Causes

PNH occurs because of a genetic change in bone marrow stem cells. This creates a family of abnormal blood cells referred to as a PNH clone. These PNH blood cells lack a key protein that protects them from being destroyed by your immune system.

Causes of PNH

PNH happens because of a change (mutation) in the PIG-A gene of a single stem cell in your bone marrow. This gene controls the creation of substance that helps certain proteins to stick to blood cells. Therefore, any blood cells created by this mutant bone marrow stem cell are abnormal.

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 a part of your immune system called the complement system. These PNH cells are attacked and destroyed by the complement system proteins.

Many healthy people have a small number of stem cells with a PIG-A mutation. 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.

If you have had aplastic anemia before, you are more likely to get PNH. There are no other known factors that increase your chances of getting PNH.