Heparin-induced thrombocytopenia in the critically ill

Interpreting the 4Ts test in a randomized trial

Mark Crowther, Deborah J 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 J Jacka, Olivier Lesur, Jim Kutsiogiannis, Jan Friedrich, James R Klinger & 223 others Ismael Qushmaq, Lisa Burry, Kosar Khwaja, Jo-Ann I 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 E 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 N. 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 F. Myers, Amber Robinson, Sean Keenan, Steven Reynolds, Miroslav Svetik, Mary Van Osch, Dean R 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 H 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 R 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 Anne O'Bree, Katherine Shepherd, Alan Davey-Quinn, Martin Sterba, Bronwyn Ruth Johnson, Renee Xu, Francisco Hill, Rajaram Ramadoss, Josette Wood

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

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
JournalJournal of Critical Care
Volume29
Issue number3
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

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

Cite this

Crowther, M., Cook, D. J., Guyatt, G., Zytaruk, N., McDonald, E., Williamson, D., ... Wood, J. (2014). Heparin-induced thrombocytopenia in the critically ill: Interpreting the 4Ts test in a randomized trial. Journal of Critical Care, 29(3). https://doi.org/10.1016/j.jcrc.2014.02.004
Crowther, Mark ; Cook, Deborah J ; Guyatt, Gordon ; Zytaruk, Nicole ; McDonald, Ellen ; Williamson, David ; Albert, Martin ; Dodek, Peter ; Finfer, Simon ; Vallance, Shirley ; Heels-Ansdell, Diane ; Mcintyre, Lauralyn ; Mehta, Sangeeta ; Lamontagne, Francois ; Muscedere, John ; Jacka, Michael J ; Lesur, Olivier ; Kutsiogiannis, Jim ; Friedrich, Jan ; Klinger, James R ; Qushmaq, Ismael ; Burry, Lisa ; Khwaja, Kosar ; Sheppard, Jo-Ann I ; Warkentin, Theodore E. ; Tkaczyk, Andrea ; Clarke, France ; Hall, Rickand ; Rocker, Graeme ; Julien, Lisa ; Wright, Debbie ; Roy, Caroline ; Theriault, Judy ; Pleasance, Susan ; Meade, Maureen ; Hand, Lori E ; Freitag, Andreas ; Wynne, Christine ; Duffett, Mark ; Kho, Michelle ; Granton, John ; Matte, Andrea ; Farias, Paulina ; Chu, Leslie ; Brockest, Nancy ; Go, Stephanie ; McGrath-Chong, Margaret ; Dennis, Madison ; Lipkus, Marc ; Stern, Emily N. ; Albert, Ryan ; Langevin, Stephan ; Lauzier, Francois ; Turgeon, Alexis F ; Blais, Martine ; Beauparlant, Maxime ; Asselin, Julie ; Gagne, Chantal ; Thibodeau, Marie ; Poirier, Germain ; Neas, Isabelle ; Spearson, Sandrine ; Hebert, Paul ; Watpool, Irene ; McArdle, Tracy ; Gaudert, Claude ; Marchand, Paule ; Davidson, Carson ; Pagliarello, Joe ; Lewis, Mary Jo ; Murphy, Erin ; Foxall, Julia ; Skrobik, Yoanna ; Harvey, Johanne ; Chitu, Stefania ; Sirois, Carole ; Nadon, Carole ; Dolle, Stephanie ; Gosselin, Audrey Anne ; Deroy, Patrice ; Ethier, Cheryl ; Tirgari, Sam ; Steinberg, Lindsay ; McDonald, Rod ; Sivanantham, Vidhya ; Bandayrel, Kristofer ; Quittnat-Pelletier, Friederike ; Kramer-Kile, Marnie ; Brown, Maedean ; Kim, Scott ; Fowler, Robert ; Marinoff, Nicole ; Code, Karen ; Bojilov, Boris ; Parsotam, Derek ; Marshall, John ; Smith, Orla ; Fry, Beth ; Porretta, Kerri ; Lee, Yoon ; Morrissey, Jeanna ; Wen, Victoria ; Fleury, Susan ; Godfrey, Nicole ; Hammond, Sharlene ; Mann, Elizabeth ; Myers, Monica F. ; Robinson, Amber ; Keenan, Sean ; Reynolds, Steven ; Svetik, Miroslav ; Osch, Mary Van ; Chittock, Dean R ; Dhingra, Vinay ; Gardner, Maureen ; Logie, Susan ; Foster, Denise ; Autio, Roger ; Davies, Dara ; Ganz, Pia ; Smith, Laurie ; Ashley, Betty Jean ; Mans, Sheilagh ; Doig, Chip ; Knox, Linda ; Wilson, Crystal ; Champagne, Kevin ; Ferguson, Niall ; Stevenson, James ; Elman, Joel ; Kutsogiannis, Jim ; Thompson, Patrica ; Whalen, Norine ; Lellouche, Francois ; Ferland, Marie Claude ; Dussault, Patrick H ; Jacob, Caroline ; Morneau, Marie Eve ; Laberge, Nancy ; Karachi, Tim ; Irwin, Marleen ; Chan, Carmen ; Sonnema, Leeca ; Marsh, Kelly ; Maurer, Jennifer ; Kreidl, Tamara ; Varden, Candice ; Kinjerski, Carey ; Banici, Laura ; Havell, Lena ; Wood, Gordon ; Auld, Fiona ; Atkins, Leslie ; Proulx, Sandra ; Hollinger, Gerald ; Shende, Vasanti ; Belcastro, Vanessa ; Plaxton, Bill ; Foss, Anders ; Paunovic, Bojan ; Wiebe, Kym ; Marten, Nicole ; Eisenstat, Jonathan ; Doerle, Tammy ; Sharpe, Michael ; Madady, Mona ; Cooper, Jamie ; Davies, Andrew R ; Weatherburn, Cindy ; Board, Jasmin ; Bennett, Victoria ; Ramakrishnan, Naresh ; Bird, Simon ; Potter, Julie ; O'Connor, Anne ; Ankers, Susan ; Cade, Jack ; Barge, Deborah ; Caf, Tania ; Howe, Belinda ; Bellomo, Rinaldo ; Eastwood, Glenn ; Peck, Leah ; Goldsmith, Donna ; O'Sullivan, Kim ; Ernest, David ; Radford, Sam ; Whitfield, Ann ; Cross, Anthony ; Eliott, Suzanne ; Sidhu, Jaspreet ; Mercer, Inga ; Hamilton, Angela ; Botha, John ; Vuat, Jodi ; Allsop, Sharon ; Fowler, Nina ; Crozier, Tim ; Barrett, Jonathan ; Wright, Chris ; Galt, Pauline ; Culhane, Carly ; Ioannidis, Rebecca ; Burton, Sue ; Reily, Marnie ; Weeraratna, Cyveen ; Seppelt, Ian ; Weisbrodt, Leonie ; Bond, Robyn ; Evans, David ; Rivett, Justine ; O'Connor, Stephanie ; Poole, Alex ; Woolfe, Clive ; Rajbhandari, Dorrilyn ; Rees, Caitlin ; Edington, John ; Fletcher, Jason ; Smith, Julie ; Boschert, Catherine ; Reece, Graham ; Sara, Treena ; Nand, Kiran ; Bersten, Andrew ; Gallus, Alex ; Matheson, Elisha ; O'Callaghan, Margie ; Orford, Neil ; Elderkin, Tania ; Fraser, Melissa ; Bone, Allison ; Salerno, Tania ; Kinmonth, Anne ; Arora, Subhash ; O'Bree, Bridget Anne ; Shepherd, Katherine ; Davey-Quinn, Alan ; Sterba, Martin ; Johnson, Bronwyn Ruth ; Xu, Renee ; Hill, Francisco ; Ramadoss, Rajaram ; Wood, Josette. / Heparin-induced thrombocytopenia in the critically ill : Interpreting the 4Ts test in a randomized trial. In: Journal of Critical Care. 2014 ; Vol. 29, No. 3.
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title = "Heparin-induced thrombocytopenia in the critically ill: Interpreting the 4Ts test in a randomized trial",
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.",
keywords = "Critical care, Heparin-induced thrombocytopenia, Intensive care unit, Thrombocytopenia",
author = "Mark Crowther and Cook, {Deborah J} and Gordon Guyatt and Nicole Zytaruk and Ellen McDonald and David Williamson and Martin Albert and Peter Dodek and Simon Finfer and Shirley Vallance and Diane Heels-Ansdell and Lauralyn Mcintyre and Sangeeta Mehta and Francois Lamontagne and John Muscedere and Jacka, {Michael J} and Olivier Lesur and Jim Kutsiogiannis and Jan Friedrich and Klinger, {James R} and Ismael Qushmaq and Lisa Burry and Kosar Khwaja and Sheppard, {Jo-Ann I} and Warkentin, {Theodore E.} and Andrea Tkaczyk and France Clarke and Rickand Hall and Graeme Rocker and Lisa Julien and Debbie Wright and Caroline Roy and Judy Theriault and Susan Pleasance and Maureen Meade and Hand, {Lori E} and Andreas Freitag and Christine Wynne and Mark Duffett and Michelle Kho and John Granton and Andrea Matte and Paulina Farias and Leslie Chu and Nancy Brockest and Stephanie Go and Margaret McGrath-Chong and Madison Dennis and Marc Lipkus and Stern, {Emily N.