Disseminated Intravascular Coagulation Diagnostic Criteria Research Articles

A retrospective study on safety and efficacy of recombinant human soluble thrombomodulin to acute aortic dissection with disseminated intravascular coagulation

ObjectivesRecombinant human soluble thrombomodulin (rTM) has recently been used as a promising therapeutic natural anti-coagulant drug for disseminated intravascular coagulation (DIC). Here we investigated the safety and efficacy of rTM after aortic surgery in patients with acute aortic dissection (AAD).MethodsA total of 316 patients diagnosed with AAD underwent emergent ascending aortic replacement or total arch replacement between 2010 and 2019. We retrospectively analyzed the clinical information of 62 patients with the Japanese Association for Acute Medicine’s acute-stage DIC diagnostic criteria (JAAM criteria) with a score of ≥ 4. We assigned 62 patients to two groups, either non-rTM group (n = 29) or rTM group (n = 33). Patient characteristics, surgical procedures, and postoperative outcome data including coagulation function and the JAAM DIC score in both groups were collected.ResultsThe decrease in the number of platelets was clearly suppressed on days 1–3 in the rTM group. On days 1–4, fibrin degradation product levels were upregulated in the non-rTM group but significantly downregulated in the rTM group. Five operative deaths occurred within 30 days postoperative (two [6.9%] in the non-rTM group vs. three [9.1%] in the rTM group). The JAAM DIC score showed a gradually improving trend from postoperative day 1 in the rTM group.ConclusionsPostoperative rTM administration for AAD may be a safe and promising novel treatment strategy for improving the JAAM DIC score.

Current Clinical Practice of Laboratory Testing of the Hemostasis and Coagulation System in Patients with Sepsis: A Nationwide Observational Study in Japan.

The clinical benefit of hemostasis molecular indicators such as thrombin-antithrombin complex (TAT), soluble fibrin (SF), and prothrombin fragment 1 + 2 (F1+2) for the diagnosis of disseminated intravascular coagulation (DIC) is reported. Recently, novel DIC diagnostic criteria that adopt them were proposed in Japan. Despite the theoretical understanding of their function, the practical use of these markers remains unclear. The present study aimed to provide a descriptive overview of current clinical practice regarding the measurement of hemostasis markers in sepsis management in Japan. This retrospective observational analysis used the Japanese Diagnosis Procedure Combination inpatient database containing data from more than 1500 acute-care hospitals in Japan. We identified adult patients hospitalized for sepsis between April 2018 and March 2021. Descriptive statistics for measuring several hemostasis laboratory markers were summarized using patient disease characteristics, hospital characteristic, and geographical location. This study included 153,474 adult sepsis patients. Crude in-hospital mortality was 30.0%. Frequency of measurement of fibrinogen, fibrin degradation products (FDP), and D-dimer in sepsis patients on admission was 43.2%, 36.1%, and 46.4%, respectively. Novel and specific hemostasis molecular markers such as TAT, SF, and F1+2 were seldom measured (1.9%, 1.7%, and 0.02%, respectively). Hemostasis molecular markers were more frequently measured with progression of thrombocytopenia. Measurement of these clinically favorite hemostasis markers was influenced not only by disease characteristics but also hospital characteristic or geographical location. Hemostasis molecular markers such as TAT, SF, and F1+2 were rarely measured in clinical settings. Although adopted by several DIC scoring systems, neither fibrinogen, FDP, nor D-dimer was routinely measured.

