Search Results (110)

Sepsis remains a leading cause of global mortality, and early management in the emergency department (ED) is a key determinant of clinical outcomes. Among the earliest physiological derangements in sepsis are abnormalities in coagulation, which represent not merely laboratory disturbances but fundamental reflections of dysregulated host response, endothelial injury, and evolving microvascular thrombosis. Sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) form a dynamic continuum that frequently begins before shock is clinically apparent. Despite their prognostic value and pathophysiologic significance, these abnormalities are often underrecognized in the ED, where coagulation tests are still commonly interpreted through the narrow lens of bleeding risk rather than as markers of systemic thromboinflammation. This narrative review synthesizes current understanding of the mechanisms linking sepsis, endothelial dysfunction, and coagulation abnormalities; outlines the distinction between SIC and overt DIC; and highlights why early identification of coagulopathy in the ED is essential. We discuss practical bedside approaches, including recommended laboratory testing, pattern recognition, and application of validated scores such as the SIC and ISTH DIC criteria. System-level strategies, such as embedding coagulation testing into sepsis bundles, automating score calculation, and enhancing communication between the ED and ICU teams, are explored as avenues to improve early detection. Evidence suggests that ED recognition of SIC/DIC may refine risk stratification, guide triage decisions, and identify patients who may benefit from targeted anticoagulant strategies once stabilized. Ultimately, recognizing coagulation disorders in the ED reframes sepsis not solely as a hemodynamic crisis but as a complex, thromboinflammatory syndrome in which early intervention may alter trajectory and improve outcomes. Full article

Background/Objectives: Acute promyelocytic leukemia (APL) is a medical emergency associated with life-threatening complications such as disseminated intravascular coagulation (DIC), necessitating prompt therapeutic intervention and rapid diagnostic confirmation. APL is characterized by a translocation of the PML gene (15q24) with the RARA gene (17q21), resulting in the PML::RARA fusion gene on the derivative chromosome 15. Atypical PML::RARA rearrangements may escape detection by standard FISH probes. This study highlights limitations of commonly used probe sets and underscores the need for alternative FISH probe sets and complementary molecular testing. Methods: Two unique APL cases with atypical PML::RARA rearrangements were identified in our laboratory. Each case was evaluated at diagnosis using two commercially available FISH probe sets from Abbott Molecular and Cytocell. Metaphase FISH was performed to characterize the atypical FISH signal pattern further, and qRT-PCR was used to confirm the presence of the PML::RARA transcript. Results: Both cases demonstrated atypical rearrangements with a single fusion signal. In the first case, the Abbott probe detected a single fusion signal, while the Cytocell probe was negative. Metaphase FISH revealed an insertion of the PML region near RARA on chromosome 17. In the second case, the Cytocell probe was positive, and the Abbott probe was negative; metaphase FISH demonstrated insertion of the RARA region near PML on chromosome 15. qRT-PCR confirmed the presence of the PML::RARA transcript in both cases. Conclusions: These findings reveal limitations in commonly used PML::RARA FISH probes and support reflex testing with alternative probes and molecular confirmation to ensure accurate diagnosis. Full article

Background and Objectives: Hyperleukocytosis in acute myeloid leukemia (AML) is life-threatening, often complicated by leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulation (DIC), with very high early mortality. Leukapheresis (LA) can rapidly reduce circulating blast burden, but its effect on survival and prognostic relevance of disease markers remains unclear. Materials and Methods: We retrospectively analyzed 74 adult AML patients with WBC > 100 × 10⁹/L treated at the University Clinical Center of Serbia between 2014 and 2024: 28 received LA plus cytoreduction (LA group), and 46 received cytoreduction alone (non-LA group). We evaluated 15-, 30-, and 90-day mortality and overall survival (OS), and assessed clinical, laboratory, and immunophenotypic predictors using Cox regression, with separate subgroup analyses. Results: Patients in the LA group had significantly higher baseline leukocyte counts and LDH (p = 0.18 and p = 0.024, respectively). Although LA resulted in a median 34% reduction in WBC, there was no statistically significant difference in early mortality: 15-day survival was 68% vs. 76% (HR 0.70, p = 0.423), 30-day survival 50% vs. 65% (HR 0.62, p = 0.197), and 90-day survival 39.3% vs. 41.3% (HR 0.85, p = 0.604). Median OS was similarly poor, about 1 month in the LA group compared to 2 months in the non-LA (HR 0.73). Across all patients, ECOG PS ≥2, elevated LDH, TLS, and DIC were the strongest indicators of early death. In the LA group, elevated LDH and increased peripheral blood (PB) monocyte count predicted 15-day mortality (p = 0.021 and p = 0.031, respectively), but lost significance by day 90. In non-LA patients, CD25 positivity (p = 0.034) and DIC (p = 0.045) predicted 15-day death. By day 90, CD25 expression (p = 0.048) remained prognostic, while PB blast percentage (p = 0.045) and PB monocyte count (p = 0.017) emerged as additional adverse prognostic predictors in the non-LA group. In multivariate analysis, higher PB blast percentage, CD25 positivity, and ECOG PS ≥ 2 independently predicted poorer OS. Conclusions: Although LA did not reduce early mortality in the entire cohort, the loss of prognostic significance of elevated LDH, high PB blast percentage, PB monocyte burden, and CD25 expression in the LA group may suggest that the intervention can attenuate the impact of biologically aggressive disease. Full article

