Development Of Disseminated Intravascular Coagulation Research Articles

Thromboelastography: a more accurate assessment of global hemostasis

A 47-year-old male with acute myeloid leukemia underwent resection of a paraspinous mass. Preoperative laboratory study results were as follows: white blood cell count, 2.6 × 10 9 /L; hematocrit (Hct), 29%; platelet (PLT) count, 878 × 10 9 /L; prothrombin time, 17.2 seconds (normal, 11.9-14.4 sec); and partial thromboplastin time, 41 seconds (normal, 22-37 sec). Intraoperatively, hemostasis was difficult to achieve. Two units of plasma and one plateletpheresis were transfused. Postoperatively, incisional bleeding continued and Hct decreased to 24%. Bleeding in the setting of thrombocytosis (921 × 10 9 /L), minimally prolonged prothrombin time (16.6 sec), and mildly elevated fibrinogen concentration (420 mg/dL) prompted a transfusion medicine consultation. To assess the coagulation system, thromboelastograph (TEG 5000, Haemonetics, Braintree, MA) was obtained. TEG monitors the mechanical properties of the developing clot and subsequent lysis. Movement of an immersed transducer transmits a signal that generates a hemostasis profile. Initial TEG showed normal thrombin generation (R), but clot lysis indices (LY30 = 9.5% and CI > 1) suggested early secondary fibrinolysis, commonly seen in early disseminated intravascular coagulation (DIC). To prevent development of overt DIC, treatment with low-dose subcutaneous heparin was recommended. Four hours after heparin administration, repeat TEG showed LY30 normalized to 0%, suggesting cessation of the fibrinolytic phase of DIC. However, elevated angle and MA/G indicated higher fibrin(ogen) stabilization and PLT function, suggesting hypercoagulability. The patient received subcutaneous heparin every 12 hours for 48 hours. His bleeding resolved and he was discharged on Postoperative Day 4. This case demonstrates the clinical utility of thromboelastography. Routine laboratory testing did not suggest DIC, and transfusion of plasma and PLTs did not lead to clinical improvement; TEG evaluation allowed a more accurate assessment of all phases of coagulation, which revealed incipient DIC. As a result, more appropriate therapy was instituted with a successful outcome.

Predictors of Disseminated Intravascular Coagulation in Patients with Septic Shock

Purpose. The goal of this study was to identify potential clinical predictors for the development of disseminated intravascular coagulation (DIC) in patients with septic shock. Material and Methods. We performed a retrospective analysis of a cohort of adult (>18 years of age) patients with septic shock admitted to a medical ICU in a tertiary care hospital from July 2005 until September 2007. A multivariate logistic regression model was used to determine the association of risk factors with overt DIC. Results. In this study, a total of 390 patients with septic shock were analyzed, of whom 66 (17%) developed overt DIC. Hospital mortality was significantly greater in patients who developed overt DIC (68% versus 38%, P<0.001). A delay in the timing of antibiotics was associated with an increased risk of the development of overt DIC (P<0.001). Patients on antiplatelet therapy prior to hospital admission and who that received adequate early goal-directed therapy (EGDT) were associated with a decreased risk of overt DIC (P<0.001). Conclusions. In our cohort of patients with septic shock, there was a risk reduction for overt DIC in patients on antiplatelet therapy and adequate EGDT, while there was an increased risk of DIC with antibiotic delay.

Effect of recombinant human soluble thrombomodulin on clinical outcomes of patients with coagulopathy after hematopoietic stem cell transplantation

From 2001 to 2012, 71 individuals with hematological diseases received HSCT in our institution. Of these, 41 developed disseminated intravascular coagulation (DIC) in association with various underlying conditions. The patients who developed DIC after 2008 (n = 23) were treated by recombinant human soluble thrombomodulin (rTM), and the others (n = 11) were treated by either heparin and/or antithrombin III concentrate. Seven patients did not receive any anticoagulant therapy. Of note, treatment for coagulopathy by rTM significantly improved clinical outcomes of patients at day 100 and dramatically prolonged their overall survival (P = 0.044). Taken together, rTM is useful to improve clinical outcomes of transplant recipients with coagulopathy.

