A-160 Optimization of Serotonin Release Assay Utilization for Heparin-Induced Thrombocytopenia Diagnosis
Authors: Koch C , Gulseth M P , Zochert S 
Published: October 2024

Abstract

Background
Heparin-induced thrombocytopenia (HIT) is screened for using an assay that detects antibodies to platelet factor 4 (PF4). While the presence of PF4 antibodies is a strong indicator for HIT, some PF4 antibodies are not functionally pathogenic. The gold standard test for HIT diagnosis is the serotonin release assay (SRA), which more directly measures the presence of pathogenic platelet activation. Therefore, the SRA facilitates proper anticoagulation management of PF4-positive or -indeterminate patients, yet a significant number of these patients in our institution do not receive follow-up SRA testing. Conversely, a positive SRA is very unlikely when the PF4 is negative, so an SRA may not be clinically useful. This prompted us to investigate the SRA ordering practices across different regions of our healthcare system with the intention of further optimizing SRA utilization.

Methods
PF4 and SRA data was collected over a 10 month period, January 2023 - October 2023. SRA ordering frequency, stratified by qualitative PF4 results based on a 0.4 OD threshold, from two similarly sized medical centers within the Sanford Health system was compared. The probability of SRA-positivity in relation to PF4 OD value was determined by logistic regression. Receiver operator characteristic (ROC) analysis was subsequently utilized to select a PF4 OD threshold for SRA reflex.

Results
System-wide, 14.4% (36/250) of PF4-negative patients and 40.5% (17/42) of PF4-positive patients received SRA testing. Within our health system, the Department of Pharmacy in hospital “A” maintains close oversight of anticoagulation therapy through an anticoagulation stewardship workgroup, while hospital “B” has not implemented a similar strategy. Stratifying by hospital demonstrated significant differences in local ordering practice. Hospital “B” performed SRA testing on 24.4% (32/131) of PF4-negative patients vs. 3.4% (4/119) for hospital “A. SRA testing frequency for PF4-positive patients was similar at 42.96% and 35.7%, for hospitals “B” and “A”, respectively. Logistic regression suggested a low probability (≤10%) for SRA-positivity when PF4 values are &lt;0.8 OD. The ROC AUC was 0.862 (95% CI: 0.778-0.946) with an estimated sensitivity of 83% (95% CI: 77.8-90.8%) and specificity of 22.6% (95% CI: 13.5-35.5%) at a reflex decision threshold of 0.82 OD. Despite the ROC estimates, in this dataset the 0.82 OD threshold would have produced 100% sensitivity and 75% specificity. The discrepancy between the estimated and observed sensitivity/specificity is likely a factor of our small dataset used for ROC analysis (n = 53); optimization efforts would thus likely benefit from ongoing threshold performance monitoring.

Conclusions
An anticoagulation stewardship strategy was moderately successful in optimizing SRA ordering on suspected HIT patients, specifically in minimizing SRA testing on PF4-negative patients. The PF4-positive OD value generally corresponds to the probability of SRA-positivity, i.e., strongly positive-PF4s are more likely to also be SRA-positive. Thus, further optimization can be achieved by implementation of an SRA reflex threshold. This is especially important for low OD-positive PF4 cases in which the likelihood for HIT diagnosis via positive-SRA is reduced.