PMID- 20566900 OWN - NLM STAT- MEDLINE DCOM- 20101029 LR - 20210206 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 116 IP - 11 DP - 2010 Sep 16 TI - 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. PG - 1958-60 LID - 10.1182/blood-2010-02-268326 [doi] AB - 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 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. FAU - Liang, Simon X AU - Liang SX AD - St George Clinical School, University of New South Wales, Sydney, Australia. FAU - Pinkevych, Mykola AU - Pinkevych M FAU - Khachigian, Levon M AU - Khachigian LM FAU - Parish, Christopher R AU - Parish CR FAU - Davenport, Miles P AU - Davenport MP FAU - Chong, Beng H AU - Chong BH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100621 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antibodies) RN - 0 (Immunoglobulins, Intravenous) RN - A7V27PHC7A (Quinine) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Animals MH - Antibodies/immunology/metabolism/pharmacology MH - Antibody Specificity/immunology MH - Blood Platelets/cytology/immunology/*metabolism MH - Cell Survival/drug effects MH - *Disease Models, Animal MH - Female MH - Flow Cytometry MH - Humans MH - Immunoglobulins, Intravenous/administration & dosage/*pharmacology MH - Male MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - Middle Aged MH - Quinine/administration & dosage/adverse effects MH - Thrombocytopenia/blood/chemically induced/*drug therapy MH - Time Factors MH - Treatment Outcome MH - Young Adult EDAT- 2010/06/23 06:00 MHDA- 2010/10/30 06:00 CRDT- 2010/06/23 06:00 PHST- 2010/06/23 06:00 [entrez] PHST- 2010/06/23 06:00 [pubmed] PHST- 2010/10/30 06:00 [medline] AID - S0006-4971(20)33000-7 [pii] AID - 10.1182/blood-2010-02-268326 [doi] PST - ppublish SO - Blood. 2010 Sep 16;116(11):1958-60. doi: 10.1182/blood-2010-02-268326. Epub 2010 Jun 21.