Open Access

The approval of revised diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis

  • Hideo Wada1Email author,
  • Hoyu Takahashi2,
  • Toshimasa Uchiyama3,
  • Yutaka Eguchi4,
  • Kohji Okamoto5,
  • Kazuo Kawasugi6,
  • Seiji Madoiwa7,
  • Hidesaku Asakura8 and
  • DIC subcommittee of the Japanese Society on Thrombosis and Hemostasis
Thrombosis Journal201715:17

https://doi.org/10.1186/s12959-017-0142-4

Received: 15 May 2017

Accepted: 27 June 2017

Published: 3 July 2017

Abstract

As proposed diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis has been approved and revised, the contents and changes are informed.

Keywords

DICJSTHDiagnostic criteriaHemostatic molecular markers

Although disseminated intravascular coagulation (DIC) is a serious disease, there is no gold standard for its diagnosis, no single biomarker by which DIC can be clearly diagnosed, and no anticoagulants have been recommended for the treatment of DIC in worldwide [1]. We reviewed the diagnostic criteria for DIC including the newly proposed diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis (JSTH) [2, 3]. Three diagnostic criteria for DIC have been established by the Japanese Ministry of Health and Welfare (JMHW) [4], the International Society of Thrombosis and Haemostasis [5] and the Japanese Association for Acute Medicine [6]. The three diagnostic criteria involve a scoring system based on the results of global coagulation tests (GCTs) such as the platelet count, prothrombin time (PT), fibrinogen and fibrin-related markers. Thus, there were no significant differences in the usefulness among three different diagnostic criteria for DIC [7].

For this reason, the JSTH proposed a provisional draft of the DIC diagnostic criteria, which used the classifications of “hematopoietic disorder type” which omitted the platelet count score, “infectious type” which omitted the fibrinogen score, and “basic type” based on the underlying pathology [2, 3]. An additional point was added to the GCTs scoring system if the platelet count decreased with time, and molecular markers and the antithrombin (AT) activity were added to the new criteria. To protect against misdiagnosis, 3 points were deducted if a patient had liver failure.

After the drafting of the proposed criteria [3], several evaluations were carried out to examine the issues associated with the diagnosis of the three types of DIC [810]. 1) What is the most useful combination for diagnosing DIC? The combination of GCTs, decreased platelet count, AT, increased soluble fibrin (SF), thrombin AT complex (TAT) or prothrombin complex F1 + 2 (F1 + 2) scores had the highest area under the curve (ARC) values and odds ratio in a analysis [810]. 2) Can this scoring system diagnose early-phase DIC? The JSTH diagnostic criteria could diagnose DIC several days before its onset (as defined by the JMHW criteria). 3) What score is appropriate for making a diagnosis of DIC? The ROC analysis revealed that a score of 4 points was an adequate cutoff value for hematopoietic disorder-type DIC {area under the curve (AUC) 0.979; sensitivity 97.2%; specificity 96.0%; positive predictive value (PPV) 95.4; negative predictive value (NPV) 97.6% and odd’s ratio 832} [8], while a score of 5 points (instead of the 6 points in the previous criteria) [2, 3] was suitable for the diagnosis of infectious-type DIC {AUC 0.984; sensitivity 93.7%; specificity 97.8%; positive predictive value (PPV) 98.3; negative predictive value (NPV) 91.7% and odd’s ratio 649} [9] and a score of 6 points was suitable for the diagnosis of basic-type DIC [10] {AUC 0.987; sensitivity 98.4%; specificity 94.8%; positive predictive value (PPV) 91.2; negative predictive value (NPV) 99.1% and odd’s ratio 1137}. 4) Can these diagnostic criteria predict a poor outcome? Although these diagnostic criteria can predict a poor outcome (odds ratio 2–3), there were no significant differences in the odds ratios of any of the combinations [811]. Thus, these diagnostic criteria have been approved as JSTH diagnostic criteria (Table 1) [12].
Table 1

JSTH’s DIC diagnostic criteria

 

Classification of type

Basic

Hematopoietic disorder

Infectious

GCTs

Platelet count (×103/μl)

>120

0 p

 

>120

0 p

80 < − ≤ 120

1 p

80 < − ≤ 120

1 p

50 < − ≤ 80

2 p

50 < − ≤ 80

2 p

≤50

3 p

≤50

3 p

≥30% decrease w/in 24 h (*1)

+1 p

≥30% decrease w/in 24 h (*1)

+1 p

FDP

(μg/ml)

