Abstract

Malignancy is associated with a high risk of venous thromboembolism (VTE), and treatment with anticoagulant therapy is associated with a high risk of bleeding. Thus, accurate and timely VTE diagnosis in cancer patients is essential for identifying individuals who would benefit from anticoagulant therapy and for avoiding unnecessary treatment that can cause anticoagulant-related bleeding. The approach to the diagnosis of VTE in non-cancer patients involves a stepwise process beginning with an assessment of the pretest probability (PTP) of VTE using a validated clinical prediction rule (CPR) followed by D-dimer testing and/or diagnostic imaging. In patients with a low PTP and a negative D-dimer result, VTE can be excluded without additional imaging. However, published data suggest that CPRs and D-dimer testing may not be as accurate or as useful in patients with cancer. Studies have shown that the combination of a low PTP and negative D-dimer result is not efficient for exclusion of deep vein thrombosis (DVT) or pulmonary embolism (PE) in the cancer patient population because the vast majority of patients still require radiologic imaging. We propose that cancer patients with suspected VTE should proceed directly to radiologic imaging to confirm or exclude a diagnosis of DVT or PE.

References

References
1.
Khorana
AA
,
Dalal
M
,
Lin
J
,
Connolly
GC
.
Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States
.
Cancer
.
2013
;
119
(
3
):
648
-
655
.
2.
Horsted
F
,
West
J
,
Grainge
MJ
.
Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis
.
PLoS Med
.
2012
;
9
(
7
):
e1001275
.
3.
Prandoni
P
,
Lensing
AW
,
Piccioli
A
, et al
.
Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis
.
Blood
.
2002
;
100
(
10
):
3484
-
3488
.
4.
Kuderer
NM
,
Ortel
TL
,
Francis
CW
.
Impact of venous thromboembolism and anticoagulation on cancer and cancer survival
.
J Clin Oncol
.
2009
;
27
(
29
):
4902
-
4911
.
5.
Khorana
AA
,
Francis
CW
,
Culakova
E
,
Kuderer
NM
,
Lyman
GH
.
Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy
.
J Thromb Haemost
.
2007
;
5
(
3
):
632
-
634
.
6.
Lim
W
,
Le Gal
G
,
Bates
SM
, et al
.
American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism
.
Blood Adv
.
2018
;
2
(
22
):
3226
-
3256
.
7.
van Beek
EJ
,
Brouwerst
EM
,
Song
B
,
Stein
PD
,
Oudkerk
M
.
Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism--a critical review
.
Clin Radiol
.
2001
;
56
(
10
):
838
-
842
.
8.
Hull
R
,
Hirsh
J
,
Sackett
DL
, et al
.
Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis
.
Circulation
.
1981
;
64
(
3
):
622
-
625
.
9.
Ceriani
E
,
Combescure
C
,
Le Gal
G
, et al
.
Clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis
.
J Thromb Haemost
.
2010
;
8
(
5
):
957
-
970
.
10.
Lucassen
W
,
Geersing
GJ
,
Erkens
PM
, et al
.
Clinical decision rules for excluding pulmonary embolism: a meta-analysis
.
Ann Intern Med
.
2011
;
155
(
7
):
448
-
460
.
11.
Ten Cate-Hoek
AJ
,
Prins
MH
.
Management studies using a combination of D-dimer test result and clinical probability to rule out venous thromboembolism: a systematic review
.
J Thromb Haemost
.
2005
;
3
(
11
):
2465
-
2470
.
12.
Geersing
GJ
,
Zuithoff
NP
,
Kearon
C
, et al
.
Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis
.
BMJ
.
2014
;
348
:
g1340
.
13.
van Es
N
,
van der Hulle
T
,
van Es
J
, et al
.
Wells rule and D-dimer testing to rule out pulmonary embolism: A systematic review and individual-patient data meta-analysis
.
Ann Intern Med
.
2016
;
165
(
4
):
253
-
261
.
14.
Douma
RA
,
van Sluis
GL
,
Kamphuisen
PW
, et al
.
Clinical decision rule and D-dimer have lower clinical utility to exclude pulmonary embolism in cancer patients. Explanations and potential ameliorations
.
Thromb Haemost
.
2010
;
104
(
4
):
831
-
836
.
15.