} and Ryan Albert and Stephan Langevin and Francois Lauzier and Turgeon, {Alexis F} and Martine Blais and Maxime Beauparlant and Julie Asselin and Chantal Gagne and Marie Thibodeau and Germain Poirier and Isabelle Neas and Sandrine Spearson and Paul Hebert and Irene Watpool and Tracy McArdle and Claude Gaudert and Paule Marchand and Carson Davidson and Joe Pagliarello and Lewis, {Mary Jo} and Erin Murphy and Julia Foxall and Yoanna Skrobik and Johanne Harvey and Stefania Chitu and Carole Sirois and Carole Nadon and Stephanie Dolle and Gosselin, {Audrey Anne} and Patrice Deroy and Cheryl Ethier and Sam Tirgari and Lindsay Steinberg and Rod McDonald and Vidhya Sivanantham and Kristofer Bandayrel and Friederike Quittnat-Pelletier and Marnie Kramer-Kile and Maedean Brown and Scott Kim and Robert Fowler and Nicole Marinoff and Karen Code and Boris Bojilov and Derek Parsotam and John Marshall and Orla Smith and Beth Fry and Kerri Porretta and Yoon Lee and Jeanna Morrissey and Victoria Wen and Susan Fleury and Nicole Godfrey and Sharlene Hammond and Elizabeth Mann and Myers, {Monica F.} and Amber Robinson and Sean Keenan and Steven Reynolds and Miroslav Svetik and Osch, {Mary Van} and Chittock, {Dean R} and Vinay Dhingra and Maureen Gardner and Susan Logie and Denise Foster and Roger Autio and Dara Davies and Pia Ganz and Laurie Smith and Ashley, {Betty Jean} and Sheilagh Mans and Chip Doig and Linda Knox and Crystal Wilson and Kevin Champagne and Niall Ferguson and James Stevenson and Joel Elman and Jim Kutsogiannis and Patrica Thompson and Norine Whalen and Francois Lellouche and Ferland, {Marie Claude} and Dussault, {Patrick H} and Caroline Jacob and Morneau, {Marie Eve} and Nancy Laberge and Tim Karachi and Marleen Irwin and Carmen Chan and Leeca Sonnema and Kelly Marsh and Jennifer Maurer and Tamara Kreidl and Candice Varden and Carey Kinjerski and Laura Banici and Lena Havell and Gordon Wood and Fiona Auld and Leslie Atkins and Sandra Proulx and Gerald Hollinger and Vasanti Shende and Vanessa Belcastro and Bill Plaxton and Anders Foss and Bojan Paunovic and Kym Wiebe and Nicole Marten and Jonathan Eisenstat and Tammy Doerle and Michael Sharpe and Mona Madady and Jamie Cooper and Davies, {Andrew R} and Cindy Weatherburn and Jasmin Board and Victoria Bennett and Naresh Ramakrishnan and Simon Bird and Julie Potter and Anne O'Connor and Susan Ankers and Jack Cade and Deborah Barge and Tania Caf and Belinda Howe and Rinaldo Bellomo and Glenn Eastwood and Leah Peck and Donna Goldsmith and Kim O'Sullivan and David Ernest and Sam Radford and Ann Whitfield and Anthony Cross and Suzanne Eliott and Jaspreet Sidhu and Inga Mercer and Angela Hamilton and John Botha and Jodi Vuat and Sharon Allsop and Nina Fowler and Tim Crozier and Jonathan Barrett and Chris Wright and Pauline Galt and Carly Culhane and Rebecca Ioannidis and Sue Burton and Marnie Reily and Cyveen Weeraratna and Ian Seppelt and Leonie Weisbrodt and Robyn Bond and David Evans and Justine Rivett and Stephanie O'Connor and Alex Poole and Clive Woolfe and Dorrilyn Rajbhandari and Caitlin Rees and John Edington and Jason Fletcher and Julie Smith and Catherine Boschert and Graham Reece and Treena Sara and Kiran Nand and Andrew Bersten and Alex Gallus and Elisha Matheson and Margie O'Callaghan and Neil Orford and Tania Elderkin and Melissa Fraser and Allison Bone and Tania Salerno and Anne Kinmonth and Subhash Arora and O'Bree, {Bridget Anne} and Katherine Shepherd and Alan Davey-Quinn and Martin Sterba and Johnson, {Bronwyn Ruth} and Renee Xu and Francisco Hill and Rajaram Ramadoss and Josette Wood",
year = "2014",
doi = "10.1016/j.jcrc.2014.02.004",
language = "English",
volume = "29",
journal = "Journal of Critical Care",
issn = "0883-9441",
publisher = "Elsevier",
number = "3",