Net reclassification index in comparison of prognostic value of disseminated intravascular coagulation diagnostic criteria by Japanese Society on Thrombosis and Hemostasis and International Society on Thrombosis and Haemostasis: a multicenter prospective cohort study

BackgroundWe compared the prognostic value of the Japanese Society on Thrombosis and Hemostasis (JSTH) disseminated intravascular coagulation (DIC) diagnostic criteria with that of the International Society on Thrombosis and Haemostasis (ISTH) DIC diagnostic criteria for 28-day in-hospital mortality.MethodsWe conducted a multicenter prospective cohort study involving two hematology departments, four emergency departments, and one general medicine department in Japan between August 2017 and July 2021. We assessed three ISTH DIC diagnostic criteria categories using low cutoff levels of D-dimer (low D-dimer), high cutoff levels of D-dimer (high D-dimer), and fibrinogen/fibrin degradation products (FDP) as fibrin-related markers. The main outcome was diagnosis-based category additive net reclassification index (NRI).ResultsA total of 222 patients were included: 82 with hematopoietic disorders, 86 with infections, and 54 with other diseases. The 28-day in-hospital mortality rate was 14% (n = 31). The DIC rates diagnosed by the JSTH, ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were 52.7%, 47.3%, 42.8%, and 27.0%, respectively. The overall category additive NRI by JSTH DIC diagnosis vs. ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were − 10 (95% confidence interval [CI]: −28 to 8, p = 0.282), − 7.8 (95% CI: −26 to 10, p = 0.401), and − 11 (95% CI: −26 to 3, p = 0.131), respectively.ConclusionsJSTH criterion showed the highest sensitivity for DIC diagnosis that did not improve but reflected the same prognostic value for mortality evaluated using ISTH DIC diagnosis criteria. This finding may help clinicians to use JSTH DIC criterion as an early intervention strategy in patients with coagulopathy.

The usefulness of tranexamic acid for bleeding symptoms of chronic consumptive coagulopathy complicated by aortic disease: a single-institute, retrospective study of 14 patients

BackgroundTranexamic acid (TXA) is an antifibrinolytic drug that blocks lysine-binding sites on the profibrinolytic enzyme plasminogen. Aortic diseases with chronic consumption coagulopathy may lead to disseminated intravascular coagulation (DIC) and cause fatal bleeding. Although the use of antifibrinolytic agents in DIC is generally not recommended due to enhanced fibrin deposition risking thrombotic symptoms, the efficacy of TXA has been reported in several cases of DIC with aortic diseases. However, the efficacy and safety of TXA for bleeding symptoms of chronic consumption coagulopathy with aortic diseases have not been studied in detail.MethodsWe evaluated the efficacy of TXA in 14 patients with chronic consumptive coagulopathy due to aortic disease complicated by bleeding symptoms. Changes in coagulation and fibrinolysis parameters from baseline were analyzed with Wilcoxon matched-pairs signed-rank tests, excluding missing values. Kaplan-Meier curves were used to analyze overall survival.ResultsMedian age was 78.5 years (range, 66–89 years) and median observation period was 448 days (range, 0–2282 days). Twelve patients had chronic renal failure and 1 patient had chronic liver failure. Before starting treatment, median Japanese Ministry of Health and Welfare DIC diagnostic criteria score was 8 (range, 4–11) and median platelet count was 64 × 109/L (range, 25–97 × 109/L). Twelve patients underwent evaluation of bleeding symptoms after introduction of TXA, and 10 of those 12 patients showed improved bleeding tendencies within 30 days (median, 5.0 days). One patient with chronic liver failure showed worsening of bleeding symptoms. Although only one patient was initiated TXA in combination with anticoagulants, no significant worsening of thrombotic events was observed within 30 days.ConclusionsTXA therapy appears effective against chronic consumptive coagulopathy with bleeding due to aortic disease, with few side effects.

Differential Diagnosis Distinguishing Immune TTP from Septic DIC Using Plasma Levels of Haptoglobin and Factor XIII Activity

