Cause Of Disseminated Intravascular Coagulation Research Articles

Case Study: Disseminated intravascular coagulation at autopsy of a child with severe burns resulting in death

Childhood is a time of growth and development, both intellectually and emotionally. The Indonesian Child Protection Commission has observed a growing number of cases of violence against children, including physical and verbal abuse, which require special attention and handling. Physical violence can include burns, which are particularly dangerous in developing countries, where the mortality rate is high. Severe burns can result in inhalation injury and sepsis, which can cause coagulation disorders, making it easier for Disseminated Intravascular Coagulation (DIC) to occur. This study aims to describe the coagulation function of severely burnt patients, investigate the potential causes of DIC, and examine other clinical data. The study used a case study approach, analyzing the corpse of a child who suffered from severe burns. An autopsy was performed and supporting examinations were conducted to determine the cause of death. The examination of the patient's laboratory results, treatment records, corpse, and anatomical pathology revealed the presence of DIC. The autopsy of the child's corpse showed severe burns, pale coloring in the tissues under the nails, and blood clots in the epidural, left ventricle, right ventricle, and veins. The cause of death was determined to be severe burns causing multiple organ dysfunction.

Recurrent Disseminated Intravascular Coagulation in Metastatic Castration-Resistant Prostate Cancer: A Case Report.

Disseminated intravascular coagulation (DIC) is a systemic disease characterized by simultaneous thrombosis, bleeding, and partially excessive fibrinolysis. Systemic shock, trauma, bacterial toxins, and procoagulants-expressing solid and hematologic malignancies are common causes of this life-threatening hemorrhagic complication and often require treatment in intensive care units. We describe a case of an elderly man with recurrent severe bleeding events in the cause of DIC, including epistaxis, hemoptysis, hematuria, and gastrointestinal bleeding. Laboratory investigations revealed elevated prostate-specific antigen (PSA), suggesting an underlying prostate cancer. Despite intensified coagulatory therapy, the coagulation disorder could not be stabilized. A single injection of degarelix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, led to rapid stabilization of the coagulation and decreased PSA within days. One year after initiating androgen-deprivation therapy, there were recurrent transfusion-requiring bleeding events, and a concomitant PSA increase occurred, suggesting metastatic castration-resistant disease associated with DIC. This case emphasizes DIC as a possible primary phenomenon and indicator for the progression of the underlying malignancy, as well as the importance of etiological therapies in the management of DIC.

Disseminated Intravascular Coagulation in Pediatric Scoliosis Surgery: A Systematic Review

Disseminated intravascular coagulation (DIC) is a rare but serious complication of pediatric scoliosis surgery; sparse current evidence warrants more information on causality and prevention. This systematic review sought to identify incidence of DIC in pediatric patients during or shortly after corrective scoliosis surgery and identify any predictive factors for DIC. Medline/PubMed, EMBASE, and Ovid databases were systematically reviewed through July 2017 to identify pediatric patients with DIC in the setting of scoliosis surgery. Patient demographics, medical history, surgery performed, clinical course, suspected causes of DIC, and outcomes were collected. Eleven studies met inclusion criteria. Thirteen cases from 1974 to 2012 (mean age: 15.3 ± 4.3 years, 72% women) were identified, with neuromuscular (n = 7; 54%) scoliosis as the most common indication. There were no prior bleeding disorder histories; all preoperative labs were within normal limits. Procedures included 8 posterior segmental fusions (54%), 3 Harrington rods (31%), 1 Cotrel-Dubousset, and 1 unit rod. Eight patients experienced DIC intraoperatively and 5 patients experienced DIC postoperatively. Probable DIC causes included coagulopathy following intraoperatively retrieved blood reinfusion, infection from transfusion, rhabdomyolysis, hemostatic matrix application, heparin use, and hypovolemic shock. Most common complications included increased intraoperative blood loss (n = 8) and hypotension (n = 7). The mortality rate was 7.69%; one fatality occurred in the acute postoperative period. Prior bleeding disorder status notwithstanding, this review identified preliminary associations between variables during corrective scoliosis surgery and DIC incidence among pediatric patients, suggesting multiple etiologies for DIC in the setting of scoliosis surgery. Further investigation is warranted to quantify associated risk. This study brings awareness to a previously rarely discussed complication of pediatric scoliosis surgery. Further cognizance of DIC by scoliosis surgeons may help identify and prevent causes thereof.