}

Crowther, M, Cook, DJ, Guyatt, G, Zytaruk, N, McDonald, E, Williamson, D, Albert, M, Dodek, P, Finfer, S, Vallance, S, Heels-Ansdell, D, Mcintyre, L, Mehta, S, Lamontagne, F, Muscedere, J, Jacka, MJ, Lesur, O, Kutsiogiannis, J, Friedrich, J, Klinger, JR, Qushmaq, I, Burry, L, Khwaja, K, Sheppard, J-AI, Warkentin, TE, Tkaczyk, A, Clarke, F, Hall, R, Rocker, G, Julien, L, Wright, D, Roy, C, Theriault, J, Pleasance, S, Meade, M, Hand, LE, Freitag, A, Wynne, C, Duffett, M, Kho, M, Granton, J, Matte, A, Farias, P, Chu, L, Brockest, N, Go, S, McGrath-Chong, M, Dennis, M, Lipkus, M, Stern, EN, Albert, R, Langevin, S, Lauzier, F, Turgeon, AF, Blais, M, Beauparlant, M, Asselin, J, Gagne, C, Thibodeau, M, Poirier, G, Neas, I, Spearson, S, Hebert, P, Watpool, I, McArdle, T, Gaudert, C, Marchand, P, Davidson, C, Pagliarello, J, Lewis, MJ, Murphy, E, Foxall, J, Skrobik, Y, Harvey, J, Chitu, S, Sirois, C, Nadon, C, Dolle, S, Gosselin, AA, Deroy, P, Ethier, C, Tirgari, S, Steinberg, L, McDonald, R, Sivanantham, V, Bandayrel, K, Quittnat-Pelletier, F, Kramer-Kile, M, Brown, M, Kim, S, Fowler, R, Marinoff, N, Code, K, Bojilov, B, Parsotam, D, Marshall, J, Smith, O, Fry, B, Porretta, K, Lee, Y, Morrissey, J, Wen, V, Fleury, S, Godfrey, N, Hammond, S, Mann, E, Myers, MF, Robinson, A, Keenan, S, Reynolds, S, Svetik, M, Osch, MV, Chittock, DR, Dhingra, V, Gardner, M, Logie, S, Foster, D, Autio, R, Davies, D, Ganz, P, Smith, L, Ashley, BJ, Mans, S, Doig, C, Knox, L, Wilson, C, Champagne, K, Ferguson, N, Stevenson, J, Elman, J, Kutsogiannis, J, Thompson, P, Whalen, N, Lellouche, F, Ferland, MC, Dussault, PH, Jacob, C, Morneau, ME, Laberge, N, Karachi, T, Irwin, M, Chan, C, Sonnema, L, Marsh, K, Maurer, J, Kreidl, T, Varden, C, Kinjerski, C, Banici, L, Havell, L, Wood, G, Auld, F, Atkins, L, Proulx, S, Hollinger, G, Shende, V, Belcastro, V, Plaxton, B, Foss, A, Paunovic, B, Wiebe, K, Marten, N, Eisenstat, J, Doerle, T, Sharpe, M, Madady, M, Cooper, J, Davies, AR, Weatherburn, C, Board, J, Bennett, V, Ramakrishnan, N, Bird, S, Potter, J, O'Connor, A, Ankers, S, Cade, J, Barge, D, Caf, T, Howe, B, Bellomo, R, Eastwood, G, Peck, L, Goldsmith, D, O'Sullivan, K, Ernest, D, Radford, S, Whitfield, A, Cross, A, Eliott, S, Sidhu, J, Mercer, I, Hamilton, A, Botha, J, Vuat, J, Allsop, S, Fowler, N, Crozier, T, Barrett, J, Wright, C, Galt, P, Culhane, C, Ioannidis, R, Burton, S, Reily, M, Weeraratna, C, Seppelt, I, Weisbrodt, L, Bond, R, Evans, D, Rivett, J, O'Connor, S, Poole, A, Woolfe, C, Rajbhandari, D, Rees, C, Edington, J, Fletcher, J, Smith, J, Boschert, C, Reece, G, Sara, T, Nand, K, Bersten, A, Gallus, A, Matheson, E, O'Callaghan, M, Orford, N, Elderkin, T, Fraser, M, Bone, A, Salerno, T, Kinmonth, A, Arora, S, O'Bree, BA, Shepherd, K, Davey-Quinn, A, Sterba, M, Johnson, BR, Xu, R, Hill, F, Ramadoss, R & Wood, J 2014, 'Heparin-induced thrombocytopenia in the critically ill: Interpreting the 4Ts test in a randomized trial', Journal of Critical Care, vol. 29, no. 3. https://doi.org/10.1016/j.jcrc.2014.02.004