Nursing of acute promyelocytic leukemia complicated with disseminated intravascular coagulation after hematopoietic stem cell transplantation

Objective To analyze the procedure of nursing care in one patient with acute promyelocytic leukemia (APL)who developed disseminated intravascular coagulation (DIC)after hematopoietic stem cell transplantation (HSCT).Methods Peripheral venous indwelling needle was used as a pathway of intravenous infusion instead of subclavian central venous catheterization.And coagulation test was monitored and evaluated during HSCT.Results Through the monitoring of coagulation test and environment protective isolation,bleeding was controlled and the patient left laminar flow room successfully.Conclusions DIC is a complicated coagulation disorder.This patient developed life-threatening DIC during HSCT,therefore,for this patient,nursing care is a systematic work.So,only the specified targeted nursing care plans and accurate implementation could ensure the success of HSCT. Key words: Hematopoietic stem cell transplantation; Disseminated intravascular coagulation; Nursing care

Two Patients with Antiphospholipid Antibody Developed Disseminated Intravascular Coagulation

One hundred and eleven patients with antiphospholipid antibodies (aPL) were diagnosed at Mie University Hospital during the past 17 years. Two of these patients developed disseminated intravascular coagulation (DIC). The first patient twice developed DIC complicated by pancreatitis and pregnancy, while in the second case, no specific causative complications for DIC were identified. The details of these cases imply that aPL is associated with DIC and/or is a potent triggering factor for DIC.

Interleukin-10 inhibits lipopolysaccharide-induced upregulation of tissue factor in canine peripheral blood monocytes

The potentially fatal hemostatic disorder of disseminated intravascular coagulation (DIC) is initiated in bacterial sepsis by lipopolysaccharide (LPS)-induced tissue factor (TF) expression on monocytes. Interleukin-10 (IL-10) is a potent inhibitory cytokine that downregulates monocyte inflammatory and procoagulant responses. We hypothesized that canine recombinant IL-10 (rIL-10) would inhibit LPS-induced TF upregulation on canine monocytes in a dose-dependent manner. Canine peripheral blood mononuclear cells (PBMC), obtained by double-density gradient centrifugation, and monocytes, purified from PBMC by immunomagnetic bead separation with an anti-canine CD14 antibody (Ab), were stimulated in suspension with LPS (0.1–1000ng/mL) for various times. Recombinant IL-10 (10–5000pg/mL) was added with LPS or up to 2h later. Tissue factor procoagulant activity was measured by cleavage of a chromogenic substrate by activated Factor X generated by the TF-factor VII complex. We found that rIL-10, when given concurrently or 1h after LPS, strongly inhibited LPS-induced TF procoagulant activity in canine PBMC and monocytes. This inhibition was dose-dependent and blocked by an anti-canine IL-10 Ab. Our results indicate that rIL-10 effectively inhibits LPS-induced TF upregulation in canine monocytes and could potentially be useful in limiting the development of DIC in dogs with endotoxemia.

Diagnosis from a blood film following dog‐bite

A 60-year-old woman presented in septic shock two days after being bitten on the calf by a dog. Twenty-four years previously she had required a splenectomy for autoimmune thrombocytopenic purpura with the platelet count remaining normal thereafter. On clinical examination, the patient had a mottled rash on her left leg which, within 24 hours, had developed into extensive purpura fulminans involving the extremities and the buttocks. She also developed disseminated intravascular coagulation (DIC) and multiorgan failure. 1 The full blood count on admission showed a white cell count of 11.3 × 109/l, neutrophils 8.3 × 109/l, hemoglobin concentration 11.3 g/dl and platelet count 38 × 109/l. The blood film showed features of hyposplenism and in addition the presence of bacilli within neutrophils (image), supporting a diagnosis of Capnocytophaga canimorsus septicaemia. This was subsequently confirmed by blood culture. Histology of the excised dog bite site showed necrotic skin with thrombi in small vessels in the underlying subcutaneous tissue. Despite early diagnosis, broad spectrum antibiotics and intensive support the patient developed gangrene of one hand and the soles of her feet and died twelve days after presentation. Capnocytophaga canimorsus, formerly known as dysgonic fermenter 2 (DF-2), is a commensal bacterium of dog and cat saliva. It can be transmitted to humans by a bite, a scratch or mere licking. Hyposplenic patients are particularly at risk of septicaemia, DIC and death and should be warned about the risks of close contact with cats and dogs. Urgent examination of a blood film is indicated in such patients presenting with a febrile illness after dog-bite, although even rapid diagnosis and urgent treatment may not prevent death.

