PNH
Loss of CD55 and CD59 due to loss of PIGA coded proteins which bind these proteins using GPI anchors--> alternative pathway for complement activation --> RBC hemolysis.
-C5 inhibitor Ravulizumab
-C3 inhibitor Pegcetacoplan: FDA approved, given subcut twice a week. Main AE infection with encapsulated bacteria. black box warning meningococcal d/s
Cold Agglutinin disease
Ig M binds to RBC and brings along C3b as a companion in lower temp.
In warmer temp, Ig M dissociates from the RBC, leaving C3b on the RBCs --> hemolysis.
Current rx: avoid cold, rituxan front line, relapsed disease fludarabine rituxan, velcade, BR therapy
-FDA approved sutimlimab--> inhibits classical complement C1
Caution: vaccinate against encapsulated bacteria before starting the treatment.
Initially weekly for 2 doses then every other week.
Transplantation-associated microangiopathy:
thrombocytopenia, microangiopathic hemolytic anemia, organ damage
Current rx: stop the calcineurin inhibitor, PLEX, rituxan, steroids eculizumab
Lectin pathway and complement inhibition are being investigated in those resistant to eculizumab ( narsoplimab and conversion)
ITP: Sutimlimab being investigated for ITP resistant to prior therapies
Ref: Blood June 2022
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