A machine learning model for early and accurate prediction of overt disseminated intravascular coagulation before its progression to an overt stage.

Background: Recent studies suggested an expected survival benefit associated with anticoagulant therapies for sepsis in patients with disseminated intravascular coagulation (DIC). However, anticoagulant therapies for overt DIC are no longer assumed to regulate pathologic progression as overt DIC is a late-phase coagulation disorder. Therefore, methods for early prediction of sepsis-induced DIC before its progression to an overt stage are strongly required. Objectives: We aimed to develop a prediction model for overt DIC using machine learning. Methods: This retrospective, observational study included adult septic patients without overt DIC. The objective variable was binary classification of whether patients developed overt DIC based on International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. Explanatory variables were the baseline and time series data within 7 days from sepsis diagnosis. Light Gradient Boosted Machine method was used to construct the prediction model. For controls, we assessed sensitivity and specificity of Japanese Association for Acute Medicine DIC criteria and ISTH sepsis-induced coagulopathy criteria for subsequent onset of overt DIC. Results: Among 912 patients with sepsis, 139 patients developed overt DIC within 7 days from diagnosis of sepsis. Sensitivity, specificity, and area under the receiver operating characteristic curve for predicting onset of overt DIC within 7 days were 84.4%, 87.5%, and 0.867 in the test cohort and 95.0%, 75.9%, and 0.851 in the validation cohort, respectively. Sensitivity and specificity by the diagnostic thresholds were 54.7% and 74.9% for Japanese Association for Acute Medicine DIC criteria and 63.3% and 71.9% for ISTH sepsis-induced coagulopathy criteria, respectively. Conclusion: Compared with conventional DIC scoring systems, a machine learning model might exhibit higher prediction accuracy.

Thyroid storm with acute liver failure and disseminated intravascular coagulation- lessons in diagnosis and treatment.

Thyroid storm is a medical emergency with a high mortality rate. Acute liver failure (ALF) and disseminated intravascular coagulation (DIC) are rarely reported with thyroid storm, and their occurrence is unrelated to the degree of free circulating thyroxine.We present the case of a 41-year-old Sri Lankan female, with a fatal case of thyroid storm. She initially presented with palpitations and heat intolerance, and subsequently developed acute liver failure with hepatic encephalopathy and coagulopathy. There was hypoglycemia and resistant lactic acidosis consequent to the liver failure. The clinical course progressed to DIC and she eventually succumbed to the illness. Treatment comprised the standard management of thyroid storm.This case report highlights the importance of bearing ALF and DIC in mind as complications of thyroid storm, outlines their pathophysiology, and uses pathophysiological mechanisms to justify, evolving extracorporeal therapeutic strategies for resistant cases.

A Case of Recurrent Liver Injury-Associated Acute Pancreatitis (LIAAP).

Many etiologies of acute liver injury (ALI) include drug-induced liver injury (DILI), viral illness, and autoimmune disease. Acute pancreatitis is an uncommon though significant etiology of ALI caused by inflammation, fluid shifts, and ischemia secondary to microthrombi formation that can progress to liver failure if left untreated. We present a case of hypertriglyceridemia-induced pancreatitis resulting in liver injury-associated acute pancreatitis (LIAAP) and a concurrent consumptive coagulopathy consistent with an ischemic hepatopathy. Through treatment of her pancreatitis with intravenous insulin and plasmapheresis and subsequent transition to an oral regimen for her hypertriglyceridemia upon hospital discharge, the patient demonstrated full resolution of her ALI and coagulopathy. Through this case, we hope to highlight the importance of recognizing LIAAP and its underlying pathogenesis.

Exploring the Mediating Role of Multiple Organ Dysfunction in Sepsis-Induced Disseminated Intravascular Coagulation and Its Impact on Worsening Prognosis.