<10

0 p

<10

0 p

<10

0 p

10 ≤ − < 20

1 p

10 ≤ − < 20

1 p

10 ≤ − < 20

1 p

20 ≤ − < 40

2 p

20 ≤ − < 40

2 p

20 ≤ − < 40

2 p

≥40

3 p

≥40

3 p

≥40

3 p

Fibrinogen

(mg/dl)

>150

0 p

>150

0 p

 

100 < − ≤ 150

1 p

100 < − ≤ 150

1 p

≤100

2 p

≤100

2 p

Prothrombin time ratio

<1.25

0 p

<1.25

0 p

<1.25

0 p

1.25 ≤ − < 1.67

1 p

1.25 ≤ − < 1.67

1 p

1.25 ≤ − < 1.67

1 p

≥1.67

2 p

≥1.67

2 p

≥1.67

2 p

HMMs

Antithrombin

(%)

>70

0 p

>70

0 p

>70

0 p

≤70

1 p

≤70

1 p

≤70

1 p

TAT, SF or F1+2

<2-fold of normal upper limit

0 p

<2-fold of normal upper limit

0 p

<2-fold of normal upper limit

0 p

≥2-fold of normal upper limit

1 p

≥2-fold of normal upper limit

1 p

≥2-fold of normal upper limit

1 p

Liver failure

(*2)

No

0 p

No

0 p

No

0 p

Yes

−3 p

Yes

−3 p

Yes

−3 p

DIC diagnosis

≥6 p

≥4 p

≥5 p

Abbreviations: p points, GCT:global coagulation tests, HMMs hemostatic molecular markers

(*1): For a platelet count of >50 × 103/μL, points will be added if the time-course conditions of decrease are met (no points will be added for a platelet count of ≤50 × 103/μL). The maximum score for the platelet count is 3 points.

For institutions that do not measure FDP (institutions that measure only D-dimer), 1 point will be added if D-dimer increases ≥2-fold the normal upper limit. The upper limit of D-dimer is different among various D-dimer kits. However, in principle, FDP should also be measured and re-evaluation performed after the results are in hand. Fibrinogen levels are usually measured using thrombin time method in Japan.

DIC may be excluded in case within normal range of FDP or D-dimer.

Prothrombin time ratio: If ISI is close to 1.0, INR will also be acceptable (However, there is no evidence supporting recommendation of the use of PT-INR for diagnosis of DIC.). For determination of PT ratio, it is recommended to use normal pooled plasma.

DIC may be excluded in case with elevated prothrombin time ratio due to vitamin K deficiency.

Thrombin-antithrombin complex (TAT), soluble fibrin (SF), prothrombin fragment 1 + 2 (F1+2): For blood sampling in difficult cases and route blood sampling, false-high values may increase. Thus, in comparison with elevation of FDP and/or D-dimer, re-testing should be done if TAT and/or SF is markedly elevated. Confirmation is needed even if the results on the same day are not in time. Normal reference range is 56–213 pmol/L in F1+2, 0–3.2 μg/ml in SF and 0.3–1.5 ng/ml in TAT in Mie University Hospital.

Regardless of the presence or absence of DIC immediately after surgery, changes in DIC-like markers such as elevation of TAT, SF, FDP, or D-dimer or a decrease in AT, may be observed, and judgment should be made with care.

(*2) Liver failure: Corresponds to “a prothrombin time activity of ≤40% or an INR value of ≥1.5 due to severe liver dysfunction seen within 8 weeks of onset of initial symptoms following liver impairment that develops in a normal liver or a liver that is thought to exhibit normal liver function” (acute liver failure) or “cirrhosis with a Child-Pugh classification of B or C (≥7 points)” (chronic liver failure) that may be viral or autoimmune in origin, drug-induced, or caused by circulatory failure.”

Even when DIC is strongly suspected but these diagnostic criteria are not met, there should be no interference with anti-coagulation therapy based on the physician’s judgment, but repeated evaluation is necessary

In conclusion, the JSTH diagnostic criteria for DIC have been revised and approved: Infectious-type DIC is now diagnosed based on a score of 5 points instead of 6 points.

Abbreviations

ARC: 

Area under the curve

AT: 

AntithrombinSF

Soluble fibrin

DIC: 

Disseminated intravascular coagulation

F1+2

Prothrombin fragment 1 + 2

GCTs: 

Global coagulation tests

JMHW: 

Japanese Ministry of Health and Welfare

JSTH: 

Japanese Society on Thrombosis and Hemostasis

PT: 

Prothrombin time

ROC: 

Receiver operating characteristic curve

TAT: 

Thrombin-antithrombin complex

Declarations

Acknowledgements

None.

Funding

Meeting expenses were funded by Japanese Society on Thrombosis and Hemostasis. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Availability of data and materials

This review paper includes some of the material contained in a Japanese- language report that was published in Jpn J Thromb Hemost (Ref. [3, 12]).

