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Article: Special Issue on "Disseminated Intravascular Coagulation: Current Understanding and Future Perspectives".

Yamakawa, Kazuma

2022 Volume 11, Issue 12

Abstract: Disseminated intravascular coagulation (DIC) is characterized by the systemic activation of blood coagulation that generates and deposits fibrin that causes microvascular thrombi to develop in various organs, which contributes to multiple organ ... ...

Abstract	Disseminated intravascular coagulation (DIC) is characterized by the systemic activation of blood coagulation that generates and deposits fibrin that causes microvascular thrombi to develop in various organs, which contributes to multiple organ dysfunction [...].
Language	English
Publishing date	2022-06-09
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11123315
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Article ; Online: Real-world evidence on disseminated intravascular coagulation from Japan.

Hisamune, Ryo / Mochizuki, Katsunori / Yamakawa, Kazuma

Acute medicine & surgery

2023 Volume 10, Issue 1, Page(s) e836

Abstract: Many descriptive epidemiological and comparative studies using big data have been reported recently from outside Japan. Within Japan, diagnosis procedure combination (DPC) data and medical receipt data are being stored in electronic media, and real-world ...

Abstract	Many descriptive epidemiological and comparative studies using big data have been reported recently from outside Japan. Within Japan, diagnosis procedure combination (DPC) data and medical receipt data are being stored in electronic media, and real-world evidence in various fields has started to be reported. We reviewed clinical studies on disseminated intravascular coagulation (DIC) using DPC data obtained from an insurance database with large numbers of cases and a related commercially available dataset including DPC and laboratory data. After DPC was introduced in 2003, 19 studies on DIC using Japanese national DPC data and two studies using the Medical Data Vision database were reported. Epidemiological findings in seven studies showed that the proportion of drugs administered for each underlying disease differed, with antithrombin and recombinant thrombomodulin (rTM) being used more frequently in clinical settings. In 14 comparative studies on anti-DIC agents, antithrombin for severe pneumonia, postoperative intestinal perforation, and severe burn, and rTM for acute cholangitis were associated with improved survival rates. Large-scale observational studies using big data can show results similar to those of randomized control trials if the quality of individual research is high. Real-world data analysis will be increasingly necessary to complement the evidence gap unfilled by randomized control trials.
Language	English
Publishing date	2023-04-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2751184-4
ISSN	2052-8817 ; 2052-8817
ISSN (online)	2052-8817
ISSN	2052-8817
DOI	10.1002/ams2.836
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Article ; Online: Sepsis-induced disseminated intravascular coagulation: an international estrangement of disease concept.

Ushio, Noritaka / Wada, Takeshi / Ono, Yuichiro / Yamakawa, Kazuma

Acute medicine & surgery

2023 Volume 10, Issue 1, Page(s) e00843

Abstract: Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by widespread intravascular activation of coagulation, which can be caused by infectious and noninfectious insults, such as trauma, postcardiac arrest syndrome, and ... ...

Abstract	Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by widespread intravascular activation of coagulation, which can be caused by infectious and noninfectious insults, such as trauma, postcardiac arrest syndrome, and malignant diseases. At present, diagnosis and treatment of DIC clearly differ between Japan and Western countries; in Japan, DIC has long been considered a therapeutic target, and much evidence on DIC has been published. However, there has recently been no international consensus on whether DIC should be a therapeutic target with anticoagulant therapy. This review describes the coagulofibrinolytic system abnormalities associated with sepsis and discusses related management strategies. It also explores the reasons why DIC is perceived differently in different regions. There is a major discrepancy between diagnostic and treatment options in Japan, which are based on holistic assessments of trials, as well as the results of post hoc subgroup analyses and observational studies, and those in Western countries, which are based mainly on the results of sepsis mega trials, especially randomized controlled trials. The differences might also be due to various patient factors in each region, especially racial characteristics in thrombolytic mechanisms, and differences in interpretation of evidence for candidate drugs. Hence, Japanese researchers need to distribute their high-quality clinical research data not only to Japan but also to the rest of the world.
Language	English
Publishing date	2023-05-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2751184-4
ISSN	2052-8817 ; 2052-8817
ISSN (online)	2052-8817
ISSN	2052-8817
DOI	10.1002/ams2.843
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Article: Understanding the pathophysiology of acute critical illness: translational lessons from zebrafish models.

