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Journal Article
Review
Ten Years of Clinical Experience With Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria.
Seminars in Hematology 2018 July
Paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation in the phosphatidylinositol glycan class A, X-linked gene, responsible for a deficiency in glycosyl phosphatidylinositol-anchored proteins. The absence of one of the glycosyl phosphatidylinositol-anchored protein complement regulatory proteins (CD59) leads to hemolysis. Clinical manifestations include chronic hemolysis, thromboembolic disease, infectious complications, chronic kidney injury, pulmonary hypertension, and smooth muscle dysfunction. Until 10 years ago, treatment was mainly supportive, with most patients suffering from significant morbidity and shortened survival compared with age-matched controls. The development of eculizumab, a humanized monoclonal antibody directed against the terminal complement protein C5, has led to dramatic improvements in survival and reduced complications. In this article, we review 10 years of clinical experience with eculizumab in PNH along with specific related situations. Extravascular hemolysis and the use of eculizumab in pregnant patients with PNH are also addressed.
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