In vitro thrombogenicity testing of pulsatile mechanical circulatory support systems: Design and proof‐of‐concept

• Published in: Artificial organs Vol. 45; no. 12; pp. 1513 - 1521
• Main Authors: Brockhaus, Moritz K., Behbahani, Mehdi J., Muris, Farina, Jansen, Sebastian V., Schmitz‐Rode, Thomas, Steinseifer, Ulrich, Clauser, Johanna C.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-12-2021
• Subjects: Animals; Blood; Blood clots; Clotting; Coagulation; Complications; Design; Equipment Design; Heart, Artificial - adverse effects; Hemodynamics; In vitro methods and tests; Low molecular weights; mechanical circulatory support; Mechanical properties; mock circulatory loop; Molecular weight; Parameters; porcine blood; pulsatile mechanical circulatory support; Support systems; Swine - blood; Thrombelastography - instrumentation; Thrombelastography - methods; thromboelastometry; thrombogenicity; Thrombosis; Thrombosis - etiology; mechanical circulatory support; porcine blood; mock circulatory loop; pulsatile mechanical circulatory support; thromboelastometry; thrombogenicity
• ISSN: 0160-564X; 1525-1594
• DOI: 10.1111/aor.14046

Thrombogenic complications are a main issue in mechanical circulatory support (MCS). There is no validated in vitro method available to quantitatively assess the thrombogenic performance of pulsatile MCS devices under realistic hemodynamic conditions. The aim of this study is to propose a method to evaluate the thrombogenic potential of new designs without the use of complex in‐vivo trials. This study presents a novel in vitro method for reproducible thrombogenicity testing of pulsatile MCS systems using low molecular weight heparinized porcine blood. Blood parameters are continuously measured with full blood thromboelastometry (ROTEM; EXTEM, FIBTEM and a custom‐made analysis HEPNATEM). Thrombus formation is optically observed after four hours of testing. The results of three experiments are presented each with two parallel loops. The area of thrombus formation inside the MCS device was reproducible. The implantation of a filter inside the loop catches embolizing thrombi without a measurable increase of platelet activation, allowing conclusions of the place of origin of thrombi inside the device. EXTEM and FIBTEM parameters such as clotting velocity (α) and maximum clot firmness (MCF) show a total decrease by around 6% with a characteristic kink after 180 minutes. HEPNATEM α and MCF rise within the first 180 minutes indicate a continuously increasing activation level of coagulation. After 180 minutes, the consumption of clotting factors prevails, resulting in a decrease of α and MCF. With the designed mock loop and the presented protocol we are able to identify thrombogenic hot spots inside a pulsatile pump and characterize their thrombogenic potential.
In this study, an in‐vitro test method is presented for thrombogenic characterisation of pulsatile mechanical circulatory support systems. The presented method uses porcine blood in a four‐hour experiment with a specially designed mock circulatory loop. Blood is analysed using thromboelastometry (EXTEM, FIBTEM and HEPNATEM). Results of six experiments are presented and discussed.