Disseminated Intravascular Coagulation Patients 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.

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

Recombinant human soluble thrombomodulin (rhTM) is commonly used in Japan to treat disseminated intravascular coagulation (DIC), but its efficacy compared with other anticoagulants is unclear. We conducted a systematic review and meta-analysis to investigate this issue in DIC patients with hematological malignancies. We searched PubMed, Cochrane, and Scopus for prospective and retrospective studies evaluating the efficacy and safety of rhTM in DIC patients with hematological malignancies between April 2008 and April 2023. We performed a systematic review and meta-analysis evaluating recovery from DIC, hemorrhagic adverse events (AEs), and overall survival (OS). We analyzed one prospective (64 patients) and seven retrospective studies (209 patients). Use of rhTM was associated with a higher rate of recovery from DIC (OR: 2.25 [1.09-4.63] and 1.98 [1.12-3.50] in prospective and retrospective studies, respectively; same order below) and fewer hemorrhagic AEs (OR: 0.83 [0.30-2.30] and 0.21 [0.08-0.57]). rhTM did not improve OS (OR: 1.06 [0.42-2.66] and 1.72 [0.87-3.39]), although the incidence of hemorrhagic death was lower in the rhTM group (0 of 94 patients). Use of rhTM in patients with hematological malignancy-associated DIC is strongly expected to be effective and safe.

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.

Decoding the DIC-Lymphoma Relationship: A Nationwide Analysis of Increased Risk in Adult Patients

Background: Disseminated intravascular coagulation (DIC) is a severe, often fatal condition characterized by systemic coagulation activation leading to both widespread microvascular thrombosis and profuse hemorrhaging. Frequently associated with malignancies, DIC represents a serious clinical challenge. Lymphomas, characterized by their clinical diversity and varying prognoses, may present differing DIC risks across their subtypes. Aim of the study The study aims to understand how various lymphoma subtypes influence the development of DIC in hospitalized individuals, utilizing data from a national inpatient sample. Methods and Materials This study retrospectively examines a cohort of adult patients in the United States, hospitalized with DIC, both with and without lymphoma, utilizing the 2020 National Inpatient Sample (NIS). Patients were identified using the International Classification of Diseases (ICD-10) codes. Patients who were younger than age 18 years were excluded from the study. We used STATA for our analyses. Fisher's exact test was utilized for comparing proportions, while Student's t-test was employed for the comparison of continuous variables. We performed a multivariate logistic regression analysis, taking into consideration various patient, and hospital characteristics including age, gender, race, median zip income, insurance status, hospital geographical region and location, bed size, urban or rural setting, teaching status to identify the adjusted odds ratio for the development of DIC in different lymphoma subtypes. The Charlson comorbidity index was utilized to account for the burden of comorbidities in the analysis. Results Among 48,310 adult DIC patients in the 2020 NIS dataset, 2.48% concurrently had lymphoma. A significant disparity was noted in gender distribution, with fewer females in the lymphoma group (40% vs 49%, p=0.0135). Patients with lymphoma were, on average, older with a mean age of 62.72 years. The racial composition between the two groups was not significantly different (p=0.651). The odds of developing DIC were significantly increased overall in lymphoma patients (aOR=2.14, p &amp;lt;0.001). Of the lymphoma subtypes, other specified types of T/NK- cell lymphoma (natural killer) (grouped under the ICD-10 code: C86, and further sub-categorized into extra-nodal NK/T cell lymphoma, hepatosplenic, intestinal, subcutaneous, angioimmunoblastic, primary cutaneous T cell lymphoma, and blastic NK-cell lymphoma) exhibited the highest risk of DIC development (aOR=16.85, p &amp;lt;0.001). Non-follicular, mature T-NK-cell, other specified and unspecified types of Non-Hodgkin, and Hodgkin lymphomas also showed significant DIC risks (p&amp;lt;0.05), whereas no statistically significant risks were found in follicular lymphoma (p=0.753) and malignant immunoproliferative diseases and certain other B-cell lymphomas (p=0.726). See Table 1 for further details. Conclusion: This study underlines a significant association between lymphoma and elevated risk of DIC, with the highest odds observed in other specified types of T/NK- cell lymphoma. Clinical diversity within lymphoma subtypes influenced DIC risks differently, underlining the importance of individualized care. In clinical practice, increased vigilance for DIC is suggested in lymphoma patients. Prompt identification and management of DIC in this patient population could potentially improve outcomes in healthcare optimization. Further studies are warranted to elucidate the underlying mechanisms and to explore potential targeted interventions.