Disseminated intravascular coagulation (DIC) poses a high mortality risk, yet its exact impact remains contentious. This study investigates DIC's association with mortality in individuals with sepsis, emphasizing multiple organ function. Using data from the Peking University People's Hospital Investigation on Sepsis-Induced Coagulopathy database, we categorized patients into DIC and non-DIC groups based on DIC scores within 24 h of ICU admission (< 5 cutoff). ICU mortality was the main outcome. Initial data comparison preceded logistic regression analysis of mortality factors post-propensity score matching (PSM). Employing mediation analysis estimated direct and indirect associations. Of 549 participants, 131 were in the DIC group, with the remaining 418 in the non-DIC group. Following baseline characteristic presentation, PSM was conducted, revealing significantly higher nonplatelet sequential organ failure assessment (nonplt-SOFA) scores (6.3 ± 2.7 vs 5.0 ± 2.5, P < 0.001) and in-hospital mortality rates (47.3% vs 29.5%, P = 0.003) in the DIC group. A significant correlation between DIC and in-hospital mortality persisted (OR 2.15, 95% CI 1.29-3.59, P = 0.003), with nonplt-SOFA scores (OR 1.16, 95% CI 1.05-1.28, P = 0.004) and hemorrhage (OR 2.33, 95% CI 1.08-5.03, P = 0.032) as predictors. The overall effect size was 0.1786 (95% CI 0.0542-0.2886), comprising a direct effect size of 0.1423 (95% CI 0.0153-0.2551) and an indirect effect size of 0.0363 (95% CI 0.0034-0.0739), with approximately 20.3% of effects mediated. These findings underscore DIC's association with increased mortality risk in patients with sepsis, urging anticoagulation focus over bleeding management, with organ dysfunction assessment recommended for anticoagulant treatment efficacy.

Outcomes and prognosis of postpartum hemorrhage according to management protocol: an 11-year retrospective study from two referral centers.

BACKGROUND: No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment. METHODS: This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26). RESULTS: Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p < 0.001, respectively). Conversely, initial heart rate and body temperature were significantly lower in group 2 (92.5 ± 21.0 vs. 109.0 ± 28.1 beat/min, p < 0.001, and 37.3 ± 0.8 °C vs. 37.0 ± 0.9 °C, p = 0.011, respectively). Logistic regression analysis identified low initial body temperature, high lactic acid level, and shock index as independent predictors of surgical intervention (p = 0.029, p = 0.027, and p = 0.049, respectively). Regarding the causes of PPH, tone was significantly more prevalent in group 1 (57.2% vs. 35.2%, p = 0.002), whereas trauma was significantly more prevalent in group 2 (24.5% vs. 39.4%, p = 0.030). Group 2 had worse overall outcomes and prognoses than group 1. The subgroup analysis showed significantly higher rates of uterine atony combined with other causes, hysterectomy, and disseminated intravascular coagulopathy in the delayed surgical intervention group than the immediate surgical intervention group (42.2% vs. 69.2%, p = 0.027; 51.1% vs. 73.1%, p = 0.049; and 17.8% vs. 46.2%, p = 0.018, respectively). CONCLUSIONS: Patients with PPH presenting with increased lactic acid levels and shock index and decreased body temperature may be surgical candidates. Additionally, immediate surgical intervention in patients with uterine atony combined with other causes of PPH could improve prognosis and reduce postoperative complications.

Comparison of Three Different Disseminated Intravascular Coagulation (DIC) Criteria and Diagnostic and Prognostic Value of Antithrombin Investigation in Patients with Confirmed Sepsis-Induced Coagulopathy (SIC).

A new scoring system termed sepsis-induced coagulopathy (SIC) has been proposed to diagnose early sepsis-induced disseminated intravascular coagulation (DIC). This study performed DIC-related analyses in patients with confirmed SIC. Data from the intensive care unit (ICU) departments of the three hospitals between 2020 and 2022 were retrospectively analyzed. Finally, 125 patients with confirmed SIC were enrolled in the study. The diagnostic value of three widely used DIC criteria was assessed in patients with newly diagnosed SIC. In addition, the diagnostic and prognostic value of antithrombin (AT) was analyzed in patients with SIC. The Japanese Association for Acute Medicine DIC criteria (JAAM) exhibited the highest DIC diagnostic rate, while the mortality risk of SIC patients demonstrated a proportional increase with higher International Society on Thrombosis and Haemostasis (ISTH) and Chinese DIC scoring system (CDSS) scores. Low AT activity (<70%) in septic patients upon SIC diagnosis predicted a very high 28-day mortality rate, almost twice as high as in the normal AT activity (≥70%) group. A decreasing tendency in AT activity after clinical interventions was correlated with increased mortality. The area under the ROC curve (AU-ROC) of AT in DIC diagnosis was statistically significant when CDSS and ISTH were used as diagnostic criteria, but not JAAM. Each of the three DIC diagnostic criteria showed diagnostic and prognostic advantages for SIC. AT could be an independent prognostic indicator for SIC but demonstrated a relatively limited DIC diagnostic value. Adding AT to the SIC scoring system may increase its prognostic power.

