Thrombotic microparticles (MPs) released from cells and platelets in response to various stimuli are present in elevated numbers in various disease states that increase the risk for thrombotic events. In order to understand how particles of this size may localize in nonparallel flow regimes and increase thrombotic risk, a computational analysis of flow and MP deposition was performed for 3 deg of stenosis at moderate Reynolds number (20 < Re < 80) and for recirculation zones at low Reynolds (∼1) number. The results indicate that MP deposition results primarily from impaction and not by diffusive flux.

References

References
1.
Owens Iii
,
A. P.
, and
Mackman
,
N.
,
2011
, “
Microparticles in Hemostasis and Thrombosis
,”
Circ. Res.
,
108
(
10
), pp.
1284
1297
.10.1161/CIRCRESAHA.110.233056
2.
Berckmans
,
R. J.
,
Nieuwland
,
R.
,
Böing
,
A. N.
,
Romjin
,
F. P. H. T. M.
,
Hack
,
C. E.
, and
Sturk
,
A.
,
2001
, “
Cell-Derived Microparticles Circulate in Healthy Humans and Support Low Grade Thrombin Generation
,”
Thromb. Haemostasis
,
85
(
4
), pp.
639
646
.
3.
Diamant
,
M.
,
Nieuwland
,
R.
,
Pablo
,
R.
,
Sturk
,
A.
,
Smit
,
J. W. A.
, and
Radder
,
J. K.
,
2002
, “
Elevated Numbers of Tissue Factor Exposing Microparticles Correlate With Components of the Metabolic Syndrome in Uncomplicated Type 2 Diabetes Mellitus
,”
Circulation
,
106
(
19
), pp.
2442
2447
.10.1161/01.CIR.0000036596.59665.C6
4.
Diamant
,
M.
,
Tushuizen
,
M. E.
,
Sturk
,
A.
, and
Nieuwland
,
R.
,
2004
, “
Cellular Microparticles: New Players in the Field of Vascular Disease?
,”
Eur. J. Clin. Invest.
,
34
(
6
), pp.
392
401
.10.1111/j.1365-2362.2004.01355.x
5.
Mallat
,
Z.
,
Benamer
,
H.
,
Hugel
,
B.
,
Benessiano
,
J.
,
Steg
,
P. G.
,
Freyssinet
,
J.-M.
, and
Tedgui
,
A.
,
2000
, “
Elevated Levels of Shed Membrane Microparticles With Procoagulant Potential in the Peripheral Circulating Blood of Patients With Acute Coronary Syndromes
,”
Circulation
,
101
(
8
), pp.
841
843
.10.1161/01.CIR.101.8.841
6.
Yu
,
J. L.
, and
Rak
,
J. W.
,
2004
, “
Shedding of Tissue Factor (TF)-Containing Microparticles Rather Than Alternatively Spliced TF Is the Main Source of TF Activity Released From Human Cancer Cells
,”
J. Thromb. Haemostasis
,
2
(
11
), pp.
2065
2067
.10.1111/j.1538-7836.2004.00972.x
7.
Lynch
,
S. F.
, and
Ludlam
,
C. A.
,
2007
, “
Plasma Microparticles and Vascular Disorders
,”
Br. J. Haematol.
,
137
(
1
), pp.
36
48
.10.1111/j.1365-2141.2007.06514.x
8.
Vanwijk
,
M. J.
,
Vanbavel
,
E.
,
Sturk
,
A.
, and
Nieuwland
,
R.
,
2003
, “
Microparticles in Cardiovascular Diseases
,”
Cardiovasc. Res.
,
59
(
2
), pp.
277
287
.10.1016/S0008-6363(03)00367-5
9.
Nieuwland
,
R.
,
Berckmans
,
R. J.
,
Rotteveel-Eijkman
,
R. C.
,
Maquelin
,
K. N.
,
Roozendaal
,
K.
,
Jansen
,
P. G. M.
,
Ten Have
,
K.
,
Hack
,
E.
, and
Sturk
,
A.
,
1997
, “
Cell-Derived Microparticles Generated in Patients During Cardiopulmonary Bypass are Highly Procoagulant
,”
Circulation
,
96
(
10
), pp.
3534
3541
.10.1161/01.CIR.96.10.3534
10.
Philippou
,
H.
,
Adami
,
A.