Disseminated intravascular coagulation diagnosis: Positive predictive value of the ISTH score in a Danish population

BackgroundThe diagnostic accuracy of the ISTH’s disseminated intravascular coagulation (DIC) score remains to be investigated in contemporary patient populations. ObjectiveTo examine the positive predictive value (PPV) of an ISTH DIC score ≥5 for identifying patients with overt DIC in a Danish hospital laboratory information system database. Materials and MethodsA population‐based cross‐sectional validation study in the Central Denmark Region (2015‐2018). Patients with a DIC score ≥5 were identified from the hospital laboratory information system database. Only patients with a potential underlying cause of DIC were included in the analyses. Cases were adjudicated by the authors as the gold standard for DIC diagnosis. The diagnosis of overt DIC was assigned on the basis of clinical signs of microthrombosis and/or bleeding and available laboratory records. PPVs with 95% confidence intervals (CIs) were computed. ResultsMedical records of 225 patients were included. The overall PPV for overt DIC was 68% (95% CI, 61‐74) and for overt + subclinical DIC, 83% (95% CI, 77%‐88%) and increased with higher scores from 47% (95% CI, 35‐59) for DIC score 5 to 88 (95% CI, 79‐94) for DIC score ≥7. PPV was higher among intensive care patients and patient with sepsis, low antithrombin activity, prolonged activated partial thromboplastin time, or high Sequential Organ Failure Assessment score. ConclusionThe accuracy of ISTH DIC score ≥5 was moderate for overt DIC but increased with increasing scores and depended on the underlying cause of DIC. This new knowledge provides guidance to physicians and enables DIC research using laboratory‐based data.

A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia.

IntroductionA neutrophilic infiltrate characterizes bacterial pneumonia. Macrophage infiltration is similarly characteristic of the viral pneumonia caused by SARS‐CoV‐2. These infiltrating macrophages, while phagocytic and capable of engulfing virus laden alveolar cells, are also rich in tissue factor—a thromboplastin. This prothrombotic aspect likely explains how a respiratory virus whose malign effects should be confined to the oropharynx, bronchi and lungs, can cause a panoply of extra‐pulmonary organ disorders. Elevated ferritin levels in ICU Covid 19 patients, and elevated acute phase proteins suggest immune overreaction. Elevated d‐dimers implicate clotting as well. This evidence links hyperactive innate immunity (macrophage lung infiltrates) with the elevated levels of oligomeric fibrin present in the bloodstream of these patients.MethodsAn in‐house assay measuring oligomeric (soluble) fibrin (also referred to as soluble fibrin monomer complexes or SFMC) in whole blood, previously developed for monitoring incipient disseminated intravascular coagulation (DIC) during liver transplantation, was made available to COVID ICU attendings. Since SFMC constitutes the input to intravascular fibrin clots and d‐dimer reflects fibrin clot dissolution, it was thought that the two tests, run in tandem along with assays of immune activation, might clarify the frequency and possibly the cause of DIC in patients with severe COVID‐19 pneumonia.ResultsClassical DIC with intravascular clotting and thrombocytopenia was documented only rarely. However, early in the pandemic shortly after the assay was made available, it identified three patients undergoing acute defibrination. In each patient virtually all of the body's fibrinogen was transformed into SFMC over 3–4 days and deposited somewhere in the vasculature without any gross clots being detected.ConclusionsThree COVID‐19 patients with evidence of a hyperactive immune response (elevated ferritin and acute phase proteins) defibrinated while blood levels of SFMC were being monitored. SFMC levels that were five times higher than normal appeared in the circulation during the defibrination process. SFMC at these levels may precipitate as showers of microclots, damaging heart, kidney, brain, and so forth.