Effect of platelet dynamic changes on disseminated intravascular coagulation and prognosis in severe heatstroke patients.

OBJECTIVE: This study aimed to investigate the dynamic changes in the platelets of patients with severe heatstroke and the impact of these changes on the occurrence of disseminated intravascular coagulation (DIC) and prognosis in them. METHODS: This retrospective cohort study conducted at two tertiary hospitals recruited 264 patients with severe heatstroke. Logistic regression was used to analyze the association between platelet counts and DIC. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of platelets count for DIC occurrence. We used mediation effect to analysis the role of DIC as a mediating variable to mediate the relationship between platelet count decrease after 24 hours and death. RESULTS: There were 214 patients with lower platelet counts compared to admission (107 × 109/L[69,168] vs.171 × 109/L[126,215], p < 0.001). The DIC patients had lower platelet counts than the non-DIC patients when measured in the emergency department and after 24 hours. The platelet count decrease after 24 hours was a risk factor for DIC (odds ratio [OR] = 2.710, 95% confidence interval [CI] = 1.069-6.869). The results of the ROC curve revealed that the predictive performance of the platelet count after 24 hours (area under the curve [AUC] = 0.8685, 95% CI = 0.8173-0.9197) was significantly better than that of the platelet count measured in the emergency department (AUC = 0.7080, 95% CI = 0.6345-0.7815). Mediation analyses showed that PLT decrease after 24 hours did not directly lead to death, but can indirectly cause death by inducing the development of DIC. CONCLUSIONS: Decreased platelet count is an independent risk factor for DIC in patients with severe heatstroke. Although the platelet counts measured in the emergency department and after 24 hours show a good predictive performance for DIC occurrence, the prediction performance of the latter is better.

Púrpura fulminante postinfecciosa: a propósito de un caso / Postinfectious purpura fulminans: A case report

La púrpura fulminante adquirida postinfecciosa es una entidad aguda y grave, poco frecuente, caracterizada por necrosis cutánea asociada a coagulopatía intravascular diseminada (CID), en ausencia de infección activa o alteraciones previas de la coagulación. Afecta fundamentalmente a la población pediátrica y, en el 90 % de los casos, está precedida por un proceso infeccioso. El mecanismo fisiopatológico es un déficit transitorio de proteína S mediado por autoanticuerpos que favorece un estado de hipercoagulabilidad. Se presenta el caso de un varón de 8 años previamente sano, con lesiones cutáneas purpúricas características de púrpura fulminante asociada a CID en ausencia de sepsis. Se constató deficiencia plasmática transitoria de proteína S. Requirió tratamiento sustitutivo con plasma fresco congelado y anticoagulación; la evolución fue favorable. La actividad de la proteína S permaneció disminuida durante 2 meses.

Acquired postinfectious purpura fulminans is a rare, acute, and severe disease characterized by skin necrosis associated with disseminated intravascular coagulation (DIC) in the absence of active infection or previous coagulation disorders. It mainly affects the pediatric population and, in 90% of cases, it is preceded by an infectious process. The pathophysiological mechanism is a transient autoantibodymediated protein S deficiency that favors a hypercoagulable state. Here we describe the case of a previously healthy 8-year-old boy with purpuric skin lesions typical of purpura fulminans associated with DIC in the absence of sepsis. A transient plasma protein S deficiency was confirmed. He required replacement therapy with fresh frozen plasma and anticoagulation; he had a favorable course. Protein S activity remained decreased for 2 months.