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.

Clinicopathologic features and prognosis of 71 patients with gastric cancer and disseminated intravascular coagulation.

Gastric cancer consists of solid tumors with a tendency for disseminated intravascular coagulation (DIC). DIC is rare in patients with stomach cancer, and there have been few studies on this condition. We aimed to perform comprehensive analyses of the prognosis and clinicopathologic characteristics of stomach cancer patients with DIC. Between June 2006 and March 2020, 14,016 patients at Fujian Cancer Hospital were diagnosed with stomach cancer. We reviewed their medical records and found that 105 of these patients were diagnosed with DIC. After excluding patients who were lost to follow-up, 71 patients with DIC remained. The clinical data were retrospectively analyzed to observe clinical characteristics and prognostic factors, and the Kaplan-Meier survival analysis was performed. Prognostic variables were investigated by the Cox proportional hazards method. The median age was 54 (range, 21-83) years, and 38 patients (53.5%) were male. The histological category was poorly differentiated gastric cancer in 58 patients (81.7%). Eleven patients (15.5%) developed DIC after curative gastric resection. Sixty patients (84.5%) had DIC at the initial presentation of gastric cancer or developed DIC when the tumor progressed during treatment. Fifty-one patients (71.8%) had bleeding symptoms, and 43 (60.6%) patients had comorbidities at the time of DIC diagnosis. Among the 71 patients, 42 (59.2%) had multiple metastatic patterns. Twenty-one (29.6%) patients received chemotherapy. The median overall survival (OS) was 57.0 days (95% confidence interval [CI] [33.1-80.9] days). Tumor status (P = 0.000) and treatment (P = 0.003) were found to be significant variables associated with OS by univariate analysis. Multivariate analysis showed that tumor status (P = 0.000) and treatment (P = 0.000) had independent effects on OS. Gastrointestinal bleeding, multiple metastatic patterns and comorbidities at diagnosis with DIC are common in patients with gastric cancer complicated with DIC. Patients with poorly differentiated gastric cancer are more likely to develop DIC. Treatment and tumor status are separate risk variables for the survival of gastric cancer patients with DIC.DIC patients without tumors have a good prognosis and can be cured by appropriate etiological correction and symptomatic treatment. Chemotherapy can improve the prognosis of DIC patients with tumors.

Persistent and Late-Onset Disseminated Intravascular Coagulation Are Closely Related to Poor Prognosis in Patients with Sepsis.

Septic-associated disseminated intravascular coagulation (DIC) is heterogeneous regarding prognosis and responsiveness to anticoagulant therapy. To investigate the relationship between the timing of development and recovery of DIC, its prognosis, and the difference in response to anticoagulant therapy in sepsis-associated DIC patients. This study was performed with a dataset from a multicenter nationwide retrospective cohort study (J-Septic DIC registry) in Japan between 2011 and 2013 to reveal the subgroup "high risk of death in DIC" and investigate the relationship between anticoagulant use and mortality. Patients were assigned to four groups based on the International Society on Thrombosis and Haemostasis-overt DIC status at days 1 and 3: non-DIC (-/-), early-recovered DIC (+/-), late-onset DIC (-/+), and persistent DIC (+/+). A total of 1,922 patients were included. In-hospital mortality in persistent and late-onset DIC patients was significantly higher than in patients with non-DIC and early-recovered DIC. This finding indicates that persistent DIC and late-onset DIC were a poor-prognosis subgroup, "high-risk" DIC. Meanwhile, patients with high-risk DIC treated with anticoagulants had significantly better outcomes than those without anticoagulants after adjusting for confounding factors. This study showed that individuals with a high risk of death, persistent DIC, and late-onset DIC were a poor-prognostic subgroup in septic DIC; however, high-risk DIC is also a subgroup that can obtain more benefits from anticoagulant therapy.

