title: Eculizumab effect on the hemostatic state in patients with paroxysmal nocturnal hemoglobinuria.
abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a hypercoagulable state associated with acute hemolysis. Eculizumab is used to reduce the intensity of intravascular hemolysis in PNH patients. The hemostatic status of three patients with PNH was assessed during eculizumab treatment by D-dimer assay and the global assays: thromboelastography (TEG), thrombin generation test (TGТ), and thrombodynamics (TD). In the state of hemolytic crisis before the therapy D-dimer concentration was increased in two patients accompanied by hypercoagulation changes in TEG parameter angle (α). TD parameter the clot growth velocity (V) revealed hypercoagulability while TGT parameter ETP was within the normal range in all patients. The lactate dehydrogenase (LDH) activity decreased during the 8months of eculizumab therapy. The physical health was improved, the frequency of hemolytic crisis decreased. Patients periodically exhibited hypercoagulable state: the mean values α=38±11° (with normal range 20-40°), ETP=1311±442nM·min (with normal range 800-1560nM·min), V=31±4μm/min (with normal range 20-29μm/min). During the eculizumab therapy two patients had the repeated clinical manifestation of acute hemolytic crisis, the parameters of the global tests were increased compared to the previous measurement. The global hemostasis tests TEG, TGT and TD revealed hypercoagulability in patients with PNH during eculizumab therapy.
authors.affiliation: Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Electronic address: elsereg@inbox.ru.
authors.forename: E A
authors.initials: EA
authors.lastname: Seregina
authors.affiliation: National Research Center for Hematology, Moscow, Russia.
authors.forename: N V
authors.initials: NV
authors.lastname: Tsvetaeva
authors.affiliation: National Research Center for Hematology, Moscow, Russia.
authors.forename: O F
authors.initials: OF
authors.lastname: Nikulina
authors.affiliation: HemaCore LLC, Moscow, Russia.
authors.forename: A P
authors.initials: AP
authors.lastname: Zapariy
authors.affiliation: HemaCore LLC, Moscow, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Erasov
authors.affiliation: National Research Center for Hematology, Moscow, Russia; Center for Theoretical Problems of Physicochemical Pharmacology RAS, Moscow, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Gribkova
authors.affiliation: National Research Center for Hematology, Moscow, Russia.
authors.forename: E B
authors.initials: EB
authors.lastname: Orel
authors.affiliation: Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; National Research Center for Hematology, Moscow, Russia; HemaCore LLC, Moscow, Russia; Center for Theoretical Problems of Physicochemical Pharmacology RAS, Moscow, Russia; Department of Physics, Moscow State University, Moscow, Russia; The Faculty of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
authors.forename: F I
authors.initials: FI
authors.lastname: Ataullakhanov
authors.affiliation: Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; Center for Theoretical Problems of Physicochemical Pharmacology RAS, Moscow, Russia; Department of Physics, Moscow State University, Moscow, Russia.
authors.forename: A N
authors.initials: AN
authors.lastname: Balandina
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001780:Blood Coagulation Tests; D016903:Drug Monitoring; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000188:drug therapy*; D006461:Hemolysis / Q000187:drug effects*; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D013916:Thrombelastography
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005338:Fibrin Fibrinogen Degradation Products; D006490:Hemostatics; C036309:fibrin fragment D; C481642:eculizumab; D007770:L-Lactate Dehydrogenase
keywords: Eculizumab; Global haemostatic tests; Paroxysmal nocturnal hemoglobinuria; Thrombin generation test; Thrombodynamics; Thromboelastography