Abstract Number: PB0075
Meeting: ISTH 2021 Congress
Theme: Coagulation and Natural Anticoagulants » Contact Pathway
Background: Titanium (Ti) is incorporated into a variety of medical implants because of its strength, resistance to corrosion, capacity for osseo-integration and presumed inertness. However, it is now clear that Ti-containing metals are not completely bio-inert. Ti is thrombogenic, complicating its use in devices that contact blood such as Ventricular Assist Devices (VAD).
Aims: investigate the effects of Ti-containing compounds and VAD components on the plasma contact zymogen/proteases factor XII(a) [fXII(a)] and prekallikrein/kallikrein.
Methods: Normal plasma (NP) was incubated on surfaces of Ti or titanium nitride (TiN) components of a HeartWare VAD (Framingham, MA) for 10 min, followed by determination of the recalcification clotting time (RCT). Suspensions of Ti and TiN powders were incubated with normal plasma in the absence or presence of fXIIa or kallikrein inhibiting antibodies for 10 min, followed by determination of RCTs.
Results: 
Western blots. Normal plasma was incubated with Ti or TiN microspheres or without microspheres (C – control) for 15 min. Microspheres were pelleted and supernatant plasma was subjected to western blotting using HRP-conjugated antibodies to factor XII (fXII) or prekallikrein (PK). Left hand lanes contain 50ng of pure fXII (XII) or PK.
RCTs of normal plasma were substantially reduced after incubation on Ti (207±28s) or TiN (226±51s) VAD surfaces, compared to polypropylene (607.7±46.5s). RCTs of normal plasma were also reduced after incubation with Ti (308±83s) or TiN (184±58s) powders compared with control (611±126s). RCTs of fXII-deficient plasma were not shortened by incubation with Ti or TiN. An anti-fXIIa IgG prolonged RCTs with Ti and TiN, while anti-kallikrein IgG prolonged clotting only with TiN. Both Ti and TiN bind fXII and prekallikrein, and deplete plasma of both proteins (figure).
Conclusions: Ti-containing compounds used in biomedical devices bind the plasma contact factors fXII and prekallikrein, facilitating contact activation. The importance of prekallikrein to contact activation may vary depending on the type of Ti-containing compound. Ti surfaces likely contribute to the thrombotic potential of VADs and related intravascular devices. Pharmaceuticals targeting of fXIIa and/or kallikrein may help alleviate this effect without exacerbating bleeding.
To cite this abstract in AMA style:
Litvak M, Matafonov A, Shamanaev A, Kobrin A, Gruber A, McCarty OJ, Gailani D. Titanium Compounds Bind and Activate Factor XII and Prekallikrein [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/titanium-compounds-bind-and-activate-factor-xii-and-prekallikrein/. Accessed August 16, 2022.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/titanium-compounds-bind-and-activate-factor-xii-and-prekallikrein/