H D Husseinzadeh1, P A Gimotty2, A M Pishko1, M Buckley2, T E Warkentin3, A Cuker1,4. 1. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 2. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 3. Departments of Pathology and Molecular Medicine, and Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada. 4. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abstract
Essentials Immunoassay specificity varies in heparin-induced thrombocytopenia (HIT) testing. This meta-analysis examined 9 studies that tested samples by both IgG and polyspecific methods. IgG-specific assays confer superior diagnostic accuracy compared with polyspecific assays. These results further support recommendations in favor of IgG-specific testing. SUMMARY: Background There are conflicting data on whether the IgG-specific or polyspecific antiplatelet factor 4/heparin (PF4/H) enzyme-linked immunosorbent assay (ELISA) is preferred for the laboratory diagnosis of heparin-induced thrombocytopenia (HIT). Objectives To directly compare diagnostic accuracy of IgG-specific versus polyspecific ELISA in HIT. Patients/Methods A systematic search yielded nine studies comprising 1948 patients with suspected HIT tested by both IgG-specific and polyspecific ELISAs and a reference standard against which the diagnostic accuracy of the ELISAs could be measured. Study quality was assessed by QUADAS-2 criteria. Results There was identical sensitivity for IgG-specific and polyspecific ELISAs (0.97; 95% confidence interval (CI), 0.95-0.99) and superior specificity of IgG-specific compared with polyspecific ELISA (0.87 [0.85-0.88] vs. 0.82 [0.80-0.84], respectively). Performance was similar in subgroups using the serotonin release assay and a single commercial ELISA manufacturer. The negative predictive values of IgG-specific and polyspecific ELISA were similarly high (0.99, [0.99-1.00], but the positive predictive value was superior with IgG-specific compared with polyspecific ELISA (0.56 [0.52-0.61] vs. 0.32 [0.28-0.35], respectively). The positive likelihood ratio (LR) was higher in IgG-specific than polyspecific ELISA, although negative LRs were similar. There was high risk of quality concerns in domains of index test and reference standard. Conclusions The superior diagnostic accuracy of IgG-specific ELISA reinforces the ISTH-SSC recommendation for standardization of laboratory testing for HIT. Likelihood ratios of individual assays may be used in combination with clinical scoring systems as part of an integrated diagnostic algorithm for HIT.
Essentials Immunoassay specificity varies in heparin-induced thrombocytopenia (HIT) testing. This meta-analysis examined 9 studies that tested samples by both IgG and polyspecific methods. IgG-specific assays confer superior diagnostic accuracy compared with polyspecific assays. These results further support recommendations in favor of IgG-specific testing. SUMMARY: Background There are conflicting data on whether the IgG-specific or polyspecific antiplatelet factor 4/heparin (PF4/H) enzyme-linked immunosorbent assay (ELISA) is preferred for the laboratory diagnosis of heparin-induced thrombocytopenia (HIT). Objectives To directly compare diagnostic accuracy of IgG-specific versus polyspecific ELISA in HIT. Patients/Methods A systematic search yielded nine studies comprising 1948 patients with suspected HIT tested by both IgG-specific and polyspecific ELISAs and a reference standard against which the diagnostic accuracy of the ELISAs could be measured. Study quality was assessed by QUADAS-2 criteria. Results There was identical sensitivity for IgG-specific and polyspecific ELISAs (0.97; 95% confidence interval (CI), 0.95-0.99) and superior specificity of IgG-specific compared with polyspecific ELISA (0.87 [0.85-0.88] vs. 0.82 [0.80-0.84], respectively). Performance was similar in subgroups using the serotonin release assay and a single commercial ELISA manufacturer. The negative predictive values of IgG-specific and polyspecific ELISA were similarly high (0.99, [0.99-1.00], but the positive predictive value was superior with IgG-specific compared with polyspecific ELISA (0.56 [0.52-0.61] vs. 0.32 [0.28-0.35], respectively). The positive likelihood ratio (LR) was higher in IgG-specific than polyspecific ELISA, although negative LRs were similar. There was high risk of quality concerns in domains of index test and reference standard. Conclusions The superior diagnostic accuracy of IgG-specific ELISA reinforces the ISTH-SSC recommendation for standardization of laboratory testing for HIT. Likelihood ratios of individual assays may be used in combination with clinical scoring systems as part of an integrated diagnostic algorithm for HIT.
