Generation of active
Factor XII (FXIIa) triggers blood clotting on artificial surfaces and may also enhance intravascular
thrombosis. We developed a patterned
kaolin (0 to 0.3 pg/μm(2))/
type 1 collagen fibril surface for controlled microfluidic clotting assays. Perfusion of whole blood (treated only with a low level of 4 μg/mL of the XIIa inhibitor,
corn trypsin inhibitor) drove platelet deposition followed by
fibrin formation. At venous wall shear rate (100 s(-1)),
kaolin accelerated onset of
fibrin formation by ~100 sec when compared to
collagen alone (250 sec vs. 350 sec), with little effect on platelet deposition. Even with
kaolin present, arterial wall shear rate (1000 s(-1)) delayed and suppressed
fibrin formation compared to venous wall shear rate. A comparison of surfaces for extrinsic activation (
tissue factor TF/
collagen) versus contact activation (
kaolin/
collagen) that each generated equal platelet deposition at 100 s(-1) revealed: (1) TF surfaces promoted much faster
fibrin onset (at 100 sec) and more endpoint
fibrin at 600 sec at either 100 s(-1) or 1000 s(-1), and (2)
kaolin and TF surfaces had a similar sensitivity for reduced
fibrin deposition at 1000 s(-1) (compared to
fibrin formed at 100 s(-1)) despite differing coagulation triggers. Anti-platelet drugs inhibiting P2Y1, P2Y12,
cyclooxygenase-1 or activating IP-receptor or
guanylate cyclase reduced platelet and
fibrin deposition on
kaolin/
collagen. Since FXIIa or FXIa inhibition may offer safe antithrombotic
therapy, especially for
biomaterial thrombosis, these defined
collagen/
kaolin surfaces may prove useful in
drug screening tests or in clinical diagnostic assays of blood under flow conditions.