Acute Cardiovascular Complications of Disseminated Intravascular Coagulation in Acute Myeloid Leukemia

Background: Disseminated intravascular coagulation (DIC), an acute or chronic systemic process with multifactorial etiology, can present as a life-threatening emergency with the potential for causing thrombosis and hemorrhage. DIC may be seen with all leukemia subtypes, but it is an especially prominent feature of Acute Myeloid Leukemias (AML). DIC complicating AML can lead to a variety of complications and has been implicated in worse clinical outcome, however, its association with acute cardiovascular complications has not been reported before. Methods: National Inpatient Sample (NIS) Database 2016 -2018 was used to procure individuals with AML, and baseline demographics and comorbidities were collected using ICD-10-DM codes. Patients with missing data or those receiving immunotherapy, chemotherapy, or radiation during hospitalization were excluded. Patients were stratified into those with and without DIC. Greedy propensity matching using R was performed to match the two cohorts in 1:1 ratio on age, gender, medications (aspirin/ antiplatelet/ anticoagulation) and fourteen other baseline cardiovascular comorbidities. Univariate analysis pre and post-match along with binary logistic regression analysis post-match were used to analyze outcomes. P-value of &amp;lt;0.05 was considered statistically significant. Results: Out of a total of 37344 patients with AML, 996 had DIC. DIC patients were younger, predominantly males, and had lower prevalence of baseline cardiovascular comorbidities. On pre-match univariate analysis, DIC patients had statistically significant higher mortality (30.2% vs 7.8%), acute myocardial infarction (5.1% vs 1.8%), acute pulmonary edema (2.3% vs 0.7%), cardiac arrest (6.4% vs 0.9%), and acute DVT/PE (6.6% vs 2.7%). Multivariate logistic regression model after matching showed similar outcomes with higher mortality (OR:4.63), acute myocardial infarction (OR:2.64), acute pulmonary edema (OR:2.75), cardiac arrest (OR:3.77), acute DVT/PE (OR:2.98), and acute heart failure becoming statistically significant (OR:1.89) in DIC patients. Conclusion: DIC was significantly associated with higher mortality and acute cardiovascular complications in patients with AML. The underlying mechanisms involve a complex interplay of procoagulant factors, anticoagulant deficiencies, cytokine release, and endothelial dysfunction. Additionally, leukemic blasts and their interactions with platelets and endothelial cells contribute to microthrombi formation and subsequent organ damage. These findings highlight the importance of close cardiovascular monitoring and prompt recognition of complications in AML patients with DIC. Further studies are needed to corroborate these findings and develop targeted interventions for prevention and management of these complications.

Establishment and validation of a risk prediction model for disseminated intravascular coagulation patients with electrical burns

Establishment and validation of a risk prediction model for disseminated intravascular coagulation patients with electrical burns

Total arch replacement for the enhanced-fibrinolytic-type disseminated intravascular coagulation patient with endoleak after thoracic endovascular aortic repair for aortic dissection

BackgroundEndoleaks after stent graft treatment can cause disseminated intravascular coagulation (DIC), leading to a bleeding tendency.Case presentationA 69-year-old man received thoracic endovascular aortic repair (TEVAR) for acute type B aortic dissection. After that, he developed bleeding tendency, and the diameter of his distal aortic arch increased. We diagnosed him with enhanced fibrinolytic-type DIC associated with a type Ia endoleak. We decided to perform a total arch replacement for the endoleak closure. To reduce the risk of massive bleeding, transfusion of fresh frozen plasma and platelets, oral tranexamic acid, and intravenous recombinant human soluble thrombomodulin were administered in the perioperative period. According to the multidisciplinary approach, the DIC improved, and the patient recovered.ConclusionWe successfully treated an endoleak-related DIC patient with bleeding tendency and combined correction for coagulopathy with supportive treatments.

A Systematic Review and Meta-Analysis of the Proportion Estimates of Disseminated Intravascular Coagulation (DIC) in Malaria.

Disseminated intravascular coagulation (DIC) is a potentially life-threatening condition that causes systemic coagulation to be turned on and coagulation factors to be used up. However, the evidence for DIC in malaria patients is still not clear, and small case series and retrospective studies have shown varying results. This meta-analysis was intended for the evaluation of the evidence of DIC among malaria patients using a meta-analysis approach. The protocol for the systematic review was registered at PROSPERO as CRD42023392194. Studies that investigated DIC in patients with malaria were searched in Ovid, Scopus, Embase, PubMed, and MEDLINE. The pooled proportion with 95% confidence intervals (CI) of DIC among malaria patients was estimated using a random-effects model. A total of 1837 articles were identified, and 38 articles were included in the meta-analysis. The overall proportion of DIC in malaria was 11.6% (95% CI: 8.9%-14.3%, I2: 93.2%, 38 studies). DIC in severe falciparum malaria and fatal malaria was 14.6% (95% CI: 5.0-24.3%, I2: 95.5%, 11 studies) and 82.2% (95% CI: 56.2-100%, I2: 87.3, 4 studies). The estimates of DIC among severe malaria patients who had multi-organ dysfunction with bleeding, cerebral malaria, acute renal failure, and ≥2 complications were 79.6% (95% CI: 67.1-88.2%, one study), 11.9% (95% CI: 7.9-17.6%, one study), 16.7% (95% CI: 10.2-23.3%, ten studies), and 4.8% (95% CI: 1.9-7.7%, nine studies), respectively. The proportion estimates of DIC among the patients with malaria depended on the Plasmodium species, clinical severity, and types of severe complications. The information from this study provided useful information to guide the management of malaria patients. Future studies are needed to investigate the association between Plasmodium infection and DIC and to understand the mechanism of malaria-induced DIC.

