Different Profiles of Cytokines, Chemokines and Coagulation Mediators Associated with Severity in Brazilian Patients Infected with Dengue Virus.

The incidence of dengue in Latin America has increased dramatically during the last decade. Understanding the pathogenic mechanisms in dengue is crucial for the identification of biomarkers for the triage of patients. We aimed to characterize the profile of cytokines (IFN-γ, TNF-α, IL-1ß, IL-6, IL-18 and IL-10), chemokines (CXCL8/IL-8, CCL2/MCP-1 and CXCL10/IP-10) and coagulation mediators (Fibrinogen, D-dimer, Tissue factor-TF, Tissue factor pathway inhibitor-TFPI and Thrombomodulin) during the dengue-4 epidemic in Brazil. Laboratory-confirmed dengue cases had higher levels of TNF-α (p < 0.001), IL-6 (p = 0.005), IL-10 (p < 0.001), IL-18 (p = 0.001), CXCL8/IL-8 (p < 0.001), CCL2/MCP-1 (p < 0.001), CXCL10/IP-10 (p = 0.001), fibrinogen (p = 0.037), D-dimer (p = 0.01) and TFPI (p = 0.042) and lower levels of TF (p = 0.042) compared to healthy controls. A principal component analysis (PCA) distinguished between two profiles of mediators of inflammation and coagulation: protective (TNF-α, IL-1ß and CXCL8/IL-8) and pathological (IL-6, TF and TFPI). Lastly, multivariate logistic regression analysis identified high aspartate aminotransferase-to-platelet ratio index (APRI) as independent risk factors associated with severity (adjusted OR: 1.33; 95% CI 1.03-1.71; p = 0.027), the area under the receiver operating characteristics curve (AUC) was 0.775 (95% CI 0.681-0.869) and an optimal cutoff value was 1.4 (sensitivity: 76%; specificity: 79%), so it could be a useful marker for the triage of patients attending primary care centers.

Pharmacist Presence Decreases Time to Prothrombin Complex Concentrate in Emergency Department Patients with Life-Threatening Bleeding and Urgent Procedures.

BACKGROUND: Reversal of anticoagulation with four-factor prothrombin complex concentrate (4F-PCC) is critical, yet the optimal timing to 4F-PCC administration and whether quicker administration improves hemostasis remains unknown. OBJECTIVE: The objective of this study was to determine if pharmacist presence is predictive of faster time to 4F-PCC. METHODS: This retrospective cohort study included patients receiving 4F-PCC for life-threatening bleeding or urgent procedure in the emergency department (ED) from 2014 to 2018. Patients with pharmacists at bedside (PharmD group) were compared with physician teams alone (control group). The primary outcome was time from ED presentation to 4F-PCC administration. RESULTS: Of 252 patients evaluated, 116 patients (46%) were included (n = 50 PharmD group; n = 66 control group). Most patients presented on warfarin (68.1%), and of the life-threatening bleeds (94%), intracranial hemorrhage was most common (67.2%). The median time to 4F-PCC administration was significantly shorter in the PharmD group (66.5 vs. 206.5 min, p < 0.001). Pharmacist at bedside was the only factor independently associated with reduction in time to 4F-PCC (ß coefficient -163.5 min, 95% confidence interval -249.4 to -77.7). Although there was no difference in hemostasis or mortality, patients in the PharmD group had a shorter intensive care unit length of stay (LOS) (2 vs. 5 days, p < 0.01) and hospital LOS (5.5 vs. 8 days, p = 0.02). CONCLUSION: A pharmacist at the bedside of patients who present to the ED with life-threatening bleeding or need for emergent procedure decreased time to 4F-PCC administration by 140 min, even after accounting for confounders. Faster time to 4F-PCC was associated with significantly shorter intensive care unit and hospital LOS.

Comparison of the safety and efficacy between 3-factor and 4-factor prothrombin complex concentrates for the reversal of warfarin.

PURPOSE: Prior to the Food and Drug Administration approval of 4-factor prothrombin complex concentrate (4F-PCC), only 3-factor PCC (3F-PCC) products were available in the US. There is limited data comparing the safety and efficacy of 3F-PCC versus 4F-PCC. The purpose of our study, therefore, was to compare the safety and efficacy profiles of 3F-PCC versus 4F-PCC for the emergent reversal of warfarin. METHODS: A single-center, retrospective cohort analysis compared patients who received 3F-PCC or 4F-PCC for the emergent reversal of warfarin due to life-threating bleeding from January 2013 to September 2015. The primary objective of this study was the percentage of patients whose international normalized ratio (INR) reversed to ≤1.5 within 8h of PCC administration. The secondary safety objective was incidence of thromboembolic events at 7days post PCC. RESULTS: A total of 137 patients were included. The median baseline INR was 3.15 in the 3F-PCC group and 3.1 in the 4F-PCC group. The median post-PCC INR was 1.4 in the 3F-PCC group and 1.3 in the 4F-PCC group. INR ≤1.5 was achieved in 45/58 (78%) patients in the 3F-PCC group and 46/58 (79%) patients in the 4F-PCC group (p=0.61). The thromboembolic event rate between the two groups at 7days was similar, 4/68 (5.9%) for 3F-PCC versus 4/69 (5.8%) for 4F-PCC (p=1.0). CONCLUSIONS: There was no significant difference in the percentage of patients who achieved an INR ≤1.5 between the 3F-PCC and 4F-PCC groups for emergent reversal of warfarin.

Natural coagulation inhibitory proteins and activated protein C resistance in Turkish patients with inflammatory bowel disease.

BACKGROUND/AIMS: Thromboembolic events are a rare but significant complication of inflammatory bowel disease. The aim of this study was to investigate the level of natural coagulation inhibitors and activated protein C resistance in Turkish patients with inflammatory bowel disease. METHODS: Fifty patients (29 male, 21 female) without venous thrombosis history and 37 healthy controls were included in the study. Erythrocyte sedimentation rate, C-reactive protein, thrombocyte count, prothrombin time, activated partial thromboplastin time, fibrinogen concentration, von Willebrand factor antigen, factor VIII activity, activated protein C resistance, functional levels of antithrombin III, protein C and protein S were measured. Patients and controls with activated protein C resistance were further studied using a polymerase chain reaction assay for factor V Leiden mutation. RESULTS: There was no significant difference between patients and the controls in terms of antithrombin III, protein C, protein S, factor (F) VIII and Willebrand factor levels. The mean thrombocyte counts, fibrinogen levels, and Willebrand factor levels were found to be significantly higher in patients who were in the active period of the disease than in controls and patients in remission. No significant difference was observed in those showing activated protein C resistance and factor V Leiden mutation between patients and controls. CONCLUSIONS: The presence of inherited thrombophilic defects, in particular activated protein C resistance and natural coagulation inhibitor deficiency, is uncommon in Turkish patients with inflammatory bowel disease in both active and remission periods. As a result, a controlled study in inflammatory bowel disease patients with thrombosis history is recommended.

Normal clotting.

OBJECTIVE: To review the normal coagulation process and the mechanisms that lead to abnormal clotting. DATA SOURCES: Primary and tertiary literature and the authors' clinical experience. CONCLUSION: The process of coagulation is complex and can be easily misunderstood. It is important to be familiar with normal coagulation before one can comprehend the coagulopathies associated with malignancies. IMPLICATIONS FOR NURSING PRACTICE: A thorough understanding of the coagulation process is a critical prerequisite to caring for patients with clotting disorders. Once the normal clotting process is understood, the abnormal becomes easier to recognize and the cancer-associated dysfunctions more readily identified.