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Drug-induced thrombocytopenia: Development of a novel NOD/SCID mouse model to evaluate clearance of circulating platelets by drug-dependent antibodies and the efficacy of IVIG

Liang, Simon; Pinkevych, Mykola; Khachigian, Levon M; Davenport, Miles P.; Chong, Beng; Parish, Christopher

Description

Drug-induced immune thrombocytopenia (DITP) is an adverse drug effect mediated by drug-dependent antibodies. Intravenous immunoglobulin (IVIG) is frequently used to treat DITP and primary immune thrombocytopenia (ITP). Despite IVIG's proven beneficial effects in ITP, its efficacy in DITP is unclear. We have established a nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of DITP in which human platelets survive for more than 24 hours, allowing platelet clearance by...[Show more]

dc.contributor.authorLiang, Simon
dc.contributor.authorPinkevych, Mykola
dc.contributor.authorKhachigian, Levon M
dc.contributor.authorDavenport, Miles P.
dc.contributor.authorChong, Beng
dc.contributor.authorParish, Christopher
dc.date.accessioned2015-12-10T22:26:03Z
dc.identifier.issn0006-4971
dc.identifier.urihttp://hdl.handle.net/1885/53744
dc.description.abstractDrug-induced immune thrombocytopenia (DITP) is an adverse drug effect mediated by drug-dependent antibodies. Intravenous immunoglobulin (IVIG) is frequently used to treat DITP and primary immune thrombocytopenia (ITP). Despite IVIG's proven beneficial effects in ITP, its efficacy in DITP is unclear. We have established a nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of DITP in which human platelets survive for more than 24 hours, allowing platelet clearance by DITP/ITP antibodies to be studied. Rapid human platelet clearance was uniformly observed with all quinine-induced thrombocytopenia (QITP) patient sera studied (mean platelet lifespans: QITP 1.5 ± 0.3 hours vs controls 16.5 ± 4.3 hours), consistent with the clinical presentation of DITP. In contrast, clearance rates with ITP antibodies were more variable. IVIG treatment partially prevented platelet clearance by DITP and ITP antibodies. Our results suggest that the NOD/SCID mouse model is useful for investigating the efficacy of current and future DITP therapies, an area in which there is little experimental evidence to guide treatment.
dc.publisherAmerican Society of Hematology
dc.sourceBlood
dc.subjectKeywords: immunoglobulin; quinine; animal experiment; animal model; article; clinical feature; combined immunodeficiency; controlled study; diabetes control; disease model; drug dose increase; drug efficacy; drug induced immune thrombocytopenia; female; male; mouse
dc.titleDrug-induced thrombocytopenia: Development of a novel NOD/SCID mouse model to evaluate clearance of circulating platelets by drug-dependent antibodies and the efficacy of IVIG
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume116
dc.date.issued2010
local.identifier.absfor110799 - Immunology not elsewhere classified
local.identifier.ariespublicationf2965xPUB282
local.type.statusPublished Version
local.contributor.affiliationLiang, Simon, St George Clinical School, University of New South Wales
local.contributor.affiliationPinkevych, Mykola, University of New South Wales
local.contributor.affiliationKhachigian, Levon M, University of New South Wales
local.contributor.affiliationParish, Christopher, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationDavenport, Miles P., University of New South Wales
local.contributor.affiliationChong, Beng, University of New South Wales
local.description.embargo2037-12-31
local.bibliographicCitation.issue11
local.bibliographicCitation.startpage1958
local.bibliographicCitation.lastpage1960
local.identifier.doi10.1182/blood-2010-02-268326
local.identifier.absseo920101 - Blood Disorders
dc.date.updated2016-02-24T08:26:56Z
local.identifier.scopusID2-s2.0-77956901240
local.identifier.thomsonID000282152000022
CollectionsANU Research Publications

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