A Case for Calculating 4T Scores: Predictive Value in the Diagnosis of Heparin-Induced Thrombocytopenia

Introduction: Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin administration that occurs when heparin-dependent IgG antibodies bind to platelet factor 4 on the platelet surface, causing platelet aggregation and subsequent clinical symptoms associated with thrombosis. The 4T score is comprised of the following criteria for HIT diagnosis: Timing of platelet count decrease, Thrombosis, Thrombocytopenia, and absence of other causes of Thrombocytopenia. A low probability 4T score effectively excludes the need for further HIT testing; in one meta-analysis, a low probability 4T score was found to have a negative predictive value (NPV) of .998 (95% CI, .970-1.000) and intermediate and high probability 4T scores had positive predictive values (PPV) of .14 (.09-.22) and .64 (.40-.82), respectively (Cuker et. al, Blood 2012). The aim of our study is to determine the frequency with which 4T scores are calculated before the HIT ELISA and reflex serotonin release assay (SRA) test is ordered in a large community health care system. Additionally, we sought to compare the NPV and PPV of 4T scores in this cohort of patients with those in other studies of 4T score predictive value.

Methods: This is a retrospective analysis of HIT panels ordered from 2018 to 2019 at hospitals within the Memorial Hermann Health system in the Greater Houston area. Age, sex, optical density value, SRA result, and charted 4T scores calculated by the patients' care teams were recorded for 2014 patients. From there, predictive values were calculated based on 4T score tier, HIT ELISA positivity, and SRA positivity. A patient with a low 4T score and negative HIT ELISA or negative reflex SRA was considered a "true negative," whereas a patient with an intermediate or high 4T score and both positive HIT ELISA and SRA was a "true positive." Patients who were lost to follow-up after a positive HIT ELISA were excluded from predictive value analysis.

Results: This study included HIT panel results for 2014 patients in the Memorial Hermann Health system. 1125 (55.9%) of these patients were male and 889 (44.1%) were female, and the median age overall was 68 years (range, .08-100). In total, there were 173 (8.60%) positive and 1841 (91.4%) negative HIT ELISA results; there were 48 abnormal SRA results (2.38%), of which 43 (89.6%) were positive and 5 (10.4%) were borderline. Of all the patients, 149 (7.40%) had calculated 4T scores available in their records. Of these, 83 (55.7%) individuals had low (0-3) scores, 51 (34.2%) had intermediate (4-5) probability scores, and 15 (10.1%) had high (6-8) probability scores. In the low 4T score group, the NPV was determined to be .975. In the intermediate group, the PPV was .149. Finally, in the high 4T score group, the PPV was .385 (Table 1). One limitation of this study is that patients lost to follow-up were excluded from predictive value calculations; of the 149 patients with 4T scores, only 10 were lost to follow-up.

Conclusions: Our results show that the 4T score is a useful, albeit underutilized, diagnostic tool in cost-effective evaluation for HIT. They also support the effectiveness of a low 4T score in HIT exclusion. Calculating a 4T score before ordering a HIT panel could not only lower costs from non-heparin anticoagulants and unnecessary HIT antibody testing, but also prevent complications from inappropriately ceasing heparin.

Kadia:Genfleet: Research Funding; Iterion: Research Funding; Delta-Fly: Research Funding; JAZZ: Consultancy, Research Funding; Astellas: Research Funding; Glycomimetics: Research Funding; Ascentage: Research Funding; Genentech: Consultancy, Research Funding; cellenkos: Research Funding; Astex: Honoraria; PinotBio: Consultancy; Servier: Consultancy; BMS: Consultancy, Research Funding; Novartis: Consultancy; Pfizer: Research Funding; AstraZeneca: Research Funding; Amgen: Research Funding; cyclacel: Research Funding; Regeneron: Research Funding; Agios: Consultancy; Abbvie: Consultancy, Research Funding.