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

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

Disseminated intravascular coagulation scores as predictors for progressive hemorrhage and neurological prognosis following traumatic brain injury

Coagulation abnormalities, such as disseminated intravascular coagulation （DIC）, are associated with progressive hemcrrhagic injury （PHI） following head trauma. However, the exact relationship between coagulopathy and PHI remains unclear. The present study utilized a scoring system defined by the International Society of Thrombosis and Haemostasis to investigate whether a high DIC score is predictive for PHI. This study was a multicenter prospective design involving four hospitals, a 6-month observation, and follow-up. Of 352 traumatic brain injury （TBI） patients, serial CT scan indicated approximately one third of patients developed progressive hemorrhage, which was most frequently observed in the frontal, temporal, and orbitofrontal lobes of patients with brain contusion. PHI-positive patients exhibited poor prognosis, as indicated by prolonged length of hospital/intensive care unit stay and high mortality. More importantly, a DIC score after TBI, as well as patient age and sex, could serve as predictors for PHI. In addition, DIC scores were closely associated with injury severity. Therefore, the DIC scoring system facilitated early PHI diagnosis in TBI patients, and DIC scores might serve as a valuable predictor for TBI patients with PHI.

Myricetin protects against lipopolysaccharide-induced disseminated intravascular coagulation by anti-inflammatory and anticoagulation effect

Objective: To explore the therapeutic effect and mechanism of myricctin on disseminated intravascular coagulation(DIC). Methods: The DIC model was established by injection of60 mg/kg LPS in KM mice, and the treatment groups were injected myricetin with different concentrations(25 or 50 mg/kg) 30 min before the model was established. Both coagulation indicators and organ function were tested, including PT, APTT, fibrinogen. AST, ALT. BUN and tissue section. In vitro, the inflammatory model of RAW 264.7 macrophage cells were established by 10 μg/mL LPS. The treatment group was treated with 50 μmol/mL myricetin for 30 min before LPS, and the expression of TNF-a and p-NF-KB was detected, further to explore the therapeutic mechanism. Results: LPS-induced DIC led to a reduction of fibrinogen and a rise of PT, APTT,AST, ALT, BUN levels, but the treatment of myricctin significantly inhibited these abnormalities. Histopathology analysis also revealed that myricetin remarkably protected the liver and renal damage. In vitro, the expression of TNF-α and p-NF-κB induced by LPS was repressed by myricetin. Conclusions: This study provides new insights into the protective effects of myricetin in LPS-induced DIC by anticoagulant and anti-inflammatory via suppressing the activation of p-NF-κB which decreased TNF-α level.

Fatal rhabdomyolysis and disseminated intravascular coagulation after total knee arthroplasty under spinal anesthesia:A case report

BACKGROUND Rhabdomyolysis develops as a result of skeletal muscle cell collapse from leakage of the intracellular contents into circulation.In severe cases,it can be associated with acute kidney injury and disseminated intravascular coagulation,leading to life threatening outcomes.Rhabdomyolysis can occur in the perioperative period from various etiologies but is rarely induced by tourniquet use during orthopedic surgery.CASE SUMMARY A 77-year-old male underwent right total knee arthroplasty using a tourniquet under spinal anesthesia.About 24 h after surgery,he was found in a drowsy mental state and manifested features of severe rhabdomyolysis,including fever,hypotension,oliguria,high creatine kinase,myoglobinuria,and disseminated intravascular coagulation.Despite supportive care,cardiac arrest developed abruptly,and the patient was not able to be resuscitated.CONCLUSION Severe rhabdomyolysis and disseminated intravascular coagulation can develop from surgical tourniquet,requiring prompt,aggressive treatments to save the patient.

Blue rubber bleb nevus syndrome complicated with disseminated intravascular coagulation and intestinal obstruction: A case report

BACKGROUND Blue rubber bleb nevus syndrome is a rare vascular malformation syndrome with unclear etiopathogenesis and noncurative treatments.It is characterized by multiple vascular malformations of the skin,gastrointestinal tract,and other visceral organs.The most common symptoms are intermittent gastrointestinal bleeding and secondary iron deficiency anemia,thus requiring repeated blood transfusions and hospitalizations.It is easily missed and misdiagnosed,and there is no specific treatment.CASE SUMMARY We report a case of blue rubber bleb nevus syndrome combined with disseminated intravascular coagulation and efficacy of treatment with argon plasma coagulation under enteroscopy and sirolimus.A 56-year-old female patient was admitted to the hospital with 3-year history of fatigue and dizziness that had aggravated over the past 10 d with melena.The patient had a history of repeated melena and multiple venous hemangiomas from childhood.After treatment with argon plasma coagulation combined with sirolimus for nearly 8 wk,the patient’s serum hemoglobin increased to 100 g/L.At the 12-mo follow-up,the patient was well with stable hemoglobin(102 g/L)and no recurrent intestinal bleeding.CONCLUSION Argon plasma coagulation and sirolimus may be an efficacious and safe treatment for blue rubber bleb nevus syndrome,which currently has no recommended treatments.