A Rare Cause of Septicemia After Pork Meat Ingestion.

Streptococcus suis infection in humans occurs due to consuming raw or undercooked pork meat and after contact with pigs. The highest prevalence occurs in Southeast Asian countries, which have the largest pork industry. We report the first case of a 50-year-old healthy male patient from a rural area of São Paulo, Brazil, with septicemia from undercooked pork meat ingestion. The patient was diagnosed at the emergency department with septicemia and multiple organ dysfunctions, including streptococcal toxic shock syndrome. Blood cultures yielded the growth of S. suis. The patient was treated with ceftriaxone and was maintained for two weeks, according to sensitivity tests. The outcome was favorable but developed deafness as a sequela. This report aims to give importance to recognizing this disease regarding typical signs and symptoms and occupational and epidemiological history.

Development and validation of a nomogram to predict mortality of patients with DIC in ICU.

Background: Disseminated intravascular coagulation (DIC) is a devastating condition, which always cause poor outcome of critically ill patients in intensive care unit. Studies concerning short-term mortality prediction in DIC patients is scarce. This study aimed to identify risk factors contributing to DIC mortality and construct a predictive nomogram. Methods: A total of 676 overt DIC patients were included. A Cox proportional hazards regression model was developed based on covariates identified using least absolute shrinkage and selection operator (LASSO) regression. The prediction performance was independently evaluated in the MIMIC-III and MIMIC-IV Clinical Database, as well as the 908th Hospital Database (908thH). Model performance was independently assessed using MIMIC-III, MIMIC-IV, and the 908th Hospital Clinical Database. Results: The Cox model incorporated variables identified by Lasso regression including heart failure, sepsis, height, SBP, lactate levels, HCT, PLT, INR, AST, and norepinephrine use. The model effectively stratified patients into different mortality risk groups, with a C-index of >0.65 across the MIMIC-III, MIMIC-IV, and 908th Hospital databases. The calibration curves of the model at 7 and 28 days demonstrated that the prediction performance was good. And then, a nomogram was developed to facilitate result visualization. Decision curve analysis indicated superior net benefits of the nomogram. Conclusion: This study provides a predictive nomogram for short-term overt DIC mortality risk based on a Lasso-Cox regression model, offering individualized and reliable mortality risk predictions.

Heat stroke: Pathogenesis, diagnosis, and current treatment.

Recently, the incidence of heat-related illnesses has exhibited a steadily upward trend, which is closely associated with several environmental factors such as climate change and air pollution. The progression of heat-related illnesses is a continuous process and can progress to the terminal period when it transforms into heat stroke, the most severe form. Heat stroke is markedly by a core body temperature above 40°C and central nervous system dysfunction. Current knowledge suggests that the pathogenesis of heat stroke is complex and varied, including inflammatory response, oxidative stress, cell death, and coagulation dysfunction. This review consolidated recent research progress on the pathophysiology and pathogenesis of heat stroke, with a focus on the related molecular mechanisms. In addition, we reviewed common strategies and sorted out the drugs in various preclinical stages for heat stroke, aiming to offer a comprehensive research roadmap for more in-depth researches into the mechanisms of heat stroke and the reduction in the mortality of heat stroke in the future.

Factor VIII Levels and ISTH Disseminated Intravascular Coagulation Scores Do Not Distinguish Disseminated Intravascular Coagulation from the Coagulopathy of Liver Disease.