Fujii, Kensuke / Yamakawa, Kazuma / Takeda, Yuriko / Okuda, Natsuko / Takasu, Akira / Ono, Fumihito

Intensive care medicine experimental

2024 Volume 12, Issue 1, Page(s) 8

Abstract: The models used to investigate the pathophysiological mechanisms of acute critical illness are not limited to mammalian species. The zebrafish (Danio rerio) is a popular model organism for studying diseases due to its transparency and rapid development. ... ...

Abstract	The models used to investigate the pathophysiological mechanisms of acute critical illness are not limited to mammalian species. The zebrafish (Danio rerio) is a popular model organism for studying diseases due to its transparency and rapid development. The genes and signaling pathways involved in acute critical illness appear highly conserved among zebrafish and humans. Forward genetics such as random mutagenesis by a chemical mutagen or reverse genetics methods represented by CRISPR/Cas9 allowed researchers to reveal multiple novel aspects of pathological processes in areas including infection, immunity, and regeneration. As a model of sepsis, transgenic zebrafish allowed the visualization of lipopolysaccharide (LPS)-induced vascular leakage in vivo and the demonstration of changes in the expression of cellular junction proteins. Other transgenic zebrafish visualizing the extravascular migration of neutrophils and macrophages have demonstrated a decrease in neutrophil numbers and an increased expression of an inflammatory gene, which replicates a phenomenon observed in humans in clinically encountered sepsis. The regenerative potential and the visibility of zebrafish organs also enabled clarification of important mechanisms in wound healing, angiogenesis, and neurogenesis. After spinal cord injury (SCI), a marker gene expressed in glial bridging was discovered. Furthermore, localized epithelial-to-mesenchymal transition (EMT) and molecular mechanisms leading to spinal cord repair were revealed. These translational studies using zebrafish show the potential of the model system for the treatment of acute critical illnesses such as sepsis, organ failure, and trauma.
Language	English
Publishing date	2024-01-31
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2740385-3
ISSN	2197-425X
ISSN	2197-425X
DOI	10.1186/s40635-024-00595-x
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Article: Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis.

Totoki, Takaaki / Makino, Yuto / Yamakawa, Kazuma / Koami, Hiroyuki / Wada, Takeshi / Ito, Takashi / Iba, Toshiaki

Thrombosis journal

2024 Volume 22, Issue 1, Page(s) 10

Abstract: Background: Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC ... ...

Abstract	Background: Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC syndrome have previously been examined, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review on the combined administration of AT and rTM for the treatment of septic DIC to investigate the superiority of the combination therapy over either AT or rTM monotherapy using a random-effects analysis model. Method: We searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was occurrence of serious bleeding complications compared to monotherapy. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study. Results: We analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy (HR 0.67 [0.43-1.05], OR 0.73 [0.45-1.18]). The I Conclusions: Although the findings in this analysis could not confirm a statistically significant effect of AT and rTM combination therapy for septic DIC, it showed a promising effect in terms of improving mortality. The incidence of bleeding was low and clinically feasible. Further research is warranted to draw more conclusive results. Trial registration: This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: 000049820).
Language	English
Publishing date	2024-01-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2118392-2
ISSN	1477-9560
ISSN	1477-9560
DOI	10.1186/s12959-023-00579-z
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Article ; Online: A systematic review and meta-analysis of recombinant human soluble thrombomodulin for the treatment of DIC associated with hematological malignancies.

Kawano, Noriaki / Fukatsu, Masahiko / Yamakawa, Kazuma / Seki, Yoshinobu / Wada, Hideo / Okamoto, Kohji / Ikezoe, Takayuki

International journal of hematology

2024 Volume 119, Issue 4, Page(s) 416–425

Abstract: Background: Recombinant human soluble thrombomodulin (rhTM) is commonly used in Japan to treat disseminated intravascular coagulation (DIC), but its efficacy compared with other anticoagulants is unclear. We conducted a systematic review and meta- ... ...

