Abstract

Blood platelets are crucial in hemostasis, thrombosis, and thromboinflammation. Current evidence highlights the considerable heterogeneity within individuals in platelet structure, age, and activation properties. This heterogeneity has major implications for the diverse functions of platelets in physiology and pathophysiology, extending to therapeutic targeting in hemostasis and cancer. In this review, we provide a general concept of heterogeneity or diversity of platelet populations, with emphasis on the diagnostic and advanced methodologies to assess and study differences between platelets. We describe conventional and novel approaches to address clinical and in research questions addressing platelet heterogeneity and discuss strengths and limitations of the available techniques.

1.
Versteeg
HH
,
Heemskerk
JW
,
Levi
M
,
Reitsma
PH
.
New fundamentals in hemostasis
.
Physiol Rev
.
2013
;
93
(
1
):
327
-
358
.
2.
Swieringa
F
,
Heemskerk
JW
,
Assinger
A
.
Platelet activation and signaling in thrombus formation
.
Blood
.
2025
;
146
(
12
):
1400
-
1411
.
3.
Colicchia
M
,
Schrottmaier
WC
,
Perrella
G
, et al
.
S100A8/A9 drives the formation of procoagulant platelets through GPIbα
.
Blood
.
2022
;
140
(
24
):
2626
-
2643
.
4.
Greinacher
A
,
Selleng
K
,
Palankar
R
, et al
.
Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia
.
Blood
.
2021
;
138
(
22
):
2256
-
2268
.
5.
Rayes
J
,
Watson
SP
,
Nieswandt
B
.
Functional significance of the platelet immune receptors GPVI and CLEC-2
.
J Clin Invest
.
2019
;
129
(
1
):
12
-
23
.
6.
Malloy
MW
,
McGrath
KE
,
Morrell
CN
.
Platelet heterogeneity: variety makes immune and vascular function better
.
Blood
.
2025
;
146
(
24
):
2882
-
2888
.
7.
Kaiser
R
,
Anjum
A
,
Nicolai
L
.
Platelet heterogeneity in disease: the many and the diverse?
.
Blood
.
2025
;
146
(
24
):
2870
-
2881
.
8.
Handtke
S
,
Steil
L
,
Palankar
R
, et al
.
Role of platelet size revisited-function and protein composition of large and small platelets
.
Thromb Haemost
.
2019
;
119
(
3
):
407
-
420
.
9.
Veninga
A
,
Handtke
S
,
Aurich
K
, et al
.
GPVI expression is linked to platelet size, age, and reactivity
.
Blood Adv
.
2022
;
6
(
14
):
4162
-
4173
.
10.
Baaten
CC
,
ten Cate
H
,
van der Meijden
PE
,
Heemskerk
JW
.
Platelet populations and priming in hematological diseases
.
Blood Rev
.
2017
;
31
(
6
):
389
-
399
.
11.
Veninga
A
,
Baaten
CC
,
De Simone
I
, et al
.
Effects of platelet agonists and priming on the formation of platelet populations
.
Thromb Haemost
.
2022
;
122
(
5
):
726
-
738
.
12.
Baaten
CC
,
Swieringa
F
,
Misztal
T
, et al
.
Platelet heterogeneity in activation-induced glycoprotein shedding: functional effects
.
Blood Adv
.
2018
;
2
(
18
):
2320
-
2331
.
13.
Petersen
R
,
Lambourne
JJ
,
Javierre
BM
, et al
.
Platelet function is modified by common sequence variation in megakaryocyte super enhancers
.
Nat Commun
.
2017
;
8
:
16058
.
14.
Baker-Groberg
SM
,
Lattimore
S
,
Recht
M
,
McCarty
OJ
,
Haley
KM
.
Assessment of neonatal platelet adhesion, activation, and aggregation
.
J Thromb Haemost
.
2016
;
14
(
4
):
815
-
827
.
15.
Best
MG
,
Sol
N
,
Kooi
I
, et al
.
RNA-seq of tumor-educated platelets enables blood-based pan-cancer, multiclass, and molecular pathway cancer diagnostics
.