Disseminated Intravascular Coagulation and Annual Trends in in-Hospital Outcomes Based on Etiology from 2002 to 2014

Introduction:Disseminated Intravascular Coagulation (DIC) is a systemic pathophysiologic process which occurs in response to an underlying inciting event resulting in a complex interaction between the inflammatory and coagulation pathways. The development of DIC inpatient is often an ominous prognostic indicator with fulminant cases resulting in bleeding and widespread thrombosis ultimately resulting in death. It is not a disease by itself, but rather a sign of underlying disease incited by causes such as sepsis, acute pancreatitis, leukemia, burns, crush injuries, solid tumors, and viral illnesses. The purpose of this study is to identify the annual trends in mortality and morbidity associated with DIC in hospital and its association with specific etiologies.Methods:Using the National Inpatient Sample (NIS) for years 2002-2014, DIC was defined as ICD-9 code 286.6 for a primary or secondary diagnosis in conjunction with ICD-9 and clinical classification software codes to identify the most common etiologies of DIC. Linear regression analysis was used to assess the annual trends in incidence and mortality. We employed univariate logistic regression analysis to calculate odds ratios (OR) for the most common causes of DIC and their relationship with mortality.Results:Among in-hospital admissions between 2002 and 2014, 101,030 patients (N=481,657, weighted) developed DIC. Annual incidence has been increasing steadily from 28,119 in 2002 to 43,570 in 2014. Mortality has remained relatively unchanged at 47% in 2002 and 45% in 2014 (p <0.0001). The mean length of stay (LOS) remained unchanged from 14.10 to 14.25 (p = 0.6369), however the total costs of admission increased from $94,726 to $226,929. Sepsis was associated with 55.5% of all incdiecnes of DIC, pancreatitis 3.7%, burns 0.19%, viral illnesses 1.7%, solid tumors 10%, leukemia 5.8%, and crush injuries 2.4%. A univariate analysis identified an increase association between mortality and etiologies such as sepsis (OR=2.34), burns (OR=1.61), and crush injuries (OR=1.39). A decreased mortality was seen with viral (OR=0.44), leukemia (OR=0.71), solid tumors(OR=0.68), and pancreatitis (OR=0.91).Conclusion:Our study indicated that among the patients admitted with DIC between 2002 and 2014, there was a significant increase in annual incidence while mortality and length of stay remained the same. Notably, the total costs of admissions associated with DIC more than doubled. Sepsis is by far the most commonly associated comorbidity in these patients, and also associated with a higher mortality. Burns and crush injuries also had higher mortalities, while the lowest mortality was seen in viral illnesses and cancers. Due to the highly variable course and high mortality associated with DIC extra vigilance should be exercised when identifying the cause of DIC and the expected course. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Disseminated intravascular coagulation: epidemiology, biomarkers, and management.

Disseminated intravascular coagulation (DIC) is a systemic activation of the coagulation system, which results in microvascular thrombosis and, simultaneously, potentially life-threatening haemorrhage attributed to consumption of platelets and coagulation factors. Underlying conditions, e.g. infection, cancer, or obstetrical complications are responsible for the initiation and propagation of the DIC process. This review provides insights into the epidemiology of DIC and the current understanding of its pathophysiology. It details the use of diagnostic biomarkers, current diagnostic recommendations from international medical societies, and it provides an overview of emerging diagnostic and prognostic biomarkers. Last, it provides guidance on management. It is concluded that timely and accurate diagnosis of DIC and its underlying condition is essential for the prognosis. Treatment should primarily focus on the underlying cause of DIC and supportive treatment should be individualised according to the underlying aetiology, patient's symptoms and laboratory records.

Human Soluble Recombinant Thrombomodulin, ART-123, Resolved Early Phase Coagulopathies, but Did Not Significantly Alter the 28 Day Outcome in the Treatment of DIC Associated with Infectious Systemic Inflammatory Response Syndromes.

