Frequency and Clinical Impact of Platelet Factor 4-Specific Antibodies in Patients Undergoing Extracorporeal Membrane Oxygenation

Abstract

Introduction/Objectives Extracorporeal membrane oxygenation (ECMO) provides circulatory support in patients with severe heart failure, but the frequent use of unfractionated heparin exposes patients to high risk of heparin-induced thrombocytopenia (HIT). We prospectively evaluated the development and clinical impact of platelet factor 4 (PF4)-specific antibodies (Abs) during ECMO and whether specific biological characteristics could predict HIT.

Materials and Methods From 2014 to 2018, we studied 57 adults who underwent an ECMO for at least 5 days. The plasma samples collected daily were tested for PF4-specific Abs using immunoassays to detect immunoglobulin (Ig) G, A, and M isotypes or only IgG. Serotonin release assay was performed without and with PF4 to detect pathogenic Abs.

Results Twenty-nine patients (50%) were positive for PF4-specific Abs (IgG, A, M), with IgG in 17/57 (30%) and 16 of them (94%) were immunized within 10 days. PF4-specific IgG Abs did not affect the clinical or biological course of most patients. HIT was suspected in only two patients with ECMO circuit dysfunction and unexpected platelet count decrease after day 5. High levels of PF4-specific IgG were detected in both patients, and HIT was confirmed by a serotonin release assay, which was also more sensitive when exogenous PF4 was present.

Conclusion PF4-specific Abs are common during ECMO but are mostly non-pathogenic and not associated with a less favorable prognosis. However, an abnormal platelet count evolution, in particular if associated with ECMO circuit dysfunction, should prompt the search for pathogenic PF4-specific IgG.

Keywords

extracorporeal membrane oxygenation - extracorporeal life support - heparin-induced thrombocytopenia - platelet factor 4

Authors' Contributions

M.A.M., T.B., E.L., C.V., C.P., and E.A.G. have contributed to patient recruitment and clinical data collection. J.R., Y.G., and C.P. participated in the design and development of the study. C.V. and E.A.G. performed the experiments described. C.V., M.A.M., T.B., E.L., E.A.G., J.R., C.P., and Y.G. contributed to the data analysis. C.V., C.P., and Y.G. wrote the article and all authors reviewed the intellectual content of the manuscript and approved the final version.

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