Abstract

Hemorrhage causes millions of deaths and hundreds of billions of dollars in medical costs every year, and a large percentage of trauma bleeding–associated deaths occur in the prehospital setting. Bleeding is typically treated with transfused blood products, but this is difficult in the prehospital setting due to limitations in transportation and storage, especially in rural and remote military settings. Advancements in cold-stored platelets and lyophilized blood products have the potential to address some of these limitations. However, devising novel products that continue to improve shelf life, portability, scalability, cost, and safety for patients experiencing bleeding in prehospital settings could greatly improve treatment options and patient outcomes. This review primarily focuses on rational design of material-based approaches to develop novel hemostatic agents that strive to meet limitations of current blood products, especially for use in the prehospital setting. Key topics of consideration include how material design can lead to identification of effective therapies that stop bleeding as well as strategies to iterate on existing designs to enhance healing after cessation of bleeding. Improving performance and functionality of existing and emerging materials could be achieved through the incorporation of transglutaminases, growth factors, cellular components, or inorganic molecules. Finally, consideration of patient-specific factors that influence bleeding, such as patient sex and age, through evaluation of therapies in specific populations and/or design of materials targeted for specific patient populations, is a key area for development of next-generation hemostatic materials.

1.
Shackelford
S
,
Eastridge
BJ
.
Epidemiology of prehospital and hospital traumatic deaths from life-threatening hemorrhage
.
Damage Control Resusc
.
2020
:
31
-
40
.
2.
Coleman
JR
,
Gumina
R
,
Hund
T
, et al
.
Sex dimorphisms in coagulation: Implications in trauma-induced coagulopathy and trauma resuscitation
.
Am J Hematol
.
2024
;
99
(
suppl 1
):
S28
-
S35
.
3.
Lozano
R
,
Naghavi
M
,
Foreman
K
, et al
.
Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010
.
Lancet
.
2012
;
380
(
9859
):
2095
-
2128
.
4.
Yazer
MH
,
Jenkins
DH
,
Sperry
JL
,
Spinella
PC
.
How do we forecast tomorrow’s transfusion? Prehospital transfusion
.
Transfus Clin Biol
.
2023
;
30
(
1
):
39
-
42
.
5.
Feinman
M
,
Cotton
BA
,
Haut
ER
.
Optimal fluid resuscitation in trauma: type, timing, and total
.
Curr Opin Crit Care
.
2014
;
20
(
4
):
366
-
372
.
6.
Reuter
DA
,
Chappell
D
,
Perel
A
.
The dark sides of fluid administration in the critically ill patient
.
Intensive Care Med
.
2018
;
44
(
7
):
1138
-
1140
.
7.
Bickell
WH
,
Wall
MJ
,
Pepe
PE
, et al
.
Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries
.
N Engl J Med
.
1994
;
331
(
17
):
1105
-
1109
.
8.
Sperry
JL
,
Guyette
FX
,
Brown
JB
, et al
.
Prehospital plasma during air medical transport in trauma patients at risk for hemorrhagic shock
.
N Engl J Med
.
2018
;
379
(
4
):
315
-
326
.
9.
Brill
JB
,
Tang
B
,
Hatton
G
, et al
.
Impact of incorporating whole blood into hemorrhagic shock resuscitation: analysis of 1,377 consecutive trauma patients receiving emergency-release uncrossmatched blood products
.
J Am Coll Surg
.
2022
;
234
(
4
):
408
-
418
.
10.
Shackelford
SA
,
Del Junco
DJ
,
Powell-Dunford
N
, et al
.
Association of prehospital blood product transfusion during medical evacuation of combat casualties in Afghanistan with acute and 30-day survival
.
JAMA
.
2017
;
318
(
16
):
1581
-
1591
.
11.
Kogler
VJ
,
Miles
JA
,
Özpolat
T
, et al
.
Platelet dysfunction reversal with cold-stored vs room temperature–stored platelet transfusions
.
Blood
.
2024
;
143
(
20
):
2073
-
2088
.
