COAGULOPATHY AND CORONAVIRUS DISEASE 2019

Thrombosis within the vascular system in relation to inflammation and stasis is potentially associated with poor prognosis in patients with heart failure. The aim of this study was to clarify the association between disseminated intravascular coagulation (DIC) score, a scoring system for microvascular thrombosis and multiple organ dysfunction, and outcome in hospitalized patients with acute heart failure (AHF). We retrospectively evaluated 160 AHF patients referred to a cardiac intensive care unit who had their DIC score measured according to the Japanese Association for Acute Medicine (JAAM) DIC scoring system on admission. Platelet count, prothrombin time ratio, fibrin/fibrinogen degradation products, and the criteria for systemic inflammatory response syndrome were measured. Using the JAAM DIC score, the prevalence of DIC (score ≥4) in AHF patients was 5.0% (8 of 160 patients). The risk of death for patients grouped according to the DIC score was 27.8%, 46.2%, and 87.5% for DIC scores 0-1, 2-3, and ≥4, respectively (median follow-up 460 days). In multivariate analysis adjusted for various markers of disease severity, a DIC score ≥2 was independently associated with a higher all-cause death rate (adjusted hazard ratio 2.45; P = 0.005) and a higher rate of reaching the combined endpoint of all-cause death and readmission for AHF (adjusted hazard ratio 2.10; P = 0.006) after admission for AHF. In an intensive care setting, measurement of DIC score on admission could help risk stratification in hospitalized patients with AHF.

Extravascular coagulation and fibrin deposition coupled with perturbations of intravascular coagulation occurs in association with acute respiratory distress syndrome (ARDS). To evaluate the pathogenetic role of an extrinsic coagulation pathway in the intravascular coagulation of ARDS patients and to explore the time course of the changes of tissue factor levels, platelet counts, and disseminated intravascular coagulation (DIC), we performed a prospective cohort study. The study subjects consisted of 113 patients: 27 patients with ARDS, 31 patients at risk for but not developing the syndrome, and 55 patients without ARDS. According to the underlying disease, the patients were further subdivided into two groups: patients with trauma (n = 76) and patients with sepsis (n = 37). Ten normal healthy volunteers served as control subjects. Plasma tissue factor antigen (tissue factor) levels and platelet counts were measured on the day of admission and on days 1 through 4 after admission. Simultaneously, the DIC scores were determined. The values of tissue factor in the patients with ARDS were significantly more elevated than those measured in the other two groups (p < 0.001) and control subjects (p < 0.001) on the day of admission. The values continued to be markedly high up to day 4 of admission. On the day of admission, the platelet counts in the ARDS patients showed significantly lower values (p < 0.05) than those in the other two groups. The incidence of DIC and the DIC scores in ARDS patients were significantly higher than those in the other two groups. The tissue factor levels (r(s) = 0.428, p < 0.0001) and DIC scores (r(s) = 0.357, p < 0.0002) correlated significantly with Lung Injury Score. When the patients were subdivided into two subgroups, i.e., trauma and sepsis, some differences of the tissue factor levels were noted between the two groups. We demonstrated that tissue-factor dependent coagulation pathway of plasma is extensively activated in patients with ARDS, followed by intravascular coagulation and platelet consumption. We further provide precise information on the time course of tissue factor levels and DIC in patients with ARDS and those at risk for developing this syndrome.

Biomarkers of Endothelial Function in Sepsis-Associated Disseminated Intravascular Coagulation

Biomarkers of Platelet Activation and Their Prognostic Value in Patients in Sepsis Associated Coagulopathy

ObjectiveTo determine whether treatment with recombinant human thrombomodulin (rhTM) increases survival among patients with severe septic-induced disseminated intravascular coagulation (DIC).DesignSingle-centre, open-label, randomised controlled trial.SettingSingle tertiary hospital.Participant92 patients with severe septic-induced...