Cancer Cell
.
2015
;
28
(
5
):
666
-
676
.
16.
Tunnacliffe
E
,
Chubb
JR
.
What is a transcriptional burst?
.
Trends Genet
.
2020
;
36
(
4
):
288
-
297
.
17.
Xu
B
,
Ye
X
,
Wen
Z
,
Chen
S
,
Wang
J
.
Epigenetic regulation of megakaryopoiesis and platelet formation
.
Haematologica
.
2024
;
109
(
10
):
3125
-
3137
.
18.
Furniss
JA
,
Tarassova
N
,
Poole
AW
.
Platelet generation in vivo and in vitro
.
Blood
.
2024
;
144
(
22
):
2283
-
2294
.
19.
Morcos
MN
,
Li
C
,
Munz
CM
, et al
.
Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis
.
Nat Commun
.
2022
;
13
(
1
):
4504
.
20.
Kamphuis
P
,
van Bergen
MG
,
van Zeventer
IA
, et al
.
Abnormal platelet counts and clonal hematopoiesis in the general population
.
Hemasphere
.
2023
;
7
(
1
):
e821
.
21.
Ren
X
,
Wen
W
,
Fan
X
, et al
.
COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas
.
Cell
.
2021
;
184
(
23
):
5838
. 1913.
22.
Becker
IC
,
Wilkie
AR
,
Nikols
E
, et al
.
Cell cycle-dependent centrosome clustering precedes proplatelet formation
.
Sci Adv
.
2024
;
10
(
25
):
eadl6153
.
23.
Becker
IC
,
Scheller
I
,
Wackerbarth
LM
, et al
.
Actin/microtubule crosstalk during platelet biogenesis in mice is critically regulated by twinfilin1 and cofilin1
.
Blood Adv
.
2020
;
4
(
10
):
2124
-
2134
.
24.
Heemskerk
JW
,
West
J
.
Emerging technologies for understanding platelet diversity
.
Arterioscler Thromb Vasc Biol
.
2022
;
42
(
5
):
540
-
552
.
25.
McArthur
K
,
Chappaz
S
,
Kile
BT
.
Apoptosis in megakaryocytes and platelets: the life and death of a lineage
.
Blood
.
2018
;
131
(
6
):
605
-
610
.
26.
Josefsson
EC
.
Platelet intrinsic apoptosis
.
Thromb Res
.
2023
;
231
:
206
-
213
.
27.
Jacob
S
,
Kosaka
Y
,
Bhatlekar
S
, et al
.
Mitofusin-2 regulates platelet mitochondria and function
.
Circ Res
.
2024
;
134
(
2
):
143
-
161
.
28.
Murphy
L
,
Inchauspé
J
,
Valenzano
G
, et al
.
Platelets sequester extracellular DNA, capturing tumor-derived and free fetal DNA
.
Science
.
2025
;
389
(
6761
):
eadp3971
.
29.
Valet
C
,
Magnen
M
,
Qiu
L
, et al
.
Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression
.
J Clin Invest
.
2022
;
132
(
7
):
e153920
.
30.
Li
J
,
van der Wal
DE
,
Zhu
G
, et al
.
Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia
.
Nat Commun
.
2015
;
6
:
7737
.
31.
Zou
J
,
Zhang
P
,
Solari
FA
, et al
.
Suppressed ORAI1-STIM1-dependent Ca2+ entry by protein kinase C isoforms regulating platelet procoagulant activity
.
J Biol Chem
.
2024
;
300
(
12
):
107899
.
32.
Zou
J
,
Sun
S
,
De Simone
I
, et al
.
Platelet activation pathways controlling reversible integrin αIIbβ3 activation
.
TH Open
.
2024
;
8
(
2
):
e232
-
e242
.
33.
Schubert
S
,
Weyrich
AS
,
Rowley
JW
.
A tour through the transcriptional landscape of platelets
.
Blood
.
2014
;
124
(
4
):
493
-
502
.
34.