弥漫性血管内凝血(Disseminated intravascular coagulation.DIC)的治疗

弥漫性血管内凝血是许多疾病发展过程中一组较复杂的出血征象。根据临床表现分为急性、亚急性和慢性三型。急性型病情危险且预后差。按病程又分为早期、中期和晚期、晚期治疗困难,预后不良。治疗原则1.总则(1)治疗原发病这是终止DIC的最关键措施。如控制感染。治疗恶性肿瘤,中止病理性妊振,减少内源性或外源性促凝血物质的吸收等。

Disseminated Intravascular Coagulation at Diagnosis in Acute Myeloblastic Leukaemia

Background: Disseminated Intravascular Coagulation (DIC) is a life threatening complication frequently observed in acute leukemia. Among the morphological varieties of Acute Myeloid Leukaemia (AML), Acute Promyelocytic Leukaemia (APL) is well established to cause DIC. But there have been reports noted that abnormal DIC parameters also commonly observed in the patients with non-APL AML. This study evaluated the DIC parameters & DIC score according to International Society of Thrombosis and Haemostasis (ISTH) in newly diagnosed non-APL AML patients. Materials and Methods: This cross-sectional observational study was conducted in the Department of Haematology, BSMMU, Dhaka, Bangladesh. 48 newly diagnosed non-APL AML patients were enrolled. Platelets count was measured by auto analyzer (Sysmax XT 2000i/Pentra ABX-120DX) as well as checked manually. Prothrombin time, fibrinogen, D-Dimer were measured using STAGO Coagulation analyzer. The ISTH-DIC scoring system was used to calculate DIC score. The statistical analysis was carried out using the Statistical Package for Social Sciences version 24.0 for Windows. Chi-Square test & Fisher exact test was used for categorical variables. Unpaired t-test was used to compare mean between groups. For all statistical tests, p-value less than 0.05 was considered as statistically significant. Results: By analyzing 48 newly diagnosed patients with non-APL AML, found that DIC developed in 14.6% patients at presentation. Among the DIC parameters, PT and D-dimer were significantly higher in patients presented with DIC. Patients with DIC exhibit lower expression of CD117, CD34, HLA-DR and statistically significant association with negative expression of HLA-DR (p-value 0.034). No significant association was found between presence of DIC and age, gender, bleeding at presentation, morphological type, WBC count or peripheral blast percentage. Conclusion: Abnormalities of DIC parameters in common in patients with AML. A significant portion of patients with DIC have no apparent symptom or bleeding. So, routine screening of DIC parameter at presentation is recommended for early diagnosis & effective management of DIC.

The Diagnosis and Man Disseminated Intravascular Coagulation

This review describes disseminated intravascular coagulation(DIC) as a syndrome in which hemostatic factors are activated and products are generated. This syndrome ranges in severity from an obvious decompensated coagulopathy (overt-DIC) to the subclinical compensated activation of hemostatic factors(non-overt DIC). Ths first part of this review emphasizes two points: First, activation of the hemostatic system is controlled by a vast network of capillaries and venules through anticoagulant and antiinflammatory regulatory factors that operate from the endothelium( e. G. , protein C and thrombomodulin, tissue factor pathway inhibitor).

Current approach to disseminated intravascular coagulation related to sepsis-organ failure type

Disseminated intravascular coagulation(DIC) is a syndrome characterized by the systemic activation of blood clotting, which generates large amount of intravascular thrombin and fibrin. Various diseases may cause acceleration of the clotting cascade, inactivate the endogenous anticoagulants and modify fibrinolysis, having thus the formation of micro thrombi in the systemic circulation. The abnormalities in the hemostatic system in patients with DIC result from the sum of pathways that generate both hypercoagulability and augmented fibrinolysis. When the hypercoagulability state prevails, the main manifestation is organic failure. This subtype of DIC is often referred as "organ impairment" type, frequently seen in patients suffering from severe sepsis. To identify the underlying infection, early initiation of culture-based antimicrobial treatment, and to resolve any infection source promptly are keystone actions of DIC related to sepsis prevention and treatment. These should be combined with specific treatment related to each DIC subtype. In the context of septic shock, DIC is associated to increased severity, greater number and seriousness of organ failures, more frequent side-effects from treatment itself, and worse outcomes. Therefore, we ought to review the information available in the literature about approach and management of DIC in severe sepsis.

