Platelet Factor 4 Antibodies and Severe AKI

Abstract

Key Points Patients testing positive for platelet factor 4 antibodies have a >50% higher odds of developing severe AKI compared with those who test negative.The relationship between platelet factor 4 antibodies and severe AKI was independent of demographics, comorbidities, laboratory values, and severity-of-illness characteristics. Background Heparin-induced thrombocytopenia, which results from production of antibodies that bind to heparin-platelet factor 4 (PF4) complexes, is a hypercoagulable state associated with considerable morbidity and mortality due to thrombotic complications. We investigated whether PF4 antibodies are associated with an increased risk of AKI. Methods We conducted a cohort study of hospitalized adults who underwent testing for PF4 antibodies at two large medical centers in Boston between 2015 and 2021. The primary exposure was PF4 test positivity. The primary outcome was severe AKI, defined by Kidney Disease: Improving Global Outcomes stage 3 as a ≥3-fold increase in serum creatinine or receipt of KRT within 7 days after the PF4 test. We used multivariable logistic regression to adjust for potential confounders. Results A total of 4224 patients were included in our analysis, 469 (11.1%) of whom had a positive PF4 test. Severe AKI occurred in 50 of 469 patients (10.7%) with a positive PF4 test and in 235 of 3755 patients (6.3%) with a negative test (unadjusted odds ratio, 1.79 [95% confidence interval, 1.30 to 2.47]). In multivariable analyses adjusted for demographics, comorbidities, laboratory values, and severity-of-illness characteristics, PF4 test positivity remained associated with a higher risk of severe AKI (adjusted odds ratio, 1.56 [95% confidence interval, 1.10 to 2.20]). Conclusions Among hospitalized adults, the presence of PF4 antibodies is independently associated with a 56% higher odds of developing severe AKI. Additional studies are needed to investigate potential mechanisms that may underlie these findings, such as pathogenic effects of PF4 antibodies on the microvasculature of the kidneys.