SIRS Score Reflects Clinical Features of Non-Acetaminophen-Related Acute Liver Failure with Hepatic Coma

In acetaminophen-induced acute liver failure (ALF), the hepatic coma grade worsens and mortality rates increase, as the number of systemic inflammatory response syndrome components fulfilled (SIRS score) increases. This study aimed to investigate the impact of SIRS score on clinical features of non-acetaminophen-related ALF. Ninety-nine patients with non-acetaminophen-related ALF with hepatic coma who did not undergo liver transplantation were investigated. Each patient was given a SIRS score of 0, 1, 2, 3 or 4 at the time of diagnosis. At the diagnosis of ALF with hepatic coma, with the increase of SIRS score, hepatic coma grade and prothrombin activity were deteriorated. After the diagnosis of ALF with hepatic coma, 25 patients (25%) developed acute respiratory distress syndrome (ARDS), 31 patients (31%) developed disseminated intravascular coagulation (DIC), and 21 patients (22%) developed acute renal failure (ARF). Thirty-eight patients (38%) developed MOF. With the increase of SIRS score, frequencies of the development of ARDS, DIC and MOF increased. ARF was more frequently developed in patients with a SIRS score of 2 or higher. Overall, 36 patients (36%) survived. Overall survival rate was 66% in 29 patients with a score of 0, 43% in 21 patients with a score of 1, 17% in 29 patients with a score of 2 and 15% in 20 patients with a score of 3 or 4. SIRS score will be useful for predicting not only the overall survival but also the development of complications such as ARDS, DIC and MOF in non-acetaminophen-related ALF with hepatic coma.

A Case of HELLP Syndrome with Multiple Complications

Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is a rare complication of pregnancy. The mortality rate associated with HELLP syndrome increases when life-threatening complications occur. A 37-year-old woman at 37 weeks of gestation developed severe cerebral hemorrhage at the beginning of labor induction and was transferred to our hospital, where HELLP syndrome was diagnosed. She developed disseminated intravascular coagulation (DIC), hepatic hematoma, and cerebral infarction after surgery. On day 68, she was transferred to her local hospital. Careful observation and rapid management can save patients with severe complications of HELLP syndrome.

Anti-CD19 BiTE Blinatumomab Induces High Complete Remission Rate In Adult Patients with Relapsed B-Precursor ALL: Updated Results of An Ongoing Phase II Trial

