Introduction: Elevated plasma D-dimer has been observed in acute phase of subarachnoid hemorrhage (SAH), while a quantitative evaluation for the association between D-dimer level and prognosis of SAH remains lacking. The aim of the meta-analysis was to investigate the potential predictive role of D-dimer for the short-term functional outcome of patients with SAH. Methods: Relevant observational studies were retrieved by searching PubMed, Web of Science, Embase, Wanfang, and CNKI. A poor functional outcome was generally defined by the Glasgow Outcome Scale (1–3) or the modified Rankin Scale (≥3). A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. Results: Eleven studies involving 3,748 patients with SAH were included. Among them, 1,131 patients (30.2%) developed a poor functional outcome within 6 months. The pooled results showed that a higher plasma D-dimer at admission was associated with a higher risk of poor functional outcome during follow-up (odds ratio per 1 mg/L increment of D-dimer: 1.65, 95% confidence interval: 1.49–1.82, p < 0.001; I2 = 0%). Sensitivity analysis by excluding one study at a time showed similar results. Subgroup analyses suggested that the association between D-dimer and poor functional outcome of patients with SAH was not significantly affected by study design, country, mean age, proportion of men, follow-up duration, methods for defining poor outcome, study quality scores, timing of D-dimer measurement, or the publication year. Conclusion: A high plasma D-dimer at admission is associated with a poor short-term functional outcome of patients with SAH.

1.
Etminan
N
,
Chang
HS
,
Hackenberg
K
,
de Rooij
NK
,
Vergouwen
MDI
,
Rinkel
GJE
, et al
.
Worldwide incidence of aneurysmal subarachnoid hemorrhage according to region, time period, blood pressure, and smoking prevalence in the population: a systematic review and meta-analysis
.
JAMA Neurol
.
2019
;
76
(
5
):
588
97
.
2.
Robba
C
,
Busl
KM
,
Claassen
J
,
Diringer
MN
,
Helbok
R
,
Park
S
, et al
.
Contemporary management of aneurysmal subarachnoid haemorrhage. An update for the intensivist
.
Intensive Care Med
.
2024
;
50
(
5
):
646
64
.
3.
Rabinstein
AA
.
Subarachnoid hemorrhage
.
Neurology
.
2013
;
80
(
5
):
e56
9
.
4.
Maher
M
,
Schweizer
TA
,
Macdonald
RL
.
Treatment of spontaneous subarachnoid hemorrhage: guidelines and gaps
.
Stroke
.
2020
;
51
(
4
):
1326
32
.
5.
Custal
C
,
Koehn
J
,
Borutta
M
,
Mrochen
A
,
Brandner
S
,
Eyupoglu
IY
, et al
.
Beyond functional impairment: redefining favorable outcome in patients with subarachnoid hemorrhage
.
Cerebrovasc Dis
.
2021
;
50
(
6
):
729
37
.
6.
Neifert
SN
,
Chapman
EK
,
Martini
ML
,
Shuman
WH
,
Schupper
AJ
,
Oermann
EK
, et al
.
Aneurysmal subarachnoid hemorrhage: the last decade
.
Transl Stroke Res
.
2021
;
12
(
3
):
428
46
.
7.
Haapaniemi
E
,
Tatlisumak
T
.
Is D-dimer helpful in evaluating stroke patients? A systematic review
.
Acta Neurol Scand
.
2009
;
119
(
3
):
141
50
.
8.
Boluijt
J
,
Meijers
JC
,
Rinkel
GJ
,
Vergouwen
MD
.
Hemostasis and fibrinolysis in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review
.
J Cereb Blood Flow Metab
.
2015
;
35
(
5
):
724
33
.
9.
Franchini
M
,
Focosi
D
,
Pezzo
MP
,
Mannucci
PM
.
How we manage a high D-dimer
.
Haematologica
.
2024
;
109
(
4
):
1035
45
.
10.
Zhang
P
,
Wang
C
,
Wu
J
,
Zhang
S
.
A systematic review of the predictive value of plasma D-dimer levels for predicting stroke outcome
.
Front Neurol
.
2021
;
12
:
693524
.
11.
Zhang
H
,
Yao
J
,
Huang
Z
,
Zhao
Z
,
Wang
B
,
Zhao
J
.
