Eliminating the heparin-inhibition step of standard heparin-induced thrombocytopenia (HIT) screening could reduce manual work for laboratorians performing HIT diagnostic testing while improving clinical accuracy, according to a study published January 3 in the Journal of Applied Laboratory Medicine (JALM).
This study also addresses utilization of confirmatory serotonin release assays (SRAs) and unnecessary hematology consults, according to the authors. A best-practice advisory or restriction for SRA testing could be implemented based on the findings, they concluded.
For years, testing for HIT, an adverse drug reaction to the blood thinner heparin, has included screening enzyme-linked immunosorbent assay (ELISA) and confirmatory SRAs, wherein SRA testing can be pursued following a positive ELISA result, explained Dr. Meredith Parsons and colleagues from the University of Iowa Health Care System Department of Pathology for their retrospective study.
HIT is challenging from a diagnostic stewardship standpoint, the authors noted. However, performing manual HIT ELISA testing according to manufacturers' recommendations (i.e., tested both with and without additional heparin to determine percent inhibition) is resource-intensive for the clinical laboratory.
"The utility of heparin inhibition has been evaluated on multiple occasions," noted Parsons and colleagues, adding that the University of Iowa study is novel in its real-world analysis of the impact of data-driven changes in ELISA interpretation.
A key finding of the study is that pre-intervention ELISA interpretation reliance on percent inhibition (testing samples in high-heparin and low-heparin conditions in accordance with manufacturers' recommendations) has likely led to overutilization of non-heparin anticoagulants and the pursuit of SRA testing in situations where SRA was very unlikely to be positive, according to Parsons and colleagues.
Confirmatory SRA testing itself also poses some problems, the authors noted. As a send-out test, SRA can take three to five days to result. This can delay reinitiation of heparin anticoagulation in those ultimately found not to have HIT. Non-heparin anticoagulants used in the meantime are more expensive, more difficult to reverse, and more challenging to monitor, the authors said.
For the University of Iowa study, the team considered the current 4T scoring system for HIT risk stratification. Very few clinicians outside of hematology are well-versed in using the system, and most are also unaware of the intricacies of HIT testing, Parsons and colleagues said. There is also a lack of agreement on the ideal interpretation of HIT ELISA testing.
The team queried the electronic medical record (EMR; Epic) for records from December 7, 2016, to December 31, 2021, for all HIT ELISA and SRA tests performed. The researchers saw that ELISA testing was performed irrespective of the 4T score entered.
That analysis motivated data-driven changes in ELISA reporting and HIT management recommendations in November 2023, according to the authors. In the post-intervention period, ELISA interpretation moved to low-heparin optical density (OD).
OD is the main measurement of HIT ELISA testing, explained the authors, adding that higher OD values are measured when there are increased antibody/PF4-heparin complex interactions in a sample through which the transmittance of light is hindered, and lower OD values are measured when light can pass through a sample with less obstruction from complex formation.
The researchers assessed the impact of changes: pre-intervention (from June 8, 2023 to November 7, 2023) and post-intervention (from November 29, 2023 to April 28, 2024). Ordering of both ELISA and SRA tests remained unrestricted at all periods during the study.
Analyzing the lab results of over 1,011 ELISA tests and 169 SRA tests, Parsons' team found that OD coupled with certain recommendations:
- Decreased ELISA positivity rates (13% to 5%)
- Decreased rates of SRA confirmatory testing overall (13% to 9%)
- Decreased SRA testing rates for patients with non-negative ELISAs (78% to 43%)
- Increased heparin resumption (20% to 57%)
- Hematology consults remained relatively stable (78% to 86%)
"Since the heparin inhibition step was demonstrated to not add value, it no longer contributes to the ELISA interpretation post-intervention, and differentiation between equivocal and positive ELISA results is instead based entirely on low-heparin OD," stated Parsons and colleagues.
The team found that low-heparin OD-based HIT ELISA interpretation yielded enhanced positive predictive value (PPV), or true cases, compared with percent inhibition-based interpretation.
"Positive SRA results never followed an ELISA with a low-heparin OD below 1.0, though they were observed following ELISAs with percent inhibition values spanning 0% to 100%," Parsons and colleagues wrote.
In addition, prior to the intervention, hematology consults were recommended for any non-negative ELISA result, whereas they are only recommended for equivocal ELISA results post-intervention, they said. Hematology was still consulted unnecessarily in all positive ELISAs and appropriately for three of four equivocal ELISA results in the post-intervention period, they found. None of the post-intervention SRAs were recommended by hematology, nor were they recommended in the post-intervention algorithm.
"Elimination of the heparin inhibition step significantly simplifies manual work for laboratorians performing the testing, saves reagent costs, and increases testing throughput," Parsons and colleagues concluded. "The removal of heparin inhibition also simplifies ELISA reporting and increases its utility for clinicians in guiding next steps in patient management."
Looking ahead, retrospective reassessment of 4T score accuracy by trained professionals, such as hematologists and pharmacists, may improve 4T score predictive value for both ELISA and SRA testing, the authors noted. This could be a potentially fruitful avenue of future study and/or intervention, they said.
While the authors acknowledged the study's limitations, they emphasized that, regardless, inappropriate SRA ordering adds to diagnostic testing costs without providing additional actionable information and could potentially be decreased through the linkage of management recommendations to ELISA resulting in the EMR so that management recommendations are available at time of ELISA result review.
The study is featured in a special issue of JALM highlighting the value of diagnostic stewardship, a collaborative approach to enhancing clinical laboratory testing. Read the full study and recommendations here.