Introduction Differential diagnosis of immune thrombotic thrombocytopenic purpura (iTTP) and septic disseminated intravascular coagulation (DIC) in daily clinical practice is difficult. iTTP is diagnosed by deficiency of ADAMTS13 activity and ADAMTS13 inhibitor positivity. However, it is difficult to rapidly measure ADAMTS13 activity in real-time in clinical practice. Prompt therapeutic interventions are directly dependent on iTTP prognosis. A method for differentiating between these two disorders using common laboratory tests is needed. Plasma haptoglobin levels can indicate hemolysis and are reported to be severely decreased in iTTP. Coagulation factor XIII (FXIII) activity is also severely decreased in septic DIC. To date, no reports have observed haptoglobin in septic DIC or FXIII activity in iTTP. We analyzed the plasma levels of haptoglobin and FXIII activity in patients with iTTP and septic DIC to investigate whether these markers can be used for differential diagnosis. Methods iTTP was defined as <10% normal ADAMTS13 activity, and >0.5 BU/mL ADAMTS13 inhibitor. Septic DIC was defined as meeting both Third International Consensus Definitions for Sepsis and Septic Shock, and ISTH DIC diagnostic criteria. Thirty-five patients with iTTP and 30 with septic DIC were enrolled in this study. Plasma haptoglobin levels were measured using Human Quantikine ELISA Kits (#DPHAGO, R&D Systems, Inc., Minneapolis, USA), which is a highly sensitive method compared to methods used in clinical practice. Values are expressed as medians (first quartile-third quartile). Results As shown in the table, iTTP patients were significantly younger than those with septic DIC. The iTTP group showed significantly lower ADAMTS13 activity, higher ADAMTS13 inhibitor titer, lower hemoglobin level, lower platelet counts, higher LDH level, and lower creatinine level than the septic DIC group. In a comparison of coagulation and fibrinolytic markers, the septic DIC group had significantly higher PT-INR, prolonged APTT, higher FDP and D-dimer levels, and lower AT activity than the iTTP group. The plasma haptoglobin level was 0.39 mg/dL (0.18-0.76 mg/dL) in the iTTP group, and 54.2 mg/dL (0.6-143.9 mg/dL) in the septic DIC group (P < 0.01). FXIII activity was 91.3% (80.4-115.0%) in the iTTP group, and 36.3% (14.7-61.9%) in the septic DIC group (p<0.01). The ROC curve of haptoglobin and FXIII activity in the differential diagnosis of TTP and septic DIC were investigated. The cut-off level of haptoglobin was 2.868 mg/dL, the area under the curve (AUC) was 0.832 (95% CI:0.727-0.938), specificity was 66.7%, and sensitivity was 100%. The cutoff level of FXIII activity was 76.0%, AUC was 0.931 (95%CI:0.873-0.989), specificity was 77.1%, and sensitivity was 93.3%. We developed a scoring system to differentiate iTTP from septic DIC using a combination of FXIII activity and haptoglobin; TTP/DIC index = plasma FXIII activity (%) - plasma haptoglobin (mg/dL). Laboratory TTP was defined when the index was ≥60, and laboratory DIC was defined when the index was <60. The AUC for the combination of FXIII activity and haptoglobin was 0.968 (95% CI: 0.9354-1). The accuracy of iTTP diagnosis in laboratory TTP was 89.2% (33/37), and the accuracy of septic DIC diagnosis in laboratory DIC was 92.9% (26/28). Conclusions A comparison of iTTP and septic DIC showed significant differences in haptoglobin and FXIII activity levels. A combination of haptoglobin and FXIII activity was considered helpful in differentiating iTTP from septic DIC. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Age-related differences in the survival benefit of the administration of antithrombin, recombinant human thrombomodulin, or their combination in sepsis

Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, or their combination. The increases in the risk of hospital mortality were suppressed in the high-DIC-score patients aged 60–70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk of hospital mortality in patients aged 50–60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60–70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis.

Cutting edge of diagnosis and treatment of disseminated intravascular coagulation

During the treatment of disseminated intravascular coagulation (DIC) associated with hematopoietic malignancies (particularly, acute leukemia), fatal bleeding, such as cerebral, alveolar, and gastrointestinal hemorrhages at diagnosis or immediately after initiating treatment, determines the patient's prognosis. DIC should always be suspected in such cases, and the diagnosis should be made on the basis of the former Ministry of Health and Welfare DIC diagnostic criteria or the 2017 Japanese Society on Thrombosis and Hemostasis DIC diagnostic criteria. This treatment requires the use of appropriate anticoagulants and replacement therapies. The anticoagulant should be chosen based on the patient's risk of bleeding. Here we present the recent evidence of DIC complicating hematopoietic malignancies with antithrombin agents and recombinant human soluble thrombomodulin. Moreover, prognostic markers during the course of therapy have been reported. The effect of treatment, including withdrawal from DIC, should be carefully assessed. In the future, detailed evidence regarding the tumor subtype, tumor burden, and disease severity will be required to ensure appropriate drug choice for the treatment.