Abstract 252Adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL) have a dismal prognosis with low complete remission (CR) rates with intensive salvage chemotherapy which are not durable.Blinatumomab is a bispecific T-cell engaging (BiTE®) antibody construct that directs cytotoxic T-cells to CD19 expressing B-cells. In collaboration with the German Multicenter Study Group for Adult Lymphoblastic Leukemia (GMALL), an open-label, multicenter, single-arm, exploratory phase II trial is being conducted to evaluate efficacy and safety of blinatumomab in adult patients with relapsed/refractory B-precursor ALL.The primary endpoint for this trial is the rate of patients who reach CR or CR with partial hematological recovery (CRh*) within 2 cycles of blinatumomab treatment. Secondary endpoints are the rate of minimal residual disease (MRD) response (defined by an MRD level below the quantitative detection limit of 10−4), time to hematological relapse and overall survival.Blinatumomab is administered by continuous intravenous infusion for 28-days followed by a 14-day treatment-free interval. Responding patients could proceed to allogeneic hematopoietic stem cell transplantation (HSCT) or receive a total of up to 5 cycles of blinatumomab treatment. Three dose levels have been explored as shown in Table 1.Table 1Summary of Dose Cohorts and OutcomesCohortPatients TreatedInitial Dose Week 1, Cycle 1 μg/m2/dayDose Week 2, Cycle 1 μg/m2/dayDose Weeks 3–4, Cycle 1 μg/m2/dayMaintenance Dose, Subsequent Cycles μg/m2/dayCR or CRh*Serious Adverse EventsnPts171515151551562a551515154222b65153030354310 planned5151515n.a.n.a.n.a.As of June 30, 2011, 43 cycles have been administered to a total of 18 patients (range 1–5; median 2). Twelve out of 18 patients have reached a complete remission within the first 2 cycles of single agent blinatumomab corresponding to a response rate of 67%. Of these 12 responding patients, 75% had complete hematologic recovery of peripheral blood counts. All 12 responders reached MRD negativity within the first 2 cycles and included 3 patients with t(4;11) and 1 patient with Ph-positive B-precursor ALL. Four responders proceeded to allogeneic HSCT; one experienced a CD19-negative hematological relapse after HSCT. Two responders relapsed during treatment; one had a CD19-positive extramedullary, and one a CD19-negative bone marrow relapse. The remaining 6 non-transplanted responders are still in hematological complete remission.The most common adverse events were pyrexia and chills. In cohort 1, one patient with a high tumor burden developed disseminated intravascular coagulation (DIC)/cytokine release syndrome (CRS) leading to treatment discontinuation. The implementation of a cytoreductive pre-phase and a lower initial dosing at 5μg/m2/day during the first week prevented further treatment discontinuations in such patients. Four patients had fully reversible CNS serious adverse events that led in 1 patient to discontinuation of treatment, and in 3 patients to temporary interruption of treatment. These 3 patients resumed treatment at a lower dose without further interruptions during the following cycles. There were no deaths related to blinatumomab.Blinatumomab as single agent induced an unprecedented high rate of complete hematological and MRD responses in adult patients with relapsed/refractory B-precursor ALL. A lower dose of 5μg/m2/day for the initial week of treatment, as tested in cohort 2a, demonstrated a favorable safety profile while maintaining efficacy. A maintenance dose of 30μg/m2/day, as tested in cohort 2b, did not further improve the already high efficacy but increased the number of adverse events. Therefore, the dosing of cohort 2a was selected as the basis for cohort 3 and will be applied to further clinical development in this patient population. Updated results of the study will be presented. Disclosures:Topp:Micromet: Consultancy, Honoraria. Goekbuget:Micromet: Consultancy. Zugmaier:Micromet: Employment. Klappers:Micromet AG: Employment. Mergen:Micromet Inc: Employment. Bargou:Micromet: Consultancy, Honoraria.

Primary gastric chorioadenocarcinoma: a needle in a haystack

Primary gastric chorioadenocarcinoma (PGC) is an exceedingly rare neoplasm which is often misdiagnosed as gastric adenocarcinoma at presentation. A markedly elevated serum beta human chorionic gonadotrophin (Beta HCG) level is a characteristic feature of this tumor. A 44 year old white male presented with generalized abdominal pain and fullness, tarry black stools and weight loss of 3 months duration. Medical work-up including imaging with CT scans revealed the presence of a gastric mass and multiple liver metastases. Tumor markers were significant for a Betahuman chorionic gonadotrophin (Beta HCG) of 23717.5 MIU/ML. Scrotal ultrasound did not show the presence of a testicular mass. Upper GI endoscopy with biopsy was positive for a poorly differentiated adenocarcinoma with Beta HCG staining on immunohistochemistry. The patient was diagnosed with metastatic PGC. He received four cycles of chemotherapy with Bleomycin, Etoposide and Cisplatinum. At the end of the fourth cycle, Beta HCG was 23 MIU/ML. CT scan for restaging, however showed an increase in the size of the metastatic lesions. The patient subsequently became profoundly pancytopenic, developed disseminated intravascular coagulation (DIC) and expired 12 months after initial presentation. PGC genetically and morphologically represents an adenocarcinoma and a choriocarcinoma. The significance of an elevated serum Beta HCG is controversial and it may have a role in evaluating response to treatment and tumor recurrence. Curative resection, appropriate chemotherapy and the absence of metastatic lesions is associated with improved survival. Hence, a high index of suspicion must be maintained to diagnose this tumor correctly at presentation and tailor therapy accordingly.