Pre-treatment with bone marrow-derived mesenchymal stem cells inhibits systemic intravascular coagulation and attenuates organ dysfunction in lipopolysaccharide-induced disseminated intravascular coagulation rat model

Background Bacterial lipopolysaccharide （LPS） can activate immunological cells to secrete various proinflammatory cytokines involved in the pathophysiological process of disseminated intravascular coagulation （DIC） during infection. In recent years, it has been found that bone marrow-derived mesenchymal stem cells （BMSCs） can affect the activity of these immune cells and regulate the secretion of proinflammatory cytokines. Here, we report the possible protective effect of BMSCs pre-treatment in LPS-induced DIC rat model and the mechanism. Methods Forty-eight adult male rats were divided into five experimental groups and one control group with eight animals in each group. In the treatment groups, 0, 1×10^6, 2×10^6, 3×10^6, and 5×10^6 of BMSCs were injected intravenously for 3 days before LPS injection, while the control group was treated with pure cell culture medium injection. Then, the LPS （3 mg/kg） was injected via the tail vein in the treatment groups, while the control group received 0.9% NaCI. Blood was withdrawn before and 4 and 8 hours after LPS administration. The following parameters were monitored： platelets （PLT）, fibrinogen （Fib）, D-dimer （D-D）, activated partial thromboplastin time （APTT）, prothrombin time （PT）, tumor necrosis factor-a （TNF-（a）, interferon-y （IFN-a）, interleukin-1β （IL-1β）, creatinine （Cr）, alanine aminotransferase （ALT）, creatinine kinase-MB （CK-MB）, and endothelin （ET）. Results Compared with the control group, a significant change of coagulation parameters were found in the experimental groups. The plasma level of the inflammatory mediator （TNF-a, IFN-7, IL-1β）, organ indicator （Cr, ALT, and CK-MB）, and ET in the experimental groups were much lower （P〈0.05） than that in the control group. Furthermore, some of these effects were dose-dependent; the statistical comparison of the plasma levels between the groups （from group 2 to group 5） showed a significant difference （P 〈0.05）, except the ALl and CK-MB levels （P 〉0.05）. Conclusion Pre-treatment with BMSCs can attenuate organ dysfunction and inhibit systemic intravascular coagulation effectively via the regulatory effect on immune cells and proinflammatory cytokines in LPS-induced DIC rat model.

Gefitinib-induced disseminated intravascular coagulation in a patient with non-small cell lung cancer

In February 2005, Gefitinib （Iressa）, a small-molecular .epidermal growth factor receptor and tyrosine kinaseinhibitor, was approved in China as an anticancer agent for patients with advanced （local or metastatic） non-small cell lung cancer （NSCLC）, who failed prior chemotherapy. The common adverse events of the drug include acne-like skin rash, paronychia, pruritus, diarrhea, nausea/vomiting, anorexia, hepatitis, and hyperbilirubinemia.1 However, these adverse events are generally mild in severity and reversible on cessation of the treatment. Therefore, gefitinib has been regarded as a relatively safe agent,

Recombinant activated factor Ⅶ in hemophagocytic lymphohistiocytosis with disseminated intravascular coagulation

Hemophagocytic lymphohistiocytosis （HLH） is a lifethreatening disorder due to hyperinflammation resulting in infiltration of different organs with extensive hemophagocytosis. Severe coagulopathy was one of the main reasons for death in HLH. Over secretion of plasminogen activator by activated macrophages leads to hyperfibrinolysis. We reported a 36-year-old woman who was diagnosed as HLH probably secondary to lymphoma. Massive bleeding from gut and retroperitoneal area were not able to be controlled by conventional hemostatic treatments. This patient received one dose recombinant activated factor Ⅶ （rFVlla） 3.6 mg （70 μg/kg）. Hemostatic effect was achieved in 0.5 hour and lasted 24 hours. Prothrombin time （PT） and activated partial thromboplastin time （APTT） were quickly corrected to normal ranges.Fibrinogen level elevated from 0.5 g/L before using rFVIla to 1.8 g/L 20 hours after. Although dexamethasone and etopside were administrated to treat HLH, this patient died from septic shock after persistent neutropenia. This suggests that rFVlla may be effective in the management of intractable hemorrhage in patients with HLH.

