Outcome Of Patients with Positive Heparin-Platelet Factor 4 Antibodies: A Retrospective Observational Study
Authors: Tapan Umit , Bolla Saritha , Daglilar Ebubekir , Chang Shaoyu , Kozyreva Olga 
Published: October 2019

Abstract

Introduction
Heparin-induced thrombocytopenia (HIT) is a rare but potentially serious complication of heparin use. Immunoassay (EIA) can detect the presence of antibodies directed toward heparin-platelet factor 4 (H-PF4) complexes, but provide no information about their ability to activate platelets and have only modest specificity. Significance of positive H-PF4 antibodies without clinical HIT is not known. This study evaluates the outcomes of patients with positive H-PF4 antibodies expressed in optical density (OD) units.

Objectives
To examine the correlation between positive H-PF4 antibodies, mortality and thrombotic events in hospitalized patients with suspected HIT.

Methods
A retrospective electronic medical record review was conducted in two institutions. Patients with H-PF4 antibodies detected by commercial ELISA during 2006 - 2010 were identified. We compared 30-day, 90-day and 1-year mortality in patients with negative, equivocal, and positive H-PF4 test and evaluated the relationship between H-PF4 status and rate of thrombosis. One-way ANOVA and Chi square tests were used testing continuous and categorical variables respectively. A multivariate logistic regression model was fitted to estimate relationships between patient characteristics, laboratory findings, and H-PF4 antibody test status. The Kaplan-Meier method and log-rank tests were used to compare survival between groups.

Results
A total of 417 patients were included in the study, of which 44 patients had equivocal (OD value 0.4-0.9) and 21 had positive (OD value ≥1) H-PF4 antibody test result. 30-day, 90-day and 1-year mortalities were 13.6% (48/352), 33.2% (117/352), 46.3% (163/352) respectively for H-PF4 negative patients, 4.5% (2/44), 45.4 % (20/44), 56.8% (25/44) respectively for patients with equivocal H-PF4 status and 14.3% (3/21). 33.3% (7/21), 42.8% (9/21) respectively for H-PF4 positive patients. There were no statistically significant differences in mortality between patients with negative, equivocal, and positive results at all 3 time points (p-value 0.222, 0.273, 0.385, respectively); even after excluding patients with thrombosis (p-value 0.222, 0.248, 0.310 respectively). Age and Charlson score were associated with increased in-hospital, three-months and 1 year mortality; odds ratios were 1.018 and 1.170 (p-value >0.05) for in-hospital mortality, 1.034 and 1.247 (p-value <0.05) for three-months mortality, 1.04 and 1.289 for 1 year mortality (p-value <0.05). Multiple regression analysis showed that age, gender and Charlson score had no statistically significant effect on the occurrence of thrombosis in negative, equivocal, or positive groups. There was a significant correlation between the occurrence of thrombosis and H-PF4 result. Using logistic regression analysis odds ratio of having thrombosis was 2.476 for equivocal vs. negative and positive vs. equivocal results (p <0.0001) (Table 2
).

Conclusion
Our results suggest no association between H-PF4 status positivity and mortality, as well as no difference in survival over one year between the positive and negative groups. H-PF4 positivity however showed positive correlation with thrombosis risk.

Disclosures:
No relevant conflicts of interest to declare.