Extravascular hemolysis and breakthrough hemolysis of paroxysmal nocturnal hemoglobinuria
HE Guang-sheng
QIN Cheng-tao
Abstract：Investigating the mechanisms and management strategies of extravascular hemolysis(EVH)and breakthrough hemolysis(BTH)in patients with paroxysmal nocturnal hemoglobinuria(PNH)following complement inhibitor therapy.EVH is primarily triggered by C3b deposition on erythrocyte surfaces that induces macrophage phagocytosis.Diagnostic criteria include hemoglobin ≤9.5 g/dL or a decrease ≥2 g/dL,accompanied by elevated reticulocytes(≥120×109/L)and C3 deposition on erythrocytes(C3-positive direct Coombs test or C3 fragment detection via flow cytometry).Conventional therapies show limited efficacy,while proximal complement inhibitors(e.g.,Pegcetacoplan,Iptacopan)demonstrate effective control.BTH predominantly results from breakthrough complement activation despite inhibition,diagnosed when LDH exceeds 1.5 times the upper limit of normal with acute hemoglobin decline ≥1.5 g/dL.Severity correlates with complement inhibitor targeting sites and complement-amplifying conditions(CACs).Novel complement inhibitors may optimize PNH hemolysis,though vigilance is required for potential severe BTH following proximal inhibitor therapy.
Keywords：paroxysmal nocturnal hemoglobinuriaextravascular hemolysisintravascular hemolysisremnantbreakthrough hemolysis
Publication Date：2025-07-01
Online Publishing Date：2025-09-04(First online date of this platform, not the publication date of the document)
Pages：5( 559-563 )