Disseminated intravascular coagulation (DIC) is a catastrophic systemic disorder of coagulation, resulting in uncontrollable bleeding, multiple organ failure, and death. Sepsis is one of the common causes of DIC. Despite many attempts to correct these coagulation pathologies, no adjunctive treatments have been shown to improve the mortality of DIC associated with sepsis. Although some clinical studies showed a recently developed human recombinant thrombomodulin, ART-123, might be effective in the treatment of DIC, few randomized, placebo-controlled studies have been conducted. In this study, we treated 60 DIC patients associated with systemic inflammatory response syndrome (SIRS) using ART-123 (n = 29) or saline as a placebo (n = 31). The basal clinical characteristics were similar in both groups. We compared clinical severity scores and DIC score in acute phase, and 28 day mortality between the two groups. Our study demonstrated the DIC score improved a few days earlier in the ART-123 group than the placebo group, and there were no major life-threatening adverse events in both groups. The overall survival rate at day 28 was not significantly altered. In conclusion, ART-123 can be used safely in DIC associated with infectious SIRS patients; however, its true efficacy in the treatment of DIC needs to be further investigated.

Prognosis of overt disseminated intravascular coagulation in patients admitted to a medical emergency department.

To assess the prevalence, characteristics and prognosis of overt disseminated intravascular coagulation (DIC) in adult emergency department (ED) patients and identify markers of poor outcome. In a chart review study, we analysed the occurrence of overt DIC in all patients (n=1 001 727) attending the University's ED from 2003 to 2014 applying the ISTH DIC score. The primary outcome measure was 30-day mortality. Logistic regression analysis was used to determine predictors of mortality. The initial inter-rater reliability in the diagnosis of DIC was 0.85 [κ; 95% confidence interval (CI), 0.77-0.92]. The main DIC precipitators were malignancy (47%), cardiovascular diseases (CVD, 27%) and sepsis (16%). Hyperfibrinolytic DIC occurred in 27% of patients and was over-represented in those with cardiac arrest (68%). Thirty-day mortality (52%) was inversely associated with fibrinogen levels on admission [adjusted odds ratio, 0.49; 95% CI: 0.30-0.82; P=0.006]. Afibrinogenaemia implied an even 10-fold increased risk of dying (crude odds ratio, 10.0; 95% CI: 3.2-31.4; P<0.001). D-dimer and platelet count had no predictive value. Appropriate ICD-10 coding for DIC was present in only 1.8% of cases. Overt DIC is a rare but underdiagnosed event in ED patients. In this collective, cardiac arrest is a dominant cause of DIC presenting with a fibrinolytic phenotype. The degree of hypofibrinogenaemia on admission strongly and linearly predicted early death.

