This study reports on the complex process of managing therapeutic plasma exchange (TPE) in patients with acute heparin-induced thrombocytopenia (HIT) on extracorporeal membrane oxygenation (ECMO), aiming to remove HIT antibodies for thoracic surgery. It highlights two cases where repeated TPE sessions allowed for successful surgery with brief heparin re-exposure, despite challenges in monitoring HIT antibody titers and platelet activation. The study emphasizes the necessity of serial HIT screening, including immunological and functional assays, and suggests that adding platelet factor 4 (PF4) to the heparin-induced platelet activation assay (HIPA) could improve detection of platelet-activating antibodies, aiding in the management of HIT in ECMO patients.