Authors: Mark Andrew Crowther; Deborah J Cook; Martin Albert; David Williamson; Maureen Meade; John Granton; Yoanna Skrobik; Stephan Langevin; Sangeeta Mehta; Paul Hebert; Gordon H Guyatt; William Geerts; Christian Rabbat; James Douketis; Nicole Zytaruk; Joanne Sheppard; Andreas Greinacher; Theodore E Warkentin Journal: J Crit Care Date: 2010-02-10 Impact factor: 3.425
Authors: T L Bauer; G Arepally; B A Konkle; B Mestichelli; S S Shapiro; D B Cines; M Poncz; S McNulty; J Amiral; W W Hauck; R N Edie; J D Mannion Journal: Circulation Date: 1997-03-04 Impact factor: 29.690
Authors: Theodore E Warkentin; Jo-Ann I Sheppard; Diane Heels-Ansdell; John C Marshall; Lauralyn McIntyre; Marcelo G Rocha; Sangeeta Mehta; Andrew R Davies; Andrew D Bersten; Tim M Crozier; David Ernest; Nicholas E Vlahakis; Richard I Hall; Gordon G Wood; Germain Poirier; Mark A Crowther; Deborah J Cook Journal: Chest Date: 2013-09 Impact factor: 9.410
Authors: Penny F Whiting; Anne W S Rutjes; Marie E Westwood; Susan Mallett; Jonathan J Deeks; Johannes B Reitsma; Mariska M G Leeflang; Jonathan A C Sterne; Patrick M M Bossuyt Journal: Ann Intern Med Date: 2011-10-18 Impact factor: 25.391
Authors: Rossella Marcucci; Martina Berteotti; Anna M Gori; Betti Giusti; Angela A Rogolino; Elena Sticchi; Agatina Alessandrello Liotta; Walter Ageno; Erica De Candia; Paolo Gresele; Marina Marchetti; Marco Marietta; Armando Tripodi Journal: Blood Transfus Date: 2020-12-28 Impact factor: 3.443
Authors: Allyson M Pishko; Sara Fardin; Daniel S Lefler; Koosha Paydary; Rolando Vega; Gowthami M Arepally; Mark Crowther; Lawrence Rice; Douglas B Cines; Adam Cuker Journal: Blood Adv Date: 2018-11-27
Authors: Allyson M Pishko; Daniel S Lefler; Phyllis Gimotty; Koosha Paydary; Sara Fardin; Gowthami M Arepally; Mark Crowther; Lawrence Rice; Rolando Vega; Douglas B Cines; James P Guevara; Adam Cuker Journal: J Thromb Haemost Date: 2019-08-12 Impact factor: 5.824
Authors: Jae Hwan Choi; Jessica G Y Luc; Matthew P Weber; Haritha G Reddy; Elizabeth J Maynes; Avijit K Deb; Louis E Samuels; Rohinton J Morris; H Todd Massey; Antonio Loforte; Vakhtang Tchantchaleishvili Journal: Ann Cardiothorac Surg Date: 2019-01
Authors: Sean Platton; Andrew Bartlett; Peter MacCallum; Mike Makris; Vickie McDonald; Deepak Singh; Marie Scully; Sue Pavord Journal: J Thromb Haemost Date: 2021-07-05 Impact factor: 16.036
Authors: Theodore E Warkentin; Jo-Ann I Sheppard; James W Smith; Donald M Arnold; Ishac Nazy Journal: Int J Lab Hematol Date: 2019-05-03 Impact factor: 2.877