Development Of Disseminated Intravascular Coagulation Research Articles

Prereferral management of preeclampsia with severity features in a low-income country—characteristics and challenges in a Sub-Saharan setting: a mixed method study

Background: Preeclampsia continues to be a major cause of maternal and perinatal mortality and morbidity, globally. Although pre-referral treatment constitutes a bigger part of the management package for preeclampsia with severity features in low-income settings, little is known regarding the characteristics and challenges of preeclampsia pre-referral and referral management in the Sub-Saharan setting. ObjectiveTo determine the characteristics and challenges of pre-referral and referral management of preeclampsia with severity features Study design: We conducted a mixed method study on the pre-referral management of pregnant women who complicated by preeclampsia with severity features in Ethiopia. We prospectively collected data on clinical characteristics, management outcomes, and pre-referral characteristics of pregnant women who complicated by preeclampsia with severity features. Data were collected using a structured questionnaire. For the qualitative part of our study, we conducted 20-30 minutes, semi-structured, qualitative face-face in depth-interview with 14 health professionals. Quantitative data were analyzed using SPSS version 23 and simple descriptive statistics was employed. We used thematic analysis on Open Code 4.03 software to analyze the qualitative data. - ResultsA total of 261 pregnant women who had preeclampsia with severity features were included in the study and 14 care providers were interviewed on existing challenges with pre-referral management for patients with preeclampsia with severity features. The mean systolic and diastolic blood pressures were 154.3mmHg and 100.3mmHg, respectively. The total perinatal mortality was 6.5% (17/261). Three mothers (1.1%) complicated by intra-cranial hemorrhage and other three (1.1%) other women developed pulmonary edema. Out of 261 patients, only 41 patients (15.7%) received magnesium sulphate. Similarly, antihypertensive was given only to 35 patients constituting 13.4%. Eight mothers convulsed (3.1%) during referral. Two mothers (0.8%) developed pulmonary edema when they arrived at recipient health institutions after referral. Likewise, another two (0.8%) women developed disseminated intravascular coagulation (DIC) by the time of arrival from referring health institution. Up on qualitative data analysis, three overarching themes were recognized: (i) challenges related Patient and family resistance, (ii) Challenges related to healthcare providers’ knowledge, skill and confidence, and (iii) health system related challenges. Low utilization of magnesium sulphate and ant-hypertensive drugs, patient misperceptions regarding reasons for referral, providers lack of knowledge on the pre-referral management, inadequate communication between referring and recipient health institution, and non-existence of uniform pre-eclampsia pre-referral and referral management protocols among the referring institutions were the identified gaps. ConclusionWe found a significant gap in pre-referral management for patients with preeclampsia with severity features. Preeclampsia management policy reforms should include introduction of adequate patients counselling platforms, increasing community awareness creation, providing in-service training on pre-referral management of preeclampsia for health personnel, ensuring constant availability of anti-convulsant and antihypertensive drugs and uniform implementation of preeclampsia pre-referral management protocols across health institutions.

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

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

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.

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.

The Functional Roles and the Potential as Drug Targets of Glycoproteins Regulating Complement and Coagulation Pathways

Complement (C) activation occurs via three pathways, namely the classical, lectin, and alternative pathways. Intercommunication occurs between the complement and coagulation systems, which can trigger tissue injury and inflammation. Disseminated intravascular coagulation (DIC) is a life-threatening disease characterized by disordered coagulation and systemic inflammation; here, the intercommunication between the complement and coagulation systems contributes to the development of DIC. Extracellular histones, which are contributors to the damage-associated molecular pattern, induce severe thrombosis. C5 is a key molecule in the intercommunication between the complement and coagulation systems and is associated with the development of lethal histone-induced thrombosis. Heparin and chondroitin sulfate (CS) are negatively charged, allowing them to bind to extracellular histones. As the coagulation system is less affected by CS than heparin, CS shows potential as an effective drug for the treatment of patients with DIC who have a high risk of bleeding. Complement receptor type-1-related gene Y (Crry) inhibits the complement pathway via binding to C3b and C4b. Hence, Crry is a potent inhibitor of the classical and alternative C pathways. The expression of Crry is decreased by the endothelial damage induced by extracellular histones. Crry dysfunction promotes the activation of C on the surface of endothelial cells. The prevention of C3 cleavage on endothelial cells might be a useful therapy targeting acute lung injury.

