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

[heparin-induced thrombocytopenia]

Thrombocytopenia occurs in 20 % to 45 % of critically ill medical-surgical patients . The 4 Ts 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 4 Ts scoring is uncertain in this setting .To evaluate whether a published clinical prediction rule (the "4 Ts 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 , NCT 00182143 ).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 , 4 Ts 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 4 Ts scoring by adjudicators ; 432 were scored by trained research coordinators . Heparin-induced thrombocytopenia was defined by a centrally performed positive serotonin release assay (SRA ).Of the 474 patients with central adjudication , 407 (85 .9 %) had a 4 Ts 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 (4 Ts score of 4 -5 ); of these , 4 (6 .8 %) had a positive SRA . Eight patients had a high PTP (4 Ts 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 4 Ts 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 4 Ts (oTher causes of thrombocytopenia ) generated the most disagreement .Real-time 4 Ts scoring by research coordinators at the time of testing for HIT was not consistent with 4 Ts 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 .