Effect of Reduqing (热毒清)on Plasma Interleukin-8 and Nitric Oxidein Rabbits with Endotoxin induced Disseminated intravascular Coagulation

objective: To investigate the effects of Reduqing （RDQ, 热毒清） on plasma interleukin-8 （IL-8）complement 5a （C5a）and polymorphonuclear neutrophilic leukocyte （PMN） chemotaxis Index （CI） in rabbits with endotoxin-induced disseminated intravascular coagulation （DIC）. Methods: Endotoxin-induced DIC model made by injection of LiPoPolysacchrides （LPS） was used in the experiment. Above-mentioned indexes were determined before and after RDQ treatment and compared with blank and dexamethasone treated group. Results: Plasma IL-8,C5a and CI level of PMN increased markedly in the model group, which were confirmed pathologically with obvious damage of tissues or organs. In the RDQ group, the abovementiond parameters and damage of tissues or organs were reduced significantly （P ＜ 0.01 ）. Conclusion: IL-8 and NO might be involved in pathogenesis of endotoxin-induced DIC, and RDQ could be used in preventing or treating DIC through the mechanism of regulation of cytokines network.

Aortic aneurysm and chronic disseminated intravascular coagulation： a retrospective study of 235 patients

Chronic disseminated intravascular coagulation （DIC） is a rare but devastating complication of aortic aneurysm （AA）. This study investigated the clinical manifestations, laboratory findings, and treatment of patients with AA-associated chronic DIC （AA-DIC） and explored the mechanisms, duration, and therapeutic response of AA-DIC. We retrospectively reviewed the medical records of 235 AA patients admitted at the Peking Union Medical College Hospital between September 2009 and January 2015. The patients were classified as those with DIC （AA-DIC） and those without DIC （non-DIC）. The AA-DIC group showed a significantly higher proportion of female patients and a significantly longer AA disease course than the non-DIC group did. The AA-DIC patients presented mural thrombi, dissecting aneurysms, a family history of AA, and diabetes significantly more frequently than the non-DIC patients did. Furthermore, multiple regression analyses revealed that sex, mural thrombus, aneurysm type, diabetes, and stent surgery are possible independent risk factors for AA-DIC patients. Fifty-two （22.1%） patients presented AA-DIC. Among these patients, 43 had non-typical DIC and 9 had typical DIC; the mortality rate of the latter was 22.2%. The mean age of the patients with typical DIC was significantly higher than of that of patients with non-typical DIC. The non-typical DIC patients also presented abnormal coagulation disorders of varying degrees. Furthermore, heparin or low-molecular-weight heparin improved the clinical symptoms and laboratory parameters in patients with AA and typical DIC. Thus, chronic DIC should be considered in patients with AA.

Preserving finger length in a patient with symmetric digital gangrene under local anesthesia:A case report

BACKGROUND Case reports of symmetric digital gangrene resulting from high-dose vasopressors use in patients with alcoholic ketoacidosis,leading to cardiac arrest,are rare.To date,no specific treatment method for autolysis or surgical amputation or guidelines for determining the level of amputation have been established.CASE SUMMARY In this case report,we describe a treatment method that effectively preserved the function of fingers by surgical treatment under local anesthesia with a minimum operative time,while also preserving finger length to the maximum possible extent.CONCLUSION Our approach may contribute to improved postoperative quality of life by preserving finger length.

Risk Factors for Mortality in Critically Ill Patients with Coagulation Abnormalities:A Retrospective Cohort Study

Objective Coagulation abnormalities are common and prognostically significant in intensive care units(ICUs)and are associated with increased mortality.This study aimed to explore the association between the levels of coagulation markers and the risk of mortality among ICU patients with coagulation abnormalities.Methods This retrospective study investigated patients with coagulation abnormalities in the ICU between January 2021 and December 2022.The initial point for detecting hemostatic biomarkers due to clinical assessment of coagulation abnormalities was designated day 0.Patients were followed up for 28 days,and multivariate logistic regression analysis was utilized to identify risk factors for mortality.Results Of the 451 patients analyzed,115 died,and 336 were alive at the end of the 28-day period.Multivariate analysis revealed that elevated thrombin-antithrombin complex(TAT),tissue plasminogen activator inhibitor complex(tPAIC),prolonged prothrombin time,and thrombocytopenia were independent risk factors for mortality.For nonovert disseminated intravascular coagulation(DIC)patients,older age and thrombocytopenia were associated with increased risks of mortality,whereas elevated levels of plasminα2-plasmin inhibitor complex(PIC)were found to be independent predictors of survival.In patients with overt DIC,elevated levels of tPAIC were independently associated with increased risks of mortality.Nevertheless,thrombocytopenia was independently associated with increased risks of mortality in patients with pre-DIC.Conclusion Coagulation markers such as the TAT,tPAIC,PIC,and platelet count were significantly associated with mortality,underscoring the importance of maintaining a balance between coagulation and fibrinolysis.These findings highlight the potential for targeted therapeutic interventions based on specific coagulation markers to improve patient outcomes.