Acute promyelocytic leukemia (APL) evolved from the most lethal to the most curable subtype of acute leukemia today, owing to targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide. Despite cure rates exceeding 90% and the rarity of relapse or refractoriness, early death (ED)—occurring within 30 days of diagnosis—remains unacceptably high, reaching up to 30% in population-based studies. ED is the major barrier to universal cure, with fatal hemorrhage as the predominant cause, followed by infection, differentiation syndrome, and thrombosis. Patients who survive the initial month generally achieve excellent long-term outcomes. This review synthesizes data from clinical trials and large real-world cohorts to provide a comprehensive overview of the incidence, causes, and predictors of ED in APL. Higher white blood cell count and older age emerge as the most consistently validated predictors, followed by increased IRB/BICcreatinine, low albumin, thrombocytopenia, and coagulopathy, although their predictive value is not uniform across studies. Risk scores such as the Sanz classification, the Österroos ED model, and dynamic disseminated intravascular coagulation (DIC) assessments represent practical tools for identifying patients at high risk of ED. Importantly, ED rates remain significantly higher in real-world populations than in clinical trials, highlighting the impact of age and comorbidities, delayed diagnosis, and barriers to immediate ATRA initiation and supportive care. Addressing ED in APL requires intensified early supportive strategies, physician awareness and education, and rapid treatment initiation. Refinement and validation of predictive models may guide tailored interventions and inform strategies to finally overcome this persistent unmet need. Full article

Background and Objectives: Bleeding is a major cause of mortality in cases of acute myeloid leukemia (AML)-associated disseminated intravascular coagulation (DIC). The predictive power of the standard International Society on Thrombosis and Hemostasis (ISTH) score for bleeding in patients diagnosed with AML is limited. This study aimed to evaluate the performance of the standard ISTH score and modified versions in predicting bleeding among acute promyelocytic leukemia (APL, M3) and non-APL AML subgroups. Methods: This single-center, retrospective study included 190 AML patients (61 APL, 129 non-APL). The predictive power of the original ISTH score and eight different modified scores—incorporating parameters such as lactate dehydrogenase (LDH) and genetic positivity—for DIC-related bleeding was assessed using receiver operating characteristic (ROC) analysis. Results: In the APL group, the original ISTH score was statistically significant in predicting DIC-related bleeding (AUC = 0.727), but the modifications did not improve performance. In the non-APL AML group, the original score did not predict bleeding (AUC = 0.632, p = 0.079). However, a modified ISTH score excluding D-dimer and including LDH (≥800 mg/dL) and genetic positivity significantly improved prediction (AUC = 0.710, p = 0.005). This modification increased specificity from 48.2% to 60.7% and sensitivity from 76.5% to 82.4%. Conclusions: A subtype-specific approach is required to predict bleeding risk in AML-associated DIC. Modified ISTH scores remain suboptimal for APL; however, a modified score incorporating LDH and genetic status represents a promising tool to identify non-APL AML patients at risk of bleeding and warrants prospective validation. Full article

