Disseminated Intravascular Coagulation Score Research Articles

Overt disseminated intravascular coagulation and antithrombin III predict bleeding and in-hospital mortality in patients undergoing extracorporeal membrane oxygenation.

Limited data are available on the relationship of disseminated intravascular coagulation (DIC) with mortality in patients receiving extracorporeal membrane oxygenation (ECMO). Thus, we investigated the association of DIC score and antithrombin (AT) III with clinical outcomes in patients undergoing ECMO. We analyzed 703 patients who underwent ECMO between January 2014 and May 2022 at Samsung Medical Center. The DIC score was calculated using laboratory findings within 24 h of the ECMO initiation, and ≥ 5 was defined as overt DIC. In addition, the AT III level was measured to identify the correlation with the DIC score. Among the study patients, 169 (24.0%) were diagnosed with overt DIC (DIC group) during early maintenance therapy. In-hospital mortality was significantly higher in the DIC group than in the non-DIC group (55.0% vs. 36.5%, p < 0.001). Bleeding events were significantly higher in the group of patients with a DIC score of 7 or 8 than in the other group (20.8% vs. 8.4%, p = 0.038). DIC score negatively correlated with AT III level (r = -0.417, p < 0.001). The predictive performance of AT III for overt DIC had statistical significance with a c-static of 0.81 (95% confidence interval (CI), 0.77-0.84, p < 0.001). Overt DIC was associated with higher in-hospital mortality and a tendency to bleed in ECMO patients. Furthermore, AT III plasma levels can easily predict overt DIC in patients undergoing ECMO. These findings suggest that monitoring AT III plasma levels may be important in the management of ECMO.

Coagulopathy in pediatric acute promyelocytic leukemia in Bangladesh: A single-center, prospective study

BackgroundAcute promyelocytic leukemia (APL) is one of the most curable subtypes of acute myeloid leukemia in childhood. It usually presents with a characteristic coagulopathy. The aim of the study was to determine the extent and outcome of this coagulation disorder. MethodsThis prospective observational study was conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, and included PML:RAR-α (Promyelocytic Leukemia-Retinoic Acid Receptor-α) positive APL cases. At presentation, all patients were assessed with coagulation parameters and followed up clinically and hematologically while treated with ATRA (all-trans-retinoic acid)-based chemotherapy. The presence of disseminated intravascular coagulation (DIC) was determined using the DIC scoring system of the International Society on Thrombosis and Hemostasis (ISTH). ResultsAmong 20 APL cases, the mean DIC score was 5.75 ± 0.6. DIC was detected in 90% (n = 18/20) of the patients. The incidence of fatal thrombo-hemorrhagic complications was 15% (n = 3/20). Though hemorrhagic complications are common, thrombosis may also occur in pediatric APL.

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

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. 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. 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. 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.

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.

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

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. 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-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels were determined using ELISA kits. Compared with the non-DIC group, the DIC group had higher levels of leukocytes, neutrophils, procalcitonin, C-reactive protein, IL-1β, 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. TF+-MP activity may play a major role in promoting inflammatory response in septic DIC.

Risk stratification utilizing sequential organ failure assessment (SOFA) score, antithrombin activity, and demographic data in sepsis-associated disseminated intravascular coagulation (DIC)

Disseminated intravascular coagulation (DIC) is a frequent complication in patients with sepsis and is associated with increased mortality. Anticoagulant therapy may be appropriate for certain patients with DIC, particularly those with increased disease severity and deficiency in the physiologic anticoagulant antithrombin. We retrospectively analyzed post-marketing survey data from 1562 patients with sepsis-associated DIC and antithrombin activity of 70% or less. All the patients were treated with antithrombin concentrates. Baseline sequential organ failure assessment (SOFA) score, DIC score, and antithrombin activity were assessed. Cox multivariate regression analysis, Kaplan–Meier curve analysis, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the performance of variables used to assess mortality. Furthermore, a decision tree was constructed to classify the risk of 28-day mortality. COX multivariate regression analysis demonstrated a significant association of age, sex, baseline SOFA score, baseline antithrombin activity, and the presence of pneumonia or skin/soft tissue infection with increased mortality. The area under the curve of SOFA score or antithrombin activity for mortality was 0.700 and 0.614, respectively. Kaplan–Meier analysis demonstrated that mortality was significantly higher in patients with SOFA score ≥ 12 and antithrombin activity < 47%. The decision tree analysis accurately classified the risk of death into high (> 40%), medium (40%–20%), and low (< 20%) categories in 86.1% of the cohort. Twenty eight-day mortality can be strongly predicted using baseline SOFA score, antithrombin activity, infection site, age, and sex as variables in the clinical decision tree for patients with sepsis-associated disseminated intravascular coagulation (DIC).

