Background: Danaparoid sodium and synthetic protease inhibitors (SPIs) have been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan. Objectives: To compare the clinical results of the treatment of DIC with danaparoid or SPIs. Methods: We retrospectively examined 188 patients with hematological malignancy-related DIC. Results: DIC resolution rate in the danaparoid group was higher than that in the SPIs group (61.5 vs. 42.6%; p = 0.031) on day 7. Multivariate analysis identified the response to chemotherapy as independent predictive factor for DIC resolution on day 7 (odds ratio, OR, 2.28; 95% confidence interval, CI, 1.21–4.31; p = 0.011). While there was no significant difference in the DIC resolution rate on day 14 (75.0 vs. 62.4%; p = 0.117), in a subgroup analysis of patients who did not show an improvement in the underlying disease, the danaparoid group showed a significantly better DIC resolution rate (OR 3.89; 95% CI 1.15–13.2; p = 0.030). There was no difference in the rate of cumulative mortality from bleeding within 28 days between the 2 groups (6.6 vs. 3.3%; p = 0.278). Conclusions: Danaparoid may be associated with more frequent resolution of DIC in patients with refractory underlying disease.

1.
Asakura
H
,
Takahashi
H
,
Uchiyama
T
,
Eguchi
Y
,
Okamoto
K
,
Kawasugi
K
, et al;
DIC subcommittee of the Japanese Society on Thrombosis and Hemostasis
.
Proposal for new diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis
.
Thromb J
.
2016
Sep
;
14
(
1
):
42
.
[PubMed]
1477-9560
2.
Wada
H
,
Asakura
H
,
Okamoto
K
,
Iba
T
,
Uchiyama
T
,
Kawasugi
K
, et al;
Japanese Society of Thrombosis Hemostasis/DIC subcommittee
.
Expert consensus for the treatment of disseminated intravascular coagulation in Japan
.
Thromb Res
.
2010
Jan
;
125
(
1
):
6
11
.
[PubMed]
0049-3848
3.
Levi
M
,
Ten Cate
H
.
Disseminated intravascular coagulation
.
N Engl J Med
.
1999
Aug
;
341
(
8
):
586
92
.
[PubMed]
0028-4793
4.
Gando
S
.
Microvascular thrombosis and multiple organ dysfunction syndrome
.
Crit Care Med
.
2010
Feb
;
38
(
2
Suppl
):
S35
42
.
[PubMed]
0090-3493
5.
Wada
H
,
Thachil
J
,
Di Nisio
M
,
Mathew
P
,
Kurosawa
S
,
Gando
S
, et al
The Scientific Standardization Committee on DIC of the International Society on Thrombosis Haemostasis. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines
.
J Thromb Haemost
.
2013
;
11
:
761
7
. 1538-7933
6.
Wada
H
,
Matsumoto
T
,
Yamashita
Y
.
Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines
.
J Intensive Care
.
2014
Feb
;
2
(
1
):
15
.
[PubMed]
2052-0492
7.
Ibbotson
T
,
Perry
CM
.
Danaparoid: a review of its use in thromboembolic and coagulation disorders
.
Drugs
.
2002
;
62
(
15
):
2283
314
.
[PubMed]
0012-6667
8.
Bradbrook
ID
,
Magnani
HN
,
Moelker
HC
,
Morrison
PJ
,
Robinson
J
,
Rogers
HJ
, et al
ORG 10172: a low molecular weight heparinoid anticoagulant with a long half-life in man
.
Br J Clin Pharmacol
.
1987
Jun
;
23
(
6
):
667
75
.
[PubMed]
0306-5251
9.
Yasunaga
K
,
Ogawa
N
,
Mori
K
,
Aoki
N
,
Matsuda
T
,
Nakagawa
M
, et al
Evaluation of clinical effect of danaparoid sodium (KB-101) on disseminated intravascular coagulation (DIC): double blind comparative study
.
Jpn Pharmacol Ther.
1995
;
23
:
2815
34
.
10.
Ohno
H
,
Kosaki
G
,
Kambayashi
J
,
Imaoka
S
,
Hirata
F
.
FOY: [ethyl P-(6-guanidinohexanoyloxy) benzoate] methanesulfonate as a serine proteinase inhibitor. I. Inhibition of thrombin and factor Xa in vitro
.
Thromb Res
.
1980
Aug
;
19
(
4-5
):
579
88
.
[PubMed]
0049-3848
11.
Hitomi
Y
,
Ikari
N
,
Fujii
S
.
Inhibitory effect of a new synthetic protease inhibitor (FUT-175) on the coagulation system
.
Haemostasis
.
1985
;
15
(
3
):
164
8
.
[PubMed]
0301-0147
12.
