Primary hemostasis and blood clotting is known to be influenced by the red blood cell volume fraction (hematocrit) in blood. Depressed or elevated levels of red blood cells can lead to vascular perfusion problems ranging from bleeding to thrombus formation. The early stage of hemostasis and thus blood clotting in all vessel sections from the arterial to the venous system involves the adhesion of platelets to von Willebrand factor. Here we present experimental and theoretical results showing that the adhesion probability of platelets to von Willebrand factor is strongly and nonlinearly dependent on hematocrit and flow rate. Interestingly, the actual binding forces are not markedly different, which suggest that the origin of such behavior is in the distribution of platelets. Using hydrodynamic simulations of a simple model, we explicitly show that the higher the hematocrit and the flow rate, the larger the amount of platelets residing close to the wall. Our simulation results, which are in excellent agreement with the experimental observations, explain why such phenomena occur. We believe that the nonhomogeneous red blood cell distribution as well as the shear dependent hydrodynamic interaction is key for the accumulation of platelets on the vessel wall. The work we present here is an important step forward from our earlier work on single molecules and extends into the collective cellular behavior of whole blood. It sheds new light on the correlation between hematocrit and the initial steps in hemostasis and thrombosis, and outlines advances for the treatment of vascular diseases associated with high levels of red blood cells. These results are not only highly relevant for the field of hemostasis and the physics of blood clotting but are also of powerful impact in applied science most obviously in drug delivery and colloidal science.

2.
Z.
Ruggeri
,
J. Thromb. Haemostasis
1
,
1335
(
2003
).
4.
Z.
Ruggeri
,
J. Clin. Invest.
99
,
559
(
1997
).
6.
B.
Furie
and
B.
Furie
,
J. Clin. Invest.
115
,
3355
(
2005
).
7.
Z.
Ruggeri
,
J. Clin. Invest.
105
,
699
(
2000
).
9.
D.
Ginsburg
and
E. J.
Bowie
,
Blood
79
,
2507
(
1992
); see http://bloodjournal.hematologylibrary.org/content/79/10/2507.
10.
Z. M.
Ruggeri
and
T. S.
Zimmerman
,
Blood
70
,
895
(
1987
); see http://bloodjournal.hematologylibrary.org/content/70/4/895.
11.
D.
Provan
,
R.
Stasi
,
A. C.
Newland
,
V. S.
Blanchette
,
P.
Bolton-Maggs
,
J. B.
Bussel
,
B. H.
Chong
,
D. B.
Cines
,
T. B.
Gernsheimer
,
B.
Godeau
,
J.
Grainger
,
I.
Greer
,
B. J.
Hunt
,
P. A.
Imbach
,
G.
Lyons
,
R.
McMillan
,
F.
Rodeghiero
,
M. A.
Sanz
,
M.
Tarantino
,
S.
Watson
,
J.
Young
, and
D. J.
Kuter
,
Blood
115
,
168
(
2010
).
12.
J. N.
George
,
G. E.
Raskob
,
S. R.
Shah
,
M. A.
Rizvi
,
S. A.
Hamilton
,
S.
Osborne
, and
T.
Vondracek
,
Ann. Intern Med.
129
,
886
(
1998
).
14.
G. G.
Levy
,
W. C.
Nichols
,
E. C.
Lian
,
T.
Foroud
,
J. N.
McClintick
,
B. M.
McGee
,
A. Y.
Yang
,
D. R.
Siemieniak
,
K. R.
Stark
, and
R.
Gruppo
,
Nature
413
,
488
(
2001
).
15.
B.
Boneu
and
F.
Fernandez
,
Transfus. Med. Rev.
1
,
182
(
1987
).
16.
W. S.
Uijttewaal
,
E. J.
Nijhof
,
P. J.
Bronkhorst
,
E.
Den Hartog
, and
R. M.
Heethaar
,
Am. J. Physiol. Heart Circ. Physiol.
264
,
H1239
(
1993
); see http://ajpheart.physiology.org/content/264/4/H1239.
17.
B.
Woldhuis
,
G. J.
Tangelder
,
D. W.
Slaaf
, and
R. S.
Reneman
,
Am. J. Physiol. Heart Circ. Physiol.
262
,
H1217
(
1992
); see http://ajpheart.physiology.org/content/262/4/H1217.
18.
G. J.
Tangelder
,
H. C.
Teirlinck
,
D. W.
Slaaf
, and
R. S.
Reneman
,
Am. J. Physiol. Heart Circ. Physiol.
248
,
H318
(
1985
); see http://ajpheart.physiology.org/content/248/3/H318.
19.
E. C.
Eckstein
,
A. W.
Tilles
, and
F. J.
Millero
,
Microvasc. Res.
36
,
31
(
1988
).
20.
A. W.
Tilles
and
E. C.
Eckstein
,
Microvasc. Res.
33
,
211
(
1987
).
21.
C.
Yeh
and
E. C.
Eckstein
,
Biophys. J.
66
,
1706
(
1994
).
22.
B.
Savage
,
E.
Saldivar
, and
Z.
Ruggeri
,
Cell
84
,
289
(
1996
).
23.
B.
