Impact of Rapid Latex Immunoassay (LIA) Implementation on Management of Heparin Induced Thrombocytopenia (HIT): A Retrospective Single Institution Study

Introduction

Heparin-induced thrombocytopenia (HIT) is a highly thrombogenic immune response to heparin. Per ASH guidelines, if the 4T score is ≥4, heparin should be discontinued, and alternative anticoagulation (AAC) and immunoassaying initiated. The platelet factor 4 enzyme-linked immunosorbent assay (ELISA) and serotonin release assay (SRA) have been the most widely used screening and confirmatory assays respectively. Both have prolonged turnaround time (TAT). The latex-immunoassay (LIA), a rapid immunoassay (RI), is automated with faster TAT. We reviewed the impact of implementing LIA at our institution.

Methods

This IRB-approved retrospective review conducted at Oregon Health & Science University (OHSU) identified patients who underwent HIT testing using ELISA (1/2021 – 3/2023) or LIA (3/2023 – 5/2024). Patients younger than 18 or older than 88 were excluded. Data was extracted using Tableau and subsets underwent chart review to collect basic demographic data, HIT diagnosis, timing between test ordering and initiating AAC, type of AAC, time to immunoassay result and SRA result. TAT of the immunoassay was calculated as the difference between the time the test was received in lab to the time the lab released results. A small subset of patients had multiple tests drawn over time. The “time to react” was defined as time to start AAC after ordering HIT testing. Adherence to ASH guidelines was evaluated.

Results:

A total of 627 immunoassays were ordered (ELISA=398, LIA=229) for 572 patients (ELISA=363, LIA=209). Demographics were similar between ELISA (mean age 59.6 years, 63% male) and LIA (mean age 60.1 years, 56.9% male) patients. No inpatient data associated with testing was present in 70 ELISA and 43 LIA samples. The rate of positive screening tests was 8.3% for ELISA (n=38) and 11.8% for LIA (n=27). SRA positivity was 45% for ELISA-positive tests and 42% for LIA-positive tests.

ELISA+ patients were switched to Argatroban (12), Bivalrudin (5), Apixaban (7) or no therapy (3). In 12/30 ELISA+ patients, anticoagulation switch did not occur until after a positive test result was obtained. In the ELISA negative group, 100 patients were switched to alternative anticoagulation using a preemptive test and switch strategy per ASH guidelines. However, in 192 ELISA patients, a test and wait approach was implemented with either heparin product stopped (99) or heparin product continued (93). The average TAT for ELISA was 1825 minutes, with median 374.5 minutes.

Among LIA+ patients,18/24 (75%) were treated with AAC (Argatroban 10, Bivalrudin 5, Apixaban 3). Despite a shorter average TAT of 488 minutes (median 59 minutes), time to react and switch anticoagulation was on average 1478 minutes after the LIA was collected, median 270 minutes, and an average 1321 minutes after the LIA resulted positive (range 0-7329 minutes). In ELISA+ patients, time to react and switch was on average 886 minutes after collection, median 0 minutes, and average 77 minutes (range 0-1190 minutes) after ELISA resulted positive. Fewer patients were unnecessarily switched to alternative anticoagulation in the LIA group. However, the time to react appeared longer than expected.

ELISA tested patients switched to argatroban or bivalrudin suffered adverse bleeding event including: post-operative bleeding (1 PF4+ patient on argatroban), GI bleeding (1 PF4 negative patient on argatroban, 1 PF4 negative patient on bivalrudin ), fatal intra-cranial hemorrhage (1 PF4 negative patient on bivalrudin).

Conclusion:

Significant deviation from accepted HIT guidelines occurred using both ELISA and LIA assays. Despite calculations of the 4T score and consideration for HIT, providers often chose to wait for results and, at times, continued heparin under the reasoning that HIT was deemed "unlikely." Conversely, significant numbers of patients were treated unnecessarily with alternative anticoagulation while awaiting ELISA results. The risks and benefits of anticoagulation continue to complicate the treatment of suspected HIT. Rapid testing with the LIA simplifies uncertainties and reduces the number of patients switched to alternative anticoagulation while awaiting test results. However, despite the shorter TAT of the LIA, the time to react and switch anticoagulation in LIA-positive patients was delayed. Incorporating RIs into HIT algorithms and increasing clinician awareness of the rapid TAT of RIs is warranted.