Document Detail


Thrombus growth and embolism on tissue factor-bearing collagen surfaces under flow: role of thrombin with and without fibrin.
MedLine Citation:
PMID:  22516070     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: At sites of vascular injury, thrombin is an important mediator in thrombus growth and stability. Using microfluidic flow devices as well as patterned surfaces of collagen and tissue factor (TF), we sought to determine the role that fibrin plays in clot stability without interfering with the production of thrombin.
METHODS AND RESULTS: We deployed an 8-channel microfluidic device to study coagulation during corn trypsin inhibitor-treated (XIIa-inhibited) whole blood perfusion over lipidated TF linked to a fibrillar collagen type 1 surface. Clot growth and embolization were measured at initial inlet venous (200 s(-1)) or arterial (1000 s(-1)) wall shear rates under constant flow rate or pressure relief mode in the presence or absence of Gly-Pro-Arg-Pro (GPRP) to block fibrin polymerization. Numerical calculations for each mode defined hemodynamic forces on the growing thrombi. In either mode at inlet venous flow, increasing amounts of TF on the surface led to a modest dose-dependent increase (up to 2-fold) in platelet deposition, but resulted in massive fibrin accumulation (>50-fold) only when exceeding a critical TF threshold. At a venous inlet flow, GPRP led to a slight 20% increase in platelet accumulation (P<0.01) in pressure relief mode with thrombi resisting ≈1500 s(-1) before full channel occlusion. GPRP-treated thrombi were unstable under constant flow rate, where shear forces caused embolization at a maximum shear rate of ≈2300 s(-1) (69 dynes/cm2). In constant flow rate mode, the nonocclusive platelet-fibrin deposits (no GPRP) withstood maximum shear rates of ≈29 000 s(-1) (870 dyne/cm2) at ≈95% of full channel occlusion. For arterial inlet shear rate, embolization was marked for either mode with GPRP present when shear forces reached 87 dynes/cm2 (≈2900 s(-1)). Under constant flow rate, platelet-fibrin deposits (no GPRP) withstood maximums of 2400 dynes/cm2 (80,000 s(-1)) at ≈90% of full channel occlusion prior to embolization.
CONCLUSIONS: Fibrin increased clot strength by 12- to 28-fold. Under pressure relief mode, ≈2-fold more fibrin was produced under venous flow (P<0.001). These studies define embolization criteria for clots formed with surface TF-triggered thrombin production (±fibrin) under venous and arterial flows.
Authors:
Thomas V Colace; Ryan W Muthard; Scott L Diamond
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-19
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  32     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-17     Completed Date:  2012-07-13     Revised Date:  2014-05-28    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1466-76     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Anticoagulants / pharmacology
Blood Coagulation* / drug effects
Blood Platelets / drug effects,  metabolism*
Collagen Type I / metabolism*
Computer Simulation
Embolism / blood*,  physiopathology
Factor XIIa / antagonists & inhibitors,  metabolism
Fibrin / metabolism*
Humans
Liposomes
Male
Microfluidic Analytical Techniques
Microscopy, Confocal
Models, Biological
Numerical Analysis, Computer-Assisted
Oligopeptides / pharmacology
Plant Proteins / pharmacology
Platelet Adhesiveness
Platelet Aggregation
Regional Blood Flow
Stress, Mechanical
Thrombin / metabolism*
Thromboplastin / metabolism*
Thrombosis / blood*,  physiopathology
Time Factors
Young Adult
Grant Support
ID/Acronym/Agency:
5T32HL007439-33/HL/NHLBI NIH HHS; R01 HL103419/HL/NHLBI NIH HHS; R01 HL103419/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Collagen Type I; 0/Liposomes; 0/Oligopeptides; 0/Plant Proteins; 0/trypsin inhibitor, Zea mays; 67869-62-9/glycyl-prolyl-arginyl-proline; 9001-31-4/Fibrin; 9035-58-9/Thromboplastin; EC 3.4.21.38/Factor XIIa; EC 3.4.21.5/Thrombin
Comments/Corrections

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