Prospective comparison of new Japanese Association for Acute Medicine (JAAM) DIC and International Society of Thrombosis and Hemostasis (ISTH) DIC score in critically ill septic patients

Recombinant human soluble thrombomodulin (rTM) was approved recently and has been used for treatment of disseminated intravascular coagulation (DIC). The aim of the present study was to evaluate the efficacy of rTM for DIC. The data of 53 inpatients with sepsis-induced DIC were retrospectively analyzed. Patients were classified into the rTM treatment group (n=25) and conventional treatment group (rTM not used) was the control group (n=28). Diagnosis of DIC was made according to the criteria for acute DIC of the Japan Association of Acute Medicine. Platelet count, prothrombin time-international normalized ratio, levels of fibrin/fibrinogen degradation products (FDP), C-reactive protein and DIC scores were measured on days 0, 3 and 7. Furthermore, the DIC resolution rate was assessed on days 3 and 7. Prior to treatment, DIC scores were 5.0±1.0 in the rTM group and 5.9±1.3 in the control group (P<0.05). Significant intra-group improvements were observed in all the parameters, except for FDP in the two groups. Significant improvements were observed in the DIC scores in the rTM group (Δ2.0±1.9 vs. Δ1.5±1.9, P=0.001). Therefore, the results suggest that rTM would be a useful medicine for treatment of DIC in the gastroenterology field.

Recent studies questioned "classical" concepts in trauma care, including whether disseminated intravascular coagulation (DIC) occurs in trauma. The knowledge on trauma DIC is limited to few studies built on diagnosing DIC with laboratory-based scores. This study explores whether DIC diagnosed by the well-established ISTH (International Society for Thrombosis and Hemostasis) score is corroborated by anatomopathologic findings. Prospective observational cohort study of severely injured (ISS ≥ 16) patients. DIC was diagnosed by the ISTH score throughout the first 24 hours after trauma. All organs surgically removed within 24 hours of trauma were reviewed by two independent pathologists. All autopsy reports were reviewed. Of 423 patients enrolled, ∼11% had "overt DIC" and 85% had "suggestive of non-overt DIC" scores throughout the 24 hours after trauma. "Overt DIC" patients had higher mortality and worse bleeding, receiving more blood and plasma transfusions. One hundred and sixteen patients underwent surgery within 24 hours of trauma, and all 40 excised organs were reviewed by two pathologists. Twenty-seven autopsies reports were reviewed. No anatomopathologic evidence of DIC was identified in the first 24 hours, even after additional histochemical staining. d-dimer was universally elevated after trauma. Common DIC features: platelet count, fibrinogen, clotting time, and factor VIII drop were mostly absent. d-dimer has a disproportional participation in trauma DIC scores. Within 24 hours of trauma, most severely injured patients have DIC scores "suggestive for" or of "overt DIC" but no anatomopathologic evidence of DIC. Considering pathologic findings as the gold standard diagnosis, then DIC is exceptionally uncommon and the ISTH score should not be used for trauma.

Background Streptococcal toxic shock syndrome (STSS) is a rapidly progressive infection, with potentially rapid patient deterioration in a very short period. We experienced a rare case of STSS during anticancer chemotherapy, and we continuously measured presepsin (P-SEP) and evaluated its usefulness. Case Presentation A 60-year-old woman with pulmonary metastasis from cervical cancer began anticancer chemotherapy. A fever of >40°C and right lower leg swelling developed on day 3. Symptoms worsened despite cefmetazole treatment (1.0 g/day). Blood culture was performed without suspecting STSS. On day 5, symptoms worsened and acute disseminated intravascular coagulation (DIC) and sequential organ failure assessment (SOFA) scores increased. C-reactive protein (CRP) increased from 28.8 mg/dl to 35.5 mg/dl and P-SEP also increased from 1,635 to 2,350 pg/mL. STSS was suspected due to the rapid progression of brown discoloration of the entire right lower leg. Ceftriaxone 2 g/day and clindamycin 1,200 mg/day were begun. On the evening of day 5, blood culture revealed rapidly progressive group A streptococci. After that, symptoms improved rapidly with treatment, and SOFA and DIC scores also decreased. While CRP remained at about 0.5 mg/dl, P-SEP remained slightly elevated at about 400 pg/mL. A residual infection focus was suspected. Contrast-enhanced computed tomography (CT) revealed a capsule-enclosed abscess in the right lower leg soleus muscle on day 32. Debridement was performed and antibiotics were continued until P-SEP was 88 pg/mL. CT confirmed the disappearance of the abscess. Conclusion Prompt diagnosis by blood culture and a sufficiently early, appropriate change in antibiotic therapy led to successful recovery from STSS during anticancer chemotherapy without lower limb amputation. P-SEP was useful in assessment of the residual infection focus and suspending treatments.

