According to a retrospective analysis (N=93), up to 89% of patients treated with C5 inhibition showed varying signs of ongoing hemolysis.4*
IVH, which occurs inside blood vessels, and EVH, which occurs in the liver and spleen5,6
The lectin, classical, and alternative complement pathways all converge at the point of C3
The lectin, classical, and alternative complement pathways all converge at the point of C3
PATHWAY
PATHWAY
PATHWAY
complement
inhibition
complement
inhibition
proteins bind to create the MAC, anchoring
into and puncturing the membrane of the
PNH red blood cell, causing the cell to burst in circulation6
complement activation of
the MAC5
complement cascade, may be
central to the control of
hemolysis in PNH8
complement
inhibition
proteins bind to create the MAC, anchoring
into and puncturing the membrane of the
PNH red blood cell, causing the cell to burst
in circulation7
complement
inhibition
terminal complement
activation of the MAC5
complement cascade, may be
central to the control of
hemolysis in PNH8
ARC=absolute reticulocyte count; EVH=extravascular hemolysis; IVH=intravascular hemolysis; LDH=lactate dehydrogenase; MAC=membrane attack complex; PNH=paroxysmal nocturnal hemoglobinuria; RBC=red blood cell; ULN=upper limit of normal.
References: 1. Brodsky RA, et al. Haematologica. 2021;106(1):230-237. 2. Hill A, et al. Haematologica. 2010;95(4):567-573. 3. Risitano AM, et al. Blood. 2009;113(17):4094-4100. 4. Debureaux PE, et al. Abstract presented at: 61st American Society of Hematology Annual Meeting; December 7-10, 2019; San Diego, CA. 5. Brodsky RA. Blood. 2014;124(18):2804-2811. 6. Risitano AM. Immunobiology. 2012;217(11):1080-1087. 7. Hill A, et al. Nat Rev Dis Primers. 2017;3:17028. 8. Risitano AM, et al. Front Immunol. 2019;10:1157.