Heparin-induced thrombocytopenia in the critically ill : Interpreting the 4Ts test in a randomized trial. / Crowther, Mark; Cook, Deborah J; Guyatt, Gordon; Zytaruk, Nicole; McDonald, Ellen; Williamson, David; Albert, Martin; Dodek, Peter; Finfer, Simon; Vallance, Shirley; Heels-Ansdell, Diane; Mcintyre, Lauralyn; Mehta, Sangeeta; Lamontagne, Francois; Muscedere, John; Jacka, Michael J; Lesur, Olivier; Kutsiogiannis, Jim; Friedrich, Jan; Klinger, James R; Qushmaq, Ismael; Burry, Lisa; Khwaja, Kosar; Sheppard, Jo-Ann I; Warkentin, Theodore E.; Tkaczyk, Andrea; Clarke, France; Hall, Rickand; Rocker, Graeme; Julien, Lisa; Wright, Debbie; Roy, Caroline; Theriault, Judy; Pleasance, Susan; Meade, Maureen; Hand, Lori E; Freitag, Andreas; Wynne, Christine; Duffett, Mark; Kho, Michelle; Granton, John; Matte, Andrea; Farias, Paulina; Chu, Leslie; Brockest, Nancy; Go, Stephanie; McGrath-Chong, Margaret; Dennis, Madison; Lipkus, Marc; Stern, Emily N.; Albert, Ryan; Langevin, Stephan; Lauzier, Francois; Turgeon, Alexis F; Blais, Martine; Beauparlant, Maxime; Asselin, Julie; Gagne, Chantal; Thibodeau, Marie; Poirier, Germain; Neas, Isabelle; Spearson, Sandrine; Hebert, Paul; Watpool, Irene; McArdle, Tracy; Gaudert, Claude; Marchand, Paule; Davidson, Carson; Pagliarello, Joe; Lewis, Mary Jo; Murphy, Erin; Foxall, Julia; Skrobik, Yoanna; Harvey, Johanne; Chitu, Stefania; Sirois, Carole; Nadon, Carole; Dolle, Stephanie; Gosselin, Audrey Anne; Deroy, Patrice; Ethier, Cheryl; Tirgari, Sam; Steinberg, Lindsay; McDonald, Rod; Sivanantham, Vidhya; Bandayrel, Kristofer; Quittnat-Pelletier, Friederike; Kramer-Kile, Marnie; Brown, Maedean; Kim, Scott; Fowler, Robert; Marinoff, Nicole; Code, Karen; Bojilov, Boris; Parsotam, Derek; Marshall, John; Smith, Orla; Fry, Beth; Porretta, Kerri; Lee, Yoon; Morrissey, Jeanna; Wen, Victoria; Fleury, Susan; Godfrey, Nicole; Hammond, Sharlene; Mann, Elizabeth; Myers, Monica F.; Robinson, Amber; Keenan, Sean; Reynolds, Steven; Svetik, Miroslav; Osch, Mary Van; Chittock, Dean