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Disseminated Intravascular Coagulation: Current Understanding and Future Perspectives
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Disseminated Intravascular Coagulation: Current Understanding and Future Perspectives

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 19615

Special Issue Editor

Dr. Kazuma Yamakawa

E-Mail Website
Guest Editor
Department of Emergency Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan
Interests: disseminated intravascular coagulation; sepsis; trauma; post-cardiac arrest syndrome; COVID-19; immunology; endothelial dysfunction; systematic review; clinical practice guidelines; randomized controlled trials

Special Issue Information

Dear Colleagues,

Disseminated intravascular coagulation is characterized by systemic activation of blood coagulation, which results in the generation and deposition of fibrin, leading to microvascular thrombi in various organs and contributing to multiple organ dysfunction. Also, simultaneous neutrophil activation and endothelial injury associated with glycocalyx perturbation have been observed in these patients. Although there have been several recent advances in the pathophysiology of disseminated intravascular coagulation, the clinical significance of diagnoses and therapeutic interventions targeting disseminated intravascular coagulation is uncertain so far. Therefore, understanding the pathophysiology of disseminated intravascular coagulation and novel therapeutic strategies are vitally important issues for the management of critically ill settings. In this Special Issue of the Journal of Clinical Medicine, we will discuss the etiology, pathophysiology, clinical manifestations, diagnostic, and optimal management to treat critically ill patients with disseminated intravascular coagulation.

Dr. Kazuma Yamakawa
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • anticoagulant therapy
  • cancer
  • disseminated intravascular coagulation
  • endothelial dysfunction
  • hematological malignancy
  • immunology
  • precision medicine
  • sepsis
  • systemic inflammatory response syndrome
  • trauma

Published Papers (6 papers)