The Danish Disseminated Intravascular Coagulation (DANDIC) Cohort Study: Incidence and Prognosis

Introduction: Disseminated intravascular coagulation (DIC) is a serious condition with poor prognosis and limited treatment options. Despite being a devastating disorder, data on the incidence and prognosis remains limited. Previous studies are more than 10 years old, were limited to selected patients e.g., patients admitted to university hospitals, and were unable to track transitions in sites of care. In this study, we examined the incidence and prognosis, including time trends, of DIC. Methods: Potential DIC cases were identified from the hospital laboratory database by coagulation biomarkers in the Central Denmark Region, Denmark. Patients were eligible for inclusion if they were above 18 years of age and had an International Society on Thrombosis and Haemostasis (ISTH) DIC score of five or higher or a Japanese Association for Acute Medicine (JAAM) DIC score of four or higher. An underlying disease compatible with DIC was also required for inclusion and was assessed by medical chart review. The underlying diseases were infection, malignant disorder, obstetric complications, trauma, cardiac arrest, and other less common conditions. Exclusion criteria were other conditions affecting the coagulation system. 6748 medical charts were reviewed, and 2565 patients were included in the cohort from January 2013 to December 2020. Incidence rates were computed by the number of cases per year divided with the midyear population in the Central Denmark Region and were age and sex standardized to the year 2020. Survival was determined by Kaplan-Meier estimates. Results: Out of the 2565 patients, the median age was 64 years (25th-75th percentile, 48-74 years) and 1439 (56.1%) were male. At inclusion 1055 patients had an ISTH DIC score of 5-6, 145 an ISTH DIC score of 7-8, 2014 a JAAM DIC score of 4-6 and 302 a JAAM DIC score of 7-8. The overall incidence rate per 100,000 person-years declined from 33.1 in 2013 [95% confidence interval (CI), 29.6 to 36.8] to 24.0 in 2020 [95% CI, 21.1 to 27.1]. Overall 30-day survival remained relatively unchanged at 65.0% in 2013 [95% CI, 59.9% to 70.6%] and 58.7% in 2020 [95% CI, 52.9% to 65.0%]. The incidence rate of patients with an ISTH score of 5-6 at baseline was 14.1 in 2013 [95% CI, 11.8 to 16.5] and 10.8 in 2020 [95% CI, 8.9 to 12.8]. The incidence rate of patients with an ISTH score of 7-8 at baseline remained nearly constant at 1.4 in 2013 [95% CI, 0.7 to 2.1] and 1.2 in 2020 [95% CI, 0.6 to 2.0]. Thirty-day survival was 56.2% [95% CI, 53.3% to 59.3%] for patients with an ISTH DIC score of 5-6 and 33.8% [95% CI, 26.9% to 42.4%] for patients with an ISTH DIC score of 7-8. Patients with JAAM DIC scores of 4-6 at baseline showed a decline in incidence rate from 25.8 in 2013 [95% CI, 22.7 to 29.9] to 19.4 in 2020 [95% CI, 16.8 to 22.1]. However, the incidence rate of patients with JAAM DIC scores of 7-8 remained steady at 3.6 in 2013 [95% CI, 2.4 to 4.8] and 2.3 in 2020 [95% CI, 1.4 to 3.2]. Patients with a JAAM DIC score of 4-6 at baseline had a 30-day survival rate of 62.2% [95% CI, 60.0% to 64.3%] while patients with a JAAM DIC score of 7-8 had a lower 30-day survival of 53.6% [95% CI, 48.3% to 59.6%]. Conclusion: The overall incidence of DIC declined during the study period, but overall mortality remained unchanged. The incidence rate was higher among patients with a low baseline ISTH or JAAM DIC score than among patients with a high baseline score. Survival rate was also higher for patients with a low DIC score at baseline, suggesting that DIC score at baseline may be a predictor of survival.

