Complement-driven anemia

more than just paroxysmal nocturnal hemoglobinuria

Samuel Merrill, Robert A Brodsky

Research output: Contribution to journalReview article

Abstract

Atypical hemolytic uremic syndrome (aHUS); hemolysis, elevated liver function tests, and low platelets syndrome; and transplant-associated thrombotic microangiopathy are related conditions, in that many patients harbor germline heterozygous mutations in genes that regulate the alternative pathway of complement (APC). Penetrance is variable because development of clinically significant disease appears to require supervention of a process such as inflammation. Complement activation on the endothelial surfaces leads to endothelial damage, platelet consumption, microthrombi, and a mechanical hemolytic anemia with schistocytes. Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic disease caused by expansion of a stem cell that harbors a somatic mutation in PIGA PIGA mutant blood cells are deficient in the complement regulator proteins CD55 and CD59, making them susceptible to intravascular hemolysis due to a failure to regulate the APC on erythrocytes. Eculizumab is a monoclonal antibody that binds to C5 and inhibits terminal complement by interfering with the cleavage of C5 by the C5 convertases. The drug is approved by the US Food and Drug Administration for the treatment of aHUS and PNH; however, a new generation of complement inhibitors that block C5 and other components of the complement cascade is showing promise in preclinical and clinical trials.

Original languageEnglish (US)
Pages (from-to)371-376
Number of pages6
JournalHematology. American Society of Hematology. Education Program
Volume2018
Issue number1
DOIs
StatePublished - Nov 30 2018

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Alternative Complement Pathway
Paroxysmal Hemoglobinuria
Complement Inactivating Agents
Hemolysis
Anemia
Blood Platelets
Complement C3-C5 Convertases
Thrombotic Microangiopathies
Penetrance
Germ-Line Mutation
Complement Activation
Liver Function Tests
Hemolytic Anemia
United States Food and Drug Administration
Blood Cells
Complement System Proteins
Stem Cells
Erythrocytes
Monoclonal Antibodies
Clinical Trials

ASJC Scopus subject areas

  • Hematology

Cite this

Complement-driven anemia : more than just paroxysmal nocturnal hemoglobinuria. / Merrill, Samuel; Brodsky, Robert A.

In: Hematology. American Society of Hematology. Education Program, Vol. 2018, No. 1, 30.11.2018, p. 371-376.

Research output: Contribution to journalReview article

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