Hypofibrinogenemia is associated with a high degree of risk in infectious diseases: a post-hoc analysis of post-marketing surveillance of patients with disseminated intravascular coagulation treated with thrombomodulin alfa

BackgroundIn patients with infectious diseases, disseminated intravascular coagulation (DIC) is often diagnosed without the fibrinogen value. The relationship between hypofibrinogenemia and outcomes of DIC in infectious diseases has thus remained unclear.MethodsWe analyzed 3204 patients who received with thrombomodulin alfa (TM-α) for DIC and suspected DIC. Hypofibrinogenemia was defined by a fibrinogen level < 1.5 g/L.ResultsHypofibrinogenemia was observed in 10.3% of patients with infectious diseases. The frequencies of both bleeding and organ failure symptoms, and the scores for organ failure or the DIC diagnostic criteria were significantly higher in infectious disease patients with hypofibrinogenemia, suggesting that in patients with infectious diseases, hypofibrinogenemia is associated with more progressive and severe DIC. Although the 28-day survival rate and the DIC resolution rate were both significantly lower for infectious disease patients with DIC with hypofibrinogenemia than for those without hypofibrinogenemia, this difference was not observed in DIC patients with hematological diseases.ConclusionsHypofibrinogenemia among infectious disease patients with DIC may reflect increased consumption of fibrinogen due to accelerated coagulation reactions, while hypofibrinogenemia among hematological disease patients with DIC may be caused by fibrinogenolysis due to hyperfibrinolysis, and frequently results in bleeding and multiple-organ failure.

Diagnosis and treatment of disseminated intravascular coagulation in COVID-19 patients: a scoping review.

BackgroundDisseminated intravascular coagulation (DIC) is noted in severe cases of coronavirus disease 2019 (COVID-19). Recently, a number of studies evaluating the diagnosis and treatment of DIC in COVID-19 patients have been reported.ObjectiveThe aim of this study is to identify existing gaps where further research is needed on the diagnosis and treatment of DIC complicated by COVID-19.MethodsWe used the PRISMA Extension for Scoping Reviews. MEDLINE, CENTRAL, WHO-ICTRP, ClinicalTrial.gov and PROSPERO were searched from their inception to 6 October 2020.ResultsSeven studies were selected; five were already published and two are ongoing. DIC was diagnosed using the International Society on Thrombosis and Hemostasis (ISTH) DIC score (n = 4) and the sepsis-induced coagulopathy (SIC) DIC score (n = 5). Seven studies examined the effectiveness of low molecular weight heparin (LMWH); of these, four studies used a prophylactic dose and five used a therapeutic dose of LMWH. A prophylactic dose of unfractionated heparin (UFH) was investigated in two studies.ConclusionStudies on DIC diagnostic criteria and anticoagulants were limited to the ISTH or SIC scores and heparinoids, particularly LMWH. Further studies are needed to compare these with other available DIC scoring systems and anticoagulants.

Advances in the diagnosis and treatment of disseminated intravascular coagulation in haematological malignancies.