12.
Mok
G
,
Hoang
R
,
Khan
MW
, et al
.
Freeze-dried plasma for major trauma–systematic review and meta-analysis
.
J Trauma Acute Care Surg
.
2021
;
90
(
3
):
589
-
602
.
13.
Moore
HB
,
Moore
EE
,
Chapman
MP
, et al
.
Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial
.
Lancet
.
2018
;
392
(
10144
):
283
-
291
.
14.
Jost
D
,
Lemoine
S
,
Lemoine
F
, et al
.
Prehospital lyophilized plasma transfusion for trauma-induced coagulopathy in patients at risk for hemorrhagic shock: a randomized clinical trial
.
JAMA Netw Open
.
2022
;
5
(
7
):
e2223619
.
15.
Feasibility and safety of thrombosomes on time to hemostasis in patients undergoing emergency surgery for thoracic aortic dissections-a randomized, controlled, open-label investigator-initiated pilot trial. ClinicalTrials.gov identifier: NCT05771831
. Updated 7 May 2024. Accessed 9 December 2024. https://clinicaltrial.be/en/details/261726?per_page=100&only_recruiting=0&only_eligible=0.
16.
Kuhn
BJ
,
Swanson
A
,
Cherupalla
AS
, et al
.
Mechanisms of action of an investigational new freeze-dried platelet-derived hemostatic product
.
J Thromb Haemost
.
2024
;
22
(
3
):
686
-
699
.
17.
Sekhon
UDS
,
Swingle
K
,
Girish
A
, et al
.
Platelet-mimicking procoagulant nanoparticles augment hemostasis in animal models of bleeding
.
Sci Transl Med
.
2022
;
14
(
629
):
eabb8975
.
18.
Bynum
JA
,
Meledeo
MA
,
Peltier
GC
, et al
.
Evaluation of a lyophilized platelet-derived hemostatic product
.
Transfusion (Paris)
.
2019
;
59
(
S2
):
1490
-
1498
.
19.
Trivedi
A
,
Potter
DR
,
Miyazawa
BY
, et al
.
Freeze-dried platelets promote clot formation, attenuate endothelial cell permeability, and decrease pulmonary vascular leak in a murine model of hemorrhagic shock
.
J Trauma Acute Care Surg
.
2021
;
90
(
2
):
203
-
214
.
20.
Zhao
H
,
Devine
DV
.
The missing pieces to the cold-stored platelet puzzle
.
Int J Mol Sci
.
2022
;
23
(
3
):
1100
.
21.
Nair
PM
,
Meledeo
MA
,
Wells
AR
, et al
.
Cold-stored platelets have better preserved contractile function in comparison with room temperature-stored platelets over 21 days
.
Transfusion (Paris)
.
2021
;
61
(
suppl 1
):
S68
-
S79
.
22.
Drakeford
C
,
Aguila
S
,
Roche
F
, et al
.
von Willebrand factor links primary hemostasis to innate immunity
.
Nat Commun
.
2022
;
13
(
1
):
6320
.
23.
Periayah
MH
,
Halim
AS
,
Mat Saad
AZ
.
Mechanism action of platelets and crucial blood coagulation pathways in hemostasis
.
Int J Hematol Oncol Stem Cell Res
.
2017
;
11
(
4
):
319
-
327
.
24.
Saad
J
,
Asuka
E
,
Schoenberger
L
. Physiology, Platelet Activation.
StatPearls Publishing
;
2023
.
25.
Chaudhry
R
,
Usama
SM
,
Babiker
HM
. Physiology, Coagulation Pathways.
StatPearls Publishing
;
2023
.
26.
Simpson
A
,
Shukla
A
,
Brown
AC
.
Biomaterials for hemostasis
.
Annu Rev Biomed Eng
.
2022
;
24
(
1
):
111
-
135
.
27.
Szymocha
M
,
Pacan
M
,
Anufrowicz
M
,
Jurek
T
,
Rorat
M
.
Leaving a foreign object in the body of a patient during abdominal surgery: still a current problem
.