The Proactive Diagnostic Value of Thrombin-Antithrombin Complex and Antithrombin III in Disseminated Intravascular Coagulation

Introduction Disseminated intravascular coagulation (DIC) is a life-threatening condition with high mortality, necessitating timely and accurate diagnosis for effective management. However, current diagnostic systems can not recognize DIC at its reversible phase, causing suboptimal treatment outcomes. One reason is that most venous thrombosis cases are asymptomatic. Moreover, the focus on abnormalities in coagulation consumption often fails to identify DIC until in a later and irreversible phase. Consequently, the current diagnostic criteria for DIC lacks earlier laboratory indicators. Therefore, our objective was to evaluate the diagnostic potential of selected hemostatic biomarkers (thrombin-antithrombin complex (TAT), soluble thrombomodulin (sTM), tissue plasminogen activator inhibitor complex (tPAI-C), α 2-plasmin inhibitor plasmin complex (PIC) and anti-thrombin III (ATIII)) in assessing DIC before reaching its irreversible phase. Methods We included 451 patients from intensive care unit who met the following criteria:≥18 years old, non-perinatal period, and a hospitalization length of≥3 days, excluding those with primary hematologic diseases, decompensated liver cirrhosis or chemotherapy history. In total, 101, 57, and 293 patients were diagnosed with overt-DIC (decompensated DIC), pre-DIC (compensated DIC), and non-DIC, respectively. The DIC scores were calculated in accordance with the diagnostic criteria outlined by the International Society on Thrombosis and Haemostasis (ISTH). Day 0 was defined as the day on which hemostatic biomarkers were detected. Global parameters including prothrombin time (PT), fibrinogen (FIB), fibrinogen degradation product (FDP), d-dimer, and platelet count were collected on day 0, 1, 3, 5, and 7. The spearman correlation analysis was used to analyze the linear relation. Binary logistic regression analysis and receiver operating characteristic curves were used to calculate the area under the receiver operating characteristic curve (AUC). The cutoff value maximizes the sum of the sensitivity and specificity. P&amp;lt;0.05 was considered statistically significant. Results Correlation analysis revealed significant linear correlations between TAT, ATIII, and the global parameters relevant to DIC (pre-DIC and overt-DIC). Specifically, TAT exhibited positive correlation with d-dimer and FDP, while ATIII was correlated with PT, FIB, and platelet count. Of note, TAT/ATIII ratio on day 0 exhibited strong associations not only with fibrinolytic markers but also with coagulation parameters within a week, indicating its potential to be a valuable diagnostic and predictive tool for DIC assessment. Comparative analysis demonstrated elevated TAT and decreased ATIII levels in DIC group. Remarkably, the TAT/ATIII ratio demonstrated superior diagnostic performance compared to individual biomarkers. Among individual biomarkers, TAT/ATIII ratio had the highest AUC of 0.818 with a cutoff value of 22.1, followed by ATIII (AUC=0.752) and TAT (AUC=0.749). Moreover, when a combination of TAT and ATIII was applied, the AUC increased to 0.847 higher than TAT/ATIII ratio's, improving the diagnostic accuracy for DIC. TAT and ATIII in pre-DIC group were consistent with those observed in DIC group above: elevated TAT levels, decreased ATIII activity, TAT/ATIII ratio with superior diagnostic performance. Among individual biomarkers, TAT/ATIII ratio had the highest AUC 0.771 with a cutoff value of 22.1 that maximized the sum of sensitivity (55%) and specificity (89%), followed by TAT (AUC=0.73) and ATIII (AUC=0.707). The AUC of TAT combination with ATIII was 0.796, higher than AUC 0.771 of TAT/ATIII ratio, suggesting that TAT and ATIII may also identify the pre-DIC status and predict overt-DIC. Conclusion This study underscores the remarkable potential of TAT, ATIII, and the TAT/ATIII ratio in predicting DIC with accuracies of 73%, 71%, and 77%, respectively. Moreover, for patients with an ISTH-DIC score of &amp;lt; 5, the presence of following conditions-TAT level ≥10.8 ng/mL, ATIII activity ≤0.58, or TAT/ATIII ratio ≥22.1-indicates a likelihood of developing into irreversible DIC within 7 days. Integrating TAT, ATIII, and the TAT/ATIII ratio into the diagnostic process holds the potential to expedite clinical interventions during the pre-DIC state and enhance outcomes for DIC patients, further covering the shortage of current ISTH criteria.

Low ADAMTS13 Activity in Patients with Liver Disease- Thrombotic Thrombocytopenic Purpura or Not?