Abstract	Background: Recombinant human soluble thrombomodulin (rhTM) is commonly used in Japan to treat disseminated intravascular coagulation (DIC), but its efficacy compared with other anticoagulants is unclear. We conducted a systematic review and meta-analysis to investigate this issue in DIC patients with hematological malignancies. Methods: We searched PubMed, Cochrane, and Scopus for prospective and retrospective studies evaluating the efficacy and safety of rhTM in DIC patients with hematological malignancies between April 2008 and April 2023. We performed a systematic review and meta-analysis evaluating recovery from DIC, hemorrhagic adverse events (AEs), and overall survival (OS). Results: We analyzed one prospective (64 patients) and seven retrospective studies (209 patients). Use of rhTM was associated with a higher rate of recovery from DIC (OR: 2.25 [1.09-4.63] and 1.98 [1.12-3.50] in prospective and retrospective studies, respectively; same order below) and fewer hemorrhagic AEs (OR: 0.83 [0.30-2.30] and 0.21 [0.08-0.57]). rhTM did not improve OS (OR: 1.06 [0.42-2.66] and 1.72 [0.87-3.39]), although the incidence of hemorrhagic death was lower in the rhTM group (0 of 94 patients). Conclusion: Use of rhTM in patients with hematological malignancy-associated DIC is strongly expected to be effective and safe.
MeSH term(s)	Humans ; Retrospective Studies ; Prospective Studies ; Thrombomodulin/therapeutic use ; Treatment Outcome ; Disseminated Intravascular Coagulation/drug therapy ; Disseminated Intravascular Coagulation/etiology ; Sepsis/complications ; Recombinant Proteins/adverse effects ; Hematologic Neoplasms/complications ; Hematologic Neoplasms/drug therapy ; Hemorrhage
Chemical Substances	Thrombomodulin ; Recombinant Proteins
Language	English
Publishing date	2024-01-25
Publishing country	Japan
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	1076875-0
ISSN	1865-3774 ; 0917-1258 ; 0925-5710
ISSN (online)	1865-3774
ISSN	0917-1258 ; 0925-5710
DOI	10.1007/s12185-023-03704-w
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Article ; Online: Emergency administration of fibrinogen concentrate for haemorrhage: systematic review and meta-analysis.

Itagaki, Yuki / Hayakawa, Mineji / Takahashi, Yuki / Hirano, Satoshi / Yamakawa, Kazuma

World journal of emergency surgery : WJES

2023 Volume 18, Issue 1, Page(s) 27

Abstract: Introduction: The occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen concentrate (FC) use may increase plasma fibrinogen levels more rapidly than ... ...

Abstract	Introduction: The occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen concentrate (FC) use may increase plasma fibrinogen levels more rapidly than fresh-frozen product or cryoprecipitate use. Previous several systematic reviews and meta-analyses have not effectively demonstrated FC efficacy in significantly improving the risk of mortality and reducing transfusion requirements. In this study, we investigated the use of FC for haemorrhages in emergency situations. Methods and analysis: In this systematic review and meta-analysis, we included controlled trials, but excluded randomized controlled trials (RCTs) in elective surgeries. The study population consisted of patients with haemorrhages in emergency situations, and the intervention was emergency supplementation of FC. The control group was administered with ordinal transfusion or placebo. The primary and secondary outcomes were in-hospital mortality and the amount of transfusion and thrombotic events, respectively. The electronic databases searched included MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. Results: Nine RCTs in the qualitative synthesis with a total of 701 patients were included. Results showed a slight increase in in-hospital mortality with FC treatment (RR 1.24, 95% CI 0.64-2.39, p = 0.52) with very low certainty of the evidence. There was no reduction in the use of red blood cells (RBC) transfusion in the first 24 h after admission with FC treatment (mean difference [MD] 0.0 Unit in the FC group, 95% CI - 0.99-0.98, p = 0.99) with very low certainty of the evidence. However, the use of fresh-frozen plasma (FFP) transfusion significantly increased in the first 24 h after admission with FC treatment (MD 2.61 Unit higher in the FC group, 95% CI 0.07-5.16, p = 0.04). The occurrence of thrombotic events did not significantly differ with FC treatment. Conclusions: The present study indicates that the use of FC may result in a slight increase in in-hospital mortality. While FC did not appear to reduce the use of RBC transfusion, it likely increased the use of FFP transfusion and may result in a large increase in platelet concentrate transfusion. However, the results should be interpreted cautiously due to the unbalanced severity in the patient population, high heterogeneity, and risk of bias.
MeSH term(s)	Humans ; Fibrinogen/therapeutic use ; Hemorrhage/drug therapy ; Hemostatics/therapeutic use ; Blood Transfusion ; Elective Surgical Procedures
Chemical Substances	Fibrinogen (9001-32-5) ; Hemostatics
Language	English
Publishing date	2023-03-30
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	2233734-9
ISSN	1749-7922 ; 1749-7922
ISSN (online)	1749-7922
ISSN	1749-7922
DOI	10.1186/s13017-023-00497-5
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Article ; Online: Persistent and Late-Onset Disseminated Intravascular Coagulation Are Closely Related to Poor Prognosis in Patients with Sepsis.

