Non-paroxysmal junctional tachycardia complicating disseminated intravascular coagulation during massive surgical hemorrhage: A case report.

RATIONALE: Non-paroxysmal junctional tachycardia (NPJT) is a self-limiting supraventricular tachycardia associated with primary heart disease, cardiac surgery, digitalis toxicity, and metabolic or electrolyte imbalances. However, NPJT caused enhanced normal automaticity even in the absence of structural heart disease can be fatal if not managed properly. PATIENT CONCERNS: A 74-year-old hypertensive female patient was scheduled for transureteroureterostomy and right ureteroneocystostomy under general anesthesia. DIAGNOSIS: The patient developed NPJT without visible P wave and severe hypotension due to adrenergic stimulation in response to massive hemorrhage during surgery. INTERVENTIONS: NPJT with hypotension was initially converted to sinus rhythm with normotension with administration of adenosine and esmolol. However uncontrolled surgical hemorrhage and administration of large dose of vasopressors eventually perpetuated NPJT refractory to antiarrhythmic drugs. OUTCOMES: Despite intravenous fluid resuscitation and massive transfusion, the patient was deteriorated hemodynamically due to uncontrolled bleeding and persistent NPJT, which resulted in hypovolemic shock and fatal disseminated intravascular coagulation (DIC). LESSONS: NPJT can occur by enhanced automaticity due to increased catecholamine during severe surgical hemorrhage. Although NPJT is generally self-limiting, it can be refractory to antiarrhythmic agents and accelerate hypotension if the surgical bleeding is uncontrolled. Therefore, aggressive management of the primary pathologic condition is crucial for the management of NPJT and hemodynamic collapse even in the absence of structural heart disease.

Contribution of staphylococcal virulence factors in the pathogenesis of thrombosis.

Staphylococci are responsible for many infections in humans, starting with skin and soft tissue infections and finishing with invasive diseases such as endocarditis, sepsis and pneumonia, which lead to high mortality. Patients with sepsis often demonstrate activated clotting pathways, decreased levels of anticoagulants, decreased fibrinolysis, activated endothelial surfaces and activated platelets. This results in disseminated intravascular coagulation and formation of a microthrombus, which can lead to a multiorgan failure. This review describes various staphylococcal virulence factors that contribute to vascular thrombosis, including deep vein thrombosis in infected patients. The article presents mechanisms of action of different factors released by bacteria in various host defense lines, which in turn can lead to formation of blood clots in the vessels.

Cancer-related thrombotic microangiopathy and disseminated intravascular coagulation in a patient with bone marrow carcinomatosis of unknown primary origin: A case report.

BACKGROUND: Cancer-related thrombotic microangiopathy (CR-TMA) is a rare type of Coombs-negative hemolytic anemia, which is caused by malignancy and has a poor prognosis. CASE: A 76-year-old female was referred to our hospital due to Coombs-negative hemolytic anemia, which was causing fatigue and dyspnea on exertion, accompanied by schistocytosis. A bone marrow examination demonstrated bone marrow carcinomatosis, and the tumor cells were morphologically suspected to be signet-ring cell carcinoma cells. As we failed to find the primary tumor site before the patient died, she was diagnosed with CR-TMA due to bone marrow carcinomatosis of unknown primary origin. Thrombotic thrombocytopenic purpura (TTP) was rapidly ruled out based on her PLASMIC score. In addition, immunohistochemical staining of a clot section of the bone marrow and tumor marker data were useful for narrowing down the likely primary tumor site. CONCLUSION: Although CR-TMA is an extremely rare phenomenon, clinicians who suspect CR-TMA should quickly rule out TTP and decide whether to provide appropriate chemotherapy or plan for palliative care.

Comparison of five different disseminated intravascular coagulation criteria in predicting mortality in patients with sepsis.