Haematological malignancies, including acute leukaemia and non-Hodgkin lymphoma, are one of the underlying diseases that frequently cause disseminated intravascular coagulation (DIC), an acquired thrombotic disorder. Concomitant DIC is associated with the severity of the underlying disease and poor prognosis. The Japanese Society on Thrombosis and Hemostasis released the new DIC diagnostic criteria in 2017. This criteria include coagulation markers such as soluble fibrin and the thrombin-antithrombin complex to more accurately evaluate the hypercoagulable state in patients. Among several groups of anticoagulants available, recombinant human soluble thrombomodulin is most frequently used to treat DIC caused by haematological malignancies in Japan. DIC is remitted in parallel with the improvement of the underlying haematological diseases; thus, there is room for debate regarding whether the treatment of DIC would improve the prognosis of patients. Haematopoietic stem cell transplantation as well as the recently introduced chimeric antigen receptor (CAR)-T-cell therapy are innovative therapies to produce a cure in a subset of patients with haematological malignancies. However, coagulopathy frequently occurs after these therapies, which limits the success of the treatment. For example, DIC is noted in approximately 50% of patients after CAT-T-cell therapy in conjunction with cytokine release syndrome. Hematopoietic stem cell transplantation (HSCT) causes endotheliitis, which triggers coagulopathy and the development of potentially lethal complications, such as sinusoidal obstruction syndrome/veno-occlusive disease and transplant-associated thrombotic microangiopathy. This review article describes the pathogenesis, clinical manifestation, diagnosis, and treatment of DIC caused by haematological malignancies, CAR-T-cell therapy, and HSCT.

Disseminated intravascular coagulation in perinatal medicine

Introduction. Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by intravascular activation of blood clotting without specific localization and arising from various causes. DIC is the most complex and high-priority problem in contemporary clinical medicine including obstetrics and perinatology. DIC significance is related to its peak perinatal mortality, as well as a large rate of complications during childbirth and postpartum period. Aim: to conduct comprehensive data assessment related to DIC pathogenesis and management in pregnant women and newborns. Materials and methods . A search for DIC-related publications within the past 10 years was conducted in international research databases: Scientific Electronic Library Online eLibrary, Google Scholar, ScienceDirect, Cochrane Library, PubMed/Medline. The data regarding DIC diagnostic criteria and markers, as well as current approach to its treatment are presented. Results. DIC may be considered as one of the causes resulting in massive obstetric bleeding. The majority of pregnancy-related complications is manifested as preeclampsia, premature detachment of normally situated placenta and anaphylactoid syndrome of pregnancy. Any massive bleeding should be perceived as hemorrhage resulting from the DIC progression. Conclusion. Knowledge of the DIC pathogenetic mechanisms is necessary for conducting a differential diagnosis and applying timely treatment.

Therapeutic and Adverse Effects of Thrombomodulin Alfa to Treat Sepsis-Induced Disseminated Intravascular Coagulation.

In the treatment of disseminated intravascular coagulation (DIC), which is a complication of underlying diseases such as infections and malignant tumors, effective plasma concentrations of thrombomodulin (TM) alfa range from 300 to 900 ng/mL; however, appropriate concentrations when treating sepsis-induced DIC are unknown. Thus, our aim was to determine the relationship between plasma concentrations of TM alfa and its therapeutic effects, and hemorrhagic adverse events. First, we calculated the plasma trough concentrations of TM alfa in septic DIC patients. Next, we divided patients into two groups according to their plasma concentrations into a low- and high-concentration group based on a cut-off value of 600 ng/mL. Fourteen and 35 patients were included in the low- and high-concentration groups, respectively. The Japanese Association for Acute Medicine DIC diagnostic criteria score 4 days after TM alfa administration decreased significantly by 2.06 points from baseline in the high-concentration group compared with 0.71 points in the low-concentration group. The 90-day survival rate was significantly higher in the high-concentration group (85.4%) than in the low-concentration group (49.0%) (hazard ratio, 0.27; 95% confidence interval: 0.09-0.86). In contrast, the incidence of serious hemorrhage was not significantly different between the groups. The recommended plasma concentration of TM alfa in the treatment of septic DIC was determined to be higher than 600 ng/mL, and a dose of 380 U/kg (0.06 mg/kg) was necessary to achieve this concentration.

Profiles of Coagulation and Fibrinolysis Activation-Associated Molecular Markers of Atypical Hemolytic Uremic Syndrome in the Acute Phase.