Pathophysiology of Disseminated Intravascular Coagulation in Sepsis: A Clinically Focused Overview.

Sepsis is a major global health problem that results from a dysregulated and uncontrolled host response to infection, causing organ failure. Despite effective anti-infective therapy and supportive treatments, the mortality rate of sepsis remains high. Approximately 30-80% of patients with sepsis may develop disseminated intravascular coagulation (DIC), which can double the mortality rate. There is currently no definitive treatment approach for sepsis, with etiologic treatment being the cornerstone of therapy for sepsis-associated DIC. Early detection, diagnosis, and treatment are critical factors that impact the prognosis of sepsis-related DIC. Over the past several decades, researchers have made continuous efforts to better understand the mechanisms of DIC in sepsis, as well as improve its quantitative diagnosis and treatment. This article aims to provide a comprehensive overview of the current understanding of sepsis-related DIC, focusing on common causes and diagnoses, with the goal of guiding healthcare providers in the care of patients with sepsis.

Obstetrik hastalarda dissemine intravasküler koagulasyon: maternal ve fetal sonuçları

AIM: In our study, it was aimed to obtain guiding information to prevent complications that may develop in advance and to decrease maternal and fetal morbidity and mortality by evaluating the antepartum of patients who developed DIC due to obstetric reasons. &#x0D; MATERIALS AND METHODS: Obstetric patients who were hospitalized in obstetrics and perinatology clinics and developed disseminated intravascular coagulation (DIC) were retrospectively analyzed. DIC scoring of the patients was made according to the International Society on Thrombosis and Haemostasis (ISTH) criteria. Maternal and fetal outcomes from the patients were documented.&#x0D; RESULTS: During the 6-year period in which the data were analyzed, DIC was detected in 57 pregnants out of 108281 deliveries, and the incidence of DIC was found to be 0.052%. The categories of pregnancy complication preceding DIC: placental invasion and implantation anomalies, postpartum hemorrhage (atonia), placental abruption, hypertensive disease of pregnancy and others were found. Its rate in maternal morbidity was 38.6% and maternal mortality rate was 1.75% with 1 patient. 35% of the patients had laparotomy / re-laparotomy and 21% of these patients had hysterectomy. The average birth weight of the newborn is 2341.3 grams. Neonatal intensive care need is 34.5%, stillbirth rate is 25.5%. Neonatal mortality rate was determined as 3.6%. &#x0D; CONCLUSION: The management scheme plays a key role in delivery because termination of pregnancy often eliminates the underlying obstetric disorder. Early diagnosis and active treatment protocols reduce mortality and morbidity. Because of the physiological changes seen in the coagulation cascade during pregnancy, using a pregnancy-specific DIC score instead of the ISTH DIC score developed for non-pregnant adults may facilitate diagnosis.

Circulating Syndecan-1 Levels Are Associated with Chronological Coagulofibrinolytic Responses and the Development of Disseminated Intravascular Coagulation (DIC) after Trauma: A Retrospective Observational Study.

The purpose of this study was to evaluate the association between endotheliopathy represented by high levels of circulating syndecan-1 (SDC-1) and coagulofibrinolytic responses due to trauma, which can lead to disseminated intravascular coagulation (DIC). We retrospectively evaluated 48 eligible trauma patients immediately admitted to our hospital and assessed SDC-1 and coagulofibrinolytic parameters for 7 days after admission. We compared the longitudinal changes of coagulofibrinolytic parameters and SDC-1 levels between two groups (high and low SDC-1) according to median SDC-1 value on admission. The median circulating SDC-1 level was 99.6 (61.1-214.3) ng/mL on admission, and levels remained high until 7 days after admission. Coagulofibrinolytic responses assessed by biomarkers immediately after trauma were correlated with SDC-1 elevation (thrombin-antithrombin complex, TAT: r = 0.352, p = 0.001; antithrombin, AT: r = -0.301, p < 0.001; plasmin-α2-plasmin inhibitor complex, PIC: r = 0.503, p = 0.035; tissue plasminogen activator, tPA: r = 0.630, p < 0.001). Sustained SDC-1 elevation was associated with intense and prolonged coagulation activation, impairment of anticoagulation, and fibrinolytic activation followed by inhibition of fibrinolysis, which are the primary responses associated with development of DIC in the acute phase of trauma. Elevation of circulating SDC-1 level was also associated with consumption coagulopathy and the need for transfusion, which revealed a significant association between high SDC-1 levels and the development of DIC after trauma (area under the curve, AUC = 0.845, cut-off value = 130.38 ng/mL, p = 0.001). High circulating levels of syndecan-1 were associated with intense and prolonged coagulation activation, impairment of anticoagulation, fibrinolytic activation, and consumption coagulopathy after trauma. Endotheliopathy represented by SDC-1 elevation was associated with trauma induced coagulopathy, which can lead to the development of DIC.

