are the steps that lead to PNH:

  1. The abnormal stem cell makes copies of or "clones" itself. This leads to a whole population of stem cells that have mutant PIG-A.
  2. The abnormal stem cells turn into mature red blood cells that have mutant PIG-A. These are called PNH red blood cells.
  3. The PNH red blood cells lack the shield of proteins that protect normal red blood cells from the complement system. So they may be attacked and destroyed by the complement system proteins.

Many healthy people have a small number of stem cells with mutant PIG-A. But in people with PNH, these stem cells grow fast and make lots of mature PNH red blood cells.

Some doctors believe this happens because people with PNH have bone marrow that is weaker than normal. A person's bone marrow may be weakened because they have aplastic anemia or another bone marrow failure disease. Weakened bone marrow may also result from a mild bone marrow disease that was never diagnosed.

The disease can affect people of any age. It may be associated with aplastic anemia, myelodysplastic syndrome, or acute myelogenous leukemia.

Risk factors, except for prior aplastic anemia, are not known.