Allan
HE
,
Hayman
MA
,
Marcone
S
, et al
.
Proteome and functional decline as platelets age in the circulation
.
J Thromb Haemost
.
2021
;
19
(
12
):
3095
-
3112
.
35.
Heinzmann
AC
,
Karel
MF
,
Coenen
DM
, et al
.
Complementary roles of platelet integrin αIIbβ3, phosphatidylserine exposure and cytoskeletal rearrangements in the release of extracellular vesicles
.
Atherosclerosis
.
2020
;
310
:
17
-
25
.
36.
Schoenwaelder
SM
,
Yuan
Y
,
Josefsson
EC
, et al
.
Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function
.
Blood
.
2009
;
114
(
3
):
663
-
666
.
37.
Pleines
I
,
Lebois
M
,
Gangatirkar
P
, et al
.
Intrinsic apoptosis circumvents the functional decline of circulating platelets but does not cause the storage lesion
.
Blood
.
2018
;
132
(
2
):
197
-
209
.
38.
Huang
J
,
Marini
F
,
Solari
FA
, et al
.
Human and mouse platelet transcriptomes and proteomes for phenotyping 3474 genes with hemostatic and platelet traits
.
Blood Vessel Thromb Hemost
.
2025
;
2
(
3
):
100068
.
39.
Solari
FA
,
Mattheij
NJ
,
Burkhart
JM
, et al
.
Combined quantification of the global proteome, phosphoproteome and protein cleavage to characterize altered platelet functions in the human Scott syndrome
.
Mol Cell Proteomics
.
2016
;
15
(
10
):
3154
-
3169
.
40.
Aliotta
A
,
Bertaggia Calderara
D
,
Zermatten
MG
,
Alberio
L
.
Sodium-calcium exchanger reverse mode sustains dichotomous ion fluxes required for procoagulant COAT platelet formation
.
Thromb Haemost
.
2021
;
121
(
3
):
309
-
321
.
41.
Jobe
SM
,
Wilson
KM
,
Leo
L
, et al
.
Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis
.
Blood
.
2008
;
111
(
3
):
1257
-
1265
.
42.
Van Kruchten
R
,
Mattheij
NJA
,
Saunders
C
, et al
.
Both TMEM16F-dependent and TMEM16F-independent pathways contribute to phosphatidylserine exposure in platelet apoptosis and platelet activation
.
Blood
.
2013
;
121
(
10
):
1850
-
1857
.
43.
Mattheij
NJ
,
Swieringa
F
,
Mastenbroek
TG
, et al
.
Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII
.
Haematologica
.
2016
;
101
(
4
):
427
-
436
.
44.
Agbani
EO
,
van den Bosch
MT
,
Brown
E
, et al
.
Coordinated membrane ballooning and procoagulant spreading in human platelets
.
Circulation
.
2015
;
132
(
15
):
1414
-
1424
.
45.
Podoplelova
NA
,
Nechipurenko
DY
,
Ignatova
AA
,
Sveshnikova
AN
,
Panteleev
MA
.
Procoagulant platelets: mechanisms of generation and action
.
Hamostaseologie
.
2021
;
41
(
2
):
146
-
153
.
46.
Alberio
L
,
Safa
O
,
Clemetson
KJ
,
Esmon
CT
,
Dale
GL
.
Surface expression and functional characterization of alpha-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin
.
Blood
.
2000
;
95
(
5
):
1694
-
1702
.
47.
Mattheij
NJ
,
Gilio
K
,
van Kruchten
R
, et al
.
Dual mechanism of integrin αΙIbβ3 closure in procoagulant platelets
.
J Biol Chem
.
2013
;
288
(
19
):
13325
-
13336
.
48.
Hua
VM
,
Chen
VM
.
Procoagulant platelets and the pathways leading to cell death
.
Semin Thromb Hemost
.
2015
;
41
(
4
):
405
-
412
.
49.
Handagama
PJ
,
George
JN
,
Shuman
MA
,
McEver
RP
,
Bainton
DF
.
Incorporation of a circulating protein into megakaryocyte and platelet granules
.