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

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

HMG-CoA Reductase Inhibitors and the Modification of Risk for Disseminated Intravascular Coagulation in Patients with Sepsis

Background: Disseminated intravascular coagulation (DIC) is a highly morbid syndrome characterized by uncontrolled activation of coagulation leading to the consumption of clotting factors and platelets and increasing risk for life-threatening hemorrhage. Sepsis is one of the underlying disorders that can provoke DIC. The mechanism of DIC is thought to involve tissue factor overexpression, defective anticoagulation pathways, endothelial and monocytic cytokines, oxidation, and calpains. HMG-CoA reductase inhibitors (statins) have demonstrated anti-inflammatory and mild anti-coagulant properties effecting the pathways proposed to mediate DIC. Objectives: The aim of this study is to evaluate whether septic patients who take statin medications are at reduced risk for the development of DIC. Methods: In a retrospective cohort study, 120,397 critically ill patients with sepsis with and without shock were identified within a three year period from 2019 to 2021. Patients were stratified by whether they were medicated with low, medium, high intensity statins or none. Odds ratios for the development of DIC were calculated. Results: Overall, 2795 patients would develop DIC. The odds ratio for the development of DIC were .700 (95% CI .617-.794), .615 (95% CI .529-.714), and .901 (95% CI .635-1.277) when comparing high, moderate, and low intensity statin therapy to no statin therapy. Conclusion: The use of moderate and high intensity statins correlated with a significantly reduced association between critically ill septic patients and the development of DIC. More research is needed to clarify the potential for this class of medication to be protective against DIC. This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.

Brown Recluse Spider Bite: A Case Report of Severe Hemolysis and Sepsis

Abstract Introduction/Objective The brown recluse spider, Loxosceles reclusa, is commonly found in the southern and central United States and is known for its venomous bite. It has six eyes, uniformly colored abdomen and legs, is around 1 cm in length and prefers to live in warm, dark and dry places. Its bite in humans can cause skin necrosis as well as more severe manifestations including acute hemolytic anemia, disseminated intravascular coagulation (DIC), rhabdomyolysis and renal failure. Methods/Case Report We present a case report of a 27 year old male with no known past medical history who was referred from another medical center with a critical hemoglobin of 3.6 g/dl and acute hemolytic anemia that was not responsive to packed red blood cell transfusion and intravenous immunoglobulin treatment. He reported of having bitten by a brown recluse spider 8 days ago on the right scapular region. He started developing wound and pain in the area 2 days later when he was admitted to the hospital for a day and treated with antibiotics. His white blood cell count (WBC) at the time was mildly elevated with near normal hemoglobin and was incidentally found to have COVID 19 positivity. After being discharged, he developed fever with chills, dark urine, body ache, headache, nausea and vomiting. When presented to our hospital, laboratory review exhibited normocytic normochromic anemia with elevated bilirubin and decreased haptoglobin showing a hemolytic picture. The patient also displayed severe leukocytosis (WBC count: 53.50) with absolute neutrophilia, lymphocytosis, and monocytosis. Monocyte distribution width (MDW) was 30.02. These changes were attributed to be reactive to venom effect and sepsis. The patient showed significant improvement with plasmapheresis. Results (if a Case Study enter NA) NA. Conclusion The diagnosis of systemic loxoscelism is often difficult and delayed. Brown recluse spider bites may not always present with sharp stings to be noticed and reported by the patient. Presence of another infectious condition, like COVID 19 in this case, may divert the diagnosis. An elaborate patient history, physical examination for bite wound and patient education may help in identifying the cause early. Spider bites should be considered as a differential diagnosis in a patient with dermonecrosis and abrupt onset hemolysis or sepsis. Prompt treatment can prevent development of DIC, renal failure and life threatening conditions.