OBJECTIVE: Even though patients with sepsis and DIC have a higher mortality rate compared to those without DIC, screening for DIC is not currently part of sepsis management protocols. This may be due to a lack of literature on the frequency of DIC occurrence in sepsis patients, as well as the absence of evidence on the optimal DIC criteria to use for identifying DIC and predicting mortality among the five criteria available. To address this gap, this study investigates the predictive value of five different criteria for diagnosing DIC and its relationship to patient outcomes in our population of sepsis patients. METHODS: In the Medicine department of Aga Khan University Hospital, a retrospective observational study was conducted, enrolling all adult patients with International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) coding of sepsis and clinical suspicion of DIC between January 2018 and December 2020. To diagnose DIC, five different criteria were utilized, namely the International Society of Thrombosis and Hemostasis (ISTH), the Korean Society on Thrombosis and Hemostasis (KSTH), the Japanese Association for Acute Medicine (JAAM), the revised-JAAM (RJAAM), and the Japanese Ministry of Health and Welfare (JMHW). The study analyzed the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of these five criteria, as well as the overall prediction of mortality. RESULTS: Of 222 septic patients included in this study with clinical suspicion of DIC, 94.6% of patient had DIC according to KSTH criteria, followed by JAAM (69.4%), ISTH (64.0%), JMHW (53.2%) and lastly R-JAAM (48.6%). KSTH had sensitivity of 95.4% in diagnosing DIC and predicting mortality with a positive predictive value of 70% but specificity of 7.3% only. JAAM had sensitivity of 75.9%, positive predictive value of 75.9% with a specificity of 45.5%. ISTH had sensitivity of 69.4%, positive predictive value 75.3% and specificity of 48.5%. CONCLUSION: DIC can impose a significant burden on septic patients and its presence can lead to higher mortality rates. Early detection through screening for DIC in septic patients can potentially reduce mortality. However, it is necessary to identify the most appropriate diagnostic criteria for each population, as various criteria have demonstrated different performance in different populations. Establishing a gold standard for each population can aid in accurate diagnosis of DIC.

Disseminated intravascular coagulation score evolution in 48 h predicts early death in acute promyelocytic leukemia patients.

INTRODUCTION: Early death (ED) is the unsolved issue of acute promyelocytic leukemia (APL). The disseminated intravascular coagulation (DIC) score has been proposed as a marker of bleeding and death in APL; whether its temporal evolution predicts outcomes in APL is unknown. We evaluated whether an increasing score 48 h after diagnosis associates with ED. METHODS: Retrospective, single-center study, including patients with newly diagnosed APL between 2000 and 2023, treated with all-transretinoic acid (ATRA) plus anthracycline or arsenic trioxide (ATO). "DIC score worsening" was defined as ≥1 point increase in the score after 48 h, and ED as death within 30 days of diagnosis. RESULTS: Eighty-six patients were included, with median age of 46 years (17-82). ED patients (26.7%) more frequently had age >60 years and worsening DIC score after 48 h. These were also the only predictors of ED identified in both univariate and multivariate (OR 4.18, p = .011; OR 7.8, p = .005, respectively) logistic regression analysis. CONCLUSION: This is the first study on DIC score evolution in APL-a worsening DIC score 48 h after diagnosis is a strong independent predictive factor of ED. We propose a reduction of the DIC score from diagnosis as a new treatment goal in APL care.

The ISTH DIC-score predicts early mortality in patients with non-promyelocitic acute myeloid leukemia.

Coagulation disorders frequently complicate the clinical course of acute myeloid leukemia (AML) patients. This study examined the frequency and prognostic significance, with regards of early mortality, of the presence of overt disseminated intravascular coagulation (DIC) at AML diagnosis and its correlation with clinical and biological characteristics. A retrospective analysis of 351 newly diagnosed non-promyelocytic AML patients was conducted, utilizing the 2018 ISTH DIC-Score criteria to evaluate the presence of overt DIC at AML onset. The study cohort had a median age of 65 years with a predominance of male gender (59 %). Overt DIC was present in 21 % of cases and was associated with advanced age, comorbidities, poor performance status, hyperleukocytosis, LDH levels, NPM1 mutations, expression of CD33 and CD4, and lack of expression of CD34. With a median follow-up of 72 months (3-147 months), the 6-year overall survival (OS) was 17.4 %, with patients having overt DIC showing significantly poorer outcomes (7.2 % compared to 20.3 % of those without DIC, p < 0.001). Patients with overt DIC showed markedly high early mortality rates at 30 (42.5 % vs 8 %), 60 (49.3 % vs 16.9 %), and 120 days (64.4 % vs 25.6 %) from disease onset. In multivariate analysis overt DIC retained its independent prognostic value for early mortality. In conclusion, the prevalence and clinical relevance of DIC in non-promyelocytic AML is not negligible, underlining its potential as an unfavorable prognostic marker. In newly diagnosed patients with AML, early recognition and measure to counteract coagulation disturbances might help mitigate the elevated mortality risk associated with DIC.