Pol J Surg
.
2019
;
91
(
3
):
1
-
5
.
28.
Bennett
BL
,
Littlejohn
LF
,
Kheriabadi
BS
, et al
.
Management of external hemorrhage in tactical combat casualty care: chitosan-based hemostatic gauze dressings--TCCC guidelines-change 13-05
.
J Spec Oper Med
.
2014
;
14
(
3
):
40
-
57
.
29.
Wang
C-H
,
Cherng
J-H
,
Liu
C-C
, et al
.
Procoagulant and antimicrobial effects of chitosan in wound healing
.
Int J Mol Sci
.
2021
;
22
(
13
):
7067
.
30.
Chan
LW
,
Kim
CH
,
Wang
X
,
Pun
SH
,
White
NJ
,
Kim
TH
.
PolySTAT-modified chitosan gauzes for improved hemostasis in external hemorrhage
.
Acta Biomater
.
2016
;
31
:
178
-
185
.
31.
Lee
VK
,
Lee
T
,
Ghosh
A
, et al
.
An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy
.
Proc Natl Acad Sci U S A
.
2024
;
121
(
5
):
e2316170121
.
32.
Baylis
JR
,
Finkelstein-Kulka
A
,
Macias-Valle
L
, et al
.
Rapid hemostasis in a sheep model using particles that propel thrombin and tranexamic acid
.
Laryngoscope
.
2017
;
127
(
4
):
787
-
793
.
33.
Ali-Mohamad
N
,
Cau
MF
,
Wang
X
, et al
.
Ruggedized self-propelling hemostatic gauze delivers low dose of thrombin and systemic tranexamic acid and achieves high survival in swine with junctional hemorrhage
.
Mil Med
.
2023
;
188
(
suppl 6
):
280
-
287
.
34.
Yu
L
,
Liu
Z
,
Tong
Z
, et al
.
Sequential-crosslinking fibrin glue for rapid and reinforced hemostasis
.
Adv Sci
.
2024
;
11
(
7
):
e2308171
.
35.
Teng
L
,
Shao
Z
,
Bai
Q
, et al
.
Biomimetic glycopolypeptide hydrogels with tunable adhesion and microporous structure for fast hemostasis and highly efficient wound healing
.
Adv Funct Mater
.
2021
;
31
(
43
):
2105628
.
36.
Su
L-Y
,
Yao
M
,
Xu
W
,
Zhong
M
,
Cao
Y
,
Zhou
H
.
Cascade encapsulation of antimicrobial peptides, exosomes and antibiotics in fibrin-gel for first-aid hemostasis and infected wound healing
.
Int J Biol Macromol
.
2024
;
269
(
pt 2
):
132140
.
37.
Park
SM
,
Kang
DR
,
Lee
JH
, et al
.
Efficacy and safety of a thrombin-containing collagen-based hemostatic agent in spinal surgery: a randomized clinical trial
.
World Neurosurg
.
2021
;
154
:
e215
-
e221
.
38.
Assmann
A
,
Vegh
A
,
Ghasemi-Rad
M
, et al
.
A highly adhesive and naturally derived sealant
.
Biomaterials
.
2017
;
140
:
115
-
127
.
39.
Baghdasarian
S
,
Saleh
B
,
Baidya
A
, et al
.
Engineering a naturally derived hemostatic sealant for sealing internal organs
.
Mater Today Bio
.
2022
;
13
:
100199
.
40.
Gaharwar
AK
,
Avery
RK
,
Assmann
A
, et al
.
Shear-thinning nanocomposite hydrogels for the treatment of hemorrhage
.
ACS Nano
.
2014
;
8
(
10
):
9833
-
9842
.
41.
Peng
X
,
Xu
X
,
Deng
Y
, et al
.
Ultrafast self-gelling and wet adhesive powder for acute hemostasis and wound healing
.
Adv Funct Mater
.
2021
;
31
(
33
):
2102583
.
42.