The utilisation of cardiopulmonary bypass (CPB) during cardiac surgery is often associated with complex haemostatic perturbations, frequently manifesting as a paradoxical risk of both bleeding and thrombosis. This is postulated to be driven by systemic inflammation, endothelial activation and contact activation of the coagulation cascade due to extracorporeal circulation. However, the coronavirus disease 2019 (COVID-19) pandemic revealed a unique hypercoagulable state, termed COVID-19-associated coagulopathy (CAC), also observed in those vaccinated against COVID-19. CAC displays similar physiological manifestations to those of disseminated intravascular coagulation (DIC), characterised by elevated fibrinogen and D-dimer values. The precise pathogenesis of CAC requires further elucidation though proposed mechanisms include: an exaggerated inflammatory response to COVID-19 infection or antibody proliferation due to vaccination, direct epithelial cell damage mediated by angiotensin converting enzyme 2, and ‘hypoxithrombosis’. CAC has since provided a unique framework to understand and potentially mitigate coagulation complications encountered during CPB in the post-pandemic era, as it is no longer sufficient to view COVID-19 as a transient influence on surgical risk. Rather, it must be recognized as a persistent modifier of the haemostatic environment across the population, with direct implications upon patient selection, intraoperative management and postoperative care in cardiac surgery. This review examines the pathological drivers behind CAC alongside the insights obtained from CAC management during ECMO deployment, to investigate the potential translation of such knowledge into improved anticoagulation strategies and monitoring during cardiac surgery. The use of alternative anticoagulants including factor XI inhibitors and the modulation of heparinase activity offers promising avenues to attenuate coagulopathies more commonly observed during CPB in the post-pandemic climate, whilst anti-Xa assays and viscoelastic testing have offered applicability to modern perfusion practices. By bridging the knowledge gained during the pandemic with that of conventional CPB, this review aims to inform future strategies for haemostasis management in cardiac surgery in a novel cohort of surgical patients. Full article

Background: Diagnostic criteria for disseminated intravascular coagulation (DIC) have been established by the Japanese Ministry of Health, Labor, and Welfare (JMHLW), the International Society of Thrombosis Hemostasis (ISTH), and the Japanese Association for Acute Medicine (JAAM). These criteria vary and are complicated, and the cutoff values differ, so a simple and rapid diagnostic approach for DIC is needed. Materials and Methods: The usefulness of the DIC index (prothrombin time-international normalized ratio [PT-INR] x D-dimer/platelet count) for diagnosing DIC and predicting outcomes in 1500 critically ill patients was assessed. Results: The PT-INR, D-dimer level, and DIC index were significantly higher in patients with DIC than in those without DIC, and their platelet count was significantly lower. Receiver operating characteristic (ROC) analyses showed that the diagnostic agreement was the highest for the JMHLW score among the three diagnostic criteria. The PT-INR, D-dimer level, DIC index, and JMHLW, ISTH overt-DIC, and modified JAAM DIC scores were significantly higher in non-survivors than in survivors, and their platelet counts were significantly lower. Although ROC analyses showed that the PT-INR, D-dimer level, platelet count, DIC index, JMHLW, ISTH overt-DIC, and modified JAAM DIC scores were related to the outcome, the cutoff values of the DIC index, and JMHLW, ISTH overt-DIC and modified JAAM DIC scores were low. Conclusions: The DIC index was highly consistent with the three diagnostic criteria for DIC and related outcomes. Full article

Background/Objectives: Sepsis is a life-threatening condition characterized by an uncontrolled immune response due to systemic infections. It is responsible for millions of deaths worldwide. Although inflammasomes play an important role in host defense, they have a detrimental role in sepsis induced by LPS or Gram-negative bacteria. We aimed to revise the molecular mechanisms of inflammasome activation in sepsis by LPS and Gram-negative bacteria other than cytokine release as treatments blocking TNF-α and IL-1 cytokines have been ineffective even though cytokine storm is associated with lethality. Results: Studies with knockout mice deficient in inflammasome-derived cytokines have shown contrasting results on the role of these proinflammatory cytokines in the lethality of LPS- and Gram-negative-induced sepsis. However, DAMPs released after non-canonical inflammasome activation such as extracellular DNA, histones, HMGB1, and tissue factor result in disseminated-intravascular coagulation (DIC) and mortality in mice. Blocking these products in preclinical studies with animal models showed improved clinical scores and survival after LPS-induced sepsis or polymicrobial sepsis induced by Cecal Ligation and Puncture. Conclusions: Even though immunomodulatory drugs have shown inconclusive results as therapies for sepsis, blocking DAMPs associated with DIC may be considered for clinical trials in the future, especially in patients presenting biomarkers of coagulopathies. Full article

