Heparin-induced thrombocytopenia in the critically ill: Interpreting the 4Ts test in a randomized trial

Mark Crowther, Deborah Cook, Gordon Guyatt, Nicole Zytaruk, Ellen McDonald, David Williamson, Martin Albert, Peter Dodek, Simon Finfer, Shirley Vallance, Diane Heels-Ansdell, Lauralyn McIntyre, Sangeeta Mehta, Francois Lamontagne, John Muscedere, Michael Jacka, Olivier Lesur, Jim Kutsiogiannis, Jan Friedrich, James R. KlingerIsmael Qushmaq, Lisa Burry, Kosar Khwaja, Jo Ann Sheppard, Theodore E. Warkentin, Andrea Tkaczyk, France Clarke, Rickand Hall, Graeme Rocker, Lisa Julien, Debbie Wright, Caroline Roy, Judy Theriault, Susan Pleasance, Maureen Meade, Lori Hand, Andreas Freitag, Christine Wynne, Mark Duffett, Michelle Kho, John Granton, Andrea Matte, Paulina Farias, Leslie Chu, Nancy Brockest, Stephanie Go, Margaret McGrath-Chong, Madison Dennis, Marc Lipkus, Emily Stern, Ryan Albert, Stephan Langevin, Francois Lauzier, Alexis F. Turgeon, Martine Blais, Maxime Beauparlant, Julie Asselin, Chantal Gagne, Marie Thibodeau, Germain Poirier, Isabelle Neas, Sandrine Spearson, Paul Hebert, Irene Watpool, Tracy McArdle, Claude Gaudert, Paule Marchand, Carson Davidson, Joe Pagliarello, Mary Jo Lewis, Erin Murphy, Julia Foxall, Yoanna Skrobik, Johanne Harvey, Stefania Chitu, Carole Sirois, Carole Nadon, Stephanie Dolle, Audrey Anne Gosselin, Patrice Deroy, Cheryl Ethier, Sam Tirgari, Lindsay Steinberg, Rod McDonald, Vidhya Sivanantham, Kristofer Bandayrel, Friederike Quittnat-Pelletier, Marnie Kramer-Kile, Maedean Brown, Scott Kim, Robert Fowler, Nicole Marinoff, Karen Code, Boris Bojilov, Derek Parsotam, John Marshall, Orla Smith, Beth Fry, Kerri Porretta, Yoon Lee, Jeanna Morrissey, Victoria Wen, Susan Fleury, Nicole Godfrey, Sharlene Hammond, Elizabeth Mann, Monica Myers, Amber Robinson, Sean Keenan, Steven Reynolds, Miroslav Svetik, Mary Van Osch, Dean Chittock, Vinay Dhingra, Maureen Gardner, Susan Logie, Denise Foster, Roger Autio, Dara Davies, Pia Ganz, Laurie Smith, Betty Jean Ashley, Sheilagh Mans, Chip Doig, Linda Knox, Crystal Wilson, Kevin Champagne, Niall Ferguson, James Stevenson, Joel Elman, Jim Kutsogiannis, Patrica Thompson, Norine Whalen, Francois Lellouche, Marie Claude Ferland, Patrick Dussault, Caroline Jacob, Marie Eve Morneau, Nancy Laberge, Tim Karachi, Marleen Irwin, Carmen Chan, Leeca Sonnema, Kelly Marsh, Jennifer Maurer, Tamara Kreidl, Candice Varden, Carey Kinjerski, Laura Banici, Lena Havell, Gordon Wood, Fiona Auld, Leslie Atkins, Sandra Proulx, Gerald Hollinger, Vasanti Shende, Vanessa Belcastro, Bill Plaxton, Anders Foss, Bojan Paunovic, Kym Wiebe, Nicole Marten, Jonathan Eisenstat, Tammy Doerle, Michael Sharpe, Mona Madady, Jamie Cooper, Andrew Davies, Cindy Weatherburn, Jasmin Board, Victoria Bennett, Naresh Ramakrishnan, Simon Bird, Julie Potter, Anne O'Connor, Susan Ankers, Jack Cade, Deborah Barge, Tania Caf, Belinda Howe, Rinaldo Bellomo, Glenn Eastwood, Leah Peck, Donna Goldsmith, Kim O'Sullivan, David Ernest, Sam Radford, Ann Whitfield, Anthony Cross, Suzanne Eliott, Jaspreet Sidhu, Inga Mercer, Angela Hamilton, John Botha, Jodi Vuat, Sharon Allsop, Nina Fowler, Tim Crozier, Jonathan Barrett, Chris Wright, Pauline Galt, Carly Culhane, Rebecca Ioannidis, Sue Burton, Marnie Reily, Cyveen Weeraratna, Ian Seppelt, Leonie Weisbrodt, Robyn Bond, David Evans, Justine Rivett, Stephanie O'Connor, Alex Poole, Clive Woolfe, Dorrilyn Rajbhandari, Caitlin Rees, John Edington, Jason Fletcher, Julie Smith, Catherine Boschert, Graham Reece, Treena Sara, Kiran Nand, Andrew Bersten, Alex Gallus, Elisha Matheson, Margie O'Callaghan, Neil Orford, Tania Elderkin, Melissa Fraser, Allison Bone, Tania Salerno, Anne Kinmonth, Subhash Arora, Bridget O'Bree, Katherine Shepherd, Alan Davey-Quinn, Martin Sterba, Bronwyn Ruth Johnson, Renee Xu, Francisco Hill, Rajaram Ramadoss, Josette Wood