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Research

11 pages, 718 KiB  
Article
Role of Thromboelastography as an Early Predictor of Disseminated Intravascular Coagulation in Patients with Septic Shock
by Sang Min Kim, Sang-Il Kim, Gina Yu, June-Sung Kim, Seok In Hong, Bora Chae, Yo Sep Shin, Youn Jung Kim, Seongsoo Jang and Won Young Kim
J. Clin. Med. 2020, 9(12), 3883; https://doi.org/10.3390/jcm9123883 - 29 Nov 2020
Cited by 17 | Viewed by 2805
Abstract
(1) Background: The currently proposed criteria for diagnosing overt disseminated intravascular coagulation (DIC) are not suitable for early detection of DIC. Thromboelastography (TEG) rapidly provides a comprehensive assessment of the entire coagulation process and is helpful as a guide for correcting consumptive coagulopathy [...] Read more.
(1) Background: The currently proposed criteria for diagnosing overt disseminated intravascular coagulation (DIC) are not suitable for early detection of DIC. Thromboelastography (TEG) rapidly provides a comprehensive assessment of the entire coagulation process and is helpful as a guide for correcting consumptive coagulopathy in sepsis-induced DIC. This study aimed to investigate the role of TEG in the prediction of DIC in patients with septic shock. (2) Methods: TEG was conducted prospectively in 1294 patients with septic shock at the emergency department (ED) between January 2016 and December 2019. After exclusion of 405 patients with “do not attempt resuscitation” orders, those refusing enrollment, and those developing septic shock after ED presentation, 889 patients were included. DIC was defined as an International Society on Thrombosis and Hemostasis score ≥ 5 points within 24 h. (3) Results: Of the 889 patients with septic shock (mean age 65.6 ± 12.7 years, 58.6% male), 158 (17.8%) developed DIC. TEG values, except lysis after 30 min, were significantly different between the DIC and non-DIC groups. Among the TEG values, the maximal amplitude (MA) had the highest discriminating power for DIC, with an area under the curve of 0.814. An MA < 60 indicated DIC with 79% sensitivity, 73% specificity, and 94% negative predictive value. Based on multivariable analysis, MA < 60 was an independent predictor of DIC (odds ratio 5.616 (95% confidence interval: 3.213–9.818)). (4) Conclusions: In patients with septic shock, the MA value in TEG could be a valuable tool for early prediction of DIC. Full article
(This article belongs to the Special Issue Disseminated Intravascular Coagulation: Current Understanding and Future Perspectives)
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11 pages, 907 KiB  
Article
Etiology of Ischemic Strokes of Patients with Atrial Fibrillation and Therapy with Anticoagulants
by Jan C. Purrucker, Kyra Hölscher, Jennifer Kollmer and Peter A. Ringleb
J. Clin. Med. 2020, 9(9), 2938; https://doi.org/10.3390/jcm9092938 - 11 Sep 2020
Cited by 18 | Viewed by 4519
Abstract
Background: Reducing the number of ischemic strokes in patients with atrial fibrillation despite oral anticoagulation remains an important, yet largely unsolved challenge. Therefore, we assessed the etiology of ischemic strokes despite anticoagulation with vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs). Methods: [...] Read more.
Background: Reducing the number of ischemic strokes in patients with atrial fibrillation despite oral anticoagulation remains an important, yet largely unsolved challenge. Therefore, we assessed the etiology of ischemic strokes despite anticoagulation with vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs). Methods: Patients with known atrial fibrillation (AF), treatment with VKA or NOAC, and acute ischemic stroke admitted between 2015 and 2018 (1st half) were identified from the hospital database. Brain imaging data were independently reviewed. An integrated etiologic classification according to the ASCOD system was made. Medication errors (admission INR <2.0 in the VKA- or NOAC-specific concentration <10 ng/mL) or dosage/dosing errors were also analyzed. Results: Of 3610 patients screened, n = 341 were included (VKA, n = 127; NOAC, n = 214). An overall increasing rate of OAC-associated stroke per year was observed. In 95.3% of patients with adequate diagnostic work-up (n = 321/337), at least one additional potential, uncertain, or unlikely non-cardiac cause of stroke was identified. More patients in the VKA than in the NOAC group had a medication error (81/127, 63.8% vs. 102/205, 49.8%; p = 0.013). Conclusions: Stroke risk factors despite atrial fibrillation were highly prevalent. Although less common with NOACs than VKAs, medication errors are still frequent. Full article
(This article belongs to the Special Issue Disseminated Intravascular Coagulation: Current Understanding and Future Perspectives)
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11 pages, 2324 KiB  
Article
Hematological Phenotype of COVID-19-Induced Coagulopathy: Far from Typical Sepsis-Induced Coagulopathy
by Yutaka Umemura, Kazuma Yamakawa, Takeyuki Kiguchi, Takeshi Nishida, Masahiro Kawada and Satoshi Fujimi
J. Clin. Med. 2020, 9(9), 2875; https://doi.org/10.3390/jcm9092875 - 5 Sep 2020
Cited by 27 | Viewed by 3553
Abstract
Background: Blood coagulation disorders commonly occur with severe coronavirus disease 2019 (COVID-19). However, there is only limited evidence on differentiating the pattern of the hemostatic parameters from those of typical sepsis-induced coagulopathy (SIC). Methods: To elucidate the specific pattern of coagulopathy induced by [...] Read more.
Background: Blood coagulation disorders commonly occur with severe coronavirus disease 2019 (COVID-19). However, there is only limited evidence on differentiating the pattern of the hemostatic parameters from those of typical sepsis-induced coagulopathy (SIC). Methods: To elucidate the specific pattern of coagulopathy induced by COVID-19 pneumonia, this retrospective, observational study targeted consecutive adult patients with COVID-19-induced acute respiratory distress syndrome (ARDS) and compared hemostatic biomarkers with non-COVID-19-induced septic ARDS. Multilevel mixed-effects regression analysis was performed and Kaplan–Meier failure curves were constructed. Results: We enrolled 24 patients with COVID-19-induced ARDS and 200 patients with non-COVID-19-induced ARDS. Platelet count, antithrombin activity, and prothrombin time in the COVID-19 group were almost within normal range and time series alterations of these markers were significantly milder than the non-COVID-19 group (p = 0.052, 0.037, and 0.005, respectively). However, fibrin/fibrinogen degradation product and D-dimer were significantly higher in the COVID-19 group (p = 0.001, 0.002, respectively). COVID-19 patients had moderately high levels of thrombin–antithrombin complex and plasmin-alpha2-plasmin inhibitor complex but normal plasminogen activator inhibitor-1 level. Conclusions: The hematological phenotype of COVID-19-induced coagulopathy is quite different from that in typical SIC characterized by systemic hypercoagulation and suppressed fibrinolysis. Instead, local thrombus formation might be promoted in severe COVID-19. Full article