Minakata
D
,
Fujiwara
SI
,
Ikeda
T
,
Kawaguchi
SI
,
Toda
Y
,
Ito
S
, et al
Comparison of gabexate mesilate and nafamostat mesilate for disseminated intravascular coagulation associated with hematological malignancies
.
Int J Hematol
.
2019
Feb
;
109
(
2
):
141
6
.
[PubMed]
0925-5710
13.
Kobayashi
N
,
Maekawa
T
,
Takada
M
,
Tanaka
H
,
Gonmori
H
.
Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan
.
Bibl Haematol
.
1983
;
49
(
49
):
265
75
.
[PubMed]
0067-7957
14.
Asakura
H
.
Classifying types of disseminated intravascular coagulation: clinical and animal models
.
J Intensive Care
.
2014
Mar
;
2
(
1
):
20
.
[PubMed]
2052-0492
15.
Saito
H
,
Maruyama
I
,
Shimazaki
S
,
Yamamoto
Y
,
Aikawa
N
,
Ohno
R
, et al
Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial
.
J Thromb Haemost
.
2007
Jan
;
5
(
1
):
31
41
.
[PubMed]
1538-7933
16.
Kanda
Y
.
Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics
.
Bone Marrow Transplant
.
2013
Mar
;
48
(
3
):
452
8
.
[PubMed]
0268-3369
17.
Yu
M
,
Nardella
A
,
Pechet
L
.
Screening tests of disseminated intravascular coagulation: guidelines for rapid and specific laboratory diagnosis
.
Crit Care Med
.
2000
Jun
;
28
(
6
):
1777
80
.
[PubMed]
0090-3493
18.
Kosaki
G
,
Kambayashi
J
,
Hirabayashi
A
,
Mori
K
,
Uchida
T
,
Abe
T
, et al
Evaluation of clinical effect of FOY on DIC: multi-center clinical comparative study
.
Igaku No Ayumi
.
1983
;
124
:
144
54
.0039-2359
19.
Shibata
S
,
Takahashi
H
,
Aoki
N
,
Takahashi
H
,
Aoki
N
,
Matsuda
T
, et al
Evaluation of clinical effect of FUT-175 on DIC: multi-center clinical comparative study
.
Rinsho To Kenkyu
.
1988
;
65
:
921
40
.0021-4965
20.
Sakuragawa
N
,
Hasegawa
H
,
Maki
M
,
Nakagawa
M
,
Nakashima
M
.
Clinical evaluation of low-molecular-weight heparin (FR-860) on disseminated intravascular coagulation (DIC)—a multicenter co-operative double-blind trial in comparison with heparin
.
Thromb Res
.
1993
Dec
;
72
(
6
):
475
500
.
[PubMed]
0049-3848
21.
Aoki
N
,
Matsuda
T
,
Saito
H
,
Takatsuki
K
,
Okajima
K
,
Takahashi
H
, et al;
CTC-111-IM Clinical Research Group
.
A comparative double-blind randomized trial of activated protein C and unfractionated heparin in the treatment of disseminated intravascular coagulation
.
Int J Hematol
.
2002
Jun
;
75
(
5
):
540
7
.
[PubMed]
0925-5710
22.
Ikezoe
T
,
Takeuchi
A
,
Isaka
M
,
Arakawa
Y
,
Iwabu
N
,
Kin
T
, et al
Recombinant human soluble thrombomodulin safely and effectively rescues acute promyelocytic leukemia patients from disseminated intravascular coagulation
.
Leuk Res
.
2012
Nov
;
36
(
11
):
1398
402
.
[PubMed]
0145-2126
23.
Takezako
N
,
Sekiguchi
N
,
Nagata
A
,
Homma
C
,
Takezako
Y
,
Noto
S
, et al
Recombinant human thrombomodulin in the treatment of acute myeloid leukemia patients complicated by disseminated intravascular coagulation: retrospective analysis of outcomes between patients treated with heparin and recombinant human thrombomodulin therapy
.
Thromb Res
.
2015
Jul
;
136
(
1
):
20
3
.
[PubMed]
0049-3848
24.
Aota
T
,
Wada
H
,
Yamashita
Y
,
Matsumoto
T
,
Ohishi
K
,
Suzuki
K
, et al
The efficacy of the administration of recombinant human soluble thrombomodulin in patients with DIC
.
Int J Hematol
.
2016
Feb
;
103
(
2
):
173
9
.
[PubMed]
0925-5710
25.
Yokoyama
H
,
Takahashi
N
,
Katsuoka
Y
,
Inomata
M
,
Ito
T
,
Meguro
K
, et al;
Tohoku Hematology Forum
.
Evaluation of the safety and efficacy of recombinant soluble thrombomodulin for patients with disseminated intravascular coagulation associated with acute leukemia: multicenter prospective study by the Tohoku Hematology Forum
.
Int J Hematol
.
2017
May
;
105
(
5
):
606
13
.
[PubMed]
0925-5710
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.