Failure of the anticoagulant therapy and psychological distress : Still far from a bridge

Background: The procoagulant stress response reflects part of a beneficial adaptation of the organism to environmental threats, but a protracted procoagulant state generates a thrombotic risk. Atrial fibrillation (AF) is the most common arrhythmia in the general population. Patients with AF have a higher risk of thromboembolic events and stroke, therefore they are treated with long-term oral anticoagulant (OAC) therapy. The aim of this study is to evaluate if there is any association between psychological distress and clinically unexplained variations of the International Normalized Ratio (INR), that is the index used to monitor both thromboembolic and bleeding risk in the case of patients under OAC therapy. Methods: Fifty-eight patients (men = 27; women = 31; mean age = 74.98) were recruited. The sample was divided according to the recognition (or not) of the reason why the INR was subtherapeutic ( < 2) and classified as "Known Reasons" (KR = 32.8%) and "Unknown Reasons" (UR = 67.2%). Psychological assessment included the following dimensions: symptoms of anxiety and depression, perceived stress, emotional regulation strategies, and alexithymia. Results: Considering Mann-Whitney test results, no significant difference was found in the scores of anxiety, depression, stress, and emotional regulation strategies. With regard to alexithymia, UR patients are characterized by a moderate tendency to an outward-oriented thinking (r = 0.25). Conclusion: A clear role for the detected psychological factors in determining abnormal INR range in patients under OAC therapy could not be found. Further studies are needed to support our findings, if possible exploring factors other than psychological distress and the related emotion regulation strategies

ProCMD: a database and 3D web resource for protein C mutants

Background: Activated Protein C (ProC) is an anticoagulant plasma serine protease which also plays an important role in controlling inflammation and cell proliferation. Several mutations of the gene are associated with phenotypic functional deficiency of protein C, and with the risk of developing venous thrombosis. Structure prediction and computational analysis of the mutants have proven to be a valuable aid in understanding the molecular aspects of clinical thrombophilia. Results: We have built a specialized relational database and a search tool for natural mutants of protein C. It contains 195 entries that include 182 missense and 13 stop mutations. A menu driven search engine allows the user to retrieve stored information for each variant, that include genetic as well as structural data and a multiple alignment highlighting the substituted position. Molecular models of variants can be visualized with interactive tools; PDB coordinates of the models are also available for further analysis. Furthermore, an automatic modelling interface allows the user to generate multiple alignments and 3D models of new variants. Conclusion: ProCMD is an up-to-date interactive mutant database that integrates phenotypical descriptions with functional and structural data obtained by computational approaches. It will be useful in the research and clinical fields to help elucidate the chain of events leading from a molecular defect to the related disease. It is available for academics at the URL http://www.itb.cnr.it/procmd/

Levels of Soluble Endothelial Protein C Receptor Are Associated with CD4+ Changes in Maraviroc-Treated HIV-Infected Patients

BACKGROUND: Inflammation is a key feature of HIV infection and is correlated with long-term negative cardiovascular outcomes. Therapy-induced increases in CD4(+) cell counts can control inflammation, as shown by decreases of coagulation and inflammation markers during efficacious therapy. Maraviroc, a CCR5-antagonist, has resulted in larger increases in CD4(+) counts both in naïve and experienced subjects compared to traditional antiretroviral therapy. OBJECTIVES AND METHODS: To examine if a member of the protein C anticoagulant and anti-inflammatory pathway, and marker of coagulation and inflammation, the soluble endothelial protein C receptor, is modified by infection and therapy-related variables in patients treated with Maraviroc. Endothelial protein C receptor, together with other established markers of inflammation and coagulation (CRP, IL-6, D-dimer and soluble thrombomodulin) was studied in 43 patients on traditional antiretroviral therapy and in 45 on Maraviroc during 48 weeks of follow-up. RESULTS: Soluble endothelial protein C receptor was the only marker that could discriminate at least partially between patients with a good response to Maraviroc and patients who did not respond with an adequate increase in CD4(+) cell counts (more than 500 cells/µL by week 48). CONCLUSIONS: Elevated levels of soluble endothelial protein C receptor, a sensitive marker of endothelial damage, indicated a low level of inflammation and coagulation activation in Maraviroc treated patients not picked up by other widely used markers. Persistent elevated levels of this marker at 48 weeks from beginning of treatment with Maraviroc were related to a poor increase in CD4(+) cells