Prognostic value of baseline d-dimer level in patients with coronary artery disease: a meta-analysis
.
Angiology
.
2022
;
73
(
1
):
18
25
.
12.
Hong
CM
,
Tosun
C
,
Kurland
DB
,
Gerzanich
V
,
Schreibman
D
,
Simard
JM
.
Biomarkers as outcome predictors in subarachnoid hemorrhage--a systematic review
.
Biomarkers
.
2014
;
19
(
2
):
95
108
.
13.
Page
MJ
,
Moher
D
,
Bossuyt
PM
,
Boutron
I
,
Hoffmann
TC
,
Mulrow
CD
, et al
.
PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews
.
BMJ
.
2021
;
372
:
n160
.
14.
Higgins
J
,
Thomas
J
,
Chandler
J
,
Cumpston
M
,
Li
T
,
Page
M
, et al
.
Cochrane Handbook for systematic reviews of interventions version 6.2
.
The Cochrane Collaboration
;
2021
. Available from: www.training.cochrane.org/handbook
15.
McMillan
T
,
Wilson
L
,
Ponsford
J
,
Levin
H
,
Teasdale
G
,
Bond
M
.
The Glasgow outcome scale - 40 years of application and refinement
.
Nat Rev Neurol
.
2016
;
12
(
8
):
477
85
.
16.
Banks
JL
,
Marotta
CA
.
Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis
.
Stroke
.
2007
;
38
(
3
):
1091
6
.
17.
Wells
GA
,
Shea
B
,
O’Connell
D
,
Peterson
J
,
Welch
V
,
Losos
M
, et al
.
The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses
.
2010
. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
18.
Higgins
JP
,
Thompson
SG
.
Quantifying heterogeneity in a meta-analysis
.
Stat Med
.
2002
;
21
(
11
):
1539
58
.
19.
Patsopoulos
NA
,
Evangelou
E
,
Ioannidis
JP
.
Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation
.
Int J Epidemiol
.
2008
;
37
(
5
):
1148
57
.
20.
Egger
M
,
Davey Smith
G
,
Schneider
M
,
Minder
C
.
Bias in meta-analysis detected by a simple, graphical test
.
BMJ
.
1997
;
315
(
7109
):
629
34
.
21.
Juvela
S
,
Siironen
J
.
D-dimer as an independent predictor for poor outcome after aneurysmal subarachnoid hemorrhage
.
Stroke
.
2006
;
37
(
6
):
1451
6
.
22.
Siironen
J
,
Porras
M
,
Varis
J
,
Poussa
K
,
Hernesniemi
J
,
Juvela
S
.
Early ischemic lesion on computed tomography: predictor of poor outcome among survivors of aneurysmal subarachnoid hemorrhage
.
J Neurosurg
.
2007
;
107
(
6
):
1074
9
.
23.
Wang
YL
,
Zeng
ZL
,
Yin
HL
,
Han
B
,
Zhang
H
,
Liu
YJ
, et al
.
Relationships between the concentrations of D-dimer and prognosis after intravascular embolization treatment with aneurismal subarachnoid hemorrhage
.
Chin J Pract Nerv Dis
.
2011
;
14
(
16
):
4
7
.
24.
Chugh
C
,
Nyirjesy
SC
,
Nawalinski
KP
,
Sandsmark
DK
,
Frangos
S
,
Maloney-Wilensky
E
, et al
.
Red blood cell distribution width is associated with poor clinical outcome after subarachnoid hemorrhage: a pilot study
.
Neurocrit Care
.
2015
;
23
(
2
):
217
24
.
25.
Dong
WW
,
Li
XX
,
Wang
WQ
,
Diao
HY
,
Liu
YH
.
Elevated markers of early fibrinolysis disorder as predictors of poor 90-day prognosis in patients with aneurysmal subarachnoid hemorrhage: a large prospective cohort study
.
J Chin Physician
.
2017
;
19
(
11
):
1641
4
.
26.
Fukuda
H
,
Lo
B
,
Yamamoto
Y
,
Handa
A
,
Kurosaki
Y
,
Yamagata
S
, et al
.
Plasma D-dimer may predict poor functional outcomes through systemic complications after aneurysmal subarachnoid hemorrhage
.
J Neurosurg
.
2017
;
127
(
2
):
284
90
.