Introduction: Patients with liver injury have hemostatic defects including reduced ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). Severe deficiency of ADAMTS13 (ADMS13) activity (&amp;lt; 10%) is pathognomonic for thrombotic thrombocytopenic purpura (TTP), a rare thrombotic microangiopathy (TMA). Differentiating TTP from severe liver injury is complex for multiple reasons including 1) low baseline ADMS13 2) concomitant coagulopathies complicating differentiation from disseminated intravascular coagulation (DIC) 3) ADMS13 activity (ADMS13:AC) assay interference (hyperbilirubinemia (&amp;gt;30mg/dL) can cause artifactual reduction of ADMS13:AC). Here we sought to characterize the clinical presentation, management, and outcomes of patients with liver injury presenting with thrombocytopenia (TCP), microangiopathic hemolytic anemia (MAHA) and low ADMS13:AC at our institution. Methods: In this retrospective study, after IRB approval, electronic medical records (EMR) of institutional patients who had ADMS13:AC and inhibitor profile performed in our special coagulation laboratory between 2018 and July 17, 2023, were reviewed. Eligible patients had ADMS13:AC ≤20% were ≥ 18 years and had evidence of liver injury at time of ADMS13. Liver injury was defined as ALT or AST elevations greater than two times the upper level of normal within one month prior to ADMS13:AC testing, history of end stage liver disease or cirrhosis, or liver transplant with evidence of graft dysfunction. Details regarding clinical presentation, management and outcomes were extracted from the EMR. PLASMIC and ISTH DIC scores were retrospectively calculated. Results: 70 patients had at least one ADMS13:AC &amp;lt; 20% during the study period. 28/70 patients met liver injury inclusion criteria and 20/28 had TCP and MAHA. Of those 20 patients, median age at initial ADMS13:AC was 56.5 years (29-85). Most patients (n=14) had ADMS13:AC of 10-20%. ADMS13:AC was &amp;lt; 5% and 5-10% in 3 patients each. Eleven patients had a positive inhibitor with a median Bethesda titer of 1.85 BU (0.5-3.9). Etiology of liver included: ischemic hepatopathy (n=8), liver graft failure (n=4), liver metastasis (n=3), cirrhosis (n=2), alcoholic hepatitis (n=1), unknown (n=2). Median hemoglobin and platelet (plt) count at time of ADMS13 was 7 g/dL (6.4-13.2) and 30 x10 9/L (3-98), respectively. 7/20 patients had a PLASMIC score of ≥5; PLASMIC score was ≥5, in 2/6 patients with ADMS13:AC &amp;lt;10%. 16/18 patients had an ISTH DIC score ≥5. 18/20 patients had a creatinine &amp;gt; 2 mg/dL or were receiving renal replacement therapy the time of ADMS13: AC. 7/20 patients had total or direct bilirubin of &amp;gt;30mg/dL. Eight/20 patients were treated with plasma exchange (PEX) for a median duration of 7 days (2-13). 66.7% of pts with ADMS13:AC &amp;lt;10% received PEX. Glucocorticoids and Rituximab were used with the intent to treat TTP in 7 and 3 patients, respectively. Caplacizumab was used in 2 patients. 3/8 (37.5%) patients receiving PEX demonstrated normalization of MAHA. One of these patients demonstrated improvement but not normalization of plts (Table 1B, case 5). All patients had recurrence of hematologic abnormalities after PEX was stopped. One patient was treated with plasma infusion with stabilization in plt count. There were 13 and 15 deaths within 1 and 6 months of first ADMTS13:AC, respectively. One death was potentially attributable to management of TTP (Table 1B, case 1). There was no difference in time to death or mortality with the use of PEX. Repeat ADMS13:AC remote from PEX, TCP and MAHA was available for 1/5 surviving patients. This patient (Table1, case 2) had normalization of ADMS:AC after undergoing liver transplant. Conclusion: The differential diagnosis of TCP and MAHA in patients with liver injury includes hepatic dysfunction, DIC and TMA. In the current cohort, 89% of evaluable patients met criteria for overt DIC per ISTH criteria. Due to a low ADMTS13:AC, 40% of patients underwent a trial of PEX with 37.5% demonstrating improvement in MAHA that was not sustained upon discontinuation of PEX due to persistent liver dysfunction. Six-month mortality was 75% and use of PEX did not affect mortality. Given the high mortality, further studies evaluating which patients with TMA and liver injury are more likely to benefit from therapies typically used to treat TTP are necessary.

Efficacy of Recombinant Thrombomodulin for Sepsis-Associated Disseminated Intravascular Coagulation Caused by Urinary Tract Infections

Severe urinary tract infections occasionally cause sepsis and disseminated intravascular coagulation (DIC). We examined the efficacy of recombinant thrombomodulin (rTM) for treating DIC caused by urosepsis. We enrolled 40 patients who were diagnosed with DIC caused by urosepsis at our hospital between April 2018 and May 2022. Twenty-six patients were treated with rTM (rTM group), while 14 patients did not receive rTM (non-rTM group). The DIC score before treatment in the rTM group was significantly higher than that in the non-rTM group (P＜0.01). There was no significant difference in disease-specific survival between the two groups. There was a significant improvement in DIC scores on days 1-3 after administering rTM. However, the duration of DIC in the rTM group was significantly longer than that in the non-rTM group (P＝0.038). The administration of rTM may have benefits in patients with DIC caused by urosepsis.

