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Kim, Yun Gi; Suh, Jung-Won; Sibbing, Dirk; Kastrati, Adnan; Ko, Young-Guk; Jang, Yangsoo; Cho, Young-Seok; Youn, Tae-Jin; Chae, In-Ho; Choi, Dong-Ju; Kim, Hyo-Soo (2017): A laboratory association between hemoglobin and VerifyNow P2Y12 reaction unit: A systematic review and meta-analysis. In: American Heart Journal, Vol. 188: pp. 53-64
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Abstract

Background VerifyNow P2Y12 assay is used widely to evaluate residual platelet reactivity in patients taking P2Y12 receptor antagonists. However, a laboratory association between VerifyNow P2Y12 reaction unit (PRU) and hemoglobin, which might lead to wrong interpretation of the data, is reported. We performed these systematic review and meta-analysis to clearly define the relationship between PRU and hemoglobin and to elucidate whether the relationship, if any, is a true biological association or is just a laboratory error. Methods Through a comprehensive electronic and manual search, 10 studies were selected for the cohort level meta analysis. Among 10 studies, we were able to retrieve the raw data of 5 studies, and a patient-level meta-analysis was performed. Potential publication bias was searched by funnel plot analysis and was actively adjusted, if present, by trim and fill method. Results The pooled analysis revealed a significant inverse correlation between PRU and hemoglobin (r = 0.349;P <.001;10 studies with 4,793 patients). VerifyNow P2Y12 base unit, which reflects off-drug platelet reactivity, was also inversely correlated with hemoglobin (r = 0.526;P<.001;8 studies with 4,395 patients). % Inhibition (r = 0.081;P =.059;6 studies with 3,832 patients) and Delta PRU (r = 0.037;P =.188;5 studies with 3,521 patients) were not associated with hemoglobin. A significant inverse association between PRU and hemoglobin was also observed in the patient-level meta analysis (3,533 patients pooled from 5 studies;r = 0.335;P<.001). Light transmission aggregometry (r = 0.160;P=.072;4 studies with 1,144 patients) and multiple electrode platelet aggregometry (r = 0.029;P = .394;3 studies with 7,645 patients) showed no significant association with hemoglobin. Conclusions A significant inverse association was observed between PRU and hemoglobin which is likely to be a laboratory error. Clinicians should be aware that this association might lead to wrong interpretation of the data.