Dysfunctional Endothelium Drives a Pre-DIC State in Endotoxemia

Uncontrolled pro-coagulant responses in sepsis can lead to disseminated intravascular coagulation (DIC), a complication associated with markedly increased mortality. Abnormalities of coagulation, fibrinolysis, and platelet function can lead to both microvascular thrombosis contributing to multi-organ dysfunction syndrome or hemorrhagic complications. To understand the inciting causes of DIC in sepsis, we first evaluated the time course of platelet function, coagulation parameters and markers of endothelial activation following LPS exposure. These studies demonstrated that endothelial dysfunction preceded derangement of platelet function or coagulation parameters. To evaluate the thrombotic response of the endothelium early in endotoxemia, we injured the microvascular endothelium of cremaster arterioles of mice using a laser 1-3 hours following LPS exposure. Platelet and fibrin formation at sites of injury were significantly increased following LPS exposure to respectively 190% (p=0.026) and 195% (p<0.001) of control values. No significant differences were observed in platelet counts, platelet function (aggregation and activation) or coagulation parameters (PT) in mice treated with LPS for 3 hours compared to vehicle controls. Plasma levels of the endothelial markers VWF, soluble VCAM and E-selectin, however, were significantly increased following LPS exposure, demonstrating early endothelial activation. Furthermore, even when platelet accumulation was inhibited using the anti-platelet drug eptifibatide, fibrin generation at sites of laser injury was still significantly (p<0.01) increased in LPS-treated mice. Together, these data show that endothelial activation precedes disruption of platelets and coagulation in endotoxemia. Endothelial dysfunction is associated with perturbation of the endothelial Ang1/Tie2 pathway, characterized by significantly reduced Tie2 function and Ang1 levels. Therefore, we assessed thrombus formation in Tie2+/- mice in the absence of LPS. Fibrin generation at sites of laser injury was significantly increased in Tie2+/- mice to 192% of littermate (Tie2+/+) controls (p<0.01). As loss of Tie2 mimics the LPS-induced phenotype, we next determined whether activation of the Tie2 pathway could reduce fibrin clot formation. Ang1 stimulates phosphorylation of Tie2, promoting protective signaling in endothelium. To determine whether the pro-thrombotic consequences of endotoxemia on Tie2 signaling could be reversed using Ang1, mice were injected with adenovirus expressing Ang1 or control adenovirus prior to LPS exposure. Dephoshorylation of Tie2 associated due to LPS exposure was reduced with Ang1-treatment. In our in vivo thrombosis model, Ang1 inhibited the increased fibrin accumulation at sites of laser injury in endotoxemic mice to baseline levels. Tail snip assays showed that even though elevated Ang1 levels normalized LPS-induced augmentation of thrombus formation, increased Ang1 did not affect bleeding times. These data indicate that Ang1 stimulation of Tie2 signaling can regulate pathologic clot formation in the setting of inflammation without bleeding risk. Together, our studies show that endothelial dysfunction drives a pre-DIC state in endotoxemia. Targeting these early endothelial responses might represent an novel approach for reducing thrombosis in sepsis without enhancing bleeding risks. Future studies will evaluate the mechanism involved. DisclosuresNo relevant conflicts of interest to declare.

Blood Component Utilization for Disseminated Intravascular Coagulation (DIC) Cases with Respect to Underlying Condition.

To understand transfusion requirement in DIC with respect to (wrt) underlying cause. Patients' details were analyzed using parameters like yearly requirement, hemoglobin (Hb) and blood components utilization wrt age, sex and cause of DIC. Total 1931 DIC cases from 167 hospitals received 21,153 blood units including whole blood, red cell concentrate fresh frozen plasma, random donor platelets, single donor platelets and cryoprecipitate from year 2001 to 2013. Significant risk of DIC was for females compared to males (p<0.0001). Whole blood utilization was 25.5% in 2001 which reduced to 1.2% in 2013. Mean±SD Hb concentration was 8.6±3.0 in females and 9.8±3.2g/dL in males. The lowest mean Hb was 7g/dL in female DIC cases having malignancy. Septicemia was the major cause of DIC followed by obstetric complications. The highest requirement was for trauma associated with septicemia, requiring 35units/case. Combination of two or more underlying causes for DIC increased the blood component requirement.

Disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a reflection of an underlying systemic disorder which affects the coagulation system, simultaneously resulting in pro-coagulant activation, fibrinolytic activation, and consumption coagulopathy and finally may result in organ dysfunction and death. Though septicaemia is the most common cause of DIC, several other conditions can also lead to it. A diagnosis of DIC should be made only in the presence of a causative factor supported by repeated laboratory tests for coagulation profile and clotting factors. An effective scoring system helps to detect an overt DIC and a high score closely correlates with mortality. Treatment of DIC is aimed at combating the underlying disorder followed by supportive management. Low molecular weight heparin is advocated in special situations whereas anti-thrombin III and activated protein C are of doubtful value. Early diagnosis and prompt treatment backed by laboratory support can reduce the morbidity and mortality associated with it. The methodology of search for this review article involved hand search from text books and internet search using Medline (via PubMed) using key words DIC, thrombosis, fibrin degradation products, anti-thrombin and tissue factor for the last 25 years and also recent evidence-based reviews.