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Abstract

Background: Thrombocytopenia occurs in 20% to 45% of critically ill medical-surgical patients. The 4Ts heparin-induced thrombocytopenia (HIT) score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and o. Ther reason[s] for thrombocytopenia) might reliably identify patients at low risk for HIT. Interobserver agreement on 4Ts scoring is uncertain in this setting. Objective: To evaluate whether a published clinical prediction rule (the "4Ts score") reliably rules out HIT in "low-risk" intensive care unit (ICU) patients as assessed by research coordinators (who prospectively scored) and 2 adjudicators (who scored retrospectively) during an international heparin thromboprophylaxis trial (PROTECT, NCT00182143). Methods: Of 3746 medical-surgical ICU patients in PROTECT, 794 met the enrollment criteria for this HIT substudy. Enrollment was predicated on one of the following occurring in ICU: platelets less than 50 × 109/L, platelets decreased to 50% of ICU admission value (if admission value <100 × 109/L), any venous thrombosis, or if HIT was otherwise clinically suspected. Independently, 4Ts scores were completed in real time by research coordinators blinded to study drug and laboratory HIT results, and retrospectively by 2 adjudicators blinded to study drug, laboratory HIT results, and research coordinators' scores; the adjudicators arrived at consensus in all cases. Of the 763 patients, 474 had a central or local laboratory HIT test performed and had 4Ts scoring by adjudicators; 432 were scored by trained research coordinators. Heparin-induced thrombocytopenia was defined by a centrally performed positive serotonin release assay (SRA). Results: Of the 474 patients with central adjudication, 407 (85.9%) had a 4Ts score of 3 or lower, conferring a low pretest probability (PTP) of HIT; of these, 6 (1.5% [95% confidence interval, 0.7%-3.2%) had a positive SRA. Fifty-nine (12.4%) had a moderate PTP (4Ts score of 4-5); of these, 4 (6.8%) had a positive SRA. Eight patients had a high PTP (4Ts score of ≥. 6); of these, 1 (12.5%) had a positive SRA. Raw agreement between research coordinators and central adjudication on each domain of the 4Ts score and low, intermediate, and high PTP was good. However, chance-corrected agreement was variable between adjudicators (weighted κ values of 0.31-0.93) and between the adjudicator consensus and research coordinators (weighted κ values of 0.13 and 0.78). Post hoc review of the 6 SRA-positive cases with an adjudicated low PTP demonstrated that their scores would have been increased if the adjudicators had had additional information on heparin exposure prior to ICU admission. In general, the fourth domain of 4Ts (oTher causes of thrombocytopenia) generated the most disagreement. Conclusions: Real-time 4Ts scoring by research coordinators at the time of testing for HIT was not consistent with 4Ts scores obtained by central adjudicators. The results of this comprehensive HIT testing highlight the need for further research to improve the assessment of PTP scoring of HIT for critically ill patients.

Original languageEnglish
Pages (from-to)470.e7-470.e15
JournalJournal of Critical Care
Volume29
Issue number3
DOIs
Publication statusPublished - Jun 2014

Keywords

  • Critical care
  • Heparin-induced thrombocytopenia
  • Intensive care unit
  • Thrombocytopenia

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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