At onset, myelodysplastic syndrome (MDS) may be complicated by coagulation and fibrinolytic abnormalities, such as disseminated intravascular coagulation (DIC), tumor lysis syndrome (TLS), infection, thromboembolism, hemophagocytic syndrome/hemophagocytic lymphohistiocytosis (HPS/HLH), hemorrhage, and hematoma formation. In these cases, the cause may be secondary. On the other hand, it is known that platelet clotting dysfunction and fibrinolysis abnormalities are seen in the background of MDS, and primary fibrinolysis abnormalities may be complicated by adverse events associated with paraneoplastic syndrome (PNS). Coagulation fibrinolysis, as a PNS associated with MDS, is known to take the pattern of either consumptive coagulation abnormality or fibrinolytic coagulation abnormality. One mechanism of coagulation and fibrinolytic abnormalities has been shown to be the immunophenotypical pathway, and aberrant cytokine production is also associated with coagulopathy in MDS. We focused on how to differentiate an MDS-associated bleeding tendency resulting from either secondary or primary causes. In order to make this differentiation, we proposed a useful flowchart for the differentiation of solidified fibrinolysis seen at the initial MDS diagnosis. Additionally, we compared and summarized the molecular pathways of the secondary and primary causes of coagulopathy. Addressing coagulation and fibrinolytic abnormalities in MDS is required to differentiate the complexity and heterogeneity of bleeding and coagulation abnormalities. This review highlights the need to distinguish between the primary (disease-intrinsic) and secondary (reactive or complication-related) causes of coagulopathy. By proposing a diagnostic flowchart tailored to evaluate these causes at initial diagnosis, this study supports individualized risk stratification and management strategies. By comparing the molecular pathways of the two causes of coagulopathy, we provide a clinical discussion of the underlying pathologies. This aligns with the principles of personalized medicine by ensuring that treatment decisions (e.g., supportive care, anticoagulation, and antifibrinolytics) are based on the patient’s specific pathophysiological profile, rather than a one-size-fits-all approach. Full article

The circulatory and immune systems function in close coordination to maintain homeostasis and act as a frontline defense against infections. However, under certain conditions, this interaction becomes dysregulated, leading to thromboinflammation, a pathological process marked by the concurrent and excessive activation of coagulation, inflammation, and endothelial dysfunction. During viral infections, this phenomenon can markedly worsen clinical outcomes. Evidence indicates that viruses such as dengue, chikungunya, influenza, and SARS-CoV can trigger thromboinflammatory responses involving platelet activation, the release of procoagulant and pro-inflammatory mediators, and the formation of thrombi within blood vessels. While this response may initially help contain viral dissemination, in cases of high viremia it can progress to disseminated intravascular coagulation (DIC), hemorrhage, and multiple organ failure. This review compiles current evidence on thromboinflammatory mechanisms induced by arboviral and respiratory viruses and examines how these processes contribute to diseases’ pathogenesis and clinical severity. Full article

Background: Pregnancy-Related Acute kidney injury (PRAKI) is a critical complication of pregnancy, defined by the sudden deterioration in renal function during gestation or within the initial six weeks postpartum. Pregnancy is thought to increase the risk of acute kidney injury (AKI) by 51%. This is linked to the anatomical alterations that occur during pregnancy and special conditions, such as preeclampsia/eclampsia. PRAKI’s epidemiology and outcome vary between developed and developing nations. PRAKI is an uncommon entity in high-income countries; however, its incidence has recently increased. The aim of this systematic review is to evaluate the maternal and perinatal outcomes and risk factors affecting pregnancies affected by AKI. Methods: Comprehensive research was performed in PubMed/Medline, Scopus, and Google Scholar electronic databases from 2015 up to January 2025, using the terms AKI, PRAKI, sepsis, preeclampsia/eclampsia, liver enzymes, low platelet count (HELLP) syndrome, and pregnancy. After a thorough assessment, 25 full-text articles were obtained. Results: Our results revealed that preeclampsia, eclampsia, HELLP syndrome, and antepartum and postpartum hemorrhage predispose women to PRAKI. Other unusual factors, like disseminated intravascular coagulation (DIC) or hemolytic uremic syndrome (HUS), should not be underestimated. Furthermore, the latest published data showed unfavorable maternal and fetal outcomes in pregnancies affected by AKI compared to the general population. Conclusions: PRAKI constitutes a serious pregnancy complication that requires immediate treatment. The higher prevalence of PRAKI in developing countries (4–26%) versus wealthy nations (1.0–2.8%) has considerably indicated the impact of socioeconomic status and the accessibility of health services. Full article