Uncorrectable coagulopathy due to intestinal obstruction: A clinical dilemma of competing priorities in a child

Disseminated intravascular coagulation (DIC) is a contraindication for major surgical operations. However, if surgery is required to correct the underlying cause of DIC, a clinical conflict is created. In such complex scenario, standard resources such as textbooks and journals offer very little guidance. In this communication, we report a 22-month-old boy who developed sepsis-induced DIC following intestinal obstruction. Pre-operative attempts to normalize coagulation parameters failed. Damage control laparotomy was undertaken as it was considered essential to control the underlying cause of DIC. His abnormal coagulation status reverted quickly after surgical relief of intestinal obstruction. Paradoxically intraoperative blood loss was less than anticipated amount. There are a few case reports of adult patients who have successfully undergone major surgery despite the presence of abnormal coagulation. However, this appears to be the first paediatric report of successful surgery in DIC status. Lessons learnt from this case and hypothetical speculations of clinical paradoxes are discussed.

Acute Disseminated Intravascular Coagulation in Obstetrics: A Tertiary Centre Population Review (1980 to 2009)

ObjectiveTo determine the antecedent factors, morbidity, and mortality associated with disseminated intravascular coagulation (DIC) in a Nova Scotia tertiary maternity hospital over a 30-year period. MethodsCases of DIC were identified from the Nova Scotia Atlee Perinatal Database for the years 1980 to 2009 and the hospital charts reviewed. The clinical diagnosis of DIC was confirmed or refuted using a combination of the International Society of Thrombosis and Haemostasis scoring system and an obstetrical DIC-severity staging system. The cause of DIC was determined from chart review. Maternal outcomes included massive transfusion (≥ 5 units), hysterectomy, admission to ICU, acute tubular necrosis (ATN) requiring dialysis, and death. Neonatal outcomes included Apgar scores, birth weight, NICU admission, and death. Treatment of DIC was assessed by blood products administered, postpartum hemorrhage management, and laboratory measurements. ResultsThere were 49 cases of DIC in 151 678 deliveries (3 per 10 000) over the 30 years. Antecedent causes included placental abruption (37%), postpartum hemorrhage or hypovolemia (29%), preeclampsia/HELLP (14%), acute fatty liver (8%), sepsis (6%), and amniotic fluid embolism (6%). The associated maternal morbidity included transfusion ≥ 5 units (59%), hysterectomy (18%), ICU admission (41%), and ATN requiring dialysis (6%). There were three maternal deaths, giving a case fatality rate of 1 in 16. The perinatal outcomes included stillbirth (25%), neonatal death (5%), and NICU admission (72.5%). ConclusionObstetrical DIC is an uncommon condition associated with high maternal and perinatal morbidity and mortality. Prompt recognition and treatment with timely administration of blood products is crucial in the management of this life-threatening disorder.

Postpartum maternal death associated with undiagnosed Hodgkin's lymphoma

The authors describe the case of a 28-year-old patient who died from an extensive intracerebral haemorrhage due to disseminated intravascular coagulation (DIC) which occurred a few days after delivery. Access to an emergency department of gynaecology on three separate occasions in the three days preceding hospitalization made judicial evaluation of the case necessary. The case was studied with a methodological approach based on the following steps: (1) examination of clinical records; (2) autopsy; (3) study of the placenta; (4) anatomo-histopathological observations concerning particular organs and structures potentially involved in postpartum maternal death; and (5) evaluation of physicians' behaviour, in the light of necroscopic findings and a review of the literature. The causes of death most frequently described in the postpartum period were excluded; a mediastinal nodular sclerosing Hodgkin's lymphoma with transdiaphragmatic diffusion, not diagnosed in life, was demonstrated. The cause of death was identified as intracerebral haemorrhage following DIC, Hodgkin's disease and recent delivery by caesarean section. Analysis of the physicians' conduct, together with a review of the literature, revealed a medical error. However, no causal relationship between the error and the death of the patient was considered to exist. The interest of the case lies in the unusual cause of DIC discussed in relation to a hypothesis of obstetric-gynaecological liability.