Matsuoka, Tadashi / Yamakawa, Kazuma / Iba, Toshiaki / Homma, Koichiro / Sasaki, Junichi

Thrombosis and haemostasis

2023 Volume 124, Issue 5, Page(s) 399–407

Abstract: Background: Septic-associated disseminated intravascular coagulation (DIC) is heterogeneous regarding prognosis and responsiveness to anticoagulant therapy.: Objectives: To investigate the relationship between the timing of development and recovery ...

Abstract	Background: Septic-associated disseminated intravascular coagulation (DIC) is heterogeneous regarding prognosis and responsiveness to anticoagulant therapy. Objectives: To investigate the relationship between the timing of development and recovery of DIC, its prognosis, and the difference in response to anticoagulant therapy in sepsis-associated DIC patients. Methods: This study was performed with a dataset from a multicenter nationwide retrospective cohort study (J-Septic DIC registry) in Japan between 2011 and 2013 to reveal the subgroup "high risk of death in DIC" and investigate the relationship between anticoagulant use and mortality. Patients were assigned to four groups based on the International Society on Thrombosis and Haemostasis-overt DIC status at days 1 and 3: non-DIC (-/-), early-recovered DIC (+/-), late-onset DIC (-/+), and persistent DIC (+/+). Results: A total of 1,922 patients were included. In-hospital mortality in persistent and late-onset DIC patients was significantly higher than in patients with non-DIC and early-recovered DIC. This finding indicates that persistent DIC and late-onset DIC were a poor-prognosis subgroup, "high-risk" DIC. Meanwhile, patients with high-risk DIC treated with anticoagulants had significantly better outcomes than those without anticoagulants after adjusting for confounding factors. Conclusion: This study showed that individuals with a high risk of death, persistent DIC, and late-onset DIC were a poor-prognostic subgroup in septic DIC; however, high-risk DIC is also a subgroup that can obtain more benefits from anticoagulant therapy.
MeSH term(s)	Humans ; Disseminated Intravascular Coagulation/mortality ; Disseminated Intravascular Coagulation/diagnosis ; Disseminated Intravascular Coagulation/drug therapy ; Disseminated Intravascular Coagulation/etiology ; Male ; Retrospective Studies ; Female ; Sepsis/complications ; Sepsis/mortality ; Sepsis/diagnosis ; Aged ; Japan/epidemiology ; Middle Aged ; Anticoagulants/therapeutic use ; Prognosis ; Hospital Mortality ; Registries ; Time Factors ; Aged, 80 and over ; Risk Factors ; Treatment Outcome
Chemical Substances	Anticoagulants
Language	English
Publishing date	2023-10-23
Publishing country	Germany
Document type	Journal Article ; Multicenter Study
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/a-2196-3630
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Article ; Online: Trauma-induced coagulopathy: The past, present, and future: A comment.

Wada, Takeshi / Yamakawa, Kazuma

Journal of thrombosis and haemostasis : JTH

2019 Volume 17, Issue 9, Page(s) 1571–1574

MeSH term(s)	Blood Coagulation Disorders ; Disseminated Intravascular Coagulation ; Humans
Language	English
Publishing date	2019-08-29
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1111/jth.14571
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Article: Antibiotic stewardship in critically ill patients with suspected ventilator-associated pneumonia.

Yoshimura, Jumpei / Hashimoto, Hideki / Yamakawa, Kazuma

Annals of translational medicine

2020 Volume 8, Issue 20, Page(s) 1329

Language	English
Publishing date	2020-11-03
Publishing country	China
Document type	Editorial ; Comment
ZDB-ID	2893931-1
ISSN	2305-5847 ; 2305-5839
ISSN (online)	2305-5847
ISSN	2305-5839
DOI	10.21037/atm-20-2421
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