,
Davidson
,
S. J.
,
Pepper
,
J. R.
,
Burman
,
J. F.
, and
Lane
,
D. A.
,
2000
, “
Tissue Factor is Rapidly Elevated in Plasma Collected From the Pericardial Cavity During Cardiopulmonary Bypass
,”
Thromb. Haemostasis
,
84
(
1
), pp.
124
128
.
11.
Sabatier
,
F.
,
Toux
,
V.
,
Anfosso
,
F.
,
Camoin
,
L.
,
Sampol
,
J.
, and
Dignat-George
,
F.
,
2002
, “
Interaction of Endothelial Microparticles With Monocytic Cells in Vitro Induces Tissue Factor-Dependent Coagulation
,”
Blood
,
99
(
11
), pp.
3962
3970
.10.1182/blood.V99.11.3962
12.
Morel
,
O.
,
Toti
,
F.
,
Hugel
,
B.
,
Bakouboula
,
B.
,
Camoin-Jau
,
L.
,
Dignat-George
,
F.
, and
Freyssinet
,
J.-M.
,
2006
, “
Procoagulant Microparticles, Disrupting the Vascular Homeostasis Equation?
,”
Arterioscler., Thromb. Vasc. Biol.
,
26
(
12
), pp.
2594
2604
.10.1161/01.ATV.0000246775.14471.26
13.
Freyssinet
,
J.-M.
,
2003
, “
Cellular Microparticles: What Are They Bad or Good For?
,”
J. Thromb. Haemostasis
,
1
(
7
), pp.
1655
1662
.10.1046/j.1538-7836.2003.00309.x
14.
Biro
,
E.
,
Sturk-Maquelin
,
K. N.
,
Vogel
,
G. M. T.
,
Meuleman
,
D. G.
,
Smit
,
M. J.
, and
Hack
,
C. E.
,
2003
, “
Human Cell-Derived Microparticles Promote Thrombus Formation in Vivo in a Tissue Factor-Dependent Manner
,”
J. Thromb. Haemostasis
,
1
(
12
), pp.
2561
2568
.10.1046/j.1538-7836.2003.00456.x
15.
Sturk-Maquelin
,
K. N.
,
Nieuwland
,
R.
,
Romjin
,
F. P. H. T. M.
,
Eijsman
,
C. E.
,
Hacks
,
C. E.
, and
Sturk
,
A.
,
2003
, “
Pro- and Non-Coagulant Forms of Non-Cell-Bound Tissue Factor in Vivo
,”
J. Thromb. Haemostasis
,
1
(
9
), pp.
1920
1926
.10.1046/j.1538-7836.2003.00361.x
16.
Vandendries
,
E. R.
,
Furie
,
B. C.
, and
Furie
,
B.
,
2004
, “
Role of P-Selectin and PSGL-1 in Coagulation and Thrombosis
,”
Thromb. Haemostasis
,
92
(
3
), pp.
459
466
.10.1160/TH04-05-0306
17.
Furie
,
B.
, and
Furie
,
B. C.
,
2004
, “
Role of Platelet P-Selectin and Microparticle PSGL-1 in Thrombus Formation
,”
Trends Mol. Med.
,
10
(
4
), pp.
171
178
.10.1016/j.molmed.2004.02.008
18.
Rauch
,
U.
,
Bonderman
,
D.
,
Bohrmann
,
B.
,
Badimon
,
J. J.
,
Himber
,
J.
,
Riederer
,
M. A.
, and
Nemerson
,
Y.
,
2000
, “
Transfer of Tissue Factor From Leukocytes to Platelets is Mediated by Cd15 and Tissue Factor
,”
Blood
,
96
(
1
), pp.
170
175
.
19.
Falati
,
S.
,
Liu
,
Q.
,
Gross
,
P.
,
Merrill-Skoloff
,
G.
,
Chou
,
J.
,
Vandendries
,
E. R.
,
Celi
,
A.
,
Croce
,
K.
,
Furie
,
B. C.
, and
Furie
,
B.
,
2003
, “
Accumulation of Tissue Factor Into the Developing Thrombi In Vivo is Dependent Upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selection
,”
J. Exp. Med.
,
197
(
11
), pp.
1585
1598
.10.1084/jem.20021868
20.
Eckstein
,
E. C.
,
Bilsker
,
D.
,
Waters
,
C.
,
Kippenhan
,
S.
, and
Tilles
,
A. W.
,
1987
,
Transport of Platelets in Flowing Blood
, Annals of the New York Academy of Sciences,
New York Acadmey of Sciences
,
New York
.
21.
Skilbeck
,
C.