Proc Natl Acad Sci U S A
.
1987
;
84
(
3
):
861
-
865
.
50.
Vulliamy
P
,
Montague
SJ
,
Gillespie
S
, et al
.
Loss of GPVI and GPIbα contributes to trauma-induced platelet dysfunction in severely injured patients
.
Blood Adv
.
2020
;
4
(
12
):
2623
-
2630
.
51.
Waitz
G
,
Handtke
S
,
Zaninetti
C
,
Schönborn
L
,
Thiele
T
.
Combining diagnostics and research in an academic laboratory
.
Hamostaseologie
.
2025
;
45
(
1
):
63
-
69
.
52.
Zaninetti
C
,
Leinøe
E
,
Lozano
ML
, et al
.
Validation of immunofluorescence analysis of blood smears in patients with inherited platelet disorders
.
J Thromb Haemost
.
2023
;
21
(
4
):
1010
-
1019
.
53.
Zaninetti
C
,
Vater
L
,
Kaderali
L
, et al
.
Immunofluorescence microscopy on the blood smear identifies patients with myeloproliferative neoplasms
.
Leukemia
.
2024
;
38
(
9
):
2051
-
2058
.
54.
Noris
P
,
Biino
G
,
Pecci
A
, et al
.
Platelet diameters in inherited thrombocytopenias: analysis of 376 patients with all known disorders
.
Blood
.
2014
;
124
(
6
):
e4
-
e10
.
55.
Lages
B
,
Shattil
SJ
,
Bainton
DF
,
Weiss
HJ
.
Decreased content and surface expression of alpha-granule membrane protein GMP-140 in one of two types of platelet alpha delta storage pool deficiency
.
J Clin Invest
.
1991
;
87
(
3
):
919
-
929
.
56.
Clauser
S
,
Cramer-Bordé
E
.
Role of platelet electron microscopy in the diagnosis of platelet disorders
.
Semin Thromb Hemost
.
2009
;
35
(
2
):
213
-
223
.
57.
Kaito
K
,
Otsubo
H
,
Usui
N
, et al
.
Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia
.
Br J Haematol
.
2005
;
128
(
5
):
698
-
702
.
58.
Briggs
C
,
Harrison
P
,
Machin
SJ
.
Continuing developments with the automated platelet count
.
Int J Lab Hematol
.
2007
;
29
(
2
):
77
-
91
.
59.
Sandfeld-Paulsen
B
,
Pedersen
,
Damgaard
TK
,
Kristiansen
HP
.
Reference intervals for platelet large cell ratio, platelet distribution width, plateletcrit and standard haematological parameters determined on the Sysmex XN-10 in a cohort of 30,917 Danish blood donors
.
Scand J Clin Lab Invest
.
2022
;
82
(
6
):
439
-
445
.
60.
Ali
U
,
Gibbs
R
,
Knight
G
,
Tsitsikas
D
.
Sex-divided reference intervals for mean platelet volume, platelet large cell ratio and plateletcrit using the Sysmex XN-10 automated haematology analyzer in a UK population
.
Hematol Transfus Cell Ther
.
2019
;
41
(
2
):
153
-
157
.
61.
Pedersen
OB
,
Hvas
AM
,
Nissen
PH
,
Pasalic
L
,
Kristensen
SD
,
Grove
EL
.
Immature platelets and platelet reactivity in patients with acute ST-segment elevation myocardial infarction using whole blood flow cytometry with SYTO-13 staining
.
Thromb Res
.
2024
;
237
:
100
-
107
.
62.
Jennings
LK
,
Ashmun
RA
,
Wang
WC
,
Dockter
ME
.
Analysis of human platelet glycoproteins IIb-IIIa and Glanzmann's thrombasthenia in whole blood by flow cytometry
.
Blood
.
1986
;
68
(
1
):
173
-
179
.
63.
Khourssaji
M
,
Bareille
M
,
Alberio
L
, et al
.
Mepacrine flow cytometry assay for the diagnosis of platelet delta-granule defects. Literature review on methods: towards a shared detailed protocol
.
