Severity Of Disseminated Intravascular Coagulation Research Articles

Platelet dysfunction in heatstroke-induced coagulopathy: A retrospective observational study

PurposeSevere heatstroke is often complicated by disseminated intravascular coagulation (DIC). The aim of this study was to evaluate platelet function assessed through thromboelastography (TEG) at the emergency department (ED) and DIC severity among patients with heatstroke. Materials and methodsWe performed a retrospective single-tertiary hospital cohort study. Patients admitted to an intensive care unit (ICU) with heatstroke were enrolled. Platelet function was evaluated as the difference between citrated functional fibrinogen-maximum amplitude (CFF-MA) and citrated rapid TEG-maximum amplitude (CRT-MA) at the ED. DIC was defined as a score ≥ 4 points based on the Japanese Association of Acute Medicine score. ResultsA total of 31 patients with heatstroke were enrolled. The median platelet count was 18.1 × 104/μL, (interquartile range [IQR]: 12.6–25.0 × 104/μL), and the median platelet function evaluated as CFF-MA-CRT-MA was 34.4 mm (IQR: 27.8–37.8 mm). Among several clinical and TEG-related parameters, the platelet function was strongly correlated with the DIC score (R = −0.63, p < 0.001) and significantly associated with DIC development (area under the receiver operating characteristic curve 0.87 [95 % confidence interval: 0.72–0.99]). ConclusionsThese results suggested that platelet dysfunction occurs in heatstroke-induced DIC, indicating that platelet function evaluation by TEG can provide complementary information and enhance our understanding about the subtypes of heatstroke.

Damage-Associated Molecular Patterns as Mediators of Thrombus Formation on Dialyzer Membrane in Critically Ill Patients.

This prospective study investigated the relationship between inflammation, damage-associated molecular patterns (DAMPs), and thrombus formation on dialyzer membranes in critically ill patients undergoing renal replacement therapy (RRT) from July 2020 to August 2022, identifying mechanisms and interventions to prevent clotting. The patients were divided into two groups: inflammatory (n = 56, serum C-reactive protein >10 mg/dl) and noninflammatory control (n = 45, serum C-reactive protein <5 mg/dl). Cell-free deoxyribonucleic acid (DNA) levels, high mobility group box 1 protein (HMGB1), histone H3, and myeloperoxidase (MPO) in the lumen of the hollow fiber membrane of the dialyzer were quantified. Immunostaining assessed leukocytes, fibrin fibers, and platelet thrombi on the luminal surface of the hollow fiber membrane. The inflammatory group, compared to controls, exhibited elevated cell-free DNA, HMGB1, and MPO levels, although histone H3 remained unchanged. Damage-associated molecular patterns increased with disseminated intravascular coagulation (DIC) severity. Immunostaining in the inflammatory group revealed leukocytes, amorphous nuclei, neutrophil extracellular trap-like structures, fibrin fibers, and platelet thrombi on the hollow fiber membrane's luminal surface. Elevated DAMP levels in severely inflamed patients' dialyzer membranes, correlating with DIC severity, indicate a link between inflammation, coagulation activation, and dialyzer clotting. Research into thrombus prevention in RRT for DIC-affected critically ill patients is warranted.

Risk of disseminated intravascular coagulation in postpartum hemorrhage associated with intrauterine infection.

To evaluate the risk of disseminated intravascular coagulation (DIC) in postpartum hemorrhage (PPH) associated with intrauterine infection. A retrospective cohort study of pregnancies complicated by PPH performed at a tertiary academic center in France from 2017 through 2021. Patients giving birth after 22 weeks of gestation with PPH were eligible. Patients with a PPH associated with an intrauterine infection were compared to patients with a PPH without intrauterine infection. Intrauterine infection was defined by a composite criterion available at delivery. DIC was defined by a specific pregnancy DIC score. The association between DIC and intrauterine infection was assessed by logistic regression. The causal effect of intrauterine infection on DIC was estimated by mediation analysis. Of 2,093 patients with PPH, 49 exposed to a clinical intrauterine infection were compared to 49 unexposed patients. The rate of DIC was higher in patients with than without infection (22 (45.8%) vs. 7 (14.6%), P=.001), and coagulation anomalies occurred sooner in patients with than without infection (7, 2-11h vs. 14, 9-19h, P < .001). In the multivariate analysis, intrauterine infection was the only factor independently associated with DIC (adjusted odds ratio 5.01, 95% CI 1.83-13.73). Mediation analysis showed that 14% (95% CI, 0-50%) of this association between intrauterine infection and DIC was mediated by severe PPH, and 86% resulted from the direct effect of intrauterine infection on DIC. In PPH, intrauterine infection had a major direct effect on the occurrence, timing, and severity of DIC.