The loss of homeostasis in hemostasis: new approaches in treating and understanding acute disseminated intravascular coagulation in critically ill patients.

Disseminated intravascular coagulation (DIC) profoundly increases the morbidity and mortality of patients who have sepsis. Both laboratory and clinical research advanced the understanding of the biology and pathophysiology of DIC. This, in turn, gave rise to improved therapies and patient outcomes. Beginning with a stimulus causing disruption of vascular integrity, cytokines and chemokines cause activation of systemic coagulation and inflammation. Seemingly paradoxically, the interplay between coagulation and inflammation also inhibits endogenous anticoagulants, fibrinolytics, and antiinflammatory pathways. The earliest documented and best-studied microbial cause of DIC is the lipopolysaccharide endotoxin of Gram-negative bacteria. Extensive microvascular thrombi emerge in the systemic vasculature due to dysregulation of coagulation. The result of this unrestrained, widespread small vessel thromboses multiorgan system failure. Consumption of platelets and coagulation factors during this process can lead to an elevated risk of hemorrhage. The management of these patients with simultaneous hemorrhage and thrombosis is complex and challenging. Definitive treatment of DIC, and attenuation of end-organ damage, requires control of the inciting cause. Currently, activated protein C is the only approved therapy in the United States for sepsis complicated by DIC. Further research is needed in this area to improve clinical outcomes for patients with sepsis.

Prospective Evaluation of Hemostatic Abnormalities in Overt DIC Due to Various Underlying Diseases

Abstract 4652 [Introduction]Disseminated intravascular coagulation (DIC) is often found in patients with infections, leukemia, solid tumors, trauma, aneurysms or obstetricdiseases. The causes of DIC associated with leukemia are considered to be an elevated expression of tissue factor, tissue type plasminogen activator or anexin II in leukemic cells. The factors thought to be responsible for DIC associated with sepsis are an elevated inflammatory response, including an increased production of inflammatory cytokines. [Materials and Methods]In this study, 692 patients with suspected DIC were prospectively evaluated for various types of underlying diseases using the DIC diagnostic criteria established by International Society of Thrombosis and Haemostasis (ISTH) and Japanese Ministry Health Labor and Welfare (JMHLW), and the usefulness of hemostatic markers were examined for each patient with DIC due to various underlying diseases. [Results]The main underlying disease of DIC was infectious diseases, hematologic malignancies, and solid tumors, and a high resolution rate from DIC was observed in obstetric diseases and hematologic malignancies. The diagnosis of DIC was related to a poor outcome in trauma/burn victims and those with infectious disease. In the main underlying disease, it is suggested that DIC would be excluded in patients with hematologic malignancies or solid tumors with a platelet count of more than 1×108/ml and in the patients with fibrinogen and fibrin degradation products (FDP) of less than 10 mg/L, and fibrinogen of less than 100 mg/dl, suggesting the presence of DIC. The prothrombin time was a sensitive marker, but fibrinogen levels were not sensitive for DIC due to infectious diseases. The plasmin plasmin inhibitor complex in hematologic malignancy, and soluble fibrin monomer complex, antithrombin and thrombomodulin in patients with infectious disease, were sensitive markers for the diagnosis of DIC. [Discussion and conclusion]Although hemostatic markers were useful for the diagnosis of DIC, the usefulness varied depending on the different underlying diseases. The global coagulation tests are therefore considered to be useful for the diagnosis of DIC, and hemostatic molecular markers are useful for examining the pathophysiology of patients with DIC. Disclosures:No relevant conflicts of interest to declare.

Haematological interventions for treating disseminated intravascular coagulation during pregnancy and postpartum.