Thromb Haemost
.
2025
;
125
(
7
):
618
-
633
.
64.
Mallouk
N
,
Varvat
J
,
Berger
A
, et al
.
Assessment of a flow cytometry technique for studying signaling pathways in platelets: monitoring of VASP phosphorylation in clinical samples
.
Pract Lab Med
.
2018
;
11
:
10
-
18
.
65.
Hrdinova
J
,
Fernández
DI
,
Ercig
B
, et al
.
Structure-based cyclic glycoprotein Ibα-derived peptides interfering with von Willebrand factor-binding, affecting platelet aggregation under shear
.
Int J Mol Sci
.
2022
;
23
(
4
):
2046
.
66.
Mehta
N
,
Uchino
K
,
Fakhran
S
, et al
.
Platelet C4d is associated with acute ischemic stroke and stroke severity
.
Stroke
.
2008
;
39
(
12
):
3236
-
3241
.
67.
Sowa
MA
,
Hannemann
C
,
Pinos
I
, et al
.
Tetraspanin CD37 regulates platelet hyperreactivity and thrombosis
.
Cardiovasc Res
.
2025
;
121
(
6
):
943
-
956
.
68.
Zlamal
J
,
Aliotta
A
,
Alberio
L
,
Chen
V
,
Bakchoul
T
;
SSC Platelet Immunology of the ISTH
.
Diagnostic value of antibody-induced procoagulant platelets in heparin-induced thrombocytopenia: communication from the ISTH SSC Subcommittee on Platelet Immunology
.
J Thromb Haemost
.
2024
;
22
(
3
):
860
-
868
.
69.
Handtke
S
,
Wolff
M
,
Zaninetti
C
, et al
.
A flow cytometric assay to detect platelet-activating antibodies in VITT after ChAdOx1 nCov-19 vaccination
.
Blood
.
2021
;
137
(
26
):
3656
-
3659
.
70.
Mordakhanova
ER
,
Nevzorova
TA
,
Synbulatova
GE
,
Rauova
L
,
Weisel
JW
,
Litvinov
RI
.
Platelet activation in heparin-induced thrombocytopenia is followed by platelet death via complex apoptotic and non-apoptotic pathways
.
Int J Mol Sci
.
2020
;
21
(
7
):
2556
.
71.
Althaus
K
,
Marini
I
,
Zlamal
J
, et al
.
Antibody-induced procoagulant platelets in severe COVID-19 infection
.
Blood
.
2021
;
137
(
8
):
1061
-
1071
.
72.
Esefeld
M
,
Handtke
S
,
Kaiser
R
, et al
.
Platelet activating histone/antihistone IgG complexes in anti-PF4 negative thrombosis and thrombocytopenia syndrome
.
Blood Adv
.
2025
;
9
(
16
):
4323
-
4335
.
73.
Panch
SR
,
Guo
L
,
Vassallo
R
.
Platelet transfusion refractoriness due to HLA alloimmunization: evolving paradigms in mechanisms and management
.
Blood Rev
.
2023
;
62
:
101135
.
74.
Goodnough
LT
,
Kuter
DJ
,
McCullough
J
, et al
.
Prophylactic platelet transfusions from healthy apheresis platelet donors undergoing treatment with thrombopoietin
.
Blood
.
2001
;
98
(
5
):
1346
-
1351
.
75.
Handtke
S
,
Steil
L
,
Greinacher
A
,
Thiele
T
.
Toward the relevance of platelet subpopulations for transfusion medicine
.
Front Med (Lausanne)
.
2018
;
5
:
17
.
76.
Anjum
A
,
Mader
M
,
Mahameed
S
, et al
.
Aging platelets shift their hemostatic properties to inflammatory functions
.
Blood
.
2025
;
145
(
14
):
1568
-
1582
.
77.
Curley
A
,
Stanworth
SJ
,
Willoughby
K
, et al;
PlaNeT2 MATISSE Collaborators
.
Randomized trial of platelet transfusion thresholds in neonates
.
N Engl J Med
.