Association of Blood Glucose Variability with Sepsis-Related Disseminated Intravascular Coagulation Morbidity and Mortality.

Sepsis-related disseminated intravascular coagulation (DIC) is closely associated with poor prognosis and high mortality. Higher blood glucose (BG) variability indicates an increased risk of mortality in sepsis; however, its relationship with sepsis-related DIC has not been investigated. This study aimed to determine the association between glucose variability and sepsis-related DIC. Patients with sepsis admitted to the intensive care unit were enrolled between October 2017 and January 2021. Baseline data and BG records from the first 72 h were collected. We calculated the glucose liability index (GLI), largest amplitude of glucose excursion, BG standard deviation, and coefficient of variation on days 1 and 3. The relationship between GLI and morbidity of sepsis-related DIC was explored using a competing risk model. In subgroup analysis, we divided patients with and without diabetes into three groups according to the BG range. Of the 238 patients enrolled, 28.2% developed DIC during hospitalization (n=67). GLI on day 3 was found to have the closest relationship with DIC incidence as it has the largest area under the ROC curve and the highest associated odds ratio of death per unit change (GLI3-day: AUC=0.891 OR=1.84), also independently increased the occurrence of DIC after adjusting for the competing risk of death (sub-distribution hazard ratios=1.866, p<0.01). In subgroup analysis, patients with diabetes had worse outcomes under hypoglycemia than under hyperglycemia. Patients without diabetes having stable BG had the best outcomes. Our study suggested that a higher GLI in patients with sepsis at 72 h was independently associated with an increased risk of sepsis-related DIC, which was not associated with pre-existing diabetes.

A Potential Driver of Disseminated Intravascular Coagulation in Heat Stroke Mice: Neutrophil Extracellular Traps.

Highlights What are the main findings? NETs contribute to the activation of the coagulation cascade and have been successfully proved to be a potential driver of DIC in HS mice. What is the implication of the main finding? This work provides a novel alternative treatment strategy for the treatment of DIC in HS patients.Aims: Disseminated intravascular coagulation (DIC) is a common complication of heat stroke (HS) patients, and it is one of the important reasons leading to multiple organ failure and even death. The association between neutrophil extracellular traps (NETs) and DIC is unclear in HS mice. Methods and results: Here, HS was induced by the combination of hyperthermia (HT) and lipopolysaccharide (LPS). The DIC was evaluated by measuring prothrombin time (PT), D-dimer, thrombomodulin (TM), fibrinogen (FIB), and platelet (PLT). The expression of citrullinated-histone (CitH3) was analyzed by Western blotting. The formation of NETs was observed by immunofluorescence microscopy. The risk of HS-induced DIC was increased when HT was combined with LPS. The markers of NETs were significantly higher than those in the control group, and the NETs derived from HS promoted the development of DIC. DNase I improved coagulation dysfunction via the clearance of NETs caused by neutrophil aggregation. Conclusions: Degradation of NETs reduced the risk of developing DIC, and thus the survival rate of mice was improved. These results indicate that NETs may hold potential alternative therapeutic strategies for the treatment of DIC in HS patients.

348.5: Life Threatening, Cytokine Release Storm (CRS) With Antithymocyte Globulin (ATG) And Its Management