INTRODUCTION: Distinguishing disseminated intravascular coagulation (DIC) from the coagulopathy of liver disease represents a common clinical challenge. Here, we evaluated the utility of two diagnostic tools frequently used to differentiate between these conditions: factor VIII (FVIII) levels and the International Society on Thrombosis and Hemostasis (ISTH) DIC score. METHODS: To this end, we conducted a retrospective chart review of patients with DIC, liver disease, or both. Multiple logistic regression was performed, and receiver operating characteristic curves were generated to calculate the area under curve (AUC) for distinguishing DIC in the setting of liver disease. RESULTS: Among 123 patients with DIC, liver disease, or liver disease plus DIC, FVIII levels did not differ significantly. ISTH scores were lower in patients with DIC than in liver disease with or without DIC. Addition of several laboratory parameters to the ISTH score, including mean platelet volume, FV, FVIII, international normalized ratio, and activated partial thromboplastin time, improved AUC for distinguishing DIC in liver disease from liver disease alone (AUC = 0.76; p < 0.0001). CONCLUSION: We conclude that FVIII levels do not distinguish DIC from liver disease, and ISTH DIC scores are not predictive of DIC in patients with liver disease. Inclusion of additional lab variables within the ISTH DIC score may aid in identifying DIC in patients with liver disease.

Practical approach to thrombocytopenia in patients with sepsis: a narrative review.

Thrombocytopenia frequently occurs in patients with sepsis. Disseminated intravascular coagulation (DIC) may be a possible cause of thrombocytopenia owing to its high prevalence and association with poor outcomes; however, it is important to keep the presence of other diseases in mind in sepsis practice. Thrombotic microangiopathy (TMA), which is characterized by thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (HUS), and complement-mediated HUS, is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ damage. TMA has become widely recognized in recent years because of the development of specific treatments. Previous studies have reported a remarkably lower prevalence of TMA than DIC; however, its epidemiology is not well defined, and there may be cases in which TMA is not correctly diagnosed, resulting in poor outcomes. Therefore, it is important to differentiate DIC from TMA. Nevertheless, differentiating between DIC and TMA remains a challenge as indicated by previous reports that most patients with TMA can be diagnosed as DIC using the universal coagulation scoring system. Several algorithms to differentiate sepsis-related DIC from TMA have been suggested, contributing to improving the care of septic patients with thrombocytopenia; however, it may be difficult to apply these algorithms to patients with coexisting DIC and TMA, which has recently been reported. This review describes the disease characteristics, including epidemiology, pathophysiology, and treatment, of DIC, TMA, and other diseases with thrombocytopenia and proposes a novel practical approach flow, which is characterized by the initiation of the diagnosis of TMA in parallel with the diagnosis of DIC. This practical flow also refers to the longitudinal diagnosis and treatment flow with TMA in mind and real clinical timeframes. In conclusion, we aim to widely disseminate the results of this review that emphasize the importance of incorporating consideration of TMA in the management of septic DIC. We anticipate that this practical new approach for the diagnostic and treatment flow will lead to the appropriate diagnosis and treatment of complex cases, improve patient outcomes, and generate new epidemiological evidence regarding TMA.

Effectiveness, reliability, and validity of new Japanese diagnostic criteria for obstetrical disseminated intravascular coagulation.

Since July 2022, obstetrical disseminated intravascular coagulation (DIC) in Japan has been diagnosed based on the new criteria (tentative version), which assesses the main underlying disease, fibrinogen level, and fibrin/fibrinogen degradation products or D-dimer level. In June 2024, the tentative version underwent minor revision and the final version was released. The previous Japanese criteria assessed underlying disease, clinical symptoms, and various laboratory findings. This study aimed to prove the effectiveness, reliability, and validity of the new criteria (final version). We analyzed 212 women with singleton pregnancies who delivered after 22 gestational weeks and experienced blood loss ≥ 1000 mL during vaginal delivery or ≥ 2000 mL during cesarean section. Those with missing laboratory findings before receiving blood transfusion at delivery were excluded. In the obstetrical DIC group, the frequency of fibrinogen levels < 150 mg/dL was significantly higher than in the control group (90% vs. 5%, p < 0.0001), as was the frequency of scores ≥ 8 according to the previous Japanese criteria (100% vs. 10%, p < 0.0001). Cronbach alpha was 0.757 and Spearman's rank-order correlation was 0.558 between the new and previous criteria. In conclusion, we proved the effectiveness, reliability, and validity of the Japanese new criteria (final version) to diagnose obstetrical DIC.

Organ Dysfunction in Sepsis-associated Intravascular Coagulation.