Prognostic value of the ADAMTS13-vWF axis in disseminated intravascular coagulation: Platelet count/vWF:Ag ratio as a strong prognostic marker.

ADAMTS13 deficiency increases the circulating level of von Willebrand factor (vWF). Low ADAMTS13 and high vWF can provide a milieu for microthrombosis, including disseminated intravascular coagulation (DIC). This study investigated the prognostic values of ADAMTS13-vWF axis markers and their correlation with DIC severity. ADAMTS13-vWF axis markers (vWF antigen (vWF:Ag), vWF ristocetin cofactor (vWF:Rco), ADAMTS13 activity, and anti-ADAMTS13 antibody) were measured in patients (n=152) suspected of having DIC along with the well-known DIC markers including antithrombin and protein C. The vWF:Ag level was significantly increased, and ADAMTS13 activity was significantly decreased in overt DIC. The vWF:Ag level (hazard ratio 7.365, p=.009), ADAMTS13 activity/vWF:Ag ratio (hazard ratio 3.777, p=.037), ADAMTS13 activity/vWF:Rco ratio (hazard ratio 3.027, p=.028), and platelet count/vWF:Ag ratio (hazard ratio 8.538, p<.001) were significant prognostic markers in Cox regression analysis and correlated well with DIC score and antithrombin and protein C levels. The platelet count/vWF:Ag was the strongest prognostic marker among ADAMTS13-vWF axis markers. The measurement of vWF:Ag may improve prognostic insights of DIC in clinical practice.

Fibrinogen may aid in the early differentiation between amniotic fluid embolism and postpartum haemorrhage: a retrospective chart review

This study aimed to determine whether blood loss and fibrinogen can differentiate amniotic fluid embolism (AFE) from postpartum haemorrhage (PPH). This retrospective case–control study included nine patients with clinical AFE (“AFE group”) and 78 patients with PPH managed at our tertiary care perinatal centre between January 2014 and March 2016. Patients meeting the Japanese diagnostic criteria for AFE were stratified into cardiopulmonary collapse-type AFE and disseminated intravascular coagulation (DIC)-type AFE groups. The relationship between blood loss and fibrinogen at onset was examined to compare DIC severity. Vital signs at onset were not significantly different. The AFE group had significantly less blood loss at onset (1506 mL vs 1843 mL, P = 0.0163), significantly more blood loss 2 h post-onset (3304 mL vs 1996 mL, P < 0.0001) and more severe coagulopathy and fibrinolysis. The blood loss/fibrinogen (B/F) ratio at onset was significantly higher in the DIC-type AFE group (23.15 ± 8.07 vs 6.28 ± 3.35 mL dL/mg, P < 0.0001). AFE was complicated by catastrophic DIC irrespective of blood loss at onset. Fibrinogen exhibited the strongest correlation among test findings at onset. The B/F ratio may help differentiate PPH from DIC-type AFE and diagnose clinical AFE, facilitating optimal replacement of coagulation factors during the early stages.

Biomarkers of Platelet Activation and Their Prognostic Value in Patients With Sepsis-Associated Disseminated Intravascular Coagulopathy

Sepsis-associated disseminated intravascular coagulation (DIC) is related to marked hemostatic changes such as transient thrombocytopenia secondary to the endogenous activation and consumption of platelets. This study measured markers of platelet function in 103 adult ICU patients with clinically established sepsis-associated DIC to determine the biomarker association with disease severity. Patients were categorized as having no DIC, nonovert DIC, or overt DIC using the International Society of Thrombosis and Hemostasis scoring system. Plasma levels of CD40L, platelet factor 4 (PF4), platelet-derived microparticles, and microparticle-associated tissue factor were quantified. Markers of platelet activation were significantly elevated in patients with DIC compared to healthy individuals. This increase was independent of platelet count. Levels of PF4 differed based on the severity of DIC and differentiated nonsurvivors and survivors. These findings suggest that the markers of platelet activation in DIC may not be regulated by the number of circulating platelets and may be independent of the factors leading to their consumption.

