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

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.

Barriers and facilitators of thromboprophylaxis for medical-surgical intensive care unit patients: a multicenter survey.

BACKGROUND: The objective of this study was to identify the self-reported barriers to and facilitators of prescribing low-molecular-weight heparin (LMWH) thromboprophylaxis in the intensive care unit (ICU). METHODS: We conducted an interviewer-administered survey of 4 individuals per ICU (the ICU director, a bedside pharmacist, a thromboprophylaxis research coordinator, and physician site investigator) regarding LMWH thromboprophylaxis for medical-surgical patients in 27 ICUs in Canada and the United States. Items were generated by the research team and adapted from previous surveys, audits, qualitative studies, and quality improvement research. Respondents rated the barriers to LMWH use, facilitators (effectiveness, affordability, and acceptability thereof), and perceptions regarding LMWH use. RESULTS: Respondents had 14.5 (SD, 7.7) years of ICU experience (response rate, 99%). The 5 most common barriers in descending order were as follows: drug acquisition cost, fear of bleeding, lack of resident education, concern about bioaccumulation in renal failure, and habit. The top 5 rated facilitators were preprinted orders, education, daily reminders, audit and feedback, and local quality improvement committee endorsement. Centers using preprinted orders (mean difference [P<.01]) and computerized physician order entry (P<.01) compared with those centers not using those tools reported higher affordability for these 2 facilitators. Compared with physicians and pharmacists, research coordinators considered ICU-specific audit and feedback of thromboprophylaxis rates to be a more effective, acceptable, and affordable facilitator (odds ratio, 6.67; 95% confidence interval, 1.97-22.53; P<.01). Facilitator acceptability ratings were similar within centers but differed across centers (P≤.01). CONCLUSIONS: This multicenter survey found several barriers to use of LMWH including cost, concern about bleeding, and lack of resident knowledge of effectiveness. The diversity of reported facilitators suggests that large scale programs may address generic barriers but also need site-specific interprofessional knowledge translation activities.