Sepsis is frequently associated with disseminated intravascular coagulation (DIC) and multiple organ damage. It is widely accepted that DIC is not merely a complication but also plays a role in the development of organ dysfunction. Thrombus formation in the microvasculature leads to impaired tissue perfusion and organ damage. Activated neutrophils interacting with platelets, endothelial injury, and an imbalance of coagulation and fibrinolysis are the essence of thromboinflammation induced in sepsis-associated DIC. The above mechanisms are typically seen in sepsis-associated acute kidney injury (AKI), and the development of AKI is known to be strongly associated with the severity of sepsis. It is important to recognize the pathway of this mechanism in the context of sepsis management.

Asymptomatic COVID-19-Associated Acquired Hemophilia A and Disseminated Intravascular Coagulation From a Bypassing Agent.

Acquired hemophilia A (AHA) is a clotting disorder characterized by the presence of neutralizing antibodies that inhibit factor VIII, resulting in increased bleeding risk. Known etiologies include malignancy, autoimmune conditions, graft-vs-host disease, and more recently coronavirus disease 2019 (COVID-19) infection. In this case report, we describe an 86-year-old female who was found to have AHA incidentally during preoperative workup for meningioma resection. She was subsequently found to have COVID-19 infection which was the likely cause of her development of AHA. She was treated with factor eight inhibitor bypassing agent (FEIBA) and recombinant factor VII (rVII) for a small hematoma on her right arm along with prednisone and cyclophosphamide. She then developed disseminated intravascular coagulation (DIC) initially secondary to FEIBA and subsequently rFVII. DIC resolved after these factor concentrates were withheld. The aim of this case report was to emphasize the importance of monitoring partial thromboplastin time (PTT) in patients with COVID-19 and proceeding with AHA workup if indicated. It is also imperative to know and understand the potentially life-threatening, albeit rare, adverse effects of DIC associated with the administration of factor concentrates, especially in the elderly population and withholding these factor concentrates once DIC is suspected.

Comparison between sepsis-induced coagulopathy and sepsis-associated coagulopathy criteria in identifying sepsis-associated disseminated intravascular coagulation.

BACKGROUND: Disseminated intravascular coagulation (DIC) is associated with increased mortality in sepsis patients. In this study, we aimed to assess the clinical ability of sepsis-induced coagulopathy (SIC) and sepsis-associated coagulopathy (SAC) criteria in identifying overt-DIC and pre-DIC status in sepsis patients. METHODS: Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022. The performances of the SIC and SAC were assessed to identify overt-DIC on days 1, 3, 7, or 14. The SIC status or SIC score on day 1, the SAC status or SAC score on day 1, and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC. The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation. RESULTS: On day 1, the incidences of coagulopathy according to overt-DIC, SIC and SAC criteria were 11.7%, 22.0% and 31.5%, respectively. The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14 (P<0.05). On day 1, the SIC score with a cut-off value > 3 had a significantly higher sensitivity (72.00%) and area under the curve (AUC) (0.69) in identifying pre-DIC than did the SIC or SAC status (sensitivity: SIC status 44.00%, SAC status 52.00%; AUC: SIC status 0.62, SAC status 0.61). The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC (0.79 vs. 0.69, P<0.001). Favorable effects of anticoagulant therapy were observed in SIC (adjusted hazard ratio [HR]=0.216, 95% confidence interval [95% CI]: 0.060-0.783, P=0.018) and SAC (adjusted HR=0.146, 95% CI: 0.041-0.513, P=0.003). CONCLUSION: The SIC and SAC seem to be valuable for predicting overt-DIC. The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

Determining prognostic indicator for anticoagulant therapy in sepsis-induced disseminated intravascular coagulation.