Ali-Mohamad
N
,
Cau
MF
,
Zenova
V
, et al
.
Self-propelling thrombin powder enables hemostasis with no observable recurrent bleeding or thrombosis over 3 days in a porcine model of upper GI bleeding
.
Gastrointest Endosc
.
2023
;
98
(
2
):
245
-
248
.
43.
Melo-Ferraz
A
,
Coelho
C
,
Miller
P
,
Criado
MB
,
Monteiro
MC
.
Platelet activation and antimicrobial activity of L-PRF: a preliminary study
.
Mol Biol Rep
.
2021
;
48
(
5
):
4573
-
4580
.
44.
Gao
Y
,
Sarode
A
,
Kokoroskos
N
, et al
.
A polymer-based systemic hemostatic agent
.
Sci Adv
.
2020
;
6
(
31
):
eaba0588
.
45.
Gao
Y
,
Ikeda-Imafuku
M
,
Zhao
Z
,
Joshi
M
,
Mitragotri
S
.
A polymer-based systemic hemostat for managing uncontrolled bleeding
.
Bioeng Transl Med
.
2023
;
8
(
3
):
e10516
.
46.
Lamm
RJ
,
Pichon
TJ
,
Huyan
F
, et al
.
Optimizing the polymer chemistry and synthesis method of PolySTAT, an injectable hemostat
.
ACS Biomater Sci Eng
.
2020
;
6
(
12
):
7011
-
7020
.
47.
La
CC
,
Takeuchi
LE
,
Abbina
S
,
Vappala
S
,
Abbasi
U
,
Kizhakkedathu
JN
.
Targeting biological polyanions in blood: strategies toward the design of therapeutics
.
Biomacromolecules
.
2020
;
21
(
7
):
2595
-
2621
.
48.
Kudela
D
,
Ploense
K
,
Lu
G
,
Pollack
C
,
Ashford-Hicks
A
,
Morrissey
JH
.
A novel synthetic short-chain polyphosphate (polyP) complexed with silica nanoparticle (SNP) improves hemostatic outcomes in severe swine and rat injury models [abstract]
.
Blood
.
2024
;
144
(
suppl 1
):
3964
.
49.
Yuan
Y
,
Liu
J
,
Duan
H
, et al
.
An anticoagulant/procoagulant self-converting and bleeding site–targeting systemic nanotherapy for rapidly controlling noncompressible bleeding without risk of thrombosis
.
J Thromb Haemost
.
2023
;
21
(
6
):
1478
-
1492
.
50.
Maisha
N
,
Kulkarni
C
,
Pandala
N
, et al
.
PEGylated polyester nanoparticles trigger adverse events in a large animal model of trauma and in naïve animals: understanding cytokine and cellular correlations with these events
.
ACS Nano
.
2022
;
16
(
7
):
10566
-
10580
.
51.
Bertram
JP
,
Williams
CA
,
Robinson
R
,
Segal
SS
,
Flynn
NT
,
Lavik
EB
.
Intravenous hemostat: nanotechnology to halt bleeding
.
Sci Transl Med
.
2009
;
1
(
11
):
11ra22
.
52.
Hickman
DA
,
Pawlowski
CL
,
Shevitz
A
, et al
.
Intravenous synthetic platelet (SynthoPlate) nanoconstructs reduce bleeding and improve ‘golden hour’ survival in a porcine model of traumatic arterial hemorrhage
.
Sci Rep
.
2018
;
8
(
1
):
3118
.
53.
Anselmo
AC
,
Modery-Pawlowski
CL
,
Menegatti
S
, et al
.
Platelet-like nanoparticles: mimicking shape, flexibility, and surface biology of platelets to target vascular injuries
.
ACS Nano
.
2014
;
8
(
11
):
11243
-
11253
.
54.
Brown
AC
,
Stabenfeldt
SE
,
Ahn
B
, et al
.
Ultrasoft microgels displaying emergent platelet-like behaviours
.
Nat Mater
.
2014
;
13
(
12
):
1108
-
1114
.
55.