2019
;
380
(
3
):
242
-
251
.
78.
Maurya
P
,
Ture
SK
,
Li
C
, et al
.
Transfusion of adult, but not neonatal, platelets promotes monocyte trafficking in neonatal mice
.
Arterioscler Thromb Vasc Biol
.
2023
;
43
(
6
):
873
-
885
.
79.
Michelson
AD
.
Flow cytometric analysis of platelet surface glycoproteins: phenotypically distinct subpopulations of platelets in children with chronic myeloid leukemia
.
J Lab Clin Med
.
1987
;
110
(
3
):
346
-
354
.
80.
Shattil
SJ
,
Cunningham
M
,
Hoxie
JA
.
Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry
.
Blood
.
1987
;
70
(
1
):
307
-
315
.
81.
Linden
MD
,
Furman
MI
,
Frelinger
AL
, et al
.
Indices of platelet activation and the stability of coronary artery disease
.
J Thromb Haemost
.
2007
;
5
(
4
):
761
-
765
.
82.
Stellos
K
,
Bigalke
B
,
Stakos
D
,
Henkelmann
N
,
Gawaz
M
.
Platelet-bound P-selectin expression in patients with coronary artery disease: impact on clinical presentation and myocardial necrosis, and effect of diabetes mellitus and anti-platelet medication
.
J Thromb Haemost
.
2010
;
8
(
1
):
205
-
207
.
83.
Dopheide
JF
,
Rubrech
J
,
Trumpp
A
, et al
.
Leukocyte-platelet aggregates-a phenotypic characterization of different stages of peripheral arterial disease
.
Platelets
.
2016
;
27
(
7
):
658
-
667
.
84.
Dachary-Prigent
J
,
Freyssinet
JM
,
Pasquet
JM
,
Carron
JC
,
Nurden
AT
.
Annexin V as a probe of aminophospholipid exposure and platelet membrane vesiculation: a flow cytometry study showing a role for free sulfhydryl groups
.
Blood
.
1993
;
81
(
10
):
2554
-
2565
.
85.
Wielders
SJ
,
Ungethüm
L
,
Reutelingsperger
CP
,
Bevers
EM
,
Lindhout
T
.
Factor Xa-driven thrombin generation in plasma: dependency on the aminophospholipid density of membranes and inhibition by phospholipid-binding proteins
.
Thromb Haemost
.
2007
;
98
(
5
):
1056
-
1062
.
86.
Josefsson
EC
,
Ramström
S
,
Thaler
J
,
Lordkipanidzé
M
;
COAGAPO study group
.
Consensus report on markers to distinguish procoagulant platelets from apoptotic platelets: communication from the Scientific and Standardization Committee of the ISTH
.
J Thromb Haemost
.
2023
;
21
(
8
):
2291
-
2299
.
87.
Zlamal
J
,
Singh
A
,
Weich
K
, et al
.
Platelet phosphatidylserine is the critical mediator of thrombosis in heparin-induced thrombocytopenia
.
Haematologica
.
2023
;
108
(
10
):
2690
-
2702
.
88.
Pedersen
OH
,
Nissen
PH
,
Hvas
AM
.
Platelet function investigation by flow cytometry: sample volume, needle size, and reference intervals
.
Platelets
.
2018
;
29
(
2
):
199
-
202
.
89.
Frelinger
AL
,
Rivera
J
,
Connor
DE
, et al
.
Consensus recommendations on flow cytometry for the assessment of inherited and acquired disorders of platelet number and function: communication from the ISTH SSC Subcommittee on Platelet Physiology
.
J Thromb Haemost
.
2021
;
19
(
12
):
3193
-
3202
.
90.
Jourdi
G
,
Ramström
S
,
Sharma
R
,
Bakchoul
T
,
Lordkipanidzé
M
;
FC-PFT in TP study group
.
Consensus report on flow cytometry for platelet function testing in thrombocytopenic patients: communication from the SSC of the ISTH
.
J Thromb Haemost
.
2023
;
21
(
10
):
2941
-
2952
.