Authors’ contributions

HA, HT, TU, YE, KO, KK, SM and HW made substantial contributions to the conception of the manuscript, revised the manuscript critically for important intellectual content, provided final approval of the version to be submitted. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests with this article. They neither benefited from any source of funding nor sponsorship.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine
(2)
Department of Internal Medicine, Niigata Prefectural Kamo Hospital
(3)
Department of Laboratory Medicine, National Hospital Organization Takasaki General Medical Center
(4)
Department of Critical and Intensive Care Medicine, Shiga University of Medical Science
(5)
Gastroenterology and Hepatology Center, Kitakyushu City Yahata Hospital
(6)
Department of Hematology, Teikyo University School of Medicine
(7)
Department of Clinical and Laboratory Medicine, Tokyo Saiseikai Central Hospital
(8)
Department of Internal Medicine (III), Kanazawa University School of Medicine

References

  1. Wada H, Matsumoto T, Yamashita Y, Hatada T. Disseminated intravascular coagulation: testing and diagnosis. Clin Chim Acta. 2014;436C:130–4.View ArticleGoogle Scholar
  2. Asakura H, Takahashi H, Uchiyama T, Eguchi Y, Okamoto K, Kawasugi K, Madoiwa S, Wada H. 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;14:42. ReviewView ArticlePubMedPubMed CentralGoogle Scholar
  3. Japanese Society on Thrombosis and Hemostasis/DIC subcommittee. Diagnostic criteria for disseminated intravascular coagulation by the Japanese Society on Thrombosis and Hemostasis -tentative criteria. Jpn J Thromb Hemost. 2014;25:629–646.(in Japanese).Google Scholar
  4. 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;49:265–75.Google Scholar
  5. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M. Scientific subcommittee on disseminated intravascular coagulation (DIC) of the international Society on Thrombosis and Haemostasis (ISTH): towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86:1327–30.PubMedGoogle Scholar
  6. Gando S, Saitoh D, Ogura H, Mayumi T, Koseki K, Ikeda T, et al. Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) study group: natural history of disseminated intravascular coagulation diagnosed based on the newly established diagnostic criteria for critically ill patients: results of a multicenter, prospective survey. Crit Care Med. 2008;36:145–50.View ArticlePubMedGoogle Scholar
  7. Takemitsu T, Wada H, Hatada T, Ohmori Y, Ishikura K, Takeda T, et al. Prospective evaluation of three different diagnostic criteria for disseminated intravascular coagulation. Thromb Haemost. 2011;105:40–4.View ArticlePubMedGoogle Scholar
  8. Aota T, Wada H, Yamashita Y, Matsumoto T, Ohishi K, Suzuki K, Imai H, Usui M, Isaji S, Asakura H, Okamoto K, Katayama N. An Evaluation of the Modified Diagnostic Criteria for DIC Established by the Japanese Society of Thrombosis and Hemostasis. Clin Appl Thromb Hemost. 2016. [Epub ahead of print].Google Scholar
  9. Aota T, Wada H, Fujimoto N, Sugimoto K, Yamashita Y, Matsumoto T, Ohishi K, Suzuki K, Imai H, Kawasugi K, Madoiwa S, Asakura H, Katayama N. The valuable diagnosis of DIC and pre-DIC and prediction of a poor outcome by the evaluation of diagnostic criteria for DIC in patients with hematopoietic injury established by the Japanese Society of Thrombosis and Hemostasis. Thromb Res. 2016;147:80–4.View ArticlePubMedGoogle Scholar
  10. Aota T, Wada H, Fujimoto N, Yamashita Y, Matsumoto T, Ohishi K, Suzuki K, Imai H, Usui M, Isaji S, Uchiyama T, Seki Y, Katayama N: Evaluation of the Diagnostic Criteria for the Basic Type of DIC Established by the Japanese Society of Thrombosis and Hemostasis. Clin Appl Thromb Hemost. 2016. [Epub ahead of print].Google Scholar
  11. Wada H, Matsumoto T, Aota T, Imai H, Suzuki K, Katayama N. Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta-analysis of randomized controlled trials: comment. J Thromb Haemost. 2016;14:2308–9.View ArticlePubMedGoogle Scholar
  12. Japanese Society on Thrombosis and Hemostasis/DIC subcommittee. Diagnostic criteria for DIC by the Japanese Society on Thrombosis and Hemostasis-2017 edition. Jpn J Thromb Hemost. 2017; 28: 369–391 (in Japanese).Google Scholar

Copyright

© The Author(s). 2017

Advertisement