(This article belongs to the Special Issue Disseminated Intravascular Coagulation: Current Understanding and Future Perspectives)
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15 pages, 1041 KiB  
Article
Disseminated Intravascular Coagulopathy Is Associated with the Outcome of Persistent Inflammation, Immunosuppression and Catabolism Syndrome
by Kensuke Nakamura, Kentaro Ogura, Hidehiko Nakano, Hiromu Naraba, Yuji Takahashi, Tomohiro Sonoo, Hideki Hashimoto and Tadahiro Goto
J. Clin. Med. 2020, 9(8), 2662; https://doi.org/10.3390/jcm9082662 - 17 Aug 2020
Cited by 10 | Viewed by 2662
Abstract
Persistent inflammation, immunosuppression and catabolism syndrome (PIICS) often occur after critical care. Disseminated intravascular coagulation (DIC) is expected to be associated independently with PIICS development. We retrospectively analyzed 5397 patients admitted to the Hitachi General Hospital emergency and critical care center during four [...] Read more.
Persistent inflammation, immunosuppression and catabolism syndrome (PIICS) often occur after critical care. Disseminated intravascular coagulation (DIC) is expected to be associated independently with PIICS development. We retrospectively analyzed 5397 patients admitted to the Hitachi General Hospital emergency and critical care center during four years. We classified PIICS as C-reactive protein > 3.0 mg/dL or albumin < 3.0 g/dL or lymphocyte count < 800/μL on day 14. Prolonged hospital stay (>14 days) without PIICS and early recovery (discharged alive within 14 days) were assigned as non-PIICS. Early death (death within 14 days) was identified. We analyzed the association between the International Society on Thrombosis and Haemostasis overt DIC and PIICS outcomes. Results revealed 488 PIICS, 416 early death and 4493 non-PIICS cases. Analyses showed DIC as associated significantly with mortality, the Barthel index at discharge and PIICS development. Multivariate regression analysis and a generalized structural equation model identified DIC on admission as an independent risk factor for PIICS in surviving patients. Full article
(This article belongs to the Special Issue Disseminated Intravascular Coagulation: Current Understanding and Future Perspectives)
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13 pages, 592 KiB  
Article
Nafamostat Mesylate Improved Survival Outcomes of Sepsis Patients Who Underwent Blood Purification: A Nationwide Registry Study in Japan
by Hiroshi Kamijo, Katsunori Mochizuki, Yuta Nakamura, Kotaro Mori, Michitaro Ichikawa, Kenichi Nitta and Hiroshi Imamura
J. Clin. Med. 2020, 9(8), 2629; https://doi.org/10.3390/jcm9082629 - 13 Aug 2020
Cited by 7 | Viewed by 2629
Abstract
Nafamostat mesylate (NM) is a synthetic serine protease inhibitor that can be used as an anticoagulant during blood purification in critically ill patients, as well as a treatment for disseminated intravascular coagulation. Although NM has been reported to reduce the risk of bleeding [...] Read more.
Nafamostat mesylate (NM) is a synthetic serine protease inhibitor that can be used as an anticoagulant during blood purification in critically ill patients, as well as a treatment for disseminated intravascular coagulation. Although NM has been reported to reduce the risk of bleeding during blood purification, its effect on survival outcomes of patients who received blood purification treatments is unclear. We hypothesized that administration of NM during blood purification can reduce mortality in patients with sepsis. A post hoc analysis was conducted on a nationwide retrospective registry that included data from 3195 sepsis patients registered at 42 intensive care units throughout Japan. We evaluated the effect of NM on hospital mortality and bleeding complications using propensity score matching in 1216 sepsis patients who underwent blood purification in the intensive care unit (ICU). Two-hundred-and-sixty-eight pairs of propensity score-matched patients who received NM and conventional therapy were compared. Hospital and ICU mortality rates in the NM group were significantly lower than those in the conventional therapy group. However, rates of bleeding complications did not differ significantly between the two groups. These data suggest that administration of NM improved the survival outcomes of sepsis patients who underwent blood purification in the ICU. Full article
(This article belongs to the Special Issue Disseminated Intravascular Coagulation: Current Understanding and Future Perspectives)
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10 pages, 766 KiB  
Article
Comparative Analysis of Three Machine-Learning Techniques and Conventional Techniques for Predicting Sepsis-Induced Coagulopathy Progression
by Daisuke Hasegawa, Kazuma Yamakawa, Kazuki Nishida, Naoki Okada, Shuhei Murao and Osamu Nishida
J. Clin. Med. 2020, 9(7), 2113; https://doi.org/10.3390/jcm9072113 - 4 Jul 2020
Cited by 8 | Viewed by 2632
Abstract
Sepsis-induced coagulopathy has poor prognosis; however, there is no established tool for predicting it. We aimed to create predictive models for coagulopathy progression using machine-learning techniques to evaluate predictive accuracies of machine-learning and conventional techniques. A post-hoc subgroup analysis was conducted based on [...] Read more.
Sepsis-induced coagulopathy has poor prognosis; however, there is no established tool for predicting it. We aimed to create predictive models for coagulopathy progression using machine-learning techniques to evaluate predictive accuracies of machine-learning and conventional techniques. A post-hoc subgroup analysis was conducted based on the Japan Septic Disseminated Intravascular Coagulation retrospective study. We used the International Society on Thrombosis and Haemostasis disseminated intravascular coagulation (DIC) score to calculate the ΔDIC score as ((DIC score on Day 3) − (DIC score on Day 1)). The primary outcome was to determine whether the predictive accuracy of ΔDIC was more than 0. The secondary outcome was the actual predictive accuracy of ΔDIC (predicted ΔDIC−real ΔDIC). We used the machine-learning methods, such as random forests (RF), support vector machines (SVM), and neural networks (NN); their predictive accuracies were compared with those of conventional methods. In total, 1017 patients were included. Regarding DIC progression, predictive accuracy of the multiple linear regression, RF, SVM, and NN models was 63.7%, 67.0%, 64.4%, and 59.8%, respectively. The difference between predicted ΔDIC and real ΔDIC was 2.05, 1.54, 2.24, and 1.77 for the multiple linear regression, RF, SVM, and NN models, respectively. RF had the highest predictive accuracy. Full article
(This article belongs to the Special Issue Disseminated Intravascular Coagulation: Current Understanding and Future Perspectives)
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