Histiocytic Sarcoma and Tumor Lysis Syndrome: An Unexpected Sequela of Neck mass

1. Vos, et al. “Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163” Modern pathology. Jan 2005 (18)p693-704 2. De Vos, FYFL, Gerding M, Ardens J, Wegmen J. Histiocytic sarcoma localised in the thyroid—a case report. Ann Hematol 2008;87(8): 681682. 3. World Health Organization Classification of Tumours (2001) Pathology and genetics of tumours of hematopoietic and lymphoid tissue. International Agency for Research on Cancer (IARC), Lyon, pp 274–289 . 4. Cairo M, Bishop M. Tumor lysis syndrome: new therapeutic strategies and classification. British J Haematology 2004;127:3-11. 5. Gokmen Akoz A, Yildirim N, Engin H, et al. An unusual case of spontaneous acute tumor lysis syndrome associated with acute lymphoblastic leukemia: A case report and review of the literature. Acto Oncol 2007; 46(8):1190-2. The patient continued to rapidly deteriorate, developing disseminated intravascular coagulation (DIC), multi-system organ failure, and decreased neurologic function. The patient was pronounced dead early the following morning, just two days after admission. Her final pathology was consistent with histiocytic sarcoma. Histology revealed sheets of large atypical cells with abundant eosinophilic cytoplasm, large irregular nuclei and prominent nucleoli (Figure 4). Staining was positive for CD4, CD45 and CD68, and negative for B and T cell markers as well as keratin and HMB-45 (Figures 5,6). Her cause of death was felt to be spontaneous tumor lysis syndrome caused by massive tumor burden. Approximately 1/3 of cases present in lymph nodes, 1/3 in skin and 1/3 in extranodal sites, with the GI tract being most common.3 Treatment of histiocytic sarcoma consists of wide local excision when possible with adjuvant radiotherapy. Chemotherapeutic regimens have been proposed without evidence-based data.2 Patients have a very poor prognosis with poor response to therapy except in the case of very limited disease where complete excision is possible.1,2 Our case is unique in that histiocytic sarcoma does not often present as a neck mass and therefore does not typically enter into the differential diagnosis of otolaryngologists.

Choline or CDP-choline attenuates coagulation abnormalities and prevents the development of acute disseminated intravascular coagulation in dogs during endotoxemia

Sepsis/endotoxemia causes platelet dysfunctions, abnormalities in coagulation and hemostatic mechanisms leading to organ dysfunctions and mortality. Choline prevents organ injury and improves survival during endotoxemia. The main objective of the present study was to determine the effects of choline or cytidine-5'-diphosphocholine (CDP-choline) on endotoxin-induced activation of coagulation and development of disseminated intravascular coagulation (DIC). Dogs were treated intravenously (i.v.) with saline, choline (20 mg/kg), or CDP-choline (70 mg/kg) three times with 4-h intervals starting 5 min before i.v. injection of endotoxin (1 mg/kg). Platelet counts and functions, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, coagulation factors, D-dimer and antithrombin (AT) were measured before and at 0.5-96 h after endotoxin. Circulating platelet, fibrinogen, coagulation factors and AT were decreased, whereas PT and aPTT were prolonged and serum D-dimer levels were elevated after endotoxin. Endotoxin-induced reductions in platelet counts and functions, fibrinogen, coagulation factors and AT were attenuated or blocked by choline or CDP-choline. Choline or CDP-choline blocked endotoxin-induced prolongation in PT and aPTT and enhancement in D-dimer. Elevated DIC scores were attenuated by choline and blocked by CDP-choline. Choline administration increased serum choline concentrations and caused bradycardia. Choline also increased choline and acetylcholine contents of circulating mononuclear cells and inhibited radioligand binding to their cholinergic receptors. These data show that choline administration, as choline chloride or CDP-choline, restores the abnormalities in the primary, secondary, and tertiary hemostasis and prevents the development of DIC during experimental endotoxemia in dogs probably by increasing both neuronal and non-neuronal cholinergic activity.