Disseminated Intravascular Coagulation in Acute Promyelocytic Leukemia Patients: A Retrospective Analysis of Outcomes and Healthcare Burden in US Hospitals

Objective: Acute promyelocytic leukemia (APL) is associated with an elevated risk of developing disseminated intravascular coagulation (DIC). The purpose of this study was to assess the outcomes of hospitalizations related to DIC in APL and their impact on healthcare. Materials and Methods: This study entailed a cross-sectional and retrospective analysis of the US National Inpatient Sample database. We identified adults with APL and categorized them into groups of patients with and without DIC. Our focus areas included in-hospital mortality, length of stay, charges, and complications associated with DIC. Unadjusted odds ratios/coefficients were computed in univariate analysis, followed by adjusted odds ratios (aOR)/coefficients from multivariate analysis that accounted for confounding factors. Results: Our analysis revealed that APL patients with DIC had a substantially higher aOR for mortality (aOR: 6.68, 95% confidence interval [CI]: 4.76-9.37, p<0.001) and a prolonged length of stay (coefficient: 10.28 days, 95% CI: 8.48-12.09, p<0.001) accompanied by notably elevated total hospital charges (coefficient: $215,512 [95% CI: 177,368-253,656], p<0.001), thereby emphasizing the reality of extended medical care and economic burden. The presence of DIC was associated with increased odds of sepsis, vasopressor support, pneumonia, acute respiratory failure, intubation/mechanical ventilation, and acute kidney injury, reflecting heightened vulnerability to these complications. Patients with DIC demonstrated significantly higher odds ratios for major bleeding, intracranial hemorrhage, gastrointestinal bleeding, red blood cell transfusion, platelet transfusion, fresh frozen plasma transfusion, and cryoprecipitate transfusion, highlighting the pronounced hematological risks posed by DIC. Conclusion: This study has revealed the significant associations between DIC in APL and various outcomes, underscoring the clinical and economic implications of these conditions. The hematological risks further increase patients' vulnerability to bleeding events and the need for transfusions.

A systematic review and meta-analysis of recombinant human soluble thrombomodulin for the treatment of DIC associated with hematological malignancies.

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.

Anaphylaxis and Severe Disseminated Intravascular Coagulation Due to Remdesivir.

A 69-year-old woman suffering with multiple myeloma developed coronavirus disease 2019 (COVID-19). Shortly after administration of remdesivir, she presented with symptoms of facial flushing, wheezing, and hypoxemia. Subsequently, thrombocytopenia and hypofibrinogenemia rapidly manifested, leading to a diagnosis of enhanced fibrinolytic-type disseminated intravascular coagulopathy (DIC). This clinical presentation was considered an immediate hypersensitivity reaction with associated coagulation abnormalities induced by remdesivir. Although remdesivir is generally considered safe and efficacious in the treatment of COVID-19, physicians should remain vigilant regarding the potential for severe adverse events associated with this medication.

Levels of peripheral blood routine, biochemical and coagulation parameters in patients with hemorrhagic fever with renal syndrome and their relationship with prognosis: an observational cohort study.

BACKGROUND: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation. METHODS: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed. RESULTS: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death). CONCLUSIONS: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.

Microparticle-associated tissue factor activity correlates with the inflammatory response in septic disseminated intravascular coagulation patients.

Background: Sepsis is often accompanied by the formation of disseminated intravascular coagulation (DIC). Microparticles can exert their procoagulant and proinflammatory properties in a variety of ways. The purpose of this study was to investigate the relationship between microparticle-associated tissue factor activity (TF+-MP activity) and the inflammatory response. Methods: Data from a total of 31 DIC patients with sepsis and 31 non-DIC patients with sepsis admitted to the ICU of the First Affiliated Hospital of Harbin Medical University from December 2017 to March 2019 were collected. Blood samples were collected and DIC scores were calculated on the day of enrollment. The hospital's clinical laboratory completed routine blood, procalcitonin, and C-reactive protein tests. TF+-MP activity was measured using a tissue factor-dependent FXa generation assay. Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels were determined using ELISA kits. Results: Compared with the non-DIC group, the DIC group had higher levels of leukocytes, neutrophils, procalcitonin, C-reactive protein, IL-1ß, and TNF-α, and more severe inflammatory reactions. TF+-MP activity in the DIC group was higher than that in the non-DIC group. In sepsis patients, TF+-MP activity was strongly correlated with inflammatory response indices and DIC scores. Conclusion: TF+-MP activity may play a major role in promoting inflammatory response in septic DIC.

