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 oTher 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 50×10(9)/L, platelets decreased to 50% of ICU admission value (if admission value<100×10(9)/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.
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada. Electronic address: debcook@mcmaster.ca.
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Zytaruk
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Ellen
authors.initials: E
authors.lastname: McDonald
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Williamson
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Albert
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Dodek
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Finfer
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Shirley
authors.initials: S
authors.lastname: Vallance
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Lauralyn
authors.initials: L
authors.lastname: McIntyre
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Lamontagne
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Muscedere
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Jacka
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lesur
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Jim
authors.initials: J
authors.lastname: Kutsiogiannis
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Friedrich
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: James R
authors.initials: JR
authors.lastname: Klinger
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Ismael
authors.initials: I
authors.lastname: Qushmaq
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Burry
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Kosar
authors.initials: K
authors.lastname: Khwaja
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Jo-Ann
authors.initials: JA
authors.lastname: Sheppard
authors.affiliation: St Joseph's Healthcare, Critical Care Research Office, Hamilton, Ontario, Canada.
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects*; D016638:Critical Illness; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D015588:Observer Variation; D010976:Platelet Count; D011336:Probability; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000175:diagnosis; D013927:Thrombosis / Q000150:complications / Q000517:prevention & control; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D006493:Heparin
keywords: Critical care; Heparin-induced thrombocytopenia; Intensive care unit; Thrombocytopenia