A reevaluation of diagnostic efficacy of International Society of Thrombosis and Haemostasis and Japanese Association for Acute Medicine criteria for the diagnosis of sepsis disseminated intravascular coagulation

Objective: To reevaluate the diagnostic efficacy of International Society of Thrombosis and Haemostasis (ISTH) and Japanese Association for Acute Medicine (JAAM) criteria for sepsis disseminated intravascular coagulation (DIC). Methods: A total of 769 patients diagnosed as sepsis were enrolled in our study. Blood samples were collected within the first hour in ICU and the index of coagulation was detected. The correlation between the conventional coagulation index and the acute physiology and chronic health evaluation (APACHE Ⅱ) and sequential organ failure assessment (SOFA) scores was analyzed. The sensitivity and specificity of diagnostic efficacy were analyzed by receiver operating characteristic (ROC) curve. Results: In the 769 cases, 95 cases (12.35%) conformed to the standard of ISTH and 271 cases (35.24%) were in accordance with the standard of JAAM. Prolonged prothrombin time (PT) was seen in 726 cases (94.41%). Activated partial thromboplastin time (APTT) was prolonged in 434 cases (56.44%). Plasma fibrinogen (Fib) was decreased in 94 cases (12.22%) and increased in 365 cases(47.46%). Platelet (PLT) count decreased in 158 cases (20.55%). D-dimer was elevated in 759 cases (98.70%). Fibrin degradation product (FDP) was increased in 724 cases (94.15%). PT, APTT, D-dimer, FDP, PLT were correlated with APACHE Ⅱ(r value were 0.259, 0.348, 0.319, 0.289,-0.275, all P values<0.05) and SOFA score(r values were 0.409, 0.445, 0.407, 0.411,-0.526, respectively, all P values<0.05). The areas under the curve (AUCs) in the ISTH standard from high to low were accordingly PT (0.813), FDP (0.792), PLT (0.746), Fib (0.563). The AUCs from high to low were FDP (0.844), PLT (0.716), and PT (0.660), respectively in the JAAM standard. Under the criteria of ISTH, the diagnostic sensitivities of PT, PLT, Fib and FDP were 92.63%, 67.37%, 9.47%, 98.95%, respectively, and specificities as 53.56%, 86.05%, 99.26% and 33.38%% respectively. As to the JAAM criteria, the diagnostic sensitivities of PT, PLT, and FDP were 74.54%, 52.77%, 91.51% and specificities as 51.61%, 84.94%, 40.76% respectively. Conclusions: According to the ISTH and JAAM diagnostic criteria, the diagnostic efficacy of PT and PLT is relatively high, which is associated with the severity of DIC. D-dimer and FDP have the high sensitivity but the specificity is poor. The diagnostic specificity of Fib is good, yet with low sensitivity and poor overall efficacy.

Relationship of Markers of Inflammation, Infection and Endothelial Function to Mortality and Severity of Coagulopathy in Patients with Sepsis-Associated DIC