Nafamostat mesylate-induced hyperkalemia in critically ill patients with COVID-19: Four case reports

BACKGROUND Nafamostat mesylate(NM)may prove to be one of the key drugs effective against coronavirus disease 2019(COVID-19)because of its anti-viral properties and the potential to manage coagulopathy.However,NM tends to increase serum potassium levels.CASE SUMMARY We observed hyperkalemia immediately after NM administration(200 mg/d)in four consecutive patients who were admitted to the Kanazawa University Hospital with severe COVID-19 pneumonia.Urinary potassium excretion decreased after NM administration in three patients who underwent urinalysis.CONCLUSION NM is likely to produce hyperkalemia in patients with COVID-19.Therefore,it is necessary to monitor serum potassium values closely after NM initiation in COVID-19 patients who need respiratory support.

Amniotic fluid embolism:literature review and an integrated concept of pathomechanism

Literature concerning procoagulant activity of the amniotic fluid and pathomechanism of amniotic fluid embolism (AFE) was surveyed and a new concept of its pathogenesis, called the integrated concept of AFE, was presented. According to this concept, two components of the amniotic fluid are involved: (i) apoptosis-affected amniotic cells showing a special role in the initiation of disseminated intravascular coagulation (DIC) and (ii) leukotrienes (formerly called slow-reacting substances), inducing bronchial and pulmonary vascular smooth muscle contraction. Although each of these components initiates a different pathogenic pathway, they both lead to the formation of a mechanical barrier on blood flow through the lungs (amniotic debris + microemboli) and/or functional barrier (pulmonary vasoconstriction). An old dilemma, concerning indications for heparin therapy in AFE was recalled in the light of the new concept.

Heparin and other anticoagulants in amniotic fluid embolism(AFE):Literature review and concept of the therapy

Aim: The objective of this study is to review all the reported outcomes of heparin application in amniotic fluid embolism (AFE) so far and to find out why, when and how heparin or other anticoagulants should be used in AFE. Material and methods: We searched Medline (from 1969 to 2011), using two key words: 1) amniotic fluid embolism;2) amniotic fluid embolism and heparin. The search for the former produced 1127 replies, of which 208 were case reports of AFE. In response to the other key word, there were 94 articles. We looked through all the articles, selecting those relevant for our study. Results: In the years 1969-2011, 208 AFE cases were reported. Heparin (unfractionated heparin) or low molecular weight heparin (LMWH) was applied in 20 cases (9.6%), being the main drug in 11 cases (5.3%) and in 6 cases as a component of spectacular treatment of AFE (surgical treatment and extracorporal membrane oxygenation). In one of these cases anithrombin (AT) with LMWH was used. In one patient heparin therapy was considered to be unsuccessful and hence recombinant plasminogen activator (rt-PA) was instituted. All the patients survived. Conclusions: 1) The attempts to use heparin in AFE could be defined as promising, although the number of treated patients is too small for conclusion;2) The postulate to use heparin at the very onset of AFE (a bolus of 10,000 U followed by monitored intravenous infusion) has serious justification: one of the pathways of AFE is the target for heparin (coagulation pathway).

Therapy-related acute promyelocytic leukemia with FMS-like tyrosine kinase 3-internal tandem duplication mutation in solitary bone plasmacytoma: A case report

BACKGROUND Therapy-related acute promyelocytic leukemia(t-APL)is a rare complication observed in solitary bone plasmacytoma(SBP),and SBP after radiotherapy evolving to APL harboring the FMS-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)mutation has never been reported.Here,we present the first case reported until now.CASE SUMMARY We describe a 64-year-old woman who presented with lumbar pain and was initially diagnosed with SBP.However,after one year of radiotherapy treatment,this patient experienced a long-standing bone-marrow-suppressive period and finally developed APL harboring the FLT3-ITD mutation,as confirmed by analyses of clinical features,bone marrow morphology,flow cytometry,cytogenetic examination,and molecular biology.On admission,the patient had disseminated intravascular coagulation and intracranial hemorrhage,and the peripheral blood and bone marrow smear displayed abundant abnormal promyelocytes.Unfortunately,she died when the definite diagnosis was made.CONCLUSION The patient with t-APL harboring FLT3-ITD mutation evolving from SBP after radiotherapy had not been reported and had poor clinical outcomes.FLT3-ITD mutation in t-APL may be a potential pathogenesis of leukemogenesis.We should consider the potential risk of secondary neoplasms in SBP patients after radiotherapy.