,
Walker
,
P. G.
,
David
,
T.
, and
Nash
,
G. B.
,
2004
, “
Disturbed Flow Promotes Deposition of Leucocytes From Flowing Whole Blood in a Model of a Damaged Vessel
,”
Br. J. Haematol.
,
126
(
3
), pp.
418
427
.10.1111/j.1365-2141.2004.05057.x
22.
Skilbeck
,
C.
,
Westwood
,
S. M.
,
Walker
,
P. G.
,
David
,
T.
, and
Nash
,
G. B.
,
2001
, “
Population of the Vessel Wall by Leukocytes Binding to P-Selectin in a Model of Disturbed Arterial Flow
,”
Arterioscler., Thromb. Vasc. Biol.
,
21
(8), pp.
1294
1300
.10.1161/hq0801.093506
23.
Turitto
,
V. T.
, and
Baumgartner
,
H. R.
,
1974
, “
Effect of Physical Factors on Platelet Adherence to Subendothelium
,”
Thromb., Diath. Haemostasis Suppl.
,
60
, pp.
17
24
.
24.
Turritto
,
V.
, and
Baumgartner
,
H.
,
1976
, “
Effect of Physical Factors on Platelet Adhesion to Subendothelium in Blood Vessels
,” Springer Verlag, Berlin.
25.
Decuzzi
,
P.
,
Gentile
,
F.
,
Granaldi
,
A.
,
Curcio
,
A.
,
Causa
,
F.
,
Indolfi
,
C.
,
Netti
,
P.
, and
Ferrari
,
M.
,
2007
, “
Flow Chamber Analysis of Size Effects in the Adhesion of Spherical Particles
,”
Int. J. Nanomed.
,
2
(
4
), pp.
689
696
.
26.
Gentile
,
F.
,
Curcio
,
A.
,
Indolfi
,
C.
,
Ferrari
,
M.
, and
Decuzzi
,
P.
,
2008
, “
The Margination Propensity of Spherical Particles for Vascular Targeting in the Microcirculation
,”
J. Nanobiotechnol.
,
6
(
9
).10.1186/1477-3155-6-9
27.
Keuren
,
J. F. W.
,
Magdeleyns
,
E. J. P.
,
Bennaghmouch
,
A.
,
Bevers
,
E. M.
,
Curvers
,
J.
, and
Lindhout
,
T.
,
2007
, “
Microparticles Adhere to Collagen Type I, Fibrinogen, Von Willebrand Factor and Surface Immobilised Platelets at Physiological Shear Rates
,”
Br. J. Haematol.
,
138
(
4
), pp.
527
533
.10.1111/j.1365-2141.2007.06650.x
28.
Longest
,
P. W.
, and
Holbrook
,
L. T.
,
2012
, “
In Silico Models of Aerosol Delivery to the Respiratory Tract—Development and Applications
,”
Adv. Drug Deliv. Rev.
,
64
(
4
), pp.
296
311
.10.1016/j.addr.2011.05.009
29.
Longest
,
P. W.
, and
Kleinstreuer
,
C.
,
2003
, “
Comparison of Blood Particle Deposition Models for Non-Parallel Flow Domains
,”
J. Biomech.
,
36
(
3
), pp.
421
430
.10.1016/S0021-9290(02)00434-7
30.
Sakariassen
,
K. S.
,
2007
, “
Thrombus Formation on Apex of Arterial Stenosies: The Need for a Fluid High Shear Stenosis Diagnostic Device
,”
Future Cardiol.
,
3
(
2
), pp.
193
201
.10.2217/14796678.3.2.193
31.
Sakariassen
,
K. S.
,
Aarts
,
P. A. M. M.
,
De Groot
,
P. G.
,
Houdijk
,
W. P. M.
, and
Sixma
,
J. J.
,
1983
, “
A Perfusion Chamber Developed to Investigate Platelet Interaction in Flowing Blood With Human Vessel Wall Cells, Their Extracellular Matrix and Purified Components
,”
J. Lab. Clin. Med.
,
102
(
4
), pp.
522
535
.
32.
Leiderman
,
K.
, and
Fogelson
,
A. L.
,
2011
, “
Grow With the Flow: A Spatial-Temporal Model of Platelet Deposition and Blood Coagulation Under Flow
,”
Math. Med. Biol.
,
28
(
1
), pp.
47
84
.10.1093/imammb/dqq005
33.
Barstad
,
R. M.
,
Roald
,
H. E.
,
Cui
,
Y.