Background: Sepsis-associated disseminated intravascular coagulation (DIC) is a complex clinical scenario involving derangement of many processes, including hemostasis. Assessment of markers of these other aspects of disease, including inflammation, immunity, endothelial function, and endogenous anticoagulants may provide insight into DIC pathophysiology and lead to improved methods for assessment of patient condition and response to treatment. This study was designed to measure biomarkers representative of multiple systems involved in DIC development in a cohort of patients with sepsis and DIC and determine the association of these biomarkers with disease severity and mortality.Materials and Methods: Citrated plasma samples were prospectively collected from 102 patients with sepsis and suspected DIC at ICU admission (day 0) and again serially on ICU days 4 and 8 under an IRB approved protocol. DIC score was determined using the ISTH scoring algorithm (e.g. platelet count, PT/INR, fibrinogen, and D-Dimer). Plasma from healthy individuals was purchased from a commercial laboratory (George King Biomedical, Overland, KS). . CD 40 Ligand (CD40L), Plasminogen inhibitor 1 ( PAI-1), nucleosomes, Procalcitonun (PCT), Microparicle Tissue Factor (MP-TF), and Prothrombin Fragment 1.2 (F1.2) were measured using commercially available ELISA kits. Protein C activity was measured using a clot-based assay. Interleukin 6 (IL-6), Interleukin 8 (IL-8), Interleukin 10 (IL-10) , Tumor Necrosis Factor Alpha (TNFα) , Monocyte Chemoattractant protein 1 (MCP-1) were measured using a biochip technology.Results: Significant differences in levels of Protein C (p=0.009), PCT (p=0.0005), IL-6 (p=0.019), IL-8 (p= 0.015), and PAI-1 (p=0.015) were observed between survivors and non-survivors (Table 1). Significant variation of Protein C (p=0.002), nucleosomes (p=0.05), PCT (P<0.001), IL-6 (p=0.001), IL-8 (p=0.003), IL-10 (p=0.011), TNFα (p=0.021), and MCP-1 (p=0.21), were observed based on severity of DIC score.Conclusion: Markers from multiple systems perturbed in DIC were associated with mortality suggesting that while these systems may not be routinely evaluated in the course of patient care, dysfunction of these system contribute significantly to mortality. In addition, numerous inflammatory cytokines showed an association with DIC score. This study suggests that the measurement of additional markers in sepsis-associated DIC may be of value in the prediction of mortality and may be helpful in guiding treatment for these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Thrombin-antithrombin complex measurement using a point-of-care testing device for diagnosis of disseminated intravascular coagulation in dogs.

Reference interval for thrombin-antithrombin complex (TAT) level was determined using an in-house TAT measurement device, and its validity for diagnosis of disseminated intravascular coagulation (DIC) was evaluated in dogs. One hundred and two clinically healthy dogs and 247 diseased dogs with conditions that potentially caused DIC were recruited in the study. Six diagnostic testing for DIC were evaluated in diseased dogs and the diseased dogs were categorized into five groups depending on abnormal findings. TAT was measured in all study animals and between-group differences were evaluated. TAT level was positively associated with severity of DIC. There were no significant differences in TAT levels among clinically healthy dogs, diseased dogs without any abnormal finding and diseased dogs with one abnormal finding in the DIC diagnostic testing. TAT levels in groups with two or more abnormal findings were significantly higher than clinically healthy dogs. Reference interval of TAT level for clinically healthy dogs was ≤ 0.25 ng/ml. Validity of using TAT for early detection of DIC was evaluated. In-house TAT measurement was suggested to be a clinically relevant and useful tool for early detection of canine DIC.

Comparison of the Serum Levels of Interferon-α in the Patients With Crimean-Congo Hemorrhagic Fever Based on Disease Severity

Introduction: Crimean-Congo hemorrhagic fever (CCHF) is an acute viral and potentially fatal disease that is endemic in the south east of Iran, especially Sistan and Baluchestan. This study aimed to measure the serum levels of interferon-[1]r (IFN-[1]r) in the patients with CCHF, considering the disseminated intravascular coagulation (DIC) severity. The second aim was to determine the correlation between the serum levels of IFN-[1]r and DIC severity using the guidance of diagnosis and treatment of the CCHF. Methods: Thirty-seven patients with CCHF were studied. The diagnosis was made, based on the detection of viral RNA by real time-polymerase chain reaction (RT-PCR) and by positive serology. These patients, based on the severity of DIC, were divided into two groups. The serum levels of IFN-[1]r were measured by the enzyme-linked immunosorbent assay (ELISA) method and compared between these two groups. Data analysis was performed using the SPSS 20.0 and non-parametric statistical tests were used for analyses. Results: The mean serum levels of IFN-[1]r were lower in the patients with CCHF on the ­rst day compared to the ­fth day of admission (P < 0.008). There was a signi­cant relationship between the serum levels of IFN-[1]r and DIC severity, as the level of IFN-[1]r was lower in the patients with overt DIC (P < 0.001). The serum level of IFN-[1]r in the patients with the overt DIC was 1.04 pg/dL with 90% speci­city and 88% sensitivity. Conclusion: The serum levels of IFN-[1]r were lower in the patients with severe CCHF, and their evaluation may be used as a marker for the diagnosis of disease severity.