Aim: Atypical hemolytic uremic syndrome (aHUS), characterized by thrombotic microangiopathy (TMA), is a genetic, life-threatening disease which needs many differential diagnoses. This study aimed to reveal coagulation and fibrinolysis profiles in aHUS and secondary TMA patients. Furthermore, we investigated whether aHUS patients progress to, and meet, disseminated intravascular coagulation (DIC) criteria.Methods: The acute phase samples were available in 15 aHUS and 20 secondary TMA patients. We measured PT-ratio, activated partial thromboplastin time (APTT), fibrinogen, fibrin degradation product (FDP), fibrin monomer complex (FMC), antithrombin (AT), plasmin-α2 plasmin inhibitor complex (PIC), and von Willebrand factor antigen (VWF:Ag). We examined and compared these tests among aHUS, secondary TMA patients, and healthy volunteer (HV), and evaluated whether patients with aHUS and secondary TMA met DIC criteria.Results: PT-ratio, APTT, FDP, FMC and PIC in patients with aHUS and secondary TMA were higher than those in HV. Fibrinogen and AT showed no significant difference among three groups. VWF:Ag was higher in only aHUS patients. No tests showed significant difference between aHUS and secondary TMA patients. Three aHUS patients out of 15 met DIC criteria.Conclusion: We revealed the profiles and distributions of coagulation and fibrinolysis tests of aHUS and secondary TMA patients. All tests were enhanced compared to HV; however, our results showed the no specificities in distinguishing aHUS from secondary TMA patients. We also clarified that some aHUS patients fulfilled DIC diagnostic criteria, indicating that DIC itself cannot be an exclusion criterion of aHUS.

DIC: state-of-the-art in diagnosis and management

Disseminated intravascular coagulation (DIC) is a serious disease that, in the presence of underlying disease, causes persistent, generalized, marked coagulation activation and recurrent formation of microthrombi in microvessels. Although the DIC pathophysiology differs from that of thrombotic microangiopathy (TMA), distinguishing the two is sometimes challenging. At least, differential diagnosis using coagulation tests of values such as PT and APTT is difficult. While the mechanisms of DIC development differ according to the underlying disease, tissue factor plays a vital role in common. The classification of the DIC type is essential not only for understanding pathophysiology but also for the appropriate choice of DIC treatment. As a revision of the old DIC diagnostic criteria of the Japanese Ministry of Health, Labour and Welfare, new diagnostic criteria for DIC have been established by the Japanese Society on Thrombosis and Hemostasis (2017 edition). The new criteria are estimated to play a pivotal role in the future diagnosis of DIC. From the perspective of analysis by genetic techniques, the protein C/thrombomodulin system and plasminogen activator inhibitor play crucial roles in the control and development of DIC.

Coagulation Derangements in Patients With Refractory Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation

Extracorporeal cardiopulmonary resuscitation (eCPR) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is gaining importance as a rescue therapy for refractory cardiac arrest. VA-ECMO, especially in the setting of eCPR, is plagued by hemorrhagic and thromboembolic complications. The authors' aims were to describe the coagulation profile in refractory cardiac arrest and assess its prognostic role. Single-center retrospective study. Cardiac surgical intensive care unit of a university hospital. One hundred eighty-eight patients treated with eCPR for intra-hospital and out-of-hospital refractory cardiac arrest, between 2008 and 2017. The authors retrospectively analyzed data from the first blood sample drawn during cannulation for VA-ECMO to understand the association of coagulation parameters with survival to hospital discharge, number of blood components transfused, anticoagulation therapy, serum lactate levels, no-flow time, and low-flow time. Platelet count was 126 ± 79 × 109/L and in 17% of the population it was lower than 50 × 109/L, prothrombin time was 3.22 ± 4.01, activated partial thromboplastin time was 117 ± 78 seconds, fibrinogen was 186 ± 148 mg/dL, antithrombin was 47 ± 16%, and D-dimer was ≥2-fold the normal upper limit in 95% of patients. Fifty percent of patients had a disseminated intravascular coagulation (DIC) score ≥6 (52% among out-of-hospital cardiac arrest, 33% among in-hospital cardiac arrest), according to the criteria of the Japanese Society on Thrombosis and Hemostasis (2016). The median DIC score was 5.5 points (interquartile range 4-8), significantly different between survivors and nonsurvivors (4 [3-6] v 6 [4-8], p = 0.007). Every DIC score point contributed to the mortality risk (OR 1.34, 95% CI 1.09-1.67, p = 0.006). Patients with overt DIC less frequently received anticoagulants (28.6% v 55.9%, p = 0.002), started anticoagulant therapy later (12 [10-23] v 8.5 [5-12] hours, p = 0.045), and received a larger quantity of blood products (11 [4-23] v 3 [0-8.5] units, p < 0.0001). Coagulation derangements are frequent in patients with refractory cardiac arrest and have important consequences for eCPR management for anticoagulant therapy and blood product transfusion. The presence of DIC diagnostic criteria should be considered among the prognostic factors in this population of patients.