Nellenbach
K
,
Mihalko
E
,
Nandi
S
, et al
.
Ultrasoft platelet-like particles stop bleeding in rodent and porcine models of trauma
.
Sci Transl Med
.
2024
;
16
(
742
):
eadi4490
.
56.
Nandi
S
,
Mihalko
E
,
Nellenbach
K
, et al
.
Synthetic platelet microgels containing fibrin Knob B mimetic motifs enhance clotting responses
.
Adv Ther
.
2021
;
4
(
5
):
2100010
.
57.
Nandi
S
,
Sproul
EP
,
Nellenbach
K
, et al
.
Platelet-like particles dynamically stiffen fibrin matrices and improve wound healing outcomes
.
Biomater Sci
.
2019
;
7
(
2
):
669
-
682
.
58.
Pan
V
,
Siva
PN
,
Modery-Pawlowski
CL
,
Singh Sekhon
UD
,
Sen Gupta
A
.
Targeted killing of metastatic cells using a platelet-inspired drug delivery system
.
RSC Adv
.
2015
;
5
(
57
):
46218
-
46228
.
59.
Chee
E
,
Nandi
S
,
Nellenbach
K
, et al
.
Nanosilver composite pNIPAm microgels for the development of antimicrobial platelet-like particles
.
J Biomed Mater Res B Appl Biomater
.
2020
;
108
(
6
):
2599
-
2609
.
60.
Bagoly
Z
,
Koncz
Z
,
Hársfalvi
J
,
Muszbek
L
.
Factor XIII, clot structure, thrombosis
.
Thromb Res
.
2012
;
129
(
3
):
382
-
387
.
61.
Chan
KYT
,
Yong
ASM
,
Wang
X
, et al
.
The adhesion of clots in wounds contributes to hemostasis and can be enhanced by coagulation factor XIII
.
Sci Rep
.
2020
;
10
(
1
):
20116
.
62.
Dickneite
G
,
Metzner
HJ
,
Kroez
M
,
Hein
B
,
Nicolay
U
.
The importance of factor XIII as a component of fibrin sealants
.
J Surg Res
.
2002
;
107
(
2
):
186
-
195
.
63.
Ząbczyk
M
,
Natorska
J
,
Undas
A
.
Factor XIII and fibrin clot properties in acute venous thromboembolism
.
Int J Mol Sci
.
2021
;
22
(
4
):
1607
.
64.
Lovejoy
AE
,
Reynolds
TC
,
Visich
JE
, et al
.
Safety and pharmacokinetics of recombinant factor XIII-A2 administration in patients with congenital factor XIII deficiency
.
Blood
.
2006
;
108
(
1
):
57
-
62
.
65.
You
C
,
Zhang
Z
,
Guo
Y
, et al
.
Application of extracellular matrix cross-linked by microbial transglutaminase to promote wound healing
.
Int J Biol Macromol
.
2024
;
266
(
pt 2
):
131384
.
66.
Xie
X
,
Tian
J
,
Lv
F
, et al
.
A novel hemostatic sealant composed of gelatin, transglutaminase and thrombin effectively controls liver trauma-induced bleeding in dogs
.
Acta Pharmacol Sin
.
2013
;
34
(
7
):
983
-
988
.
67.
Li
S
,
Jia
H
,
Liu
Z
, et al
.
Fibroblast growth factor-21 as a novel metabolic factor for regulating thrombotic homeostasis
.
Sci Rep
.
2022
;
12
(
1
):
400
.
68.
Peng
J
,
Zhao
H
,
Tu
C
, et al
.
In situ hydrogel dressing loaded with heparin and basic fibroblast growth factor for accelerating wound healing in rat
.
Mater Sci Eng C
.
2020
;
116
:
111169
.
69.
Abdelhakim
M
,
Lin
X
,
Ogawa
R
.
The Japanese experience with basic fibroblast growth factor in cutaneous wound management and scar prevention: a systematic review of clinical and biological aspects
.
Dermatol Ther
.