Evaluation of Modified Japanese Ministry Health and Labor Welfare Diagnostic Criteria for DIC to Detect Early Phase of DIC

Evaluation of the modified Japanese Ministry Health, Labour and Welfare (JMHLW) diagnostic criteria for DIC to detect the early phase of DICIntroduction: Disseminated intravascular coagulation (DIC) is a syndrome characterized by the systemic activation of blood coagulation, which generates intravascular thrombin and fibrin, resulting in the thrombosis of small-to medium-sized vessels and ultimately organ dysfunction and severe bleeding. Three different diagnostic criteria incorporating similar global coagulation tests have been established by the International Society of Thrombosis and Haemostasis (ISTH), Japanese Ministry Health, Labour and Welfare (JMHLW) and Japanese Association of Acute Medicine (JAAM). The JMHLW score is well correlated with the severity of DIC and can be used to predict the outcome of the disease, however, it has a relatively low sensitivity for the early phase of DIC (pre-DIC).Material and Methods: The Modified JMHLW criteria are shown in the Table 1. From 1996 to 2014, 282 patients with hematopoietic disorder type, 220 patients with infection type and 249 patients with other type were retrospectively diagnosed with DIC according to the JMHW criteria. There were 184 patients with pre-DIC and 256 patients without DIC.Table 1Modified Japanese Ministry Health, Labor and Welfare criteria for DICHematopoietic disorder typeOthertypeInfectiontypePlatelet count(X107/ml)none8 < < 12: 1 point, 5 < < 8: 2 points,(> 30% decrease: plus 1 point)< 5: 3 pointsFDP (ƒÊg/ml)10 < < 20: 1 point, 20 < < 40; 2 points, 40< : 3 pointsFibrinogen (g/L)1 < < 1.5 : 1 point, < 1: 2 pointsnonePT ratio1.25 < < 1.67: 1 point, 1.67 < : 2 pointsAT (%)< 70 : 1 pointTAT or SF2X (upper limit of normal range): 1 pointDIC4 points = or <6 points = or <5 points = or <AT: antithrombin, TAT: thrombin AT complex, SF: soluble fibrinResults: The agreement rate between the JMHLW and modified JMHLW criteria was 95.9%. The diagnosis rate of pre-DIC was 0% using the JMHLW criteira, 8.3% using the ISTH diagnostic criteria, 63.0% using the JAA criteria and 38.6% using the modified JMHLW criteira for DIC. The mortality of DIC was 42.5% using the JMHLW criteria, 45.5% using the ISTH criteria, 41.3% using the JAA criteria and 42.6% using the modified JMHLW criteria.Discussion and conclusion: The agreement rate between the JMHLW and modified JMHLW criteria is high. As the modified JMHLW criteria adds the score for antithrombin (AT) activity, thrombin-AT complex (TAT) or soluble fibrin (SF), these criteria increase the sensitivity for pre-DIC. DisclosuresNo relevant conflicts of interest to declare.

Can rotational thromboelastometry predict septic disseminated intravascular coagulation?

Rotational thromboelastometry (ROTEM), known as point-of-care testing, has been incorporated into various kinds of postsurgical management. However, the utility of ROTEM for rapid diagnosis of sepsis-induced disseminated intravascular coagulation (DIC) has not been investigated. This retrospective study includes 13 sepsis patients who underwent ROTEM in our emergency department in 2013. All patients were divided into two groups on the basis of the presence of DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We evaluated the demographics, clinical characteristics, laboratory data, ROTEM test and outcomes for each patient. The correlations between JAAM DIC score and significantly different parameters by univariate analysis and receiver operating characteristic (ROC) analysis were performed to assess the accuracy of the variables. There were seven and six patients in the DIC group and non-DIC group, respectively. The DIC group showed significantly longer prothrombin times, international normalized ratio of prothrombin time and clotting times (CTs) in the EXTEM test, and higher fibrinogen and fibrin degradation products and D-dimer. The CT in EXTEM test was correlated more with JAAM DIC score (r = 0.798), than the standard coagulation test. These parameters were accurate predictors in the diagnosis of septic DIC, with an AUC of 0.952, and a cut-off value of more than 46.0 s, resulting in a sensitivity of 100.0% and a specificity of 83.3%. CT in the EXTEM test was a single reliable indicator of sepsis-induced DIC diagnosed by the JAAM DIC score, and strongly associated with severity of DIC.

