Contact activation of blood coagulation on a defined kaolin/collagen surface in a microfluidic assay.

Abstract

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.

• Authors: Shu Zhu, Scott L Diamond
• Journal: Thrombosis research (Thromb Res) Vol. 134 Issue 6 Pg. 1335-43 (Dec 2014) ISSN: 1879-2472 [Electronic] United States
• PMID: 25303860 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Coated Materials, Biocompatible
• Kaolin
• Collagen

Topics

• Biosensing Techniques (instrumentation)
• Blood Coagulation (drug effects, immunology)
• Blood Coagulation Tests (instrumentation, methods)
• Cells, Cultured
• Coated Materials, Biocompatible (chemical synthesis, pharmacology)
• Collagen (chemistry, pharmacology)
• Equipment Design
• Equipment Failure
• Flow Cytometry (instrumentation)
• Humans
• Kaolin (chemistry, pharmacology)
• Micro-Electrical-Mechanical Systems (instrumentation)
• Microfluidic Analytical Techniques (instrumentation, methods)
• Molecular Imprinting (methods)
• Reproducibility of Results
• Sensitivity and Specificity
• Surface Properties