Savage
,
F.
Almus-Jacobs
, and
Z.
Ruggeri
,
Cell
94
,
657
(
1998
).
24.
A.
Reininger
,
H.
Heijnen
,
H.
Schumann
,
H.
Specht
,
W.
Schramm
, and
Z.
Ruggeri
,
Blood
107
,
3537
(
2006
).
25.
26.
A.
Kloboucek
,
A.
Behrisch
,
J.
Faix
, and
E.
Sackmann
,
Biophys. J.
77
,
2311
(
1999
).
27.
V. T.
Turitto
,
H. J.
Weiss
, and
H. R.
Baumgartner
,
Microvasc. Res.
19
,
352
(
1980
).
28.
V. T.
Turitto
and
H. R.
Baumgartner
,
Microvasc. Res.
9
,
335
(
1975
).
29.
V. T.
Turitto
and
H. J.
Weiss
,
Ann. N. Y. Acad. Sci.
416
,
363
(
1983
).
30.
P. A.
Aarts
,
P. A.
Bolhuis
,
K. S.
Sakariassen
,
R. M.
Heethaar
, and
J. J.
Sixma
,
Blood
62
,
214
(
1983
); see http://bloodjournal.hematologylibrary.org/content/62/1/214.
32.
B.
Dünweg
and
A. J. C.
Ladd
,
Adv. Polym. Sci.
221
,
89
(
2009
).
33.
C.
Aidun
,
Y.
Lu
, and
E.
Ding
,
J. Fluid Mech.
373
,
287
(
1998
).
34.
A.
Karnis
,
H. L.
Goldsmith
, and
S. G.
Mason
,
Nature
200
,
159
(
1963
).
35.
A.
Karnis
and
S. G.
Mason
,
J. Colloid Interface Sci.
24
,
164
(
1967
).
36.
P.
Chan
and
L. G.
Leal
,
J. Fluid Mech.
92
,
131
(
1979
).
37.
B. P.
Ho
and
L. G.
Leal
,
J. Fluid Mech.
65
,
365
(
1974
).
38.
S.
Doddi
and
P.
Bagchi
,
Phys. Rev. E
79
,
046318
(
2009
).
39.
C. W.
Hsu
and
Y.-L.
Chen
,
J. Chem. Phys.
133
,
034906
(
2010
).
40.
C. K.
Aidun
and
J. R.
Clausen
,
Annu. Rev. Fluid Mech.
42
,
439
(
2010
).
41.
J. R.
Clausen
and
C. K.
Aidun
,
Phys. Fluids
22
,
123302
(
2010
).
42.
A.
Kumar
and
M. D.
Graham
,
Soft Matter
8
,
10536
(
2012
).
43.
A.
Kumar
and
M.
Graham
,
Phys. Rev. Lett.
109
,
108102
(
2012
).
44.
A.
Kumar
and
M.
Graham
,
Phys. Rev. E
84
,
066316
(
2011
).
45.
H.
Zhao
and
E. S. G.
Shaqfeh
,
Phys. Rev. E
83
,
061924
(
2011
).
46.
H.
Zhao
,
E.
Shaqfeh
, and
V.
Narsimhan
,
Phys. Fluids
24
,
011902
(
2012
).
47.
D. A.
Reasor
, Jr.
,
M.
Mehrabadi
,
D. N.
Ku
, and
C. K.
Aidun
,
Ann. Biomed. Eng.
41
,
238
(
2013
).
48.
L. M.
Crowl
and
A. L.
Fogelson
,
Int. J. Numer. Meth. Biomed. Eng.
26
,
471
(
2010
).
49.
L.
Crowl
and
A. L.
Fogelson
,
J. Fluid Mech.
676
,
348
(
2011
).
50.
A. A.
Tokarev
,
A. A.
Butylin
,
E. A.
Ermakova
,
E. E.
Shnol
,
G. P.
Panasenko
, and
F. I.
Ataullakhanov
,
Biophys. J.
101
,
1835
(
2011
).
51.
E. C.
Eckstein
and
F.
Belgacem
,
Biophys. J.
60
,
53
(
1991
).
52.
C.
Yeh
,
A. C.
Calvez
, and
E. C.
Eckstein
,
Biophys. J.
67
,
1252
(
1994
).
53.
M.
Lyon
and
L.
Leal
,
J. Fluid Mech.
363
,
57
(
1998
).
54.
D.
Semwogerere
and
E.
Weeks
,
Phys. Fluids
20
,
043306
(
2008
).
55.
H. M.
Vollebregt
,
R.
Van der Sman
, and
R. M.
Boom
,
Faraday Discuss.
158
,
89
(
2012
).
56.
H.
Chen
and
A.
Alexander-Katz
,
Phys. Rev. Lett.
107
,
128301
(
2011
).
57.
H.
Chen
,
M. A.
Fallah
,
V.
Huck
,
J. I.
Angerer
,
A. J.
Reininger
,
S. W.
Schneider
,
M. F.
Schneider
, and
A.
Alexander-Katz
,
Nature Commun.
4
,
1333
(
2013
).
58.
S.
Dopheide
,
M.
Maxwell
, and
S.