Treatment of DIC associated with hematological malignancies

To improve the prognosis of patients with hematological malignancies, close attention should be paid to major hemorrhage in the clinical management of patients with disseminated intravascular coagulation (DIC) associated with hematological malignancies, especially from diagnosis to induction therapy. Cerebral, alveolar, and GI tract hemorrhages may cause a life-threatening event. Therefore, DIC should always be suspected, and careful observation for hemorrhage and hemostatic examination should be performed. The diagnostic criteria for DIC according to the Japanese Ministry of Health and Welfare and the Japanese Society on Thrombosis and Hemostasis (2017) are useful resources for the diagnosis of DIC associated with hematological malignancies. Following diagnosis, treatment for DIC should be initiated as soon as possible, and the risk of hemorrhage should be considered when choosing the anticoagulant. Sufficient amount of fresh frozen plasma or platelet concentrates should be used if necessary. Recombinant human soluble thrombomodulin has promising potential for use as a drug for the treatment of DIC associated with hematological malignancies that can manage a wide range of pathologic processes such as hypercoagulable states, inflammation, excessive fibrinolysis, and easy hemorrhage caused by endothelial cell damage.

A Proposal of the Modification of Japanese Society on Thrombosis and Hemostasis (JSTH) Disseminated Intravascular Coagulation (DIC) Diagnostic Criteria for Sepsis-Associated DIC.

Sepsis-associated disseminated intravascular coagulation (DIC) carries a high risk of death. Thus, a simple tool to quickly establish DIC diagnosis is required. The purpose of this study was to introduce the simple and reliable tool for the prediction of outcome in patients with sepsis complicated by coagulopathy. We investigated the performance of simplified Japanese Society on Thrombosis and Hemostasis (JSTH) DIC diagnostic criteria. In this study, we conducted a retrospective, multicenter survey in 107 general emergency and critical care centers in secondary and tertiary care hospitals. A total of 918 patients with sepsis-associated coagulopathy who underwent antithrombin supplementation were examined. The relationships between patient mortality and each of the baseline (ie, before treatment) JSTH-DIC diagnostic criteria were examined. A reduced platelet count, increased prothrombin time (PT) ratio, and lower antithrombin activity were correlated with 28-day mortality, while fibrinogen and fibrin degradation product (FDP) level were not. Thus, the number of points assigned to FDP levels was reduced from 3 to 1 (above 20 μg/mL). The simplified JSTH diagnostic criteria combining platelet count, PT ratio, antithrombin activity, and FDP level (reduction in the maximum score) strongly predicted 28-day mortality and allowed us to diagnose a larger/similar number of patients with DIC as compared to the original JSTH-DIC. The simplified JSTH-DIC diagnostic criteria show a similar performance to JSTH-DIC criteria in patients with septic coagulopathy. The lower number of laboratory markers used in the simplified JSTH-DIC score may increase its applicability and routine use in emergency and critical care setting.

DIC: an update on diagnosis and treatment.