Carrier
M
,
Lee
AY
,
Bates
SM
,
Anderson
DR
,
Wells
PS
.
Accuracy and usefulness of a clinical prediction rule and D-dimer testing in excluding deep vein thrombosis in cancer patients
.
Thromb Res
.
2008
;
123
(
1
):
177
-
183
.
16.
Di Nisio
M
,
Rutjes
AW
,
Büller
HR
.
Combined use of clinical pretest probability and D-dimer test in cancer patients with clinically suspected deep venous thrombosis
.
J Thromb Haemost
.
2006
;
4
(
1
):
52
-
57
.
17.
Schutgens
RE
,
Beckers
MM
,
Haas
FJ
,
Biesma
DH
.
The predictive value of D-dimer measurement for cancer in patients with deep vein thrombosis
.
Haematologica
.
2005
;
90
(
2
):
214
-
219
.
18.
Knowlson
L
,
Bacchu
S
,
Paneesha
S
,
McManus
A
,
Randall
K
,
Rose
P
.
Elevated D-dimers are also a marker of underlying malignancy and increased mortality in the absence of venous thromboembolism
.
J Clin Pathol
.
2010
;
63
(
9
):
818
-
822
.
19.
Posch
F
,
Riedl
J
,
Reitter
EM
, et al
.
Hypercoagulabilty, venous thromboembolism, and death in patients with cancer. A multi-state model
.
Thromb Haemost
.
2016
;
115
(
4
):
817
-
826
.
20.
Riley
RS
,
Gilbert
AR
,
Dalton
JB
,
Pai
S
,
McPherson
RA
.
Widely used types and clinical applications of D-dimer assay
.
Lab Med
.
2016
;
47
(
2
):
90
-
102
.
21.
Lee
AY
,
Julian
JA
,
Levine
MN
, et al
.
Clinical utility of a rapid whole-blood D-dimer assay in patients with cancer who present with suspected acute deep venous thrombosis
.
Ann Intern Med
.
1999
;
131
(
6
):
417
-
423
.
22.
Bates
SM
,
Grand’Maison
A
,
Johnston
M
,
Naguit
I
,
Kovacs
MJ
,
Ginsberg
JS
.
A latex D-dimer reliably excludes venous thromboembolism
.
Arch Intern Med
.
2001
;
161
(
3
):
447
-
453
.
23.
Bates
SM
,
Kearon
C
,
Crowther
M
, et al
.
A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis
.
Ann Intern Med
.
2003
;
138
(
10
):
787
-
794
.
24.
Di Nisio
M
,
Sohne
M
,
Kamphuisen
PW
,
Büller
HR
.
D-Dimer test in cancer patients with suspected acute pulmonary embolism
.
J Thromb Haemost
.
2005
;
3
(
6
):
1239
-
1242
.
25.
Righini
M
,
Le Gal
G
,
De Lucia
S
, et al
.
Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism
.
Thromb Haemost
.
2006
;
95
(
4
):
715
-
719
.
26.
Schutgens
RE
,
Esseboom
EU
,
Haas
FJ
,
Nieuwenhuis
HK
,
Biesma
DH
.
Usefulness of a semiquantitative D-dimer test for the exclusion of deep venous thrombosis in outpatients
.
Am J Med
.
2002
;
112
(
8
):
617
-
621
.
27.
Shitrit
D
,
Levi
H
,
Huerta
M
,
Rudensky
B
,
Bargil-Shitrit
A
,
Gutterer
N
.
Appropriate indications for venous duplex scanning based on D-dimer assay
.
Ann Vasc Surg
.
2002
;
16
(
3
):
304
-
308
.
28.
ten Wolde
M
,
Kraaijenhagen
RA
,
Prins
MH
,
Büller
HR
.
The clinical usefulness of D-dimer testing in cancer patients with suspected deep venous thrombosis
.
Arch Intern Med
.
2002
;
162
(
16
):
1880
-
1884
.
29.
Haase
C
,
Joergensen
M
,
Ellervik
C
,
Joergensen
MK
,
Bathum
L
.
Age- and sex-dependent reference intervals for D-dimer: evidence for a marked increase by age
.
Thromb Res
.
2013
;
132
(
6
):
676
-
680
.
30.
Takach Lapner
S
,
Stevens
SM
,
Woller
SC
,
Snow
G
,
Kearon
C
.
Age-adjusted versus clinical probability-adjusted D-dimer to exclude pulmonary embolism
.
Thromb Res
.
2018
;
167
:
15
-
19
.
31.
Righini
M
,
Van Es
J
,
Den Exter
PL
, et al
.
Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study
.
JAMA
.
2014
;
311
(
11
):
1117
-
1124
.
32.
Wilts
IT
,
Le Gal
G
,
Den Exter
PL
, et al
.
Performance of the age-adjusted cut-off for D-dimer in patients with cancer and suspected pulmonary embolism
.
Thromb Res
.
2017
;
152
:
49
-
51
.
33.
Streiff
MB
,
Holmstrom
B
,
Angelini
A
, et al
.
Cancer-associated venous thromboembolic disease, version 1.2019. https://nccn.org/professional/physician_gls/pdf/vte.pdf. Accessed 29 May 2019
.
You do not currently have access to this content.