Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a new disorder that emerged in the wake of COVID-19 vaccination. It is a rare but life-threating condition that requires aggressive course of treatment to improve patient outcomes. To date, there has not been an effective diagnostic assay for detecting VITT. Instead, definitive diagnosis requires satisfying several criteria including history of recent vaccination, platelet count, positive ELISA result for a closely related thrombotic disorder, heparin-induced thrombocytopenia (HIT) and PF4-dependent functional assays. Our study describes a technically simple antigenic assay for direct diagnosis of autoimmune antibodies (Abs) associated with VITT. We first show that cross-linked platelet factor 4 (PF4) represents an antigenic target specific for VITT Abs. We then incorporate this antigenic target into a microfluidic electrochemical biosensor and demonstrate specific and sensitive detection of VITT Abs in a fully automated manner while using microliter volumes of patient sera. We tested 51 patient samples using the microfluidic electrochemical biosensor and demonstrated 100% sensitivity and specificity for VITT sera compared to healthy controls and HIT patients.

A.P. reports pending/issued patents (Mayo Clinic, Retham Technologies, and Versiti Blood Center of Wisconsin), equity ownership in and serving as an officer of Retham Technologies, and equity ownership in Veralox Therapeutics. The authors declare that they have no competing interests.

This study was by a grant from the Advanced Diagnostics Laboratory of Mayo Clinic, and in part by HL158932 (A.P) and HL171911 (AJK).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Studies were approved by the Institutional Review Board of Mayo Clinic.

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All data produced in the present study are available upon reasonable request to the authors