Protein C and protein S deficiencies may be related to survival among hemodialysis patients.

BACKGROUND: Thrombophilia due to protein C (PC) and protein S (PS) deficiencies is highly prevalent among patients with stage 5 chronic kidney disease and is reported to arise due to extracorporeal circulation during hemodialysis (HD). This study aimed to evaluate the relationship between HD treatment and thrombophilia. METHODS: A total of 114 Japanese patients on maintenance HD (62 men, 52 women) were followed during 2008-2011. Their survival rates were compared against the duration of HD. Prior to each HD, coagulation/fibrinolysis parameters and PC and PS activities were measured using standard techniques. The patients were divided into two groups: Group 1, with PC and/or PS deficiencies (n = 32), and Group 2, without PC and PS deficiencies (n = 82). The influence of such deficiencies and duration of dialysis on survival was examined. Time-to-event analysis was applied using Kaplan-Meier estimates, and the log-rank test was proposed to test the equivalence of relative survival data. Hazard ratios and 95% confidence intervals (CI) were calculated. RESULTS: Of the 114 patients, 37 died (Group 1, 22; Group 2, 15). The hazard ratio (95% CI) was higher (p = 0.004) in Group 1 than Group 2. Gene analyses of PC and PS were performed in 14 patients from Group 1. No mutations in either protein were observed. We analyzed the causes of death in both groups; however, the estimated thrombophilia-related incidence of death could not be determined due to small sample size of HD patients. CONCLUSIONS: Our results suggest that PC and PS deficiencies may be related to survival in HD patients. However, this finding warrants additional research.

Cerebral Sinus Venous Thrombosis and Prothrombotic Risk Factors in Children: A Single-Center Experience From Turkey.

BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is a rare cerebrovascular disease that may be life-threatening, especially in children. OBJECTIVE: The purpose of this study was to assess the clinical presentation, radiologic imaging, underlying conditions, treatment, and outcomes of children with CSVT. PATIENTS AND METHODS: In total, 23 consecutive children aged between 1 month to 18 years with CSVT, who were followed-up in Erciyes University Children's Hospital, were retrospectively enrolled in the study from January 2000 to December 2016. RESULTS: The median age of the 23 children (13 female patients, 10 male patients) at initial diagnosis was 60 months (1 to 204 mo). The most common clinical manifestation was headache/irritability (n=9). The most common site of the CSVT was the transverse sinus (n=16). The most common prothrombotic risk factor was protein C deficiency (n=4). Underlying risk factors were detected in 15 patients. Genetic risk factors such as protein C deficiency, infections, trauma, malignancies, autoimmune hemolytic anemia, neurometabolic disorders, asphyxia, and cardiac malformations were common risk factors. Six children died. Multiple sinus involvement and parenchymal hemorrhages were seen in 4 and in 3 of the 6 children who died, respectively. CONCLUSIONS: Protein C deficiency seemed to be relatively high in the presented children. Multiple sinus involvement and additional parenchymal hemorrhages represent poor prognostic features.

[Sepsis-associated Purpura Fulminans International Registry--Europe (SAPFIRE)]. / Ein europäisches Register für sepsisassoziierte Purpura fulminans (SAPFIRE).

BACKGROUND: Purpura fulminans is a rare life-threatening condition which is characterized by disseminated thrombosis in dermal and systemic microcirculation, cutaneous hemorrhages with progressing necrosis and multiple organ failure. The underlying pathogenesis is based on the disruption of the intrinsic anticoagulation cascade, with protein C deficiency being considered the leading factor in this process. In the majority of cases, the condition emerges as consumptive coagulopathy associated with severe sepsis. OBJECTIVES: Epidemiological data on sepsis-associated purpura fulminans (SAPF) are scarce and evidence-based treatment guidelines have not been established yet. While restoration of the balance in the coagulation cascade is a declared therapeutic goal, evaluations of the efficacy of different therapeutic approaches in randomized clinical trials are still lacking. The causal role of individual microbial pathogens also requires comprehensive evaluation. METHODS: A prospective multicenter Sepsis-Associated Purpura Fulminans International Registry-Europe (SAPFIRE) will be established in the first quarter of 2015. For the first time, participating centers will systematically collect information on etiology, clinical course, biomarkers, treatment, morbidity, and mortality of SAPF. RESULTS: The SAPFIRE data will be periodically evaluated and disseminated. Retrospective analysis of each center's data and regular access to aggregated information collected by other centers will enable the participants to monitor and update care quality standards.

The influence of thrombophilia on the long-term survival of patients with a history of venous thromboembolism.

Data on the long-term survival following venous thromboembolism (VTE) are rare, and the influence of thrombophilia has not been evaluated thus far. Our aim was to assess thrombophilia-parameters as predictors for long-term survival of patients with VTE. Overall, 1,905 out-patients (99 with antithrombin-, protein C or protein S deficiency, 517 with factor V Leiden, 381 with elevated factor VIII and 160 with elevated homocysteine levels, of these 202 had a combination and 961 had none of these risk factors) were included in the study between September 1, 1994 and December 31, 2007. Retrospective survival analysis showed that a total of 78 patients (4.1%) had died during the analysis period, among those four of definite or possible pulmonary embolism and four of bleeding. In multivariable analysis including age and sex an association with increased mortality was found for hyperhomocysteinemia (hazard ratio 2.0 [1.1.-3.5]) whereas this was not the case for all other investigated parameters. We conclude that the classical hereditary thrombophilia risk factors did not have an impact on the long-term survival of patients with a history of VTE. Thus our study supports the current concept that thrombophilia should not be a determinant for decision on long term anticoagulation. However, hyperhomocysteinaemia, known as a risk factor for recurrent VTE and arterial disease, might impact survival.

Drotrecogin alfa (activated) in adults with septic shock.

BACKGROUND: There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock. METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 µg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization. RESULTS: At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81). CONCLUSIONS: DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.).