Risk of disseminated intravascular coagulation in postpartum hemorrhage associated with intrauterine infection.

To evaluate the risk of disseminated intravascular coagulation (DIC) in postpartum hemorrhage (PPH) associated with intrauterine infection. A retrospective cohort study of pregnancies complicated by PPH performed at a tertiary academic center in France from 2017 through 2021. Patients giving birth after 22 weeks of gestation with PPH were eligible. Patients with a PPH associated with an intrauterine infection were compared to patients with a PPH without intrauterine infection. Intrauterine infection was defined by a composite criterion available at delivery. DIC was defined by a specific pregnancy DIC score. The association between DIC and intrauterine infection was assessed by logistic regression. The causal effect of intrauterine infection on DIC was estimated by mediation analysis. Of 2,093 patients with PPH, 49 exposed to a clinical intrauterine infection were compared to 49 unexposed patients. The rate of DIC was higher in patients with than without infection (22 (45.8%) vs. 7 (14.6%), P=.001), and coagulation anomalies occurred sooner in patients with than without infection (7, 2-11h vs. 14, 9-19h, P < .001). In the multivariate analysis, intrauterine infection was the only factor independently associated with DIC (adjusted odds ratio 5.01, 95% CI 1.83-13.73). Mediation analysis showed that 14% (95% CI, 0-50%) of this association between intrauterine infection and DIC was mediated by severe PPH, and 86% resulted from the direct effect of intrauterine infection on DIC. In PPH, intrauterine infection had a major direct effect on the occurrence, timing, and severity of DIC.

Prediction of in-hospital mortality in patients with exertional heatstroke: a 13-year retrospective study

ABSTRACT Hyperactivity of coagulation is common in exertional heatstroke (EHS). Disseminated intravascular coagulation (DIC) is the most severe form of coagulation dysfunction and associated with poor outcome. DIC, temperature and Glasgow coma scale score were identified as independent risk factors for in-hospital mortality by multivariate logistic regression analysis, and we developed a nomogram for predicting in-hospital mortality in a 13-year EHS patient cohort. The nomogram was assessed by calibration curves and bootstrap with 1,000 resamples. The receiver operating characteristic curve was constructed, and the area under the curve (AUC) was compared. Two hundred and ten patients were included. The in-hospital mortality was 9.0%, and the incidence of DIC was 17.6%. The AUC of the nomogram was 0.897 (95% CI 0.848–0.935, p < .0001) and was non-inferior to SOFA and APACHE II scores but superior to SIRS score, which were widely-used score systems of disease severity. The nomogram contributed to the adverse outcome prediction of EHS.

Risk factors for postoperative disseminated intravascular coagulation in surgical patients with non-occlusive mesenteric ischemia.

The prognostic impact of disseminated intravascular coagulation (DIC) in surgical patients with non-occlusive mesenteric ischemia (NOMI) is unclear. This study aimed to confirm the association between postoperative DIC and prognosis and to identify preoperative risk factors associated with postoperative DIC. This retrospective study included 52 patients who underwent emergency surgery for NOMI between January 2012 and March 2022. Kaplan-Meier curve analysis with the log-rank test was used to compare 30-day survival and hospital survival between patients with and without postoperative DIC. In addition, univariable and multivariable logistic regression analyses were performed to identify the preoperative risk factors for postoperative DIC. The 30-day and hospital mortality rates were 30.8% and 36.5%, respectively, and the incidence rate of DIC was 51.9%. Compared to patients without DIC, patients with DIC showed significantly lower rates of 30-day survival (41.5% vs 96%, log-rank P < 0.001) and hospital survival (30.2% vs 86.4%, log-rank, P < 0.001). Logistic regression analyses showed that the Japanese Association for Acute Medicine (JAAM) DIC score (OR = 2.697; 95% CI, 1.408-5.169; P = 0.003) and Sequential Organ Failure Assessment (SOFA) score (OR = 1.511; 95% CI, 1.111-2.055; P = 0.009) were independent risk factors for postoperative DIC in surgical patients with NOMI. The development of postoperative DIC is a significant prognostic factor for 30-day and hospital mortalities in surgical patients with NOMI. In addition, the JAAM DIC score and SOFA score have a high discriminative ability for predicting the development of postoperative DIC.

Coagulation Abnormalities in Severe Scrub Typhus and Their Association with Complications.