27.
Liu
JH
,
Li
XK
,
Chen
ZB
,
Cai
Q
,
Wang
L
,
Ye
YH
, et al
.
D-dimer may predict poor outcomes in patients with aneurysmal subarachnoid hemorrhage: a retrospective study
.
Neural Regen Res
.
2017
;
12
(
12
):
2014
20
.
28.
Chen
C
,
Xie
YR
,
Shen
SB
,
Cong
MM
,
He
C
.
Correlation analysis of D-dimer, C-reactive protein and ischemic modified albumin with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage
.
Cardio Cerebrovasc Dis Prev Treat
.
2022
;
22
(
6
):
56
60
.
29.
Zhang
RJ
,
Yan
SY
,
Hu
X
,
Li
H
,
Liu
Y
,
Wu
C
, et al
.
Effect of D-dimer on the prognosis of patients with aneurysmal subarachnoid hemorrhage based on propensity score matching
.
Zhonghua Yixue Zazhi
.
2022
;
102
(
29
):
2256
64
.
30.
Li
T
,
Zhang
J
,
Li
R
,
Lin
F
,
Chen
Y
,
Yang
J
, et al
.
Elevated markers of early fibrinolysis disorder as predictors of poor 90-day prognosis in patients with aneurysmal subarachnoid hemorrhage: a large prospective cohort study
.
J Stroke Cerebrovasc Dis
.
2023
;
32
(
12
):
107433
.
31.
Qiu
W
,
Li
W
,
Xu
K
,
Zhu
G
,
Luo
H
,
Deng
Y
, et al
.
Prognostic significance of fibrinogen and neutrophil/lymphocyte ratio score and D-dimer/Albumin ratio for prognosis in patients with aneurysmal subarachnoid hemorrhage
.
J Stroke Cerebrovasc Dis
.
2023
;
32
(
11
):
107338
.
32.
Hokari
M
,
Shimbo
D
,
Uchida
K
,
Gekka
M
,
Asaoka
K
,
Itamoto
K
.
Characteristics of MRI findings after subarachnoid hemorrhage and D-dimer as a predictive value for early brain injury
.
J Stroke Cerebrovasc Dis
.
2022
;
31
(
1
):
106073
.
33.
Hao
Z
,
Wei
J
,
Li
X
,
Wei
W
,
Pan
Y
,
Chen
C
, et al
.
Inflammation-associated D-dimer predicts neurological outcome of recent small subcortical infarct: a prospective clinical and laboratory study
.
Clin Neurol Neurosurg
.
2024
;
237
:
108126
.
34.
Hileman
CO
,
Longenecker
CT
,
Carman
TL
,
Milne
GL
,
Labbato
DE
,
Storer
NJ
, et al
.
Elevated D-dimer is independently associated with endothelial dysfunction: a cross-sectional study in HIV-infected adults on antiretroviral therapy
.
Antivir Ther
.
2012
;
17
(
7
):
1345
9
.
35.
Hurth
H
,
Birkenhauer
U
,
Steiner
J
,
Schlak
D
,
Hennersdorf
F
,
Ebner
FH
.
Delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage - serum D-dimer and C-reactive protein as early markers
.
J Stroke Cerebrovasc Dis
.
2020
;
29
(
3
):
104558
.
36.
Fukuda
H
,
Handa
A
,
Koyanagi
M
,
Lo
B
,
Yamagata
S
.
Association of plasma D-dimer level with thromboembolic events after endovascular coil treatment of ruptured cerebral aneurysms
.
J Neurosurg
.
2018
;
130
(
2
):
509
16
.
37.
Zhang
C
,
Zhu
J
,
Zhang
M
,
Yuan
Z
,
Wang
X
,
Ye
C
, et al
.
Prognostic nomogram for predicting lower extremity deep venous thrombosis in ruptured intracranial aneurysm patients who underwent endovascular treatment
.
Front Neurol
.
2023
;
14
:
1202076
.
38.
Fang
F
,
Wang
P
,
Yao
W
,
Wang
X
,
Zhang
Y
,
Chong
W
, et al
.
Association between D-dimer levels and long-term mortality in patients with aneurysmal subarachnoid hemorrhage
.
Neurosurg Focus
.
2022
;
52
(
3
):
E8
.
You do not currently have access to this content.