Introduction: Cytokine Release Storm (CRS) leading to fatal or near fatal hypotension has been reported in association with anti thymocyte globulin (ATG) administration. This is a very rare and unusual manifestation of ATG and early recognition and management of this unexpected manifestation will help save lives. We report a near fatal case of CRS, during renal transplantation, associated with ATG administration, its diagnosis and management. Materials and Methods: A 27-year-old, otherwise healthy male with Alport’s syndrome was undergoing live related preemptive renal transplant. Patient received morning dose of Solu-Medrol and CellCept and was getting Anti Thymocyte Globulin (ATG) slowly after the test does, as the recipient vascular bed was being prepared. Patient started to become hypotensive which was treated with IV fluids and pressors including norepinephrine, epinephrine and dopamine.There was no bleeding from recipient vascular bed.A stat chest x-ray, EKG and echocardiogram on the OR table were normal with good LV function. Despite maximum dose pressor support and IV fluids, the mean blood pressure was around 45 - 50 mm Hg and a systolic blood pressure was around 65-70 mm Hg, leading to severe metabolic acidosis and lactate buildup. The transplant was canceled and the donor was closed unharmed and the patient was moved to ICU, intubated. His response to colloids was slightly better, but transient, so he was transfused 4 units of blood as volume expander that does not leak into 3rd space.This brought his blood pressure to about 90 mm Hg. A presumptive diagnosis of ATG induced CRS was made. His inflammatory markers including IL-6, ferritin, D-dimers and CRP were very high. 400 mg of Tocilizumab (Actemra) an IL-6 inhibitor along with broad-spectrum antibiotics were given. Patient also started to developed disseminated intravascular coagulation (DIC) with deranged coagulation screen and some oozing from the wound which was treated with FFPs. In next 12 hours, the patient started to stabilize and in next 48 hours he was extubated. Discussion: Cytokine Release Storm (CRS) is a potentially fatal condition unless recognized and treated early and aggressively. In COVID pandemic, much better understanding of CRS along with its symptomatology, easy availability of its lab tests and IL- 6 inhibitors became possible. High index of suspicion is extremely important in making an early diagnosis and for early treatment. In transplant patients, use of ATG is now standard of care and very few cases of ATG induced CRS are reported. In our case, early diagnosis of CRS from ATG, use of blood as volume expander, early administration of IL-6 inhibitor and aggressive management of DIC turned out to be the life Saver. Conclusion: In patients receiving ATG, with unexplained hypotension, nonresponsive to IV fluids and pressors, high index of suspicion of ATG induced CRS with early diagnosis and aggressive management can save lives.

Temporal Trends, Predictors, and Outcomes of Disseminated Intravascular Coagulation in Hospitalizations With Sepsis

BackgroundThis retrospective study was conducted to analyze the temporal trends, predictors, and impact of disseminated intravascular coagulation (DIC) on outcomes among septicemic patients using a nationally representative database.MethodsWe derived data from the National Inpatient Sample (NIS) for the years 2008-2017 for adult hospitalizations due to sepsis. The primary outcomes were in-hospital mortality and discharge to facility. The Cochran-Armitage test and multivariable survey logistic regression models were used to analyze the data.ResultsOut of 12,820,000 hospitalizations due to sepsis, 153,181 (1.18%) were complicated by DIC. The incidence of DIC decreased from 2008 to 2017. In multivariable regression analysis, demographics and comorbidities were associated with higher odds of DIC. During the study period, in-hospital mortality among patients with sepsis decreased, but the attributable risk percent of in-hospital mortality due to DIC increased. We observed similar trends for discharge to facility; however, the adjusted odds of discharge to facility due to DIC remained stable over the study period.ConclusionAlthough the incidence of sepsis complicated by DIC decreased, the attributable in-hospital mortality rate due to DIC increased during the study period. We identified several predictors associated with the development of DIC in sepsis, some of which are potentially modifiable.

Clinical Characteristics Associated with Venous Thromboembolism in Patients with Non-APL Acute Myeloid Leukemia

