Added value of the DIC score and of D-dimer to predict outcome after successfully resuscitated out-of-hospital cardiac arrest.

BACKGROUND: Recent Korean data suggest a high prevalence of overt disseminated intravascular coagulation (DIC) and a good predictive performance of the ISTH DIC score in successfully resuscitated out-of-hospital cardiac arrest. OBJECTIVES: We hypothesised that in a European cohort of resuscitated out-of-hospital cardiac arrest patients the prevalence of DIC is substantially lower. Furthermore, the determination of D-dimer levels at admission, but not the DIC score, could improve mortality prediction above traditional predictors. PATIENTS/METHODS: Data were extracted from a prospective cardiac arrest registry including patients admitted between 2006 and 2015, who achieved return of spontaneous circulation and had parameters for DIC score calculation available. The primary outcome was the prevalence of overt DIC at admission. Secondary outcomes included the association of overt DIC with 30-day mortality and the contribution of the DIC score and D-dimer levels to 30-day mortality prediction using logistic regression. Three stepwise models were evaluated by receiver-operating-characteristic analysis. RESULTS: Out of 1179 patients 388 were included in the study. Overt DIC was present in 8% of patients and associated with substantial 30-day mortality (83% vs. 39%). The AUC for model 1, including traditional mortality predictors, was 0.83. The inclusion of D-dimer levels significantly improved prognostication above traditional predictors (model 3, AUC 0.89), whereas the inclusion of the DIC Score had no effect on mortality prediction (model 2, AUC 0.83). CONCLUSION: Overt DIC was rare in a European cohort of out-of-hospital cardiac arrest patients. D-dimer levels improved 30-day mortality prediction and provided added value to assess early mortality risk after successful resuscitation.

Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients.

Essentials Neutrophil extracellular traps (NETs) might play a role in cancer-related coagulopathy. We determined NET biomarkers and followed cancer patients for venous thromboembolism (VTE). We found a constant association with VTE for citrullinated histone H3. Biomarkers of NET formation could reflect a novel pathomechanism of cancer-related VTE. SUMMARY: Background Neutrophil extracellular traps (NETs) are decondensed chromatin fibers that might play a role in the prothrombotic state of cancer patients. Objectives To investigate whether the levels of citrullinated histone H3 (H3Cit), a biomarker for NET formation, cell-free DNA (cfDNA) and nucleosomes predict venous thromboembolism (VTE) in cancer patients. Patients/Methods Nine-hundred and forty-six patients with newly diagnosed cancer or progression after remission were enrolled in this prospective observational cohort study. H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients were followed for 2 years. VTE occurred in 89 patients; the cumulative 3-month, 6-month, 12-month and 24-month incidence rates of VTE were 3.7%, 6.0%, 8.1%, and 10.0%, respectively. Results Patients with elevated H3Cit levels (> 75th percentile of its distribution, n = 236) experienced a higher cumulative incidence of VTE (2-year risk of 14.5%) than patients with levels below this cut-off (2-year risk of 8.5%, n = 710). In a competing-risk regression analysis, a 100 ng mL-1 increase in H3Cit level was associated with a 13% relative increase in VTE risk (subdistribution hazard ratio [SHR] 1.13, 95% confidence interval [CI] 1.04-1.22). This association remained after adjustment for high VTE risk and very high VTE risk tumor sites, D-dimer level, and soluble P-selectin level (SHR 1.13, 95% CI 1.04-1.22). The association of elevated nucleosome and cfDNA levels with VTE risk was time-dependent, with associations with a higher risk of VTE only during the first 3-6 months. Conclusion These data suggest that biomarkers of NET formation are associated with the occurrence of VTE in cancer patients, indicating a role of NETs in the pathogenesis of cancer-associated thrombosis.