Disseminated Intravascular Coagulation in Term and Preterm Neonates

Among critically ill patients, the risk of developing disseminated intravascular coagulation (DIC) is probably highest in neonates. Low plasma reserves in pro- and anticoagulant coagulation factors, intravascular volume contraction after birth, and a high incidence of hypoxia and sepsis in critically ill newborns rapidly lead to a decompensation of the coagulation system in this population. Global coagulation tests and single-factor plasma levels have to be interpreted in the context of age-corrected normal ranges. Platelet consumption and reduced protein C plasma levels have diagnostic value; the latter also has prognostic potential in neonates with DIC and sepsis. Therapeutic success relies heavily on reversal of the underlying condition. Some coagulation-specific therapies have been explored in small studies and case series with varying success and sometimes conflicting results. Therefore, larger controlled trials in this common and serious condition are urgently needed.

Disseminated Intravascular Coagulation in Trauma Injuries

Physical injuries, especially road traffic injuries, are a leading cause of death and morbidity worldwide, ranking fifth among the leading causes of death in the United States. Immediate and early trauma deaths are mainly determined by primary brain injuries and/or hemorrhages, whereas late mortality is caused by secondary brain injuries, host defense failure, and superimposed complications including also disseminated intravascular coagulation (DIC). Trauma patients are particularly susceptible to the early development of coagulopathy, and the most severely injured patients are coagulopathic on hospital admission. The zenith of the problem is typically seen in patients with head injuries and in those who are massively injured and transfused. The resulting coagulopathy is characterized by nonsurgical bleeding from mucosal lesions, serosal surfaces, and wound and vascular access sites. DIC associated with traumatic injury results from multiple independent but interplaying mechanisms, involving tissue trauma, shock, and inflammation. As such, the multifaceted derangement of hemostasis occurring after massive traumatic injuries, especially those involving the brain, is mainly sustained by release of procoagulants (fats, phospholipids) and constitutive tissue factor from the injured tissue into the circulation, associated with a systemic inflammatory response that also promotes tissue factor hyperexpression on monocytes and the other cells. The excessive, non-wound-related thrombin generation is insufficiently antagonized by physiological anticoagulant pathways and amplified by impaired endogenous fibrinolysis. The resulting burst of systemic thrombin generation, coupled with platelet hyperaggregability, shock, hypothermia, and tissue hypoperfusion, further contribute to the development of DIC and microvascular bleeding.

Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation

The first line of host defense is the innate immune system that includes coagulation factors and pattern recognition molecules, one of which is mannose-binding lectin (MBL). Previous studies have demonstrated that MBL deficiency increases susceptibility to infection. Several mechanisms are associated with increased susceptibility to infection, including reduced opsonophagocytic killing and reduced lectin complement pathway activation. In this study, we demonstrate that MBL and MBL-associated serine protease (MASP)-1/3 together mediate coagulation factor-like activities, including thrombin-like activity. MBL and/or MASP-1/3 deficient hosts demonstrate in vivo evidence that MBL and MASP-1/3 are involved with hemostasis following injury. Staphylococcus aureus infected MBL null mice developed disseminated intravascular coagulation (DIC), which was associated with elevated blood IL-6 levels (but not TNF-α and multi-organ inflammatory responses). Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases.

Acute Kidney Injury due to Menstruation-related Disseminated Intravascular Coagulation in an Adenomyosis Patient: A Case Report

The authors report a case of acute kidney injury (AKI) resulting from menstruation-related disseminated intravascular coagulation (DIC) in an adenomyosis patient. A 40-yr-old woman who had received gonadotropin for ovulation induction therapy presented with anuria and an elevated serum creatinine level. Her medical history showed primary infertility with diffuse adenomyosis. On admission, her pregnancy test was negative and her menstrual cycle had started 1 day previously. Laboratory data were consistent with DIC, and it was believed to be related to myometrial injury resulting from heavy intramyometrial menstrual flow. Gonadotropin is considered to play an important role in the development of fulminant DIC. This rare case suggests that physicians should be aware that gonadotropin may provoke fulminant DIC in women with adenomyosis.