Poor prognosis of hypocoagulability assessed by thrombin generation assay in disseminated intravascular coagulation

Overall assessment of the hemostatic system including procoagulant and anticoagulant changes may help assess the clinical status and prognosis of disseminated intravascular coagulation (DIC). The thrombin generation assay provides useful information about the global hemostatic status. Therefore, we measured several parameters of global hemostatic potential by the thrombin generation assay in patients suspected of having DIC. A total of 114 patients with suspected DIC were included. The thrombin generation assay was performed on the calibrated automated thrombogram using tissue factor with or without the addition of thrombomodulin, showing three parameters: lag time, endogenous thrombin potential (ETP), and peak thrombin. Both 1 and 5 pmol/l tissue factor-stimulated ETP and peak thrombin were well correlated with DIC severity. Interestingly, antithrombin level greatly affected ETP, whereas protein C influenced lag time. Prognostic analysis revealed that the area under the curve of peak thrombin stimulated by 1 pmol/l tissue factor was superior to that of D-dimer. Moreover, multivariate Cox analysis showed that the lag time and time to peak with both 1 and 5 pmol/l tissue factor were independent prognostic markers. ETP and peak thrombin well reflect DIC severity. Hypocoagulability manifesting as prolonged lag time and time to peak is expected to be an independent prognostic marker in DIC.

Changes in Plasma Levels of Natural Anticoagulants in Disseminated Intravascular Coagulation: High Prognostic Value of Antithrombin and Protein C in Patients with Underlying Sepsis or Severe Infection

BackgroundDysfunctional natural anticoagulant systems enhance intravascular fibrin for mation in disseminated intravascular coagulation (DIC), and plasma levels of natural anti coagulants can be used in the diagnosis and prognosis of DIC. Herein, the diagnostic value of 4 natural anticoagulants was assessed, and the prognostic value of antithrombin and protein C were validated in a large population.MethodsPart 1 study included 126 patients with clinically suspected DIC and estimated plasma levels of 4 candidate anticoagulant proteins: antithrombin, protein C, protein S, and protein Z. Part 2 comprised 1,846 patients, in whom plasma antithrombin and protein C levels were compared with other well-known DIC markers according to the underlying dis eases. The 28-day mortality rate was used to assess prognostic outcome.ResultsAntithrombin and protein C showed higher areas under the ROC curve than pro tein S and protein Z. In part 2 of the study, antithrombin and protein C levels significantly correlated with DIC score, suggesting that these factors are good indicators of DIC severity. Antithrombin and protein C showed significant prognostic power in Kaplan-Meier analyses. In patients with sepsis/severe infection, antithrombin and protein C showed higher hazard ratios than D-dimer. Platelet count showed the highest hazard ratio in patients with hemato logic malignancy. In patients with liver disease, the hazard ratio for antithrombin levels was significantly high.ConclusionsDecreased plasma anticoagulant levels reflect florid consumption of the phys iologic defense system against DIC-induced hypercoagulation. Plasma antithrombin and protein C levels are powerful prognostic markers of DIC, especially in patients with sepsis/severe infection.