Dugongs (Dugong dugon), classified as vulnerable marine mammals, are increasingly impacted by infectious diseases, yet the role of septicemia and disseminated intravascular coagulation (DIC) in their mortality remains uncharacterized. This study aimed to investigate the pathological and microbiological features associated with an acute mortality event in a juvenile dugong during rehabilitation in southern Thailand. Comprehensive histopathological and microbiological analyses were conducted on tissue samples collected postmortem. Bacterial isolation and identification were performed using standard culture techniques and the VITEK-2 system. Histological examination revealed multisystemic lesions, including fibrin thrombi, hemorrhage, hepatocellular degeneration, pancreatic necrosis, lymphoid depletion, and neuronal damage. Oxidative stress and DNA damage were confirmed in brain tissues through immunofluorescence detection of 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-oxodG). Achromobacter xylosoxidans, an opportunistic pathogen, was isolated from multiple organs, consistent with acute systemic infection. These findings represent the first evidence of septicemia-associated DIC in dugongs caused by A. xylosoxidans, highlighting a previously undocumented cause of mortality in dugongs. The results emphasize the role of opportunistic bacteria in triggering oxidative damage and coagulopathy and underscore the importance of early detection and targeted therapeutic strategies to improve survival in stranded or rehabilitated dugongs. Full article

Sepsis is a complex and life-threatening syndrome arising from a dysregulated immune response to infection that can lead to severe organ dysfunction and increased mortality. This multifactorial condition is marked by intricate interactions between immune, inflammatory, and coagulation pathways, which together contribute to systemic effects and multiorgan damage. The aberrant immune activation seen in sepsis includes profound leukocyte activation, endothelial dysfunction, imbalanced coagulation leading to disseminated intravascular coagulation (DIC), and the production of both pro-inflammatory and anti-inflammatory mediators. These events culminate in pathological alterations that extend beyond the initial site of infection, adversely impacting distant tissues and organs. Early recognition and timely intervention are crucial to mitigate the progression of sepsis and its associated complications. This review aims to explore the underlying biological mechanisms, including host–pathogen interactions, immune dysregulation, and the cascade of systemic and organ-specific effects that define sepsis. By delving into the pathophysiological processes, we intend to provide insights into the determinants of multiorgan failure and inform strategies for therapeutic intervention. Understanding these mechanisms is pivotal for advancing clinical outcomes and reducing mortality rates associated with this critical condition. Full article

We present a 48-year-old female with a past medical history of endometrioid adenocarcinoma who presented with symptoms of spontaneous gum bleeding, post-coital bleeding, and upper extremities–lower extremities-abdomen ecchymosis. Initial laboratory findings were significant for cytopenia and disseminated intravascular coagulation (DIC). Due to a suspected case of acute promyelocytic leukemia (APL), conventional karyotyping and fluorescence in situ hybridization (FISH) were performed. FISH analysis confirmed an unusual chromosome rearrangement that affected chromosomes 3, 15, and 17. This t(3;15;17)(q29;q24;q21) was characterized by the presence of PML::RARA fusion on the derivative chromosome 15. Treatment at the hospital with standard APL therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) was complicated by the development of differentiation syndrome, which necessitated the temporary stoppage of ATO. However, complete remission was achieved despite complications after starting consolidation treatment. Full article

Background/Objectives: We define severe postpartum hemorrhage (PPH) with macroscopic hematuria as clinical disseminated intravascular coagulation (DIC), a life-threatening condition. We also report a methodology using machine learning, a subtype of artificial intelligence, for developing the boundary criterion for predicting hematuria on the fibrinogen–fibrin/fibrinogen degradation product (FDP) plane. A positive FDP–fibrinogen/3–60 (mg/dL) value indicates hematuria; otherwise, non-hematuria is observed. We aimed to validate this criterion using severe placental abruption (PA), and to examine the activation of the coagulation–fibrinolytic system in clinical DIC. Methods: Of 17,285 deliveries across nine perinatal centers in Japan between 2020 and 2024, 13 had severe PA without hematuria, 18 had severe PPH without hematuria, and 3 had severe PPH with hematuria, i.e., clinical DIC. We calculated the values of the criterion formula for 13 cases of severe PA to validate the boundary criterion and compared the laboratory tests for coagulation–fibrinolytic activation among the three groups. Results: The calculated values using the criterion for the 13 PA without hematuria ranged from −108.91 to −5.87 and all were negative. In cases of clinical DIC, fibrinogen levels (median, 62 mg/dL) were lower (p < 0.05), while levels of FDP (96 mg/dL), the thrombin–antithrombin complex (120 ng/mL), and the plasmin-α₂–plasmin inhibitor complex (28.4 μg/mL) were significantly higher than in the other two groups. Conclusions: This study demonstrated the validity of the boundary criterion for predicting hematuria using severe PA. The coagulation–fibrinolytic test results suggested that PPH cases with hematuria were assumed to have clinical DIC, indicating that this criterion may be considered for diagnosing DIC during delivery. However, further additional patient data are needed to confirm the usefulness of this criterion because of the very low number of hematuria cases. Full article