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.

IMMUNOSUPPRESSION CORRELATES WITH THE DETERIORATION OF SEPSIS-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION.

Background: The dysregulated host responses play a crucial role in the pathophysiology process of sepsis-induced disseminated intravascular coagulation (DIC). The study aimed to characterize the dynamic alternation of immune-related biomarkers and their relationship with the progression of DIC during sepsis. Methods: A prospective, observational study was conducted in a tertiary care academic hospital. Six hundred forty patients with sepsis were classified into three groups according to the International Society on Thrombosis and Hemostasis (ISTH) score: 383 involved patients without DIC (ISTH = 0), 168 sepsis with nonovert DIC (ISTH = 1-4), and 89 sepsis with overt DIC (ISTH ≥5). Eighteen immune-related biomarkers and six routine coagulation variables were examined at D1, D3, and D7 upon enrollment. The association between the immune parameters and the DIC deterioration was assessed during sepsis. Results: The study showed a 40% coagulation disorder and a 14% incidence of overt DIC in patients with sepsis. The patients with overt DIC displayed pronounced immune disorders from D1 to D7 upon sepsis, which was characterized by the decreased percentage of monocyte HLA-DR (mHLA-DR), increased percentage of regulatory T cells, the levels of procalcitonin, neutrophil CD64 index, and systemic inflammatory cytokines relative to nonovert DIC or non-DIC patients. In multivariate analysis, the combination of anti-inflammatory cytokine IL-10 and mHLA-DR at D1 upon enrollment had a superior predictive value for predicting DIC deterioration in sepsis (area under the curve = 0.87, P < 0.0001). Conclusion: These data illustrate that immunosuppression can crosstalk with coagulation disorder during sepsis and present an additional evaluation tool to predict DIC deterioration.

Diagnosis of Disseminated Intravascular Coagulation in Patients Suffering from Sepsis using the Modified International Society of Thrombosis and Haemostasis Criteria and Japanese Association of Acute Medicine Criteria

Introduction: The international task force defines sepsis as ‘life- threatening organ dysfunction caused by a dysregulated host response to infection’. Disseminated Intravascular Coagulation (DIC) is a coagulopathy syndrome that causes microvascular and macrovascular thrombosis and increases the risk of bleeding due to consumptive coagulopathy. Sepsis causes dysfunction in coagulation due to release of inflammatory markers which leads to inappropriate deposition of intravascular fibrin. In order to facilitate the diagnostic process for detecting DIC, the scoring system recommended by International Society of Thrombosis and Haemostasis (ISTH) and Japanese Association of Acute Medicine (JAAM) were used which are based on the global coagulation tests such as the platelet count, Prothrombin time, International Normalised Ratio (INR) and Fibrin Degradation Products (FDPs)/D-dimer. Aim: To determine the prevalence and outcome of DIC in patients suffering from sepsis using ISTH criteria and JAAM criteria. Materials and Methods: A prospective cohort was carried out from January 2021 to July 2022 in the haematology section of pathology department of Government Medical College and Hospital, Aurangabad, Maharashtra, India. Hundred patients suffering from clinically suspected sepsis were included in the study. Venous blood was collected from patients in Ethylene Diamine Tetra-acetic Acid (EDTA) and Citrate bulbs. The tests performed were Complete Blood Count (CBC), Prothrombin Time (PT), INR and D-Dimer. CBC was performed on Fully automated three part cell counter. PT, INR, D-Dimer testing was done on fully automated coagulometer. The above test results were used to diagnose DIC in patients suffering from sepsis using the modified ISTH and JAAM criterias. The results were analysed using Microsoft excel 2019 i.e., chi-square test was applied for p-value calculation. Results: Out of 100 patients with clinically suspected sepsis 35 patients (35%) suffered from Overt DIC using ISTH criteria and 58 patients (58%) suffered from DIC using JAAM criteria. The total mortality in patients with sepsis in the present study was 40%. The mortality in patients with DIC in sepsis using the ISTH criteria was 26 patients (74.28%) and 37 patients (63.79%) using the JAAM criteria. Conclusion: Coagulation abnormalities are widely prevalent in patients with sepsis and are likely to play a key role in multi- organ dysfunction. Both ISTH and JAAM criteria are good predictors of mortality.