2020
;
10
(
4
):
569
-
587
.
70.
Zhang
H
,
Luo
H
,
Tang
B
,
Chen
Y
,
Fu
J
,
Sun
J
.
Endothelial progenitor cells overexpressing platelet derived growth factor-D facilitate deep vein thrombosis resolution
.
J Thromb Thrombolysis
.
2022
;
53
(
3
):
750
-
760
.
71.
Zhang
J
,
Liu
X
,
Ma
K
, et al
.
Collagen/heparin scaffold combined with vascular endothelial growth factor promotes the repair of neurological function in rats with traumatic brain injury
.
Biomater Sci
.
2021
;
9
(
3
):
745
-
764
.
72.
Bahammam
MA
,
Attia
MS
.
Expression of vascular endothelial growth factor using platelet rich fibrin (PRF) and nanohydroxyapatite (nano-HA) in treatment of periodontal intra-bony defects – a randomized controlled trial
.
Saudi J Biol Sci
.
2021
;
28
(
1
):
870
-
878
.
73.
Bhatnagar
P
,
Law
JX
,
Ng
S-F
.
Delivery systems for platelet derived growth factors in wound healing: a review of recent developments and global patent landscape
.
J Drug Deliv Sci Technol
.
2022
;
71
:
103270
.
74.
Bal
SH
,
Sağdilek
E
,
Karaçay
M
, et al
.
The effect of exosomes released from apheresis platelet concentrates under the impact of gamma irradiation and storage time upon platelet aggregation and hemostasis: the effect of exosomes isolated from aPCs on haemostasis
.
Blood Transfus
.
2023
;
21
(
3
):
257
-
267
.
75.
Zong
Y
,
Pruner
I
,
Antovic
A
, et al
.
Phosphatidylserine positive microparticles improve hemostasis in in-vitro hemophilia A plasma models
.
Sci Rep
.
2020
;
10
(
1
):
7871
.
76.
Guo
S-C
,
Tao
S-C
,
Yin
W-J
,
Qi
X
,
Yuan
T
,
Zhang
CQ
.
Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model
.
Theranostics
.
2017
;
7
(
1
):
81
-
96
.
77.
Kerris
EWJ
,
Hoptay
C
,
Calderon
T
,
Freishtat
RJ
.
Platelets and platelet extracellular vesicles in hemostasis and sepsis
.
J Investig Med
.
2020
;
68
(
4
):
813
-
820
.
78.
McVey
M
,
Tabuchi
A
,
Kuebler
WM
.
Microparticles and acute lung injury
.
Am J Physiol Lung Cell Mol Physiol
.
2012
;
303
(
5
):
L364
-
L381
.
79.
Peng
H
,
Li
H
,
Zhang
X
, et al
.
3D-exosomes laden multifunctional hydrogel enhances diabetic wound healing via accelerated angiogenesis
.
Chem Eng J
.
2023
;
475
:
146238
.
80.
Hu
X-M
,
Wang
C-C
,
Xiao
Y
,
Jiang
P
,
Liu
Y
,
Qi
ZQ
.
Enhanced wound healing and hemostasis with exosome-loaded gelatin sponges from human umbilical cord mesenchymal stem cells
.
World J Stem Cells
.
2023
;
15
(
9
):
947
-
959
.
81.
Lier
H
,
Krep
H
,
Schroeder
S
,
Stuber
F
.
Preconditions of hemostasis in trauma: a review. The influence of acidosis, hypocalcemia, anemia, and hypothermia on functional hemostasis in trauma
.
J Trauma
.
2008
;
65
(
4
):
951
-
960
.
82.
Xu
Y
,
Fang
Y
,
Ou
Y
, et al
.
Zinc metal–organic framework@chitin composite sponge for rapid hemostasis and antibacterial infection
.
ACS Sustain Chem Eng
.
2020
;
8
(
51
):
18915
-
18925
.
83.
Yang
E
,
Hou
W
,
Liu
K
, et al
.
A multifunctional chitosan hydrogel dressing for liver hemostasis and infected wound healing
.