Changes in indicators related to inflammatory cytokines, coagulation and fibrinolysis in patients with disseminated intravascular coagulation and multiple organ dysfunction syndrome caused by sepsis

Objective To investigate changes in indicators related to inflammatory cytokines, coagulation and fibrinolysis system in patients with disseminated intravascular coagulation (DIC) and multiple organ dysfunction syndrome (MODS) resulted from sepsis. Methods In total, 97 patients diagnosed as sepsis were divided into different groups and their plasma concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), tissue factor (TF) and tissue factor pathway inhibitor (TFPI), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) were measured by ELISA and plasma activity of protein C (PC:A) was measured by chromogenic substrate assay. Results Plasma concentrations of TNF-α and I L-6 were (38 ± 12) ng/L and (77 ± 9) ng/L, respectively, in patients of sepsis complicated with DIC, much higher than those without DIC [ ( 17±6) ng/L and (45 ± 6), respectively], P <0.05;and (63±25) ng/L and (103±28) ng/L, respectively, in those complicated with MODS, significantly higher than in those without MODS [ (29 ± 7 ) ng/L and (48±9)ng/L, respectively], P < 0/05 and those without DIC [( 17 ± 6) ng/L and (45 ± 6) ng/L, respectively], P <0. 05;as well as significantly higher in the dead than in survivors (P <0. 05). Plasma activity of protein C was (32 ± 10) percent in those with DIC and (24 ± 12) percent in those with MODS, both significantly lower than in those without DIC [ (57±28) percent] and without MODS [ (55 ± 17) percent], respectively, P <0. 05, as well as significantly lower in the dead than in survivors, P <0. 05. Plasma concentrations of t-PA and PAI-1 were significantly higher in sepsis patients with DIC [(48±17)μg/L] than that in those without DIC [(103 ± 38)μg/L], P < 0.05. Conclusions Inflammatory cytokines play important roles in development of DIC as well as MODS in patients with sepsis. Decreased activity of protein C and increased plasma level of PAI-1 can result in deposition of fibrin on the vessel wall and thrombosis, which can be used as indicators of poor prognosis for patients with DIC. Key words: Systemic inflammatory response syndrome; Disseminated intravascular coagulation; Multiple organ failure

Occurrence of disseminated intravascular coagulation (DIC) in active systemic anaphylaxis: role of platelet-activating factor.

The possible occurrence of DIC in active systemic anaphylaxis was investigated in mice. Induction of active systemic anaphylaxis resulted in the development of DIC symptoms such as thrombocytopenia, prolongation of prothrombin time, hypofibrinogaemia, and elevated level of fibrinogen/fibrin degradation products. In addition, in histological examinations, massive congestion and cellular infiltration in pulmonary interstitia, and considerable haemorrhage in renal medullae were observed. All these changes were nearly completely prevented by pretreatment with platelet-activating factor (PAF) antagonist (BN 50739). Moreover, the same haematological and morphological changes were produced by a bolus injection of PAF. These data strongly suggest that DIC occurs in active systemic anaphylaxis and PAF plays a pivotal role in the development of DIC in anaphylaxis.

Clinical course and outcome of disseminated intravascular coagulation diagnosed by Japanese Association for Acute Medicine criteria

The Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) study group recently announced new diagnostic criteria for DIC. These criteria have been prospectively validated and demonstrated to progress to overt DIC as defined by the International Society on Thrombosis and Haemostasis (ISTH). Although an underlying condition is essential for the development of DIC, it has never been clarified if patients with different underlying disorders have a similar course. Among 329 patients with DIC diagnosed by the JAAM criteria, those with underlying sepsis (n = 98) or trauma (n = 95) were compared. The 28-day mortality rate was significantly higher in sepsis patients than trauma patients (34.7% vs. 10.5%, p < 0.0001). Within three days of fulfilling the JAAM criteria, sepsis patients had a lower platelet count, higher prothrombin time ratio, higher systemic inflammatory response syndrome score, and higher Sequential Organ Failure Assessment score compared with trauma patients. On day 3, a significantly higher percentage of trauma patients than sepsis patients showed improvement of DIC (64.2% vs. 30.6%, p < 0.001). These differences were mainly due to patients with lower JAAM DIC scores. More than 50% of the JAAM DIC patients with sepsis who died within 28 days could not be detected by ISTH DIC criteria during the initial three days. In contrast, most trauma patients who died within 28 days had DIC simultaneously diagnosed by JAAM and ISTH criteria, except for those with brain death. These findings suggest that coagulation abnormalities, organ dysfunction, and the outcome of JAAM DIC differ between patients with sepsis and trauma.