,
Turitto
,
V. T.
, and
Sakariassen
,
K. S.
,
1994
, “
A Perfusion Chamber Developed to Investigate Thrombus Formation and Shear Profiles in Flowing Native Human Blood at the Apex of Well-Defined Stenoses
,”
Arterioscler. Thromb.
,
14
(
12
), pp.
1984
1991
.10.1161/01.ATV.14.12.1984
34.
Kleinstreuer
,
C.
,
2006
, “
Two-Phase Flows
,”
Biofluid Dynamics: Principles and Selected Applications
,
CRC Press
,
Boca Raton, FL
.
35.
Cunningham
,
E.
,
1910
, “
On the Velocity of Steady Fall of Spherical Particles Through Fluid Medium
,”
Proc. R. Soc. London, Ser. A
,
83
(
563
), pp.
357
365
.10.1098/rspa.1910.0024
36.
Li
,
A.
, and
Ahmadi
,
G.
,
1992
, “
Dispersion and Deposition of Spherical Particles From Point Sources in a Turbulent Channel Flow
,”
Aerosol Sci. Technol.
,
16
(
4
), pp.
209
226
.10.1080/02786829208959550
37.
Van Der Pol
,
E.
,
Hoeksra
,
A. G.
,
Sturk
,
A.
,
Otto
,
C.
,
Van Leeuwen
,
T. G.
, and
Nieuwland
,
R.
,
2010
, “
Optical and Non-Optical Methods for Detection and Characterization of Microparticles and Exosomes
,”
J. Thromb. Hemostasis
,
8
(
12
), pp.
2596
2607
.10.1111/j.1538-7836.2010.04074.x
38.
Suades
,
R.
,
Padro
,
T.
,
Vilahur
,
G.
, and
Badimon
,
L.
,
2012
, “
Circulating and Platelet-Derived Microparticles in Human Blood Enhance Thrombosis on Atherosclerotic Plaques
,”
Thromb. Haemostasis
,
108
(
6
), pp.
1208
1219
.10.1160/TH12-07-0486
39.
Badimon
,
L.
,
Turitto
,
V. T.
,
Rosemark
,
J.
,
Badimon
,
J. J.
, and
Fuster
,
V.
,
1987
, “
Characterization of a Tubular Flow Chamber for Studying Platelet Interaction With Biological and Prosthetic Materials. Deposition of 111-Indium-Labelled Platelets on Collagen, Subendothelium and Goretex(R)
,”
J. Lab. Clin. Med.
,
110
(
6
), pp.
706
718
.
40.
Koleski
,
J. F.
, and
Eckstein
,
E. C.
,
1991
, “
Near Wall Concentration Profiles of 1.0 and 2.5 Micron Beads During Flow of Blood Suspensions
,”
ASAIO Trans.
,
37
(
1
), pp.
9
12
.10.1097/00002480-199101000-00004
41.
Charoenphol
,
P.
,
Onyskiw
,
P. J.
,
Carrasco-Teja
,
M.
, and
Eniola-Adefeso
,
O.
,
2012
, “
Particle-Cell Dynamics in Human Bloodflow: Implications for Vascular-Targeted Drug Delivery
,”
J. Biomech.
,
45
(
16
), pp.
2822
2828
.10.1016/j.jbiomech.2012.08.035
42.
Liu
,
X.
,
Fan
,
Y.
,
Deng
,
X.
, and
Zhan
,
F.
,
2011
, “
Effect of Non-Newtonian and Pulsatile Blood Flow on Mass Transport in the Human Aorta
,”
J. Biomech.
,
44
(
6
), pp.
1123
1141
.10.1016/j.jbiomech.2011.01.024
43.
Patchipulusu
,
S.
,
Turturro
,
M.
, and
Hall
,
C. L.
,
2010
, “
Tissue Factor Bearing Monocyte-Derived Macrophage Microparticles Adhere to Biomaterials and Impart TF Activity
,”
J. Biomed. Mater. Res., Part A
,
92
(
2
), pp.
724
732
.10.1002/jbm.a.32320
44.
Kleinjan
,
A.
,
Böing
,
A. N.
,
Sturk
,
A.
, and
Nieuwland
,
R.
,
2012
, “
Microparticles in Vascular Disorders: How Tissue Factor-Exposing Vesicles Contribute to Pathology and Physiology
,”
Thromb. Res.
,
130
(
Suppl. 1
), pp.
S71
S73
.10.1016/j.thromres.2012.08.281
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