Disseminated intravascular coagulation (DIC) is an acquired syndrome characterised by systemic intravascular activation of coagulation. There are several obstetric causes of DIC during pregnancy and postpartum. To assess the clinical effectiveness and safety of haematological interventions such as heparins (low molecular weight heparin (LMWH) and unfractionated heparin (UFH), danaparoid sodium, synthetic protease inhibitor, antithrombin, human recombinant activated protein C, recombinant human soluble thrombomodulin, recombinant tissue factor pathway inhibitor, recombinant activated factor VIIa and any other types of haematological interventions (except transfusions) for treating DIC during pregnancy and postpartum. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 July 2010), LILACS (1982 to 22 July 2010), ongoing trials registries via the World Health Organization International Clinical Trials Platform Search Portal (22 July 2010), and other relevant websites (22 July 2010). Randomised controlled trials (RCTs) on any haematological interventions for treating DIC during pregnancy and postpartum. There were no included studies. We could not find any RCTs on haematological interventions (heparins (LMWH and UFH), danaparoid sodium, synthetic protease inhibitor, antithrombin, human recombinant activated protein C, recombinant human soluble thrombomodulin, recombinant tissue factor pathway inhibitor, recombinant activated factor VIIa and any other types of haematological interventions) for treating DIC during pregnancy and postpartum. This review found no RCTs on the safety and efficacy of haematological interventions for treating DIC during pregnancy and postpartum. Such interventions need to be tested in RCTs assessing outcomes such as maternal death, perinatal death and safety.

Severe hyperglycemic shock associated with hepatic portal venous gas

We report a case of hyperglycemic shock associated with hepatic portal venous gas. A 79-year-old woman with post-stroke depression developed severe tachycardiac atrial fibrillation and hypotension due to hypovolemia caused by severe hyperglycemia, as well as showing disseminated intravascular coagulation (DIC). Continuous intravenous infusion of insulin and volume loading with normal saline gradually achieved normalization of the serum glucose level and hemodynamic stability. However, the DIC did not resolve, and abdominal computed tomography (CT) revealed hepatic portal venous gas (HPVG) in the left lobe of the liver. Surgery was thus considered mandatory. However, because severe hemodynamic lability occurred again immediately after the CT examination, and persisted, surgery could not be performed, and the patient died of septic shock due to bowel perforation. It was concluded that the underlying causes of DIC should be sought promptly, without delay.

Surgical interventions in a cohort of patients with haemophilia A and inhibitors: an experiential retrospective chart review

Strategies for the management of perioperative bleeding in patients with haemophilia and inhibitors have evolved rapidly as a result of the development of the bypassing agents Factor Eight Inhibitor Bypassing Activity, Anti-inhibitor Coagulant Complex (FEIBA) and activated recombinant factor VII (rFVIIa). However, there are currently no established guidelines for perioperative use of bypassing agents, and few controlled clinical studies have been carried out. Thus, case reports, such as those presented here, provide useful anecdotal evidence to guide the treatment of inhibitor patients. The purpose of this report was to describe experiences in the use of bypassing agents in a small cohort of patients with haemophilia A and inhibitors undergoing surgical procedures. Cases from five treatment centres were reviewed. Twenty-two procedures using FEIBA, rFVIIa or a combination of both agents were compiled from seven inhibitor patients (six with an alloantibody inhibitor and one with an acquired autoantibody inhibitor). Eleven procedures used FEIBA monotherapy, two employed rFVIIa monotherapy and nine were performed using combination therapy. Supplemental therapies were required to manage bleeding in some cases. Haemostatic control was achieved in all cases, and treatment regimens were generally well tolerated. One thrombotic adverse event was reported: evidence of disseminated intravascular coagulation (DIC) was found after rFVIIa use in one case, although the direct cause of DIC was unknown. The experiences in this case review demonstrate that both major and minor surgical procedures can be safely performed in patients with haemophilia and high-titre inhibitors under the cover of bypassing agents, with a high expectation of success.