Extravascular hemolysis and complement consumption in Paroxysmal Nocturnal Hemoglobinuria patients undergoing eculizumab treatment

Abstract

Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in:

C3a receptor antagonism as a novel therapeutic target for chronic rhinosinusitis

“… 79 Eculizumab functions by inhibiting C5 activation and is therefore consider safe for systemic administration as it leaves intact complement detection pathways, activation and opsonin functions. 80 , 81 While C3 inhibitors exist, such as compstatin, their utilization systemically is not without risk due to systemic complement functions. 82 Fortunately, the sinus cavity, lends itself anatomically to topical application.…”

Soluble Membrane Attack Complex: Biochemistry and Immunobiology

“…This would usher in a new era in complement diagnostics particularly if patients could measure sMAC (and/or other complement fragments) at home and relay the information directly to their physician or clinic. This could include patients being treated for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome ( 106 , 221 , 222 ), age-related macular degeneration ( 107 ), glomerulonephritis ( 223 ), hematopoietic stem cell transplantation (transplant associated thrombotic microangiopathy) ( 224 ), thrombotic thrombocytopenia purpura ( 108 , 225 ), and acute post-infectious glomerulonephritis ( 226 ). sMAC monitoring may also have diagnostic value in anti-TNF-α treatment of spondylarthropathies ( 227 ), indicating the diagnostic value of sMAC exists beyond complement-specific therapeutics.…”

Beneficial effects of eculizumab regardless of prior transfusions or bone marrow disease: Results of the International Paroxysmal Nocturnal Hemoglobinuria Registry

“…An additional consideration when evaluating transfusion needs among patients with PNH is the potential for extravascular hemolysis (as defined by Risitano et al 22 ) occurring 1,19,22 in some patients with PNH receiving eculizumab 22‐30 ; data from some small, single‐center studies suggest that up to 72% of eculizumab‐treated patients are direct antiglobulin test positive (DAT+) 23,26 . In the absence of breakthrough hemolysis, patients may have more subtle signs of persistent low‐level hemolysis, such as slightly elevated LDH levels, or abnormal bilirubin, reticulocyte, and/or hemoglobin levels 30,31 . The clinical impact of extravascular hemolysis in patients with PNH treated with eculizumab remains unclear 26,27,30 .…”

“…In the absence of breakthrough hemolysis, patients may have more subtle signs of persistent low‐level hemolysis, such as slightly elevated LDH levels, or abnormal bilirubin, reticulocyte, and/or hemoglobin levels 30,31 . The clinical impact of extravascular hemolysis in patients with PNH treated with eculizumab remains unclear 26,27,30 . Extravascular hemolysis in untreated patients with PNH may remain inconspicuous due to dominance of signs and symptoms of intravascular hemolysis.…”