91.
Hindle
MS
,
Cheah
LT
,
Yates
DM
,
Naseem
KM
.
Preanalytical conditions for multiparameter platelet flow cytometry
.
Res Pract Thromb Haemost
.
2023
;
7
:
102205
.
92.
Tynngård
N
,
Alshamari
A
,
Månsson
F
,
Ramström
S
.
Variation in activation marker expression within the platelet population: a new parameter for evaluation of platelet flow cytometry data
.
Platelets
.
2022
;
33
(
8
):
1113
-
1118
.
93.
Munnix
IC
,
Cosemans
JM
,
Auger
JM
,
Heemskerk
JW
.
Platelet response heterogeneity in thrombus formation
.
Thromb Haemost
.
2009
;
102
(
6
):
1149
-
1156
.
94.
Bandura
DR
,
Baranov
VI
,
Ornatsky
OI
, et al
.
Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry
.
Anal Chem
.
2009
;
81
(
16
):
6813
-
6822
.
95.
Majonis
D
,
Herrera
I
,
Ornatsky
O
, et al
.
Synthesis of a functional metal-chelating polymer and steps toward quantitative mass cytometry bioassays
.
Anal Chem
.
2010
;
82
(
21
):
8961
-
8969
.
96.
Blair
TA
,
Michelson
AD
,
Frelinger
AL
.
Mass cytometry reveals distinct platelet subtypes in healthy subjects and novel alterations in surface glycoproteins in Glanzmann thrombasthenia
.
Sci Rep
.
2018
;
8
(
1
):
10300
.
97.
Dill
V
,
Kirmes
K
,
Han
J
, et al
.
Platelet mass cytometry reveals dysregulation of prothrombotic pathways in essential thrombocythemia
.
Platelets
.
2024
;
35
(
1
):
2358244
.
98.
Spurgeon
BE
,
Frelinger
AL
.
Platelet phenotyping by full spectrum flow cytometry
.
Curr Protoc
.
2023
;
3
(
2
):
e687
.
99.
Gu
SX
,
Marcus
BS
,
Gu
VW
,
Varghese
AP
,
Hwa
J
,
Faustino
EV
.
High-dimensional single-cell mass cytometry demonstrates differential platelet functional phenotypes in infants with congenital heart disease
.
Arterioscler Thromb Vasc Biol
.
2024
;
44
(
12
):
2530
-
2539
.
100.
Södergren
AL
,
Tynngård
N
,
Berlin
G
,
Ramström
S
.
Responsiveness of platelets during storage studied with flow cytometry--formation of platelet subpopulations and LAMP-1 as new markers for the platelet storage lesion
.
Vox Sang
.
2016
;
110
(
2
):
116
-
125
.
101.
Johnson
L
,
Lei
P
,
Waters
L
,
Padula
MP
,
Marks
DC
.
Identification of platelet subpopulations in cryopreserved platelet components using multi-colour imaging flow cytometry
.
Sci Rep
.
2023
;
13
(
1
):
1221
.
102.
Södergren
AL
,
Ramström
S
.
Platelet subpopulations remain despite strong dual agonist stimulation and can be characterised using a novel six-colour flow cytometry protocol
.
Sci Rep
.
2018
;
8
(
1
):
1441
.
103.
Spurgeon
BE
,
Naseem
KM
.
Phosphoflow cytometry and barcoding in blood platelets: technical and analytical considerations
.
Cytometry B
.
2020
;
98
(
2
):
123
-
130
.
104.
Hindle
MS
,
Spurgeon
BE
,
Cheah
LT
,
Webb
BA
,
Naseem
KM
.
Multidimensional flow cytometry reveals novel platelet subpopulations in response to prostacyclin
.
J Thromb Haemost
.
2021
;
19
(
7
):
1800
-
1812
.
105.
Spurgeon
BE
,
Frelinger
AL
.
Comprehensive phenotyping of human platelets by single-cell cytometry
.
Cytometry A
.
2022
;
101
(
4
):
290
-
297
.
106.
