[TonyBegg]

I cannot comment about the advisability of ATG/Cyclosporine for AA with PNH but I can clarify what PNH is (mother of my kids K has had it for 23 years and clone size is 35%). PNH is considered a secondary disease responsible for hemolysis (destruction of RBCs via the liver) and thrombophilia (tendency to clotting). Usually there is a primary disease (often AA or MDS) which causes pancytopenia (low counts for all blood components: RBCs, WBCs, and platelets). It is thought that PNH might actually be a response to the primary disease to prolong life. PNH is caused by an acquired mutation of the PIG-A gene of the hematapoietic (sp ?) stem cells of the bone marrow. This causes the blood components to lack (at least) two complement inhibitors (CD55, CD59) which happen to be the two inhibitors the HIV virus mimics to evade lysis by complement (the complement system is the non-specific immune system due to special proteins in the blood). RBCs are mostly affected by complement lysis when the complement system is activated (this can happen with sickness say due to viruses, with stress, allergies, pregnancy and poorly administered blood transfusions - say with washed platelets that are thereby activated as happened with K). Platelets are not lysed as such but can become deformed or activated in some way that makes them prone to clumping (clotting). This could also be a side-effect of the RBC lysis which starves the blood of nitric oxide. Recent research suggests that when the bone marrow is stimulated to counteract the pancytopoenia of the primary disease (AA or MDS) the PNH clone stem cells leave the marrow preferentially because they are slippier. The RBC lysis causes Coca-Cola colored pee, a rise in LDH (Lactate DeHydrogenase) which can be measured by a blood test to show the degree of lysis, and since the RBCs are destroyed by the liver can lead to jaundice (yellow skin, liver pain). So maybe the ATG/Cyclosporine needs to be administered carefully with something to inhibit the complement system from activating. Transfusions are often done with Tylenol and an anti-histamine to suppress complement reactions. There may be other ones the docs can administer.