Prevalence of Compartment Syndrome and Disseminated Intravascular Coagulation following Rhabdomyolysis; a Systematic Review and Meta-Analysis.

Rhabdomyolysis (RM) may cause some complications such as compartment syndrome and disseminated intravascular coagulation (DIC), which can affect its prognosis. This systematic review and meta-analysis aimed to investigate the prevalence of the mentioned complications following RM. Medline, Embase, and Scopus databases were searched using keywords related to compartment syndrome, DIC, and rhabdomyolysis with appropriate combination. Cohort and cross-sectional studies that conducted research on the prevalence of compartment syndrome and DIC in patients with RM were included in the present study. The desired data were extracted from the included studies and meta-analysis was conducted on them to calculate pooled prevalence of these complications. Twenty articles were included in our systematic review. The rate of compartment syndrome reported in these studies ranged from 0 to 30.7%. Our meta-analysis revealed the pooled prevalence of 4% (95% confidence interval (CI): 2.20 to 7.40) for compartment syndrome in these studies. The pooled prevalence of this complication was 7.1% (95% CI: 2.90 to 16.00) among patients with severe RM and 4.4% (95% CI: 1.80 to 10.00) in traumatic RM. The rate of DIC reported in the included studies ranged from 0 to 40.47%. Our meta-analysis showed the pooled prevalence of 8.3% (95% CI: 03.90 to 16.50) for this complication among RM patients. We reported the rates of compartment syndrome and DIC in RM patients based on rhabdomyolysis etiologies through an epidemiologic systematic review and meta-analysis. The rate of compartment syndrome was slightly higher in patients with severe RMand its rate in patients with traumatic RMwas close to the overall rate of compartment syndrome.

Sepsis-Associated DIC with Decreased Levels of Antithrombin and Fibrinogen is the Target for Combination Therapy with Thrombomodulin Alfa and Antithrombin.

Background Disseminated intravascular coagulation (DIC) is not a homogeneous condition, but rather includes heterogeneous conditions, and its pathophysiology and outcome vary considerably depending on the background. Although anticoagulant therapy is expected to be of benefit in the treatment of DIC, previous studies have suggested that the benefits are limited only to a specific subtype. Objects The purpose of this study was to identify the group that would benefit from combination therapy using thrombomodulin/antithrombin. Methods The data from 2,839 patients registered in the postmarketing surveillance of thrombomodulin were evaluated. The patients were divided into four groups depending on antithrombin and fibrinogen levels, and the additive effects of antithrombin on thrombomodulin were examined in the groups. Results The DIC score, Sequential Organ Failure Assessment score, and mortality were significantly higher in the DIC group with low-antithrombin/low-fibrinogen than in the DIC groups without either low antithrombin or low fibrinogen. The survival curve was significantly higher in DIC patients with combination therapy than in patients treated with thrombomodulin monotherapy, but this effect was seen only in patients with infection-based DIC. Conclusion DIC patients with low-antithrombin/low-fibrinogen risk poor outcomes, but they can be the target of combination therapy with antithrombin and thrombomodulin as long as the DIC is due to infection.

Association between hypomagnesemia and coagulopathy in sepsis: a retrospective observational study