English

Disseminated Intravascular Coagulation (DIC) is a pathological activation of coagulation (blood clotting) mechanisms that happens in response to a variety of diseases. It involves the generation of intravascular fibrin (small blood clots) and the consumption of pro-coagulants and platelets. It results in the disruption of normal coagulation mechanism and abnormal bleeding occurs from the skin, the gastrointestinal tract, the respiratory tract and surgical wounds. It was the prospective study of 60 patients of acute DIC, in which coagulation profile were studied from December 2010 to October 2012. 40 controls were studied. Control group include healthy voluntary blood donors. The coagulation profile was studied and DIC scoring was performed using the International Society on Thrombosis and Haemostasis (ISTH) criteria. Among the coagulation profile, the sensitivity and specificity of the parameters to diagnose and to assess the severity of DIC, in the decreasing order of frequency were of platelet count, D-dimer, PT and APTT. Fibrinogen level was not depleted below the significant level (<1 gm/l) in majority cases of DIC. According to the ISTH criteria, DIC scores among cases was ≥ 5.

Decreased thrombomodulin mRNA expression on peripheral monocytes in disseminated intravascular coagulation patients relates to poor outcomes: The ex vivo effects of lipopolysaccharide and thrombin on monocyte thrombomodulin and CD14 mRNA

Monocytes express substantial amounts of thrombomodulin, which is consumed throughout ongoing thrombin generation. The modulation of thrombomodulin may aggravate intravascular fibrin deposition and the clinical course of disseminated intravascular coagulation (DIC). Although thrombomodulin restoration has received considerable attention, no reports have been published on the in vivo expression status of thrombomodulin. CD14 expression on monocytes is important for regulation of the inflammatory response. We used an ex vivo stimulation study to evaluate the association of the levels of monocyte-expressed thrombomodulin and CD14 messenger RNA (mRNA) with the severity and prognosis of disseminated intravascular coagulation. A total of 78 patients with suspected DIC were enrolled. Thrombomodulin and CD14 mRNA levels were measured in peripheral blood by real-time quantitative reverse-transcription polymerase chain reaction. Thrombomodulin and CD14 mRNA were also assessed in ex vivo cultures of peripheral whole blood that were stimulated by lipopolysaccharide or thrombin. The levels of monocyte-expressed thrombomodulin mRNA were significantly lower in the non-survivors than in the survivors. A low level of monocyte-expressed thrombomodulin mRNA was a significant prognostic marker, but CD14 did not possess prognostic power. Monocyte-expressed CD14 mRNA correlated significantly with the severity of DIC in survivors. In addition, stimulation of ex vivo cultures of whole blood demonstrated that thrombin upregulates both thrombomodulin and CD14 mRNA, and lipopolysaccharide downregulates thrombomodulin mRNA. The downregulation of thrombomodulin on monocytes reflects the decompensated status of physiological defenses against hypercoagulopathy and represents the poor prognosis in DIC. The expression levels of thrombomodulin on monocytes may be a useful marker to screen for candidates eligible for recombinant thrombomodulin therapy in future.

Can serum ferritin level predict disease severity in patients with crimean-congo hemorrhagic Fever?

Crimean-Congo hemorrhagic fever (CCHF) is an acute viral disease. Several factors have already been suggested to explain the pathogenesis as well as predict the disease severity. In our study we aim to investigate the role of serum ferritin level as a possible predicting factor of disease severity in these patients. We evaluated all patients with laboratory confirmed diagnosis of CCHF who were admitted to Boo-Ali Hospital of Zahedan from May 2011 to June 2012. Confirmation of the disease determined using the presence of anti- CCHFV IgM in the serum by enzyme-linked immunosorbent assay (ELISA) or by polymerase chain reaction(PCR). After ethical approval, patients were categorized into two groups of mild and severe disease according to disseminated intravascular coagulation (DIC) severity using the scoring system of International Society on Thrombosis and Hemostasis (ISTH). Serum ferritin levels were evaluated and compared between these two groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the optimal cutoff value of serum ferritin for predicting the disease severity. A total of 42 patients (36 men, 6 women, age range: 17-78 years) were included in this study, of whom 38% had Persian and 62% had Baloch ethnicity. According to DIC severity score, 54.7% of the patients had severe disease and 45.3% had mild disease. The area under the ROC curve was 0.896 and 95% CI was 0.801-0.991 (p<0.0001). A cut-off point of 1060 ng/dL, had a sensitivity of 78.9%, a specificity of 87%, a positive predictive value of 6% and a negative predictive value of 100%. Positive and negative likelihood ratios for this serum ferritin level were 6.05 and 0.24, respectively. Increased serum ferritin level has a significant positive correlation with disease severity in patients with CCHF and can evaluate the prognosis of these patients with a high sensitivity and specificity.

Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia

Bleeding is the leading cause of death for patients with acute promyelocytic leukemia (APL). Blood component transfusion to correct coagulopathy is the keystone in reducing bleeding. The benefit of fresh frozen plasma transfusion is unproven. Using laboratory profiles to predict bleeding is important guidance for the determination of transfusion policies in the treatment of APL. For 116 patients of APL, bleeding events were collected and correlated with various hematologic and coagulation parameters, including leukemic cell percentages, white blood cell (WBC) and platelet counts, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen levels, and disseminated intravascular coagulation (DIC) scores. Overt DIC occurred in 77.6% of patients. Severity of DIC was associated with bone marrow leukemic cell percentages but unrelated to bleeding. Patients with bleeding had significantly higher WBC counts (26.73 ± 6.18 vs. 13.03 ± 3.03 per μL, P = 0.026) and more prolonged PT (4.85 ± 0.70 vs. 2.59 ± 0.28 s, P = 0.002) and APTT (3.98 ± 1.68 vs. 0.96 ± 0.93 s, P = 0.017). Fibrinogen levels, platelet counts, and leukemia cell percentages were not significantly different between bleeding and non-bleeding patients. PT is valuable in prediction of bleeding. Patients with PT ≧ 5 s had a relative risk of 6.14 for bleeding. Seven patients had severe bleeding before initiation of all-trans retinoic acid (ATRA). Patients with APL are susceptible to DIC and subsequent bleeding events. Prompt ATRA administration is crucial in preventing hemorrhagic events. High WBC counts, prolonged PT, and APTT are associated with clinical bleeding in our series. PT is the most accurate parameter in predicting bleeding. Based on these findings, supportive care should be directed toward correction of coagulopathy to prevent bleeding complications and fresh frozen plasma appears to be indicated for coagulopathy associated with APL.

Disseminated Intravascular Coagulation (DIC) at an Early Phase of Trauma Continuously Proceeds to DIC at a Late Phase of Trauma

The data from 254 patients with severe trauma were retrospectively analyzed. The patients were subdivided into disseminated intravascular coagulation (DIC) and non-DIC. There was a difference in the incidence of the continuous progression from the early to late phase of DIC between the patients with and without DIC on day 0. While 2 of 9 patients who newly developed late-phase DIC were complicated with sepsis, none of the 32 patients who showed a continuous progression of DIC from the early to late phase of trauma developed sepsis. The DIC and Sequential Organ Failure Assessment scores on day 0 were independent factors that predicted the continuous progression of the DIC from the early to late phase of trauma. Trauma itself, but not sepsis, contributes to the continuous progression of DIC from the early to late phase of trauma. The severity of DIC and organ dysfunction are involved in the pathogenesis of this continuous progression.

Accuracy of Platelet Counting by Automated Hematologic Analyzers in Acute Leukemia and Disseminated Intravascular Coagulation

Platelet counting in patients with acute leukemia or disseminated intravascular coagulation (DIC) may have a risk for erroneous counts owing to the presence of nonplatelet particles or platelet activation. We evaluated automated platelet counting methods using the Abbott Cell-Dyn Sapphire (Abbott Diagnostics, Santa Clara, CA), Sysmex XE-2100 (Sysmex, Kobe, Japan), ADVIA 2120 (Siemens Diagnostics, Tarrytown, NY), and Beckman Coulter LH 750 (Beckman Coulter, Miami, FL) compared with the international reference method (IRM). Automated platelet counting methods were inaccurate compared with the IRM, without evidence of interfering nonplatelet particles. It is interesting that platelet activation markers were associated with DIC severity and erroneous platelet counting, suggesting that platelet activation is a potential source of inaccuracy. Furthermore, the artifactual in vitro platelet activation induced a high degree of intermethod variation in platelet counts. The inaccuracy of automated platelet counts increased the risk for misdiagnosis of DIC. More attention needs to be given to the accuracy of platelet counts, especially in clinical conditions with florid platelet activation.