To describe coagulation abnormalities and their association with complications in patients with severe scrub typhus. A cohort study was conducted among all patients of severe scrub typhus [immunoglobulin M (IgM) positive] who reported to this facility from 1st August 2019 to 31st July 2020 and met our inclusion criteria. We estimated the incidence of severe thrombocytopenia (&lt;50,000/µL) and overt disseminated intravascular coagulation (DIC) (DIC score of ≥5). We determined the association [risk (RR) ratios] of these abnormalities with complications of scrub typhus, namely-septic shock, multiple organ dysfunction syndrome (MODS), and septic shock with MODS. In total, 71 patients were studied with a mean age of 50 ± 15.5 years, of which 45 (63.4%) were females. On presentation, fever 70 (98.5%), myalgias 22 (31.0%), loose stools 13(18.3%), cough, vomiting, headache 11 (15.5%), altered sensorium 10(14.1%), and pain abdomen 9 (12.7%) were main symptoms. On examination, hypotension 31 (43.7%), eschar 25 (35.2%), icterus 17 (23.9%), and rash 16 (22.5%) were noted. The d-dimer (&gt;0.5 µg/mL) levels were increased in all (100%) patients. Thrombocytopenia (91.5%) was the commonest hematological abnormality and 31 (43.6%) of them had severe thrombocytopenia, 25 (35.2%) patients had low fibrinogen levels (&lt;200 mg/dL) and prothrombin time (PT &gt;16.7 seconds) was prolonged in 20 (28.1%). A total of 42 (59.1%) patients developed MODS, 33 (46.4%) developed septic shock, 24 (33.8 %) had MODS with septic shock, 17 (23.9%) developed overt DIC, and eight (11.2%) died. Severe thrombocytopenia (p = -0.028) and overt DIC (p = 0.045) were significantly associated with septic shock development. In the patients admitted with severe scrub typhus; thrombocytopenia was the commonest hematological abnormality. The development of septic shock was significantly associated with severe thrombocytopenia and overt DIC.

Prognostic markers in patients with COVID-19 requiring intensive care support

ObjectivesSeveral hematological and immunological markers, particularly neutrophil count, predict the severity of COVID-19. This study aimed at assessing hematological and coagulation parameters at different time points, to predict the complications or outcomes of patients with COVID-19 admitted to the intensive care unit (ICU). MethodsWe conducted a prospective observational multicenter study in ICU departments. A total of 118 patients with COVID-19 admitted to the ICU were included. Clinical data and blood samples from routine hematology and coagulation tests were collected at admission, and on days 3, 7, and 14. The main outcome measures were high-flow-O2 requirement, thrombosis, and 30-day mortality. ResultsThe venous thromboembolism score increased from a mean of 5.10 ± 2 on day 0 to 6.40 ± 2.80 on day 14 (P = 0.0002). The disseminated intravascular coagulation (DIC) score significantly correlated with thrombosis (P = 0.031). A total of 41.20% of patients in the ICU had a DIC score ≥4, and 11.40% had a score <4. Mortality was negatively associated with patients on high-flow O2, 9 patients (10.80%) (P = 0.040), and positively associated with patients receiving ventilation, 16 patients (27.50%) (P < 0.001). An increase in white blood cell count (subdistribution hazard ratio (SHR): 0.91; 95% CI: 0.80–1) and neutrophil count (SHR: 1; 95% CI: 1.01–1.05) was associated with greater disease severity and D-dimer level (SHR: 1.60; 95% CI: 1.10–2.5). ConclusionThe venous thromboembolism score was significantly higher for patients who died than those who recovered. Furthermore, mechanical ventilation was associated with high mortality, whereas the risk of thrombosis and ICU admission correlated with high D-dimer values and DIC scores. Therefore, D-dimer levels and DIC scores are prognostic markers that may predict disease severity in patients with COVID-19.

Sepsis-related coagulopathy treatment based on the disseminated intravascular coagulation diagnostic criteria: a post-hoc analysis of a prospective multicenter observational study