Jackson
,
Blood
99
,
159
(
2002
).
59.
E. J.
Lim
,
T. J.
Ober
,
J. F.
Edd
,
G. H.
McKinley
, and
M.
Toner
,
Lab Chip
12
,
2199
(
2012
).
60.
H.
Fujiwara
,
T.
Ishikawa
,
R.
Lima
,
N.
Matsuki
,
Y.
Imai
,
H.
Kaji
,
M.
Nishizawa
, and
T.
Yamaguchi
,
J. Biomech.
42
,
838
(
2009
).
61.
R.
Lima
,
T.
Ishikawa
,
Y.
Imai
,
M.
Takeda
,
S.
Wada
, and
T.
Yamaguchi
,
Ann. Biomed. Eng.
37
,
1546
(
2009
).
62.
R.
Lima
,
T.
Ishikawa
,
Y.
Imai
,
M.
Takeda
,
S.
Wada
, and
T.
Yamaguchi
,
J. Biomech.
41
,
2188
(
2008
).
63.
C.
Migliorini
,
Y.
Qian
,
H.
Chen
,
E. B.
Brown
,
R. K.
Jain
, and
L. L.
Munn
,
Biophys. J.
83
,
1834
(
2002
).
64.
C.
Sun
,
C.
Migliorini
, and
L. L.
Munn
,
Biophys. J.
85
,
208
(
2003
).
65.
C.
Sun
and
L. L.
Munn
,
Biophys. J.
88
,
1635
(
2005
).
66.
L. L.
Munn
and
M. M.
Dupin
,
Ann. Biomed. Eng.
36
,
534
(
2008
).
68.
T.
Krüger
,
M.
Gross
,
D.
Raabe
, and
F.
Varnik
,
Soft Matter
9
,
9008
(
2013
).
69.
J.
Skotheim
and
T.
Secomb
,
Phys. Rev. Lett.
98
,
078301
(
2007
).
70.
J. M.
Brader
and
M.
Krüger
,
Mol. Phys.
109
,
1029
(
2011
).
71.
N.
Schwierz
and
P.
Nielaba
,
Phys. Rev. E
82
,
031401
(
2010
).
72.
K.
Yeo
and
M. R.
Maxey
,
Phys. Rev. E
81
,
051502
(
2010
).
73.
G.
Segre
and
A.
Silberberg
,
J. Fluid Mech.
14
,
136
(
1962
).
74.
V. T.
Turitto
,
H. J.
Weiss
, and
H. R.
Baumgartner
,
J. Rheol.
23
,
735
(
1979
).
75.
E. F.
Leonard
,
E. F.
Grabowski
, and
V. T.
Turitto
,
Ann. N. Y. Acad. Sci.
201
,
329
(
1972
).
76.
A. B.
Strong
,
G. D.
Stubley
,
G.
Chang
, and
D. R.
Absolom
,
J. Biomed. Mater. Res.
21
,
1039
(
1987
).
77.
A. A.
Tokarev
,
A. A.
Butylin
, and
F. I.
Ataullakhanov
,
Biophys. J.
100
,
799
(
2011
).
78.
K.
Konstantopoulos
,
S.
Kukreti
, and
L. V.
McIntire
,
Adv. Drug Deliver Rev.
33
,
141
(
1998
).
79.
S.
Jadhav
,
C. D.
Eggleton
, and
K.
Konstantopoulos
,
Curr. Pharm. Des.
13
,
1511
(
2007
).
80.
P.
Decuzzi
,
S.
Lee
,
B.
Bhushan
, and
M.
Ferrari
,
Ann. Biomed. Eng.
33
,
179
(
2005
).
81.
P.
Decuzzi
,
S.
Lee
,
M.
Decuzzi
, and
M.
Ferrari
,
Ann. Biomed. Eng.
32
,
793
(
2004
).
82.
J.
Tan
,
A.
Thomas
, and
Y.
Liu
,
Soft Matter
8
,
1934
(
2012
).
83.
D.
Leighton
and
A.
Acrivos
,
J. Fluid Mech.
181
,
415
(
1987
).
84.
R. J.
Phillips
,
R. C.
Armstrong
,
R. A.
Brown
,
A. L.
Graham
, and
J. R.
Abbott
,
Phys. Fluids A
4
,
30
(
1992
).
85.
R.
Fåhræus
and
T.
Lindqvist
,
Am. J. Physiol.
96
,
562
(
1931
); see http://ajplegacy.physiology.org/content/96/3/562.
86.
R. H.
Haynes
,
Am. J. Physiol.
198
,
1193
(
1960
); see http://ajplegacy.physiology.org/content/198/6/1193.
87.
A. R.
Pries
,
D.
Neuhaus
, and
P.
Gaehtgens
,
Am. J. Physiol.
263
,
H1770
(
1992
); see http://ajpheart.physiology.org/content/263/6/H1770.
88.
P. A.
Aarts
,
S. A.
Van Den Broek
,
G. W.
Prins
,
G. D.
Kuiken
,
J. J.
Sixma
, and
R. M.
Heethaar
,
Arterioscler., Thromb., Vasc. Biol.
8
,
819
(
1988
).
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