Efficacy and safety of heparin for sepsis-induced disseminated intravascular coagulation (HepSIC): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Disseminated intravascular coagulation (DIC) occurs in 30-50% of septic patients and contributes to high mortality in the intensive care unit (ICU). However, there are few proven interventions for coagulation disorder management in sepsis. Experimental and clinical data have demonstrated that sepsis could benefit from unfractionated heparin (UFH) treatment. To date, there are no large multicenter trials to determine the safety and efficacy of UFH in septic patients with suspected DIC. METHODS: A multicenter, double-blinded, placebo-controlled randomized trial is designed to recruit 600 patients who met sepsis 3.0 criteria and suspected DIC. Participants will be randomized (1:1) to receive UFH or saline via continuous intravenous administration for 7 days within 6 h of enrolment. The primary outcome is ICU mortality. The secondary outcome includes 28-day all-cause mortality, the improvement of Sequential Organ Failure Assessment scores, and the incidence of major hemorrhage. Investigators, participants, and statisticians will be blinded to the allocation. DISCUSSION: The HepSIC trial is to evaluate the efficacy and safety of UFH on sepsis-related DIC across different areas of China. The small dosage of UFH administration would offer a new potential approach for treating sepsis-related coagulation disorders. ETHICS AND DISSEMINATION: Ethical approval was granted by all the ethics committees of 20 participant centers. Results will be disseminated via peer-reviewed publications and presented at conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT02654561. Registered on 13 January 2016.

Differences between Japanese new criteria and pregnancy-specific modified ISTH DIC scores for obstetrical DIC diagnosis.

The new Japanese diagnostic criteria for obstetrical disseminated intravascular coagulation (DIC) (tentative version) were released in June 2022. We aimed to demonstrate the differences in characteristics between women with DIC diagnosed using the new Japanese criteria and those diagnosed using the pregnancy-specific modified International Society on Thrombosis and Hemostasis DIC score, also known as the pregnancy-specific modified ISTH DIC score, which was released in 2014. In this retrospective cohort study, all participants were retrospectively diagnosed based on both criteria. Six women were diagnosed with obstetrical DIC based on both criteria (Group A). Of the 43 women diagnosed with obstetrical DIC based on the worldwide criteria, 36 were diagnosed with non-obstetrical DIC based on the new Japanese criteria (Group B). Group A had significantly lower fibrinogen levels and significantly higher prothrombin time differences and scores of underlying diseases (particularly postpartum hemorrhage with coagulopathy) and laboratory findings than Group B. Additionally, Group A had significantly higher rates of platelet concentrate (PC) transfusion therapy for obstetrical DIC and more transfusions of fresh frozen plasma and/or cryoprecipitate, red blood cells and PC than Group B. Thus, the new Japanese criteria detected more severe cases of obstetrical DIC compared with the worldwide criteria.

The two therapeutic strategies of surgical intervention and medical management in a patient with enhanced-fibrinolytic type of disseminated intravascular coagulation after aortic replacement for Stanford type A aortic dissection with chronic heart and renal failure.

BACKGROUND: Management of the enhanced-fibrinolytic type of disseminated intravascular coagulation (DIC) caused by aortic disorders is the two strategies of surgical intervention and medical treatment based on the patient's age and comorbidities. CASE PRESENTATION: An 81-year-old woman with a history of two previous aortic surgeries and chronic heart and renal failure was admitted for uncontrollable subcutaneous hemorrhage. The hemorrhage was caused by the enhanced-fibrinolytic type of disseminated intravascular coagulation (DIC) caused by periprosthetic graft hematoma after aortic replacement for Stanford type A aortic dissection. Open thoracic hemostasis temporarily controlled the subcutaneous hemorrhage, but she was readmitted for the recurrence seven months after discharge. On the second admission, the combination of anticoagulant and antifibrinolytic agents was successful. CONCLUSION: Management of the enhanced-fibrinolytic type of DIC caused by aortic disorders is important of a successful combination of surgical and medical therapy tailored the patient's condition.

HMG-CoA reductase inhibitors and the attenuation of risk for disseminated intravascular coagulation in patients with sepsis.

