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Presentation Details
Detection of Contact Pathway Biomarkers in ECMO Patient Plasma to Assess Device-Associated Thrombosis

Jenny Si Han Wang1, Rosemary B.Falama2, Helen H.Vu3, Cristina Puy1, Owen J.T.McCarty1, Joseph J.Shatzel1, 3, 4.

1Department of biomedical engineering, Portland, OR, USA.2Department of medicine, Portland, OR, USA.3Knight Cancer Institute, Portland, OR, USA.4Division of Hematology and Medical Oncology, Portland, OR, USA

Abstract


Thrombosis remains a common and serious complication of extracorporeal membrane oxygenation (ECMO), contributing substantially to patient morbidity and mortality. Current anticoagulation strategies are nonspecific and often carry a high risk of bleeding. To improve thrombotic risk assessment, there is a critical need for specific biomarkers that can detect thrombin-mediated clot formation, enabling more precise monitoring and targeted intervention. We developed calibrated kinetic assays and a novel monoclonal-antibody–based ELISA engineered to selectively quantify thrombin–antithrombin (TAT), FXIa–antithrombin (FXIa-AT), and FXIIa–antithrombin (FXIIa-AT) complexes in plasma. Assays were applied to ECMO patients (N=22) using blood collected 24 hours prior to decannulation. In parallel, we implemented a CT-based imaging technique to quantify thrombus burden within retrieved ECMO oxygenators. Most patients received VV ECMO (63.6% VV vs 36.4% VA), and square circuits were more common than round (65.4% vs 34.6%). Median ECMO duration was 7.5 days, with oxygenators used for a median of 5.5 days (range 2–11), and 13.6% of patients faced device failure. Besides, the mean oxygenator clot volume identified by CT scan imaging was 13.24% (median 11.98%), with 60% of patients exhibiting clot coverage greater than 10%, and 35% exceeding 20%. A subset of patients (15%) demonstrated minimal thrombus burden (<1%). Furthermore, the plasma level of ECMO patients demonstrated marked elevation of FXIa-AT and FXIIa-AT complexes relative to healthy controls. Contact pathway biomarkers varied with device configuration; square circuits showed higher TAT and FXIa-AT levels than circular circuits. Infection status significantly modified coagulation activation, with viral infections producing the highest FXIIa-AT concentrations. Moreover, biomarkers strongly correlated with ECMO clot burden; Pearson correlations showed that TAT (r = 0.60) and FXIa-AT (r = 0.74) had the strongest positive associations with circuit clot%, supported by linear relationships. These findings support the potential utility of engineered antibody-based assays for monitoring thrombin formation in ECMO patients. These techniques can be applied to evaluate novel biomaterials or pharmacological interventions to mitigate thrombosis in ECMO devices. This approach may facilitate the development of advanced ECMO technologies and patient care.

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