R; Dhingra, Vinay; Gardner, Maureen; Logie, Susan; Foster, Denise; Autio, Roger; Davies, Dara; Ganz, Pia; Smith, Laurie; Ashley, Betty Jean; Mans, Sheilagh; Doig, Chip; Knox, Linda; Wilson, Crystal; Champagne, Kevin; Ferguson, Niall; Stevenson, James; Elman, Joel; Kutsogiannis, Jim; Thompson, Patrica; Whalen, Norine; Lellouche, Francois; Ferland, Marie Claude; Dussault, Patrick H; Jacob, Caroline; Morneau, Marie Eve; Laberge, Nancy; Karachi, Tim; Irwin, Marleen; Chan, Carmen; Sonnema, Leeca; Marsh, Kelly; Maurer, Jennifer; Kreidl, Tamara; Varden, Candice; Kinjerski, Carey; Banici, Laura; Havell, Lena; Wood, Gordon; Auld, Fiona; Atkins, Leslie; Proulx, Sandra; Hollinger, Gerald; Shende, Vasanti; Belcastro, Vanessa; Plaxton, Bill; Foss, Anders; Paunovic, Bojan; Wiebe, Kym; Marten, Nicole; Eisenstat, Jonathan; Doerle, Tammy; Sharpe, Michael; Madady, Mona; Cooper, Jamie; Davies, Andrew R; Weatherburn, Cindy; Board, Jasmin; Bennett, Victoria; Ramakrishnan, Naresh; Bird, Simon; Potter, Julie; O'Connor, Anne; Ankers, Susan; Cade, Jack; Barge, Deborah; Caf, Tania; Howe, Belinda; Bellomo, Rinaldo; Eastwood, Glenn; Peck, Leah; Goldsmith, Donna; O'Sullivan, Kim; Ernest, David; Radford, Sam; Whitfield, Ann; Cross, Anthony; Eliott, Suzanne; Sidhu, Jaspreet; Mercer, Inga; Hamilton, Angela; Botha, John; Vuat, Jodi; Allsop, Sharon; Fowler, Nina; Crozier, Tim; Barrett, Jonathan; Wright, Chris; Galt, Pauline; Culhane, Carly; Ioannidis, Rebecca; Burton, Sue; Reily, Marnie; Weeraratna, Cyveen; Seppelt, Ian; Weisbrodt, Leonie; Bond, Robyn; Evans, David; Rivett, Justine; O'Connor, Stephanie; Poole, Alex; Woolfe, Clive; Rajbhandari, Dorrilyn; Rees, Caitlin; Edington, John; Fletcher, Jason; Smith, Julie; Boschert, Catherine; Reece, Graham; Sara, Treena; Nand, Kiran; Bersten, Andrew; Gallus, Alex; Matheson, Elisha; O'Callaghan, Margie; Orford, Neil; Elderkin, Tania; Fraser, Melissa; Bone, Allison; Salerno, Tania; Kinmonth, Anne; Arora, Subhash; O'Bree, Bridget Anne; Shepherd, Katherine; Davey-Quinn, Alan; Sterba, Martin; Johnson, Bronwyn Ruth; Xu, Renee; Hill, Francisco; Ramadoss, Rajaram; Wood, Josette.