BackgroundThe development of disseminated intravascular coagulation (DIC) in patients with sepsis has been repeatedly confirmed as a factor associated with poor prognosis. Anticoagulant therapy has been expected to improve sepsis patient outcomes, whereas no randomized controlled trials have demonstrated the survival benefit of anticoagulant therapies in non-specific overall sepsis. Patient selection based on the component of “high disease severity” in addition to “sepsis with DIC” has recently proved important in identifying appropriate targets for anticoagulant therapy. The aims of this study were to characterize “severe” sepsis DIC patients and to identify the patient population benefiting from anticoagulant therapy.MethodsThis retrospective sub-analysis of a prospective multicenter study included 1,178 adult patients with severe sepsis from 59 intensive care units in Japan from January 2016 to March 2017. We examined the association of patient outcomes, including organ dysfunction and in-hospital mortality, with the DIC score and prothrombin time-international normalized ratio (PT-INR), one of the components of the DIC score, using multivariable regression models including the cross-product term between these indicators. Multivariate Cox proportional hazard regression analysis with non-linear restricted cubic spline including a three-way interaction term (anticoagulant therapy × the DIC score × PT-INR) was also performed. Anticoagulant therapy was defined as the administration of antithrombin, recombinant human thrombomodulin, or their combination.ResultsIn total, we analyzed 1013 patients. The regression model showed that organ dysfunction and in-hospital mortality deteriorated with higher PT-INR values in the range of < 1.5 and that this trend was more pronounced with higher DIC scores. Three-way interaction analysis demonstrated that anticoagulant therapy was associated with better survival outcome in patients with a high DIC score and high PT-INR. Furthermore, we identified a DIC score ≥ 5 and PT-INR ≥ 1.5 as the clinical threshold for identification of optimal targets for anticoagulant therapy.ConclusionsThe combined use of the DIC score and PT-INR helps in selecting the optimal patient population for anticoagulant therapy in sepsis-induced DIC. The results obtained from this study will provide valuable information regarding the study design of randomized controlled trials examining the effects of anticoagulant therapy for sepsis.Trial registration: UMIN-CTR, UMIN000019742. Registered on November 16, 2015.

Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis

BackgroundSepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as endotoxins, producing endotoxemia. Disseminated intravascular coagulation (DIC) is frequently observed in septic patients and is associated with organ failure and death. Sepsis activates endothelial cells (ECs), promoting a prothrombotic phenotype contributing to DIC. Ion channel-mediated calcium permeability participates in coagulation. The transient reception potential melastatin 7 (TRPM7) non-selective divalent cation channel that also contains an α-kinase domain, which is permeable to divalent cations including Ca2+, regulates endotoxin-stimulated calcium permeability in ECs and is associated with increased mortality in septic patients. However, whether endothelial TRPM7 mediates endotoxemia-induced coagulation is not known. Therefore, our aim was to examine if TRPM7 mediates coagulation during endotoxemia.ResultsThe results showed that TRPM7 regulated endotoxin-induced platelet and neutrophil adhesion to ECs, dependent on the TRPM7 ion channel activity and by the α-kinase function. Endotoxic animals showed that TRPM7 mediated neutrophil rolling on blood vessels and intravascular coagulation. TRPM7 mediated the increased expression of the adhesion proteins, von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1), and P-selectin, which were also mediated by the TRPM7 α-kinase function. Notably, endotoxin-induced expression of vWF, ICAM-1 and P-selectin were required for endotoxin-induced platelet and neutrophil adhesion to ECs. Endotoxemic rats showed increased endothelial TRPM7 expression associated with a procoagulant phenotype, liver and kidney dysfunction, increased death events and an increased relative risk of death. Interestingly, circulating ECs (CECs) from septic shock patients (SSPs) showed increased TRPM7 expression associated with increased DIC scores and decreased survival times. Additionally, SSPs with a high expression of TRPM7 in CECs showed increased mortality and relative risk of death. Notably, CECs from SSPs showed significant results from the AUROC analyses for predicting mortality in SSPs that were better than the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores.ConclusionsOur study demonstrates that sepsis-induced DIC is mediated by TRPM7 in ECs. TRPM7 ion channel activity and α-kinase function are required by DIC-mediated sepsis-induced organ dysfunction and its expression are associated with increased mortality during sepsis. TRPM7 appears as a new prognostic biomarker to predict mortality associated to DIC in SSPs, and as a novel target for drug development against DIC during infectious inflammatory diseases.

Exploration of a nomogram prediction model of 30-day survival in adult ECMO patients.

To investigate the factors of 30-day survival in ECMO patients, establish a nomogram model, and evaluate the predictive value of the model. A total of 105 patients with extracorporeal membrane oxygenation (ECMO) were admitted to the Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, from January 2018 to March 2021. Cox regression analysis screened out the risk factors. Based on the results of multivariate analysis, the nomogram model was established by using R software, and the discrimination of the model was verified by bootstrap and calibration. The results showed that sex, acute physiology and chronic health evaluation (APACHE) II score, disseminated intravascular coagulation (DIC) score before ECMO initiation and average daily dose of norepinephrine were independent risk factors for prognosis. Verify that the nomogram model is verified by bootstrap internally, and the corrected C-index is C-index: 0.886, showing a good degree of discrimination. The calibration curve (calibration) showed that the nomogram model had good agreement. The decision curve analysis(DCA) curve shows good clinical validity above the two extreme curves. Kaplan-Meier curves were drawn for patients in the tertile and compared with the first and second groups. The third group predicted the worst 30-day prognosis for ECMO patients. The nomogram prediction model constructed based on the sex, APACHE II and DIC score, average daily dose of norepinephrine can effectively screen out the factors affecting the prognosis and provide a reference for individualized treatment of ECMO patients.

Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation

BackgroundThe protease inhibitor inter-α-inhibitor heavy chain H4 (ITIH4) has been described as an acute-phase reactant and could potentially aid in sepsis monitoring and prognostication. ObjectivesTo investigate ITIH4 plasma levels in sepsis patients compared with healthy controls and to examine the association between ITIH4 and acute-phase response markers, blood coagulation, and organ dysfunction in sepsis. MethodsWe performed a post hoc study to a prospective cohort study. Patients with septic shock (n = 39) were enrolled upon intensive care unit admission. ITIH4 was analyzed using an in-house immunoassay. Standard coagulation parameters, thrombin generation, fibrin formation and lysis, C-reactive protein, organ dysfunction markers, Sequential Organ Failure Assessment score, and disseminated intravascular coagulation (DIC) score were registered. ITIH4 levels were also investigated in a murine Escherichia coli sepsis model. ResultsITIH4 did not display acute-phase behavior as mean ITIH4 levels were not increased in patients with septic shock or in E. coli-infected mice. However, ITIH4 exhibited large interindividual variation in patients with septic shock compared with healthy controls. Low ITIH4 was associated with sepsis-related coagulopathy, including a high DIC score (mean ITIH4: DIC, 203 μg/mL vs non-DIC, 267 μg/mL, P = .01), low antithrombin (r = 0.70, P < .0001) and decreased thrombin generation (mean ITIH4: first peak thrombin tertile, 210 μg/mL vs third peak thrombin tertile, 303 μg/mL, P = .01). ITIH4 showed moderate correlation with arterial blood lactate (ρ = -0.50, P < .001) but only weak correlations with C-reactive protein, alanine transaminase, bilirubin, and Sequential Organ Failure Assessment score (all, ρ < 0.26, P > .05). ConclusionITIH4 is associated with sepsis-related coagulopathy but is not an acute-phase reactant during septic shock.

D-Dimer Levels and the Disseminated Intravascular Coagulation Score to Predict Severity and Outcomes in Sepsis or Septic Shock.

Studies investigating the diagnostic and prognostic value of D-dimer levels and the disseminated intravascular coagulation (DIC) score in sepsis or septic shock commonly include preselected subgroups of patients or were published prior to the current sepsis-3 criteria. Therefore, this study investigates the diagnostic and prognostic impact of D-dimer levels and the DIC score in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock enrolled in the prospective and monocentric "MARSS" registry from 2019 to 2021 were included. First, the diagnostic value of D-dimer levels was compared to the DIC score to discriminate patients with septic shock from patients with sepsis without shock. Thereafter, the prognostic value of D-dimer levels and the DIC score was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman´s correlations, C-statistics, Kaplan-Meier, as well as uni- and multivariable cox regression analyses. One hundred patients were included (n = 63 with sepsis and n = 37 with septic shock). The overall rate of all-cause mortality at 30 days was 51%. With an area under the curve (AUC) of 0.710 and 0.739, both D-dimer level and the DIC score revealed reliable diagnostic accuracy for the discrimination of septic shock. However, D-dimer levels and the DIC scores were shown to have poor to moderate prognostic accuracy (AUC 0.590 - 0.610) with regard to 30-day all-cause mortality. Specifically, very high D-dimer levels (i.e., > 30 mg/L) (HR = 2.648; 95% CI 1.147 - 6.112; p = 0.023) and a DIC scores ≥ 3 (HR = 2.095; 95% CI 1.095 - 4.009; p = 0.0258) were associated with highest risk of 30-day all-cause mortality. Finally, both higher D-dimer levels (HR = 1.032; 95% CI 1.005 - 1.060; p = 0.021) and DIC scores (HR = 1.313; 95% CI 1.106 - 1.559; p = 0.002) were associated with increased risk of 30-day all-cause mortality after multivariable adjustment. Both D-dimer levels and the DIC scores revealed reliable diagnostic accuracy for the discrimination of septic shock, but a poor to moderate prognostic value for the discrimination of 30-day all-cause mortality. Especially very high D-dimer levels (i.e., > 30 mg/L) and a DIC score ≥ 3 were associated with highest risk of 30-day all-cause mortality.