Carbohydr Polym
.
2022
;
291
:
119631
.
84.
Kumar
A
,
Sah
DK
,
Khanna
K
, et al
.
A calcium and zinc composite alginate hydrogel for pre-hospital hemostasis and wound care
.
Carbohydr Polym
.
2023
;
299
:
120186
.
85.
Yu
X
,
Gao
Z
,
Mu
J
,
Lian
H
,
Meng
Z
.
Gelatin/calcium chloride electrospun nanofibers for rapid hemostasis
.
Biomater Sci
.
2023
;
11
(
6
):
2158
-
2166
.
86.
Li
X-F
,
Lu
P
,
Jia
H-R
, et al
.
Emerging materials for hemostasis
.
Coord Chem Rev
.
2023
;
475
:
214823
.
87.
Tian
G
,
Wang
W
,
Wang
Z
,
Wang
H
,
Zhu
C
,
Zhang
Y
.
Mixed silicates with three-dimensional micro-architecture toward accelerate the antibacterial hemostatic effects in wound healing
.
Colloids Surf Physicochem Eng Asp
.
2025
;
705
:
135644
.
88.
Horng
H-C
,
Chang
W-H
,
Yeh
C-C
, et al
.
Estrogen effects on wound healing
.
Int J Mol Sci
.
2017
;
18
(
11
):
2325
.
89.
Coleman
JR
,
Moore
EE
,
Sauaia
A
, et al
.
Untangling sex dimorphisms in coagulation: initial steps toward precision medicine for trauma resuscitation
.
Ann Surg
.
2020
;
271
(
6
):
e128
-
e130
.
90.
Coleman
JR
,
Moore
EE
,
Kelher
MR
, et al
.
Female platelets have distinct functional activity compared with male platelets: implications in transfusion practice and treatment of trauma-induced coagulopathy
.
J Trauma Acute Care Surg
.
2019
;
87
(
5
):
1052
-
1060
.
91.
Sabetta
A
,
Lombardi
L
,
Stefanini
L
.
Sex differences at the platelet–vascular interface
.
Intern Emerg Med
.
2022
;
17
(
5
):
1267
-
1276
.
92.
Kreutz
RP
,
Ipe
J
,
Skaar
TC
.
Sex specific differences of factor XI and relationship with other coagulation factors
.
Thromb Res
.
2023
;
226
:
156
-
158
.
93.
Simmons
A
,
Mihalek
O
,
Bimonte Nelson
HA
,
Sirianni
RW
,
Stabenfeldt
SE
.
Acute brain injury and nanomedicine: sex as a biological variable
.
Front Biomater Sci
.
2024
;
3
:
1348165
.
94.
Hargett
SE
,
Leslie
EF
,
Chapa
HO
,
Gaharwar
AK
.
Animal models of postpartum hemorrhage
.
Lab Anim
.
2024
;
53
(
4
):
93
-
106
.
95.
Gaharwar
AK
,
Singh
I
,
Khademhosseini
A
.
Engineered biomaterials for in situ tissue regeneration
.
Nat Rev Mater
.
2020
;
5
(
9
):
686
-
705
.
96.
Attard
C
,
Van Der Straaten
T
,
Karlaftis
V
,
Monagle
P
,
Ignjatovic
V
.
Developmental hemostasis: age-specific differences in the levels of hemostatic proteins
.
J Thromb Haemost
.
2013
;
11
(
10
):
1850
-
1854
.
97.
Alavi
P
,
Rathod
AM
,
Jahroudi
N
.
Age-associated increase in thrombogenicity and its correlation with von Willebrand factor
.
J Clin Med
.
2021
;
10
(
18
):
4190
.
98.
Nellenbach
K
,
Kyu
A
,
Guzzetta
N
,
Brown
AC
.
Differential sialic acid content in adult and neonatal fibrinogen mediates differences in clot polymerization dynamics
.
Blood Adv
.
2021
;
5
(
23
):
5202
-
5214
.
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