In: Journal of Critical Care, Vol. 29, No. 3, 2014.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Heparin-induced thrombocytopenia in the critically ill

T2 - Interpreting the 4Ts test in a randomized trial

AU - Crowther, Mark

AU - Cook, Deborah J

AU - Guyatt, Gordon

AU - Zytaruk, Nicole

AU - McDonald, Ellen

AU - Williamson, David

AU - Albert, Martin

AU - Dodek, Peter

AU - Finfer, Simon

AU - Vallance, Shirley

AU - Heels-Ansdell, Diane

AU - Mcintyre, Lauralyn

AU - Mehta, Sangeeta

AU - Lamontagne, Francois

AU - Muscedere, John

AU - Jacka, Michael J

AU - Lesur, Olivier

AU - Kutsiogiannis, Jim

AU - Friedrich, Jan

AU - Klinger, James R

AU - Qushmaq, Ismael

AU - Burry, Lisa

AU - Khwaja, Kosar

AU - Sheppard, Jo-Ann I

AU - Warkentin, Theodore E.

AU - Tkaczyk, Andrea

AU - Clarke, France

AU - Hall, Rickand

AU - Rocker, Graeme

AU - Julien, Lisa

AU - Wright, Debbie

AU - Roy, Caroline

AU - Theriault, Judy

AU - Pleasance, Susan

AU - Meade, Maureen

AU - Hand, Lori E

AU - Freitag, Andreas

AU - Wynne, Christine

AU - Duffett, Mark

AU - Kho, Michelle

AU - Granton, John

AU - Matte, Andrea

AU - Farias, Paulina

AU - Chu, Leslie

AU - Brockest, Nancy

AU - Go, Stephanie

AU - McGrath-Chong, Margaret

AU - Dennis, Madison

AU - Lipkus, Marc

AU - Stern, Emily N.

AU - Albert, Ryan

AU - Langevin, Stephan

AU - Lauzier, Francois

AU - Turgeon, Alexis F

AU - Blais, Martine

AU - Beauparlant, Maxime

AU - Asselin, Julie

AU - Gagne, Chantal

AU - Thibodeau, Marie

AU - Poirier, Germain

AU - Neas, Isabelle

AU - Spearson, Sandrine

AU - Hebert, Paul

AU - Watpool, Irene

AU - McArdle, Tracy

AU - Gaudert, Claude

AU - Marchand, Paule

AU - Davidson, Carson

AU - Pagliarello, Joe

AU - Lewis, Mary Jo

AU - Murphy, Erin

AU - Foxall, Julia

AU - Skrobik, Yoanna

AU - Harvey, Johanne

AU - Chitu, Stefania

AU - Sirois, Carole

AU - Nadon, Carole

AU - Dolle, Stephanie

AU - Gosselin, Audrey Anne

AU - Deroy, Patrice

AU - Ethier, Cheryl

AU - Tirgari, Sam

AU - Steinberg, Lindsay

AU - McDonald, Rod

AU - Sivanantham, Vidhya

AU - Bandayrel, Kristofer

AU - Quittnat-Pelletier, Friederike

AU - Kramer-Kile, Marnie

AU - Brown, Maedean

AU - Kim, Scott

AU - Fowler, Robert

AU - Marinoff, Nicole

AU - Code, Karen

AU - Bojilov, Boris

AU - Parsotam, Derek

AU - Marshall, John

AU - Smith, Orla

AU - Fry, Beth

AU - Porretta, Kerri

AU - Lee, Yoon

AU - Morrissey, Jeanna

AU - Wen, Victoria

AU - Fleury, Susan

AU - Godfrey, Nicole

AU - Hammond, Sharlene

AU - Mann, Elizabeth

AU - Myers, Monica F.