Disseminated intravascular coagulation (DIC) was considered to be a fatal disease. However, it has recently been suggested that very early DIC protects the host against microthrombosis and infection localization. Therefore, early treatment of DIC may be contraindicated in patients with sepsis. These factors suggest that the diagnosis and treatment of DIC will gain further importance. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG2016), which include details regarding the management of DIC, have been recently published. Differences in recommendations for DIC treatment, such as antithrombin and recombinant human thrombomodulin, between J-SSCG2016 and other guidelines, including the Japanese Society on Thrombosis and Hemostasis (JSTH), British Committee for Standards in Haematology (BCST), Italian Society for Thrombosis and Haemostasis (SISET), and International Society on Thrombosis and Haemostasis (ISTH) have been discussed. Furthermore, differences in the diagnostic criteria for DIC between the Japanese Ministry of Health, Labor and Welfare, ISTH overt, ISTH non-overt, Japanese Association for Acute Medicine, and JSTH have been discussed.

Emergent Uterine Arterial Embolization Using N-Butyl Cyanoacrylate in Postpartum Hemorrhage with Disseminated Intravascular Coagulation.

Although it is widely accepted that uterine artery embolization (UAE) is an effective therapeutic strategy for postpartum hemorrhage (PPH), no consensus has been reached regarding the efficacy of UAE in patients with PPH with disseminated intravascular coagulation (DIC). This single-center retrospective cohort study included patients treated with UAE using NBCA for PPH between 2010 and 2015. The patients were divided into DIC and non-DIC groups, according to the obstetrical DIC score and the overt DIC diagnostic criteria issued by the International Society of Thrombosis and Haemostasis (ISTH), and their clinical outcomes were compared. There were 28 patients treated with UAE using NBCA. Complete hemostasis was achieved by UAE in 19 of 28 patients. In eight of nine patients with unsuccessful hemostasis, surgical hemostatic interventions were performed after UAE, and hemostasis was achieved in seven patients. UAE using NBCA showed no significant intergroup differences in complete hemostasis according to the presence or absence of DIC based on obstetrical DIC score (70% versus 62.5%, P = 1.000) or ISTH DIC score (54.5% versus 76.5%, P = 0.409). UAE using NBCA may be a useful first-choice treatment for PPH with DIC.

Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with out-of-hospital cardiac arrest.

BackgroundWe tested the hypothesis that disseminated intravascular coagulation (DIC) during the early phase of post-cardiopulmonary resuscitation (CPR) is associated with systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS) and affects the outcome of out-of-hospital cardiac arrest (OHCA) patients.MethodsA review of the computer-based medical records of OHCA patients was retrospectively conducted and included 388 patients who were divided into DIC and non-DIC patients based on the Japanese Association for Acute Medicine DIC diagnostic criteria. DIC patients were subdivided into two groups: those with and without hyperfibrinolysis. Pre-hospital factors, platelet count, coagulation and fibrinolysis markers and lactate levels within 24 h after resuscitation were evaluated. The outcome measure was all-cause hospital mortality.ResultsDIC patients exhibited lower platelet counts, prolonged prothrombin time, decreased levels of fibrinogen and antithrombin associated with increased fibrinolysis than those without DIC. DIC patients more frequently developed SIRS and MODS, followed by worse outcomes than non-DIC patients. The same changes were observed in DIC patients with hyperfibrinolysis who showed a higher prevalence of MODS, leading to worse outcome than those without hyperfibrinolysis. Logistic regression analyses showed that lactate levels predicted hyperfibrinolysis and DIC is an independent predictor of patient death. Survival probabilities of DIC patients during hospital stay were significantly lower than non-DIC patients. The area under the receiver operating characteristic curve of DIC for the prediction of death was 0.704.ConclusionsThe fibrinolytic phenotype of DIC during the early phase of post-CPR more frequently results in SIRS and MODS, especially in patients with hyperfibrinolysis, and affects the outcome of OHCA patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12959-016-0116-y) contains supplementary material, which is available to authorized users.