Although the presence of decreased plasma fibrinogen has been regarded as an indicator of ongoing disseminated intravascular coagulation (DIC), fibrinogen, which is one of the acute phase reactants, is often increased in the patients with DIC. We investigated the diagnostic and prognostic utility of a new parameter [the fibrinogen/C-reactive protein (CRP) ratio] for predicting DIC in 1,056 patients with suspected DIC and who also had underlying disorders associated with DIC. Among the 535 patients with overt DIC, 46 patients (8.6%) showed low plasma fibrinogen (<100 mg/dl), suggesting that the plasma fibrinogen level is not a sensitive marker for DIC. There was a strong correlation between the increased DIC scores and increased number of patients with low (<104) fibrinogen/CRP ratios. Among the three groups with different serum fibrinogen/fibrin degradation product levels, the fibrinogen/CRP ratio showed a higher difference than did the fibrinogen level. The DIC score was highly correlated with the 28-day mortality and the number of patients with low fibrinogen/CRP ratios. The odds ratio (the relative risk of 28-day mortality) of the low fibrinogen/CRP ratio was 6.15, while the odds ratio of the low fibrinogen level was 2.13. The area under the receiver-operating characteristic curve of the fibrinogen/CRP ratio, when this was used for predicting mortality, showed significantly better discriminative power than did that of the fibrinogen level. This study demonstrates that the fibrinogen/CRP ratio may provide more discriminating power for identifying the patients with active coagulation consumption, and the fibrinogen/CRP ratio has a good predictive value concerning the 28-day mortality in the patients suspected of having DIC. The results of our study suggest that replacement of fibrinogen by the fibrinogen/CRP ratio for calculating the DIC score may lead to enhance diagnostic and prognostic power for DIC.

Changes of hemostatic markers in 226 patients with disseminated intravascular coagulation (DIC) and hematopoietic disorders were examined after treatment of DIC. The changes in prothrombin time (PT) ratio, fibrinogen, fibrin and fibrinogen degradation products (FDP), antithrombin, and protein C, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), and soluble fibrin monomer complex (SFMC) in all patients with DIC were significant during the clinical course of DIC, but those of D-dimer, thrombomodulin (TM), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) were not. Activated partial thromboplastin time (aPTT) and PT were significantly longer in the poor response group than in good response group. Plasma levels of FDP, TAT, PPIC, SFMC, TM, and DIC score were significantly higher in poor response group than in good response. Protein C and antithrombin levels were significantly lower in poor response group than in good response group. The changes of PT ratio, fibrinogen, FDP, DIC score, antithrombin, plasmin inhibitor, and protein C were significant in the good response group, but these levels were not significant in the poor response group. The changes in plasma TAT and SFMC levels were significant in the good response group but were not in poor response group. The changes in D-dimer, TM, TF, or TFPI were not significant in both groups. These findings suggest that anticoagulant agents should be administered at levels below TAT 40 ng/mL or SFMC 300 microgram/mL in patients with DIC and hematopoietic disorders.