BackgroundHypomagnesemia reportedly has significant associations with poor clinical outcomes such as increased mortality and septic shock in patients with sepsis. Although the mechanism underlying these outcomes mostly remains unclear, some experimental data suggest that magnesium deficiency could potentiate coagulation activation in sepsis. However, in sepsis, the association between serum magnesium levels and coagulopathy, including disseminated intravascular coagulation (DIC), remains unknown. Thus, we aimed to investigate the relationship between serum magnesium levels and coagulation status and the association between hypomagnesemia and DIC in patients with sepsis.MethodsThis retrospective observational study was conducted at the intensive care unit (ICU) of a university hospital from June 2011 to December 2017. Patients older than 19 years who met the Sepsis-3 definition were included. We categorized patients into three groups according to their serum magnesium levels: hypomagnesemia (< 1.6 mg/dL), normal serum magnesium level (1.6–2.4 mg/dL), and hypermagnesemia (> 2.4 mg/dL). We investigated the association between serum magnesium levels and overt DIC at the time of ICU admission according to the criteria of the International Society on Thrombosis and Haemostasis.ResultsAmong 753 patients included in this study, 181 had DIC, 105 had hypomagnesemia, 552 had normal serum magnesium levels, and 96 had hypermagnesemia. Patients with hypomagnesemia had a more activated coagulation status indicated by lower platelet counts, lower fibrinogen levels, higher prothrombin time-international normalized ratios, higher thrombin-antithrombin complex, and more frequent DIC than those with normal serum magnesium levels and hypermagnesemia (DIC: 41.9% vs. 20.6% vs. 24.0%, P < 0.001). The coagulation status in patients with hypomagnesemia was more augmented toward suppressed fibrinolysis than that in patients with normal serum magnesium levels and hypermagnesemia. Multivariate logistic regression revealed that hypomagnesemia was independently associated with DIC (odds ratio, 1.69; 95% confidence interval, 1.00–2.84; P = 0.048) after adjusting for several confounding variables.ConclusionsPatients with hypomagnesemia had a significantly activated coagulation status and suppressed fibrinolysis. Hypomagnesemia was independently associated with DIC in patients with sepsis. Therefore, the treatment of hypomagnesemia may be a potential therapeutic strategy for the treatment of coagulopathy in sepsis.

An interpretable DIC risk prediction model based on convolutional neural networks with time series data

Disseminated intravascular coagulation (DIC) is a complex, life-threatening syndrome associated with the end-stage of different coagulation disorders. Early prediction of the risk of DIC development is an urgent clinical need to reduce adverse outcomes. However, effective approaches and models to identify early DIC are still lacking. In this study, a novel interpretable deep learning based time series is used to predict the risk of DIC. The study cohort included ICU patients from a 4300-bed academic hospital between January 1, 2019, and January 1, 2022. Experimental results show that our model achieves excellent performance (AUC: 0.986, Accuracy: 95.7%, and F1:0.935). Gradient-weighted Class Activation Mapping (Grad-CAM) was used to explain how predictive models identified patients with DIC. The decision basis of the model was displayed in the form of a heat map. The model can be used to identify high-risk patients with DIC early, which will help in the early intervention of DIC patients and improve the treatment effect.

Coagulopathy during COVID-19 infection: a brief review.

The COVID-19 pandemic caused by SARS-CoV-2 continues to spread rapidly due to its virulence and ability to be transmitted by asymptomatic infected persons. If they are present, the symptoms of COVID-19 may include rhinorrhea (runny nose), headache, cough, and fever. Up to 5% of affected persons may experience more severe COVID-19 illness, including severe coagulopathy, acute respiratory distress syndrome (ARDS) characterized by respiratory failure that requires supplementary oxygen and mechanical ventilation, and multi-organ failure. Interestingly, clinical evidence has highlighted the distinction between COVID-19-associated coagulopathy (CAC) and disseminated intravascular coagulation (DIC). Patients with CAC exhibit different laboratory values than DIC patients for activated partial thromboplastin time (aPTT) and prothrombin time (PT) which may be normal or shortened, varying platelet counts, altered red blood cell morphology, unique bleeding complications, a lack of schistocytes in the peripheral blood, and no decrease in fibrinogen levels. In this review, we consider the search for 1) laboratory results that can diagnose or predict development of CAC, including serum levels of D-dimers, fibrinogen, interleukin-6 (IL-6) and the growth factor angiopoietin-2 (Ang-2), 2) mechanisms of CAC induction, and 3) novel therapeutic regimens that will successfully treat COVID-19 before development of CAC.

The Effect of Heparin and Its Preparations on Disseminated Intravascular Coagulation Mortality and Hospitalization: A Systematic Review.

Methods The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to November 2021. The quality of RCTs was assessed by Cochrane Collaboration's tool and the risk of bias was assessed for cohort studies through NOS score. Results Out of 3288 articles, eight studies were eligible to be included in this study. Our review retrieved six RCTs and two retrospective cohort studies consisting of 950 participants diagnosed by DIC. A significant effect of heparin on DIC mortality was identified in four studies. Furthermore, heparin was used as a control group in three studies. Conclusions We concluded that administration of heparin and its preparations in DIC patients could reduce the mortality rate and duration of hospitalization, especially in the earlier stages of DIC.