AU - Robinson, Amber

AU - Keenan, Sean

AU - Reynolds, Steven

AU - Svetik, Miroslav

AU - Osch, Mary Van

AU - Chittock, Dean R

AU - Dhingra, Vinay

AU - Gardner, Maureen

AU - Logie, Susan

AU - Foster, Denise

AU - Autio, Roger

AU - Davies, Dara

AU - Ganz, Pia

AU - Smith, Laurie

AU - Ashley, Betty Jean

AU - Mans, Sheilagh

AU - Doig, Chip

AU - Knox, Linda

AU - Wilson, Crystal

AU - Champagne, Kevin

AU - Ferguson, Niall

AU - Stevenson, James

AU - Elman, Joel

AU - Kutsogiannis, Jim

AU - Thompson, Patrica

AU - Whalen, Norine

AU - Lellouche, Francois

AU - Ferland, Marie Claude

AU - Dussault, Patrick H

AU - Jacob, Caroline

AU - Morneau, Marie Eve

AU - Laberge, Nancy

AU - Karachi, Tim

AU - Irwin, Marleen

AU - Chan, Carmen

AU - Sonnema, Leeca

AU - Marsh, Kelly

AU - Maurer, Jennifer

AU - Kreidl, Tamara

AU - Varden, Candice

AU - Kinjerski, Carey

AU - Banici, Laura

AU - Havell, Lena

AU - Wood, Gordon

AU - Auld, Fiona

AU - Atkins, Leslie

AU - Proulx, Sandra

AU - Hollinger, Gerald

AU - Shende, Vasanti

AU - Belcastro, Vanessa

AU - Plaxton, Bill

AU - Foss, Anders

AU - Paunovic, Bojan

AU - Wiebe, Kym

AU - Marten, Nicole

AU - Eisenstat, Jonathan

AU - Doerle, Tammy

AU - Sharpe, Michael

AU - Madady, Mona

AU - Cooper, Jamie

AU - Davies, Andrew R

AU - Weatherburn, Cindy

AU - Board, Jasmin

AU - Bennett, Victoria

AU - Ramakrishnan, Naresh

AU - Bird, Simon

AU - Potter, Julie

AU - O'Connor, Anne

AU - Ankers, Susan

AU - Cade, Jack

AU - Barge, Deborah

AU - Caf, Tania

AU - Howe, Belinda

AU - Bellomo, Rinaldo

AU - Eastwood, Glenn

AU - Peck, Leah

AU - Goldsmith, Donna

AU - O'Sullivan, Kim

AU - Ernest, David

AU - Radford, Sam

AU - Whitfield, Ann

AU - Cross, Anthony

AU - Eliott, Suzanne

AU - Sidhu, Jaspreet

AU - Mercer, Inga

AU - Hamilton, Angela

AU - Botha, John

AU - Vuat, Jodi

AU - Allsop, Sharon

AU - Fowler, Nina

AU - Crozier, Tim

AU - Barrett, Jonathan

AU - Wright, Chris

AU - Galt, Pauline

AU - Culhane, Carly

AU - Ioannidis, Rebecca

AU - Burton, Sue

AU - Reily, Marnie

AU - Weeraratna, Cyveen

AU - Seppelt, Ian

AU - Weisbrodt, Leonie

AU - Bond, Robyn

AU - Evans, David

AU - Rivett, Justine

AU - O'Connor, Stephanie

AU - Poole, Alex

AU - Woolfe, Clive

AU - Rajbhandari, Dorrilyn

AU - Rees, Caitlin

AU - Edington, John

AU - Fletcher, Jason

AU - Smith, Julie

AU - Boschert, Catherine

AU - Reece, Graham

AU - Sara, Treena

AU - Nand, Kiran

AU - Bersten, Andrew

AU - Gallus, Alex

AU - Matheson, Elisha

AU - O'Callaghan, Margie

AU - Orford, Neil

AU - Elderkin, Tania

AU - Fraser, Melissa

AU - Bone, Allison

AU - Salerno, Tania

AU - Kinmonth, Anne

AU - Arora, Subhash

AU - O'Bree, Bridget Anne

AU - Shepherd, Katherine

AU - Davey-Quinn, Alan

AU - Sterba, Martin

AU - Johnson, Bronwyn Ruth

AU - Xu, Renee

AU - Hill, Francisco

AU - Ramadoss, Rajaram

AU - Wood, Josette

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Critical care

KW - Heparin-induced thrombocytopenia

KW - Intensive care unit

KW - Thrombocytopenia

UR - http://www.scopus.com/inward/record.url?scp=84899971959&partnerID=8YFLogxK

U2 - 10.1016/j.jcrc.2014.02.004

DO - 10.1016/j.jcrc.2014.02.004

M3 - Article

VL - 29

JO - Journal of Critical Care

JF - Journal of Critical Care

SN - 0883-9441

IS - 3

ER -