PMID- 26905366 OWN - NLM STAT- MEDLINE DCOM- 20170524 LR - 20181113 IS - 1931-3543 (Electronic) IS - 0012-3692 (Print) IS - 0012-3692 (Linking) VI - 150 IP - 3 DP - 2016 Sep TI - A Novel PF4-Dependent Platelet Activation Assay Identifies Patients Likely to Have Heparin-Induced Thrombocytopenia/Thrombosis. PG - 506-15 LID - S0012-3692(16)01260-5 [pii] LID - 10.1016/j.chest.2016.02.641 [doi] AB - BACKGROUND: Almost without exception, patients with heparin-induced thrombocytopenia/thrombosis (HIT) have antibodies that recognize platelet factor 4 (PF4) in a complex with heparin; however, many heparin-treated patients without HIT are also antibody-positive. A platelet activation test, the serotonin release assay (SRA), is useful for identifying a subset of antibodies that are platelet-activating and most likely to cause HIT. However, this "gold standard" assay for HIT diagnosis is technically demanding and is routinely available only through referral laboratories, limiting its availability for timely diagnosis and management. METHODS: We compared the diagnostic performance of the SRA with that of a technically simple platelet activation assay, the PF4-dependent P-selectin expression assay (PEA), which uses platelets pretreated with PF4 as targets for antibody detection. Archived serum samples from 91 patients for whom clinical information (HIT 4Ts [thrombocytopenia, timing of platelet count fall, thrombosis, and other causes of thrombocytopenia] score) was available were used. Patients with an intermediate 4Ts score and a PF4 ELISA (enzyme-linked immunosorbent assay) optical density >/= 2.0, or a high 4Ts score and a PF4 ELISA optical density >/= 1.0, were considered HIT positive; others were designated HIT negative. RESULTS: The PEA had higher diagnostic accuracy (area under the curve, 0.92 vs 0.82; P = .02) than the SRA, using this definition of HIT. Eleven of 16 serum samples that were PEA positive and SRA negative were HIT positive. Studies done with identical target platelets and serially diluted samples from patients with HIT showed that the PEA is inherently more sensitive than the SRA for the detection of platelet-activating antibodies. CONCLUSIONS: The PEA is technically less demanding than the SRA and may be more accurate for the diagnosis of HIT. CI - Copyright (c) 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. FAU - Padmanabhan, Anand AU - Padmanabhan A AD - Medical Sciences Institute, BloodCenter of Wisconsin, Milwaukee, WI; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI. Electronic address: anand.padmanabhan@bcw.edu. FAU - Jones, Curtis G AU - Jones CG AD - Medical Sciences Institute, BloodCenter of Wisconsin, Milwaukee, WI. FAU - Curtis, Brian R AU - Curtis BR AD - Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI; Platelet and Neutrophil Immunology Laboratory, BloodCenter of Wisconsin, Milwaukee, WI. FAU - Bougie, Daniel W AU - Bougie DW AD - Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI. FAU - Sullivan, Mia J AU - Sullivan MJ AD - Platelet and Neutrophil Immunology Laboratory, BloodCenter of Wisconsin, Milwaukee, WI. FAU - Peswani, Namrata AU - Peswani N AD - Department of Medicine, Medical College of Wisconsin, Milwaukee, WI. FAU - McFarland, Janice G AU - McFarland JG AD - Platelet and Neutrophil Immunology Laboratory, BloodCenter of Wisconsin, Milwaukee, WI; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI. FAU - Eastwood, Daniel AU - Eastwood D AD - Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI. FAU - Wang, Demin AU - Wang D AD - Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI. FAU - Aster, Richard H AU - Aster RH AD - Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI. LA - eng GR - R01 AI079087/AI/NIAID NIH HHS/United States GR - R01 HL013629/HL/NHLBI NIH HHS/United States GR - R37 HL013629/HL/NHLBI NIH HHS/United States GR - R56 HL013629/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160219 PL - United States TA - Chest JT - Chest JID - 0231335 RN - 0 (Anticoagulants) RN - 0 (Autoantibodies) RN - 0 (P-Selectin) RN - 0 (SELP protein, human) RN - 37270-94-3 (Platelet Factor 4) RN - 9005-49-6 (Heparin) SB - IM CIN - Chest. 2016 Sep;150(3):478-80. PMID: 27613972 MH - Adult MH - Aged MH - Aged, 80 and over MH - Anticoagulants/*adverse effects MH - Autoantibodies/immunology MH - Case-Control Studies MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Heparin/*adverse effects MH - Humans MH - Male MH - Middle Aged MH - P-Selectin/metabolism MH - *Platelet Activation MH - Platelet Factor 4/immunology MH - Thrombocytopenia/*chemically induced/diagnosis/immunology MH - Thrombosis/*chemically induced/diagnosis/immunology PMC - PMC5028397 OTO - NOTNLM OT - heparin OT - thrombocytopenia OT - thrombosis EDAT- 2016/02/26 06:00 MHDA- 2017/05/26 06:00 PMCR- 2017/09/01 CRDT- 2016/02/25 06:00 PHST- 2015/09/16 00:00 [received] PHST- 2016/01/12 00:00 [revised] PHST- 2016/02/03 00:00 [accepted] PHST- 2016/02/25 06:00 [entrez] PHST- 2016/02/26 06:00 [pubmed] PHST- 2017/05/26 06:00 [medline] PHST- 2017/09/01 00:00 [pmc-release] AID - S0012-3692(16)01260-5 [pii] AID - 10.1016/j.chest.2016.02.641 [doi] PST - ppublish SO - Chest. 2016 Sep;150(3):506-15. doi: 10.1016/j.chest.2016.02.641. Epub 2016 Feb 19.