INTRODUCTIONVenous thromboembolism (VTE) is an important complication of many cancers. Although more widely recognized in solid tumors, VTE is still an appreciable cause of morbidity and mortality among patients with hematologic malignancies. For example, acute promyelocytic leukemia (APL) is a well-recognized risk factor for disseminated intravascular coagulation (DIC), which can lead to thrombosis. Patients with non-APL AML are also at increased risk for VTE, though the exact mechanisms are currently unclear. Thus, we sought to explore how patient demographics, comorbidities, hematologic factors, coagulation parameters, and cytogenetic and molecular profiles impact the incidence of VTE in patients with non-APL AML. METHODSThis was a retrospective observational case-control study of 120 non-APL AML patients treated at the University of Wisconsin-Madison. The electronic health record was manually reviewed for extraction of the relevant clinical information. Coagulation parameters assessed included INR, PTT, fibrinogen, D-dimer, and fibrin monomer. Coagulation data were collected both at diagnosis and during the first 7 days of induction, if applicable. Cytogenetics was categorized based on the presence of a normal karyotype or not. Genomic data were subdivided into eight different functional categories of genes that are commonly mutated in AML. Other factors that could potentially increase the risk of thrombosis were also analyzed, including age, sex, BMI, baseline blood counts, baseline bone marrow blast percentage, previous history of VTE, use of antifibrinolytic agents, and whether blood products were transfused during the early treatment period. The variables of interest between VTE cases and non-VTE cases were compared using the nonparametric Wilcoxon rank sum test. RESULTSAcross the entire cohort (n=120), VTE developed in 25 patients (20.8%) and did not develop in 95 patients (79.2%). Table 1 and Table 2 show comparisons between VTE cases and patients without VTE for both quantitative and categorical variables. Median INR values at diagnosis and across the first 7 days of induction tended to be lower in patients with VTE and reached significance on days 3-5 (p=0.032 for INR-Day 3, p=0.046 for INR-Day 4, p=0.014 for INR-Day 5). Patients with VTE had a median BMI of 30, while patients without VTE had a median BMI of 28, which approached statistical significance (p=0.055). 8% of patients with VTE (2/25) had a history of VTE prior to the diagnosis of AML, while 3% without VTE (3/95) had a history of previous VTE (OR 2.7, p=0.281). Mutation in genes involved in DNA methylation also conferred an increased risk of VTE, with the association approaching statistical significance (p=0.083). There were no other variables that were significantly different between the two groups. CONCLUSIONSIn this cohort of patients with non-APL AML, there was a trend towards lower INR correlating with an increased incidence of VTE. Additionally, higher BMI, previous history of VTE, and mutation in DNA methylation genes were associated with increased incidence of VTE, though these trends did not reach statistical significance. The pathophysiology of VTE in this setting is likely complex and multifactorial. The shorter INR in those who developed VTE suggests a mechanism independent of the development of DIC, which is distinct from APL. The finding that obesity and personal history of VTE, both known risk factors for thrombosis, were associated with an increased incidence of VTE is also consistent with a non-DIC mechanism. Mutations in DNA methylation genes may have contributed to increased risk of VTE in this cohort; while this association is compelling, further studies with larger sample sizes are needed to confirm this finding. This study was limited by small sample size and missing data, especially regarding available data on coagulation tests. However, this analysis uncovers interesting associations that shed light on the pathophysiology of VTE in AML. More research is needed to further elucidate risk factors for VTE in order to provide optimal supportive care for this patient population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effect of antithrombin III among patients with disseminated intravascular coagulation in obstetrics: a nationwide observational study in Japan.

Pregnant women may develop disseminated intravascular coagulation (DIC), possibly resulting in massive maternal haemorrhage and perinatal death. The Japan guideline recommends use of antithrombin III (ATIII) for DIC in obstetrics; however, its effect remains uncertain. The present study aimed to investigate the effect of ATIII for DIC in obstetrics, using a national inpatient database in Japan. Nationwide observational study. Japan. We used the Diagnosis Procedure Combination inpatient database to identify patients who delivered at hospital and were diagnosed with DIC from July 2010 to March 2018. Propensity score matching analyses were performed to compare in-hospital maternal mortality and hysterectomy during hospitalisation between users and non-users of ATIII on the day of delivery. In-hospital mortality, hysterectomy. A total of 9920 patients were enrolled, including 4329 patients (44%) who used ATIII and 5511 patients (56%) who did not use ATIII. One-to-one propensity score matching created 3290 pairs. In-hospital maternal mortality did not differ significantly between the propensity-matched groups (0.3% in the ATIII group versus 0.5% in the control group; odds ratio 0.73; 95% CI 0.35-1.54). A significantly lower proportion of patients in the ATIII group, compared with those in the control group, underwent hysterectomy during hospitalisation (5.3% versus 8.7%; absolute risk difference -2.9%; 95% CI -4.2 to -1.6%). Although the present study did not show a mortality-reducing effect of ATIII for patients with DIC in obstetrics, it may have clinical benefit in terms of reducing the number of patients undergoing hysterectomy. This study did not show mortality-reducing effect of antithrombin III for patients with DIC in obstetrics.