BACKGROUND: Disseminated Intravascular Coagulation (DIC) is a syndrome of dysregulated coagulation. Patients with sepsis are at increased risk for DIC. HMG-CoA Reductase Inhibitors (Statins) are primarily used as lipid-lowering agents; however, studies have suggested statins may possess anti-inflammatory, antithrombotic, anticoagulant, and endothelial stabilizing properties. These mechanisms may oppose those that underlie the pathogenesis of septic DIC. METHODS: To evaluate whether statins may be protective against the development of DIC, we conducted a multi-center, retrospective case-control study where 86,638 critically ill patients admitted to the ICU with sepsis, severe sepsis or septic shock were identified during a 3-year period. Patients who developed DIC during their hospitalization were identified and stratified by whether they received a statin or not during their hospitalization. Odds ratios for development of DIC was calculated by composite of any statin, as well as low, moderate, and high intensity statins. RESULTS: 2236 patients would develop DIC compared to 84,402 who did not. The use of any statin was associated with a reduced likelihood for developing DIC (odds ratio [OR], 0.69; 95% CI, 0.61-0.78). This was observed with use of both moderate (OR, 0.64; 95% CI, 0.53-0.77) and high (OR, 0.72; 95% CI, 0.61-0.84) but not low intensity statins (OR, 0.84; 95% CI, 0.53-1.32). CONCLUSIONS: The use of moderate and high intensity statins was associated with a significantly reduced odds of developing DIC in critically ill patients with sepsis. This present study may be the first to suggest that statin medications may independently reduce the frequency of DIC in critically ill patients with severe sepsis or septic shock. More research is needed to investigate the potential for this class of medication to be protective against DIC.

Phenotypes of Disseminated Intravascular Coagulation.

Two phenotypes of disseminated intravascular coagulation (DIC) are systematically reviewed. DIC is classified into thrombotic and fibrinolytic phenotypes characterized by thrombosis and hemorrhage, respectively. Major pathology of DIC with thrombotic phenotype is the activation of coagulation, insufficient anticoagulation with endothelial injury, and plasminogen activator inhibitor-1-mediated inhibition of fibrinolysis, leading to microvascular fibrin thrombosis and organ dysfunction. DIC with fibrinolytic phenotype is defined as massive thrombin generation commonly observed in any type of DIC, combined with systemic pathologic hyperfibrinogenolysis caused by underlying disorder that results in severe bleeding due to excessive plasmin formation. Three major pathomechanisms of systemic hyperfibrinogenolysis have been considered: (1) acceleration of tissue-type plasminogen activator (t-PA) release from hypoxic endothelial cells and t-PA-rich storage pools, (2) enhancement of the conversion of plasminogen to plasmin due to specific proteins and receptors that are expressed on cancer cells and endothelial cells, and (3) alternative pathways of fibrinolysis. DIC with fibrinolytic phenotype can be diagnosed by DIC diagnosis followed by the recognition of systemic pathologic hyperfibrin(ogen)olysis. Low fibrinogen levels, high fibrinogen and fibrin degradation products (FDPs), and the FDP/D-dimer ratio are important for the diagnosis of systemic pathologic hyperfibrin(ogen)olysis. Currently, evidence-based treatment strategies for DIC with fibrinolytic phenotypes are lacking. Tranexamic acid appears to be one of the few methods to be effective in the treatment of systemic pathologic hyperfibrin(ogen)olysis. International cooperation for the elucidation of pathomechanisms, establishment of diagnostic criteria, and treatment strategies for DIC with fibrinolytic phenotype are urgent issues in the field of thrombosis and hemostasis.

Trauma-induced innate immune activation and disseminated intravascular coagulation.

Dysregulated innate immunity participates in the pathomechanisms of disseminated intravascular coagulation (DIC) in trauma-induced coagulopathy. Accidental and regulated cell deaths and neutrophil extracellular traps release damage-associated molecular patterns (DAMPs), such as histones, nuclear and mitochondrial DNA, and high-mobility group box 1, into circulation immediately after trauma. DAMP-induced inflammation activation releases tissue factor-bearing procoagulant extracellular vesicles through gasdermin D-mediated pore formation and plasma membrane rupture by regulated cell death. DAMPs also evoke systemic inflammation, platelet, coagulation activation, and impaired fibrinolysis associated with endothelial injury, leading to the dysfunction of anticoagulation systems, which are the main pathophysiological mechanisms of DIC. All these processes induce systemic thrombin generation in vivo, not restricted to the injury sites immediately after trauma. Thrombin generation at the site of injury stops bleeding and maintains homeostasis. However, DIC associated with endothelial injury generates massive thrombin, enhancing protease-activated, receptor-mediated bidirectional interplays between inflammation and coagulation, aggravating the diverse actions of thrombin and disturbing homeostasis. Insufficiently regulated thrombin causes disseminated microvascular thrombosis, resulting in tissue hypoxia due to reduced oxygen delivery, and mitochondrial dysfunction due to DAMPs causes tissue dysoxia. In addition, DAMP-induced calcium influx and overload, as well as neutrophil activation, play a role in endothelial cell injury. Tissue hypoxia and cytotoxicity result in multiple organ dysfunction in DIC after trauma. Controls against dysregulated innate immunity evoking systemic inflammation, thrombin generation, and cytotoxicity are key issues in improving the prognosis of DIC in trauma-induced coagulopathy.