BACKGROUND: There is no reliable indicator that can assess the treatment effect of anticoagulant therapy for sepsis-associated disseminated intravascular coagulation (DIC) in the short term. The aim of this study is to develop and validate a prognostic index identifying 28-day mortality in septic DIC patients treated with antithrombin concentrate after a 3-day treatment. METHODS: The cohort for derivation was established utilizing the dataset from post-marketing surveys, while the cohort for validation was acquired from Japan's nationwide sepsis registry data. Through univariate and multivariate analyses, variables that were independently associated with 28-day mortality were identified within the derivation cohort. Risk variables were then assigned a weighted score based on the risk prediction function, leading to the development of a composite index. Subsequently, the area under the receiver operating characteristic curve (AUROC). 28-day survival was compared by Kaplan-Meier analysis. RESULTS: In the derivation cohort, 252 (16.9%) of the 1492 patients deceased within 28 days. Multivariable analysis identified DIC resolution (hazard ratio [HR]: 0.31, 95% confidence interval [CI]: 0.22-0.45, P < 0.0001) and rate of Sequential Organ Failure Assessment (SOFA) score change (HR: 0.42, 95% CI: 0.36-0.50, P < 0.0001) were identified as independent predictors of death. The composite prognostic index (CPI) was constructed as DIC resolution (yes: 1, no: 0) + rate of SOFA score change (Day 0 SOFA score-Day 3 SOFA score/Day 0 SOFA score). When the CPI is higher than 0.19, the patients are judged to survive. Concerning the derivation cohort, AUROC for survival was 0.76. As for the validation cohort, AUROC was 0.71. CONCLUSION: CPI can predict the 28-day survival of septic patients with DIC who have undergone antithrombin treatment. It is simple and easy to calculate and will be useful in practice.

FGF1 attenuates sepsis-induced coagulation dysfunction and hepatic injury via IL6/STAT3 pathway inhibition.

BACKGROUND & AIMS: Sepsis, a globally prevalent and highly lethal condition, remains a critical medical challenge. This investigation aims to assess the relevance of FGF1 as a potential therapeutic target for sepsis. METHODS: Sepsis was induced in C57BL/6 mice through LPS administration to establish an in vivo animal model. Various in vitro assays were conducted using human umbilical vein endothelial cells to elucidate the role of FGF1 in the disruption of the coagulation system and liver injury associated with sepsis, as well as to explore its underlying molecular mechanisms. RESULTS: In in vivo experiments, FGF1 ameliorated coagulation system disruption in septic mice by reducing the levels of pro-inflammatory and coagulation-related factors in the bloodstream. FGF1 also enhanced liver function in septic mice, mitigating liver inflammation and cell apoptosis, fostering liver vascular regeneration, increasing liver blood perfusion, and improving mouse survival. In vitro experiments demonstrated that FGF1 could inhibit LPS-induced inflammatory responses and apoptosis in endothelial cells, fortify endothelial cell barrier function, decrease endothelial cell permeability, promote endothelial cell proliferation, and restore endothelial cell tube-forming ability. Both in vivo and in vitro experiments substantiated that FGF1 improved sepsis by inhibiting the IL-6/STAT3 signaling pathway. CONCLUSION: In summary, our study indicates that FGF1 mitigates excessive inflammatory responses in sepsis by suppressing the IL-6/STAT3 signaling pathway, thereby improving systemic blood circulation and ameliorating liver damage in septic organisms. Consequently, this research identifies FGF1 as a potential clinical target for the treatment of human sepsis.

Coagulation abnormalities associated with CAR-T-cell therapy in haematological malignancies: A review.

Chimeric antigen receptor (CAR)-T-cell therapy has demonstrated considerable efficacy and safety in the treatment of patients with relapsed/refractory haematological malignancies. Owing to significant advances, CAR-T-cell therapeutic modality has undergone substantial shifts in its clinical application. Coagulation abnormalities, which are prevalent complications in CAR-T-cell therapy, can range in severity from simple abnormalities in coagulation parameters to serious haemorrhage or disseminated intravascular coagulation associated with life-threatening multiorgan dysfunction. Nonetheless, there is a lack of a comprehensive overview concerning the coagulation abnormalities associated with CAR-T-cell therapy. With an aim to attract heightened clinical focus and to enhance the safety of CAR-T-cell therapy, this review presents the characteristics of the coagulation abnormalities associated with CAR-T-cell therapy, including clinical manifestations, coagulation parameters, pathogenesis, risk factors and their influence on treatment efficacy in patients receiving CAR-T-cell infusion. Due to limited data, these conclusions may undergo changes as more experience accumulates.