Pedersen
CB
,
Dam
SH
,
Barnkob
MB
, et al
.
cyCombine allows for robust integration of single-cell cytometry datasets within and across technologies
.
Nat Commun
.
2022
;
13
(
1
):
1698
.
107.
Van Gassen
S
,
Gaudilliere
B
,
Angst
MS
,
Saeys
Y
,
Aghaeepour
N
.
CytoNorm: a normalization algorithm for cytometry data
.
Cytometry A
.
2020
;
97
(
3
):
268
-
278
.
108.
Van Gassen
S
,
Callebaut
B
,
Van Helden
MJ
, et al
.
FlowSOM: using self-organizing maps for visualization and interpretation of cytometry data
.
Cytometry A
.
2015
;
87
(
7
):
636
-
645
.
109.
Greene
E
,
Finak
G
,
D'Amico
LA
, et al
.
New interpretable machine-learning method for single-cell data reveals correlates of clinical response to cancer immunotherapy
.
Patterns
.
2021
;
2
(
12
):
100372
.
110.
Setty
M
,
Tadmor
MD
,
Reich-Zeliger
S
, et al
.
Wishbone identifies bifurcating developmental trajectories from single-cell data
.
Nat Biotechnol
.
2016
;
34
(
6
):
637
-
645
.
111.
Street
K
,
Risso
D
,
Fletcher
RB
, et al
.
Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics
.
BMC Genomics
.
2018
;
19
(
1
):
477
.
112.
Park
LM
,
Lannigan
J
,
Low
Q
,
Jaimes
MC
,
Bonilla
DL
.
OMIP-069 version 2: update to the 40-color full spectrum flow cytometry panel for deep immunophenotyping of major cell subsets in human peripheral blood
.
Cytometry A
.
2024
;
105
(
11
):
791
-
799
.
113.
Vadgama
A
,
Boot
J
,
Dark
N
, et al
.
Multiparameter phenotyping of platelets and characterization of the effects of agonists using machine learning
.
Res Pract Thromb Haemost
.
2024
;
8
(
5
):
102523
.
114.
Melsen
JE
,
van Ostaijen-ten Dam
MM
,
Lankester
AC
,
Schilham
MW
,
van den Akker
EB
.
A comprehensive workflow for applying single-cell clustering and pseudotime analysis to flow cytometry data
.
J Immunol
.
2020
;
205
(
3
):
864
-
871
.
115.
Ujas
TA
,
Obregon-Perko
V
,
Stowe
AM
.
A guide on analyzing flow cytometry data using clustering methods and nonlinear dimensionality reduction (tSNE or UMAP)
.
Methods Mol Biol
.
2023
;
2616
:
231
-
249
.
116.
Auber
M
,
Svenningsen
P
.
An estimate of extracellular vesicle secretion rates of human blood cells
.
J Extracell Biol
.
2022
;
1
(
6
):
e46
.
117.
In't Veld
SG
,
Wurdinger
T
.
Tumor-educated platelets
.
Blood
.
2019
;
133
(
22
):
2359
-
2364
.
118.
Allan
HE
,
Vadgama
A
,
Armstrong
PC
,
Warner
TD
.
Platelet ageing: a review
.
Thromb Res
.
2023
;
231
:
214
-
222
.
119.
Swieringa
F
,
Kuijpers
MJ
,
Lamers
MM
,
van der Meijden
PE
,
Heemskerk
JW
.
Rate-limiting roles of the tenase complex of factors VIII and IX in platelet procoagulant activity and formation of platelet-fibrin thrombi under flow
.
Haematologica
.
2015
;
100
(
6
):
748
-
756
.
120.
Baaten
CC
,
Meacham
S
,
de Witt
SM
, et al
.
A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
.
Blood
.
2018
;
132
(
24
):
e35
-
e46
.
121.
Armstrong
PC
,
Allan
HE
,
Kirkby
NS
, et al
.
Temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mRNAs
.
Blood Adv
.
2022
;
6
(
23
):
6028
-
6038
.
You do not currently have access to this content.
Sign in via your Institution