Acute necrotizing encephalopathy (ANE) is a para-infectious neurological disorder with high mortality in children. There are limited studies evaluating predictive factors for mortality in ANE patients. This study aims to investigate the predictive value of independent risk factors and the ANE Severity Score (ANE-SS), combined with ferritin levels and Disseminated Intravascular Coagulation (DIC) scores, in assessing mortality risk in children with ANE. We conducted a retrospective study of children with ANE in the pediatric intensive care unit of Beijing Children's Hospital from January 2016 to May 2024. The patients were divided into survival and non-survival groups, and clinical data were collected within 12 hours after admission. The predictive value of clinical indicators and a joint model for mortality in ANE patients was evaluated using receiver operating characteristic (ROC) curve analysis. Of 56 patients enrolled, the overall mortality rate was 51.8%. In the non-survival group, the levels of ANE-SS, DIC scores, ferritin, procalcitonin, interleukin-6, activated partial thromboplastin time, prothrombin time, D-dimer, and cerebrospinal fluid protein at admission were significantly higher than those in the survival group. Multivariate analysis identified ferritin, ANE-SS, and DIC scores as independent risk factors for mortality. Ferritin exhibited an area under the curve (AUC) of 0.827, with sensitivity of 84.6% and specificity of 87.5%, which were superior to those of ANE-SS (AUC 0.782, sensitivity 75.9%, specificity 66.7%) and the DIC scores (AUC 0.773, sensitivity 60.7%, specificity 81.5%). In combined analysis, ANE-SS, ferritin, and DIC scores demonstrated the strongest predictive performance, with an AUC of 0.99 (95% CI: 0.965-1.000), sensitivity and specificity of 92.3% and 100%, respectively. This study indicates that the combination of ANE-SS with ferritin and DIC scores provides a superior predictive value for 28-day mortality in ANE patients.

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

Objectives: Liver rupture and hematoma are rare life-threatening complications of pregnancy. The aims of the current study are to: (1) characterize in a population-based study all cases of liver hematoma and/or rupture; and (2) validate the utility of the International Society on Thrombosis and Haemostasis (ISTH) modified pregnancy specific disseminated intravascular coagulation (DIC) score in those cases. Study design: A retrospective cohort study including all patients with liver subcapsular hematoma or rupture between the years 1996 and 2012 was conducted. Information on maternal characteristics, clinical presentation, diagnostic studies, therapeutic modalities, as well as maternal and fetal outcomes was collected. The pregnancy-specific modified ISTH DIC scores were calculated from admission to discharge, a score >26 is suggestive of DIC. Results: Out of 175,000 births in our database, seven patients were identified with liver rupture or subcapsular hematoma, representing a prevalence of 4:100,000 deliveries. Of those, six had liver rupture and one had subcapsular liver hematoma. One patient died of hemorrhagic shock. Four patients underwent surgical liver packing and one also underwent hepatic artery ligation. Four out of seven patients were diagnosed during the immediate postpartum period with severe features of preeclampsia or with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Modified ISTH pregnancy-specific DIC scores were calculated for five out of seven patients, and three (60%) had a score higher than 26. Patients with higher scores received more blood product transfusions, had longer hospitalizations, and their neonates had lower 1 and 5 minutes Apgar scores. Conclusions: Elevated pregnancy-specific modified ISTH DIC score (>26) in patients with liver hematoma or rupture was associated with adverse maternal and neonatal outcomes and appeared to perform well in distinguishing high and low-risk cases. Postpartum preeclampsia may be associated with severe features and a more complicated disease course.

We evaluated the score for disseminated intravascular coagulation (DIC) recently published by the International Society for Thrombosis and Haemostasis (ISTH) in a well-defined series of sepsis patients. Thirty-two patients suffering from severe sepsis and eight patients with septic shock were evaluated following the ISTH DIC score. Fibrin monomer and D-dimer were chosen as fibrin-related markers (FRM), respectively. DIC scores for nonsurvivors (n = 13) as well as for septic shock patients were higher (P < 0.04) compared with survivors and patients with severe sepsis, respectively. Using fibrin monomer and D-dimer, 30 and 25% of patients suffered from overt DIC. Overt DIC was associated with significantly elevated thrombin-antithrombin complexes and plasminogen activator inhibitor type-1 levels as well as with significantly lower factor VII clotting activity. Patients with overt DIC had a significantly higher risk of death and of developing septic shock. Since more than 95% of the sepsis patients had elevated FRM, the DIC score was strongly dependent on prolongation of the prothrombin time and platelet counts. The ISTH DIC score is useful to identify patients with coagulation activation, predicting fatality and disease severity. It mainly depends on the prolongation of the prothrombin time and platelet counts.