Neutropenic enterocolitis-induced sepsis and disseminated intravascular coagulation after chemotherapy: a case report

BackgroundNeutropenic enterocolitis (NE) is a potentially life-threatening disease that primarily occurs in cancer patients treated with chemotherapy. NE has substantial morbidity and mortality, and its incidence has increased with the widespread use of chemotherapeutic agents such as taxanes, gemcitabine, and leucovorin in patients with lung, breast, gastric, and ovarian cancers. Sometimes NE can be a possible cause of death. Although, conservative approaches are often successful, there are currently no standardized treatment guidelines for NE and it is unclear when such strategies should be implemented. Therefore, we present this report to provide a greater insight into the possible treatment of NE.Case presentationWe report the case of a 72-year-old woman with endometrial cancer who was undergoing treatment for hypertension, obesity and diabetes mellitus. The patient initially developed paralytic ileus on the 6th postoperative day (POD) after surgery for endometrial serous carcinoma. Complete recovery was achieved after 4 days of fasting and fluid replacement therapy. On the 27th POD, she received the first cycle of combination chemotherapy consisting of paclitaxel and carboplatin. On day 5 of chemotherapy, she developed the systemic inflammatory response syndrome including febrile neutropenia and sepsis. She then developed disseminated intravascular coagulation (DIC) and septic shock. The patient was subsequently moved to the intensive care unit (ICU). Despite initiating the standard treatment for septic shock and DIC, her overall status worsened. It was assumed that gut distention had led to bowel damage, subsequently leading to bacterial translocation. Thus, she developed NE with severe DIC and septic shock. We decided to reduce the intestinal pressure using an ileus tube to suction the additional air and fluid, even though doing so had a risk of worsening her general condition. The inflammatory reaction subsided, and her general condition improved. The patient recovered after 18 days in the ICU and was discharged alive.ConclusionsHerein, we describe a patient with suspected chemotherapy-associated NE. Our observations suggest that postoperative ileus may be one of the possible causes of NE. Patients who experience postoperative ileus must be carefully monitored while undergoing chemotherapy.

ADAMTS13 activity decreases in the early phase of trauma associated with coagulopathy and systemic inflammation: a prospective observational study

BackgroundWe conducted a prospective observational study for investigating the changes in the 13th member of a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) and its association with the coagulofibrinolytic response in adult trauma patients.MethodsIn 39 trauma patients hospitalized for longer than 7 days, time-course changes in biomarkers of coagulofibrinolysis and systemic inflammation along with ADAMTS13 activity were examined. The patients were stratified into three groups based on ADAMTS13 activities on admission (day 0): normal group (≥70%), mildly decreased group (≥50 and < 70%) and moderately decreased group (< 50%).ResultsAmong 39 patients with a median Injury Severity Score (ISS) of 20, 11 patients developed disseminated intravascular coagulation (DIC) and 16 patients required transfusion. Six of 39 patients (15.4%) showed moderate decreased ADAMTS13 activity to < 50%, and 20 patients (51.3%) showed mild drops (≥50 and < 70%). These changes in ADAMTS13 activity on day 0 were significantly correlated with changes in IL-6 and other coagulofibrinolytic markers such as platelet counts, prothrombin time and fibrin/fibrinogen degradation product (FDP). Antithrombin activity (AT) and serum albumin (Alb) level showed significantly positive linear correlations with ADAMTS13 activity (AT: r = 0.513, p < 0.001; Alb: r = 0.647, p < 0.001). Simple logistic regression analyses showed that ADAMTS13 activity, if less than 50%, was significantly correlated with the development of DIC (OR 7.499, 95%CI 1.121–49.242, p = 0.038) and the need for transfusion of fresh frozen plasma (OR 9.000, 95%CI 1.327–61.025, p = 0.028).ConclusionsADAMTS13 activity decreased even in the early phase of trauma, which was complicated by coagulopathy and systemic inflammation. Furthermore, the decrease in ADAMTS13 activity was correlated with DIC and plasma transfusion.

Disseminated intravascular coagulopathy: a complication of Stevens-Johnson syndrome/toxic epidermal necrolysis.

The purpose of this study was to retrospectively assess clinical characteristics and mortality rate of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients who developed disseminated intravascular coagulation (DIC). A systematic retrospective chart review of all patients with concurrent clinical diagnosis of DIC and SJS/TEN between July 1, 2012, and January 1, 2020, at the Mayo Clinic was performed. The incidence of DIC in patients with SJS/TEN was 1.3% at our institution (5 of 396 DIC patients). Triggers of SJS/TEN included lamotrigine, clofarabine, antibiotics, and sepsis. Two patients diagnosed with SJS and two patients with TEN succumbed to the disease. DIC is a rare underlying risk in patients with SJS/TEN and is associated with increased mortality. Early clinician awareness and aggressive intervention is advised.