Recombinant human activated protein C resets thrombin generation in patients with severe sepsis – a case control study

INTRODUCTION: Recombinant human activated protein C (rhAPC) is the first drug for which a reduction of mortality in severe sepsis has been demonstrated. However, the mechanism by which this reduction in mortality is achieved is still not clearly defined. The aim of the present study was to evaluate the dynamics of the anticoagulant, anti-inflammatory and pro-fibrinolytic action of rhAPC in patients with severe sepsis, by comparing rhAPC-treated patients with case controls. METHODS: In this prospectively designed multicenter case control study, 12 patients who were participating in the ENHANCE study, an open-label study of rhAPC in severe sepsis, were treated intravenously with rhAPC at a constant rate of 24 μg/kg/h for a total of 96 h. Twelve controls with severe sepsis matching the inclusion criteria received standard therapy. The treatment was started within 48 h after the onset of organ failure. Blood samples were taken before the start of the infusion and at 4, 8, 24, 48, 96 and 168 h, for determination of parameters of coagulation and inflammation. RESULTS: Sepsis-induced thrombin generation as measured by thrombin-antithrombin complexes and prothrombin fragment F1+2, was reset by rhAPC within the first 8 h of infusion. The administration of rhAPC did not influence parameters of fibrinolysis and inflammation. There was no difference in outcome or occurrence of serious adverse events between the treatment group and the control group. CONCLUSION: Sepsis-induced thrombin generation in severely septic patients is reset by rhAPC within the first 8 h of infusion without influencing parameters of fibrinolysis and inflammation

The effects of continuous venovenous hemofiltration on coagulation activation

INTRODUCTION: The mechanism of coagulation activation during continuous venovenous hemofiltration (CVVH) has not yet been elucidated. Insight into the mechanism(s) of hemostatic activation within the extracorporeal circuit could result in a more rational approach to anticoagulation. The aim of the present study was to investigate whether CVVH using cellulose triacetate filters causes activation of the contact factor pathway or of the tissue factor pathway of coagulation. In contrast to previous studies, CVVH was performed without anticoagulation. METHODS: Ten critically ill patients were studied prior to the start of CVVH and at 5, 15 and 30 minutes and 1, 2, 3 and 6 hours thereafter, for measurement of prothrombin fragment F1+2, soluble tissue factor, activated factor VII, tissue factor pathway inhibitor, kallikrein–C1-inhibitor and activated factor XII–C1-inhibitor complexes, tissue-type plasminogen activator, plasminogen activator inhibitor type I, plasmin–antiplasmin complexes, protein C and antithrombin. RESULTS: During the study period the prothrombin fragment F1+2 levels increased significantly in four patients (defined as group A) and did not change in six patients (defined as group B). Group A also showed a rapid increase in transmembrane pressure, indicating clotting within the filter. At baseline, the activated partial thromboplastin time, the prothrombin time and the kallikrein–C1-inhibitor complex and activated factor XII–C1-inhibitor complex levels were significantly higher in group B, whereas the platelet count was significantly lower in group B. For the other studied markers the differences between group A and group B at baseline were not statistically significant. During CVVH the difference in the time course between group A and group B was not statistically significant for the markers of the tissue factor system (soluble tissue factor, activated factor VII and tissue factor pathway inhibitor), for the markers of the contact system (kallikrein–C1-inhibitor and activated factor XII–C1-inhibitor complexes) and for the markers of the fibrinolytic system (plasmin–antiplasmin complexes, tissue-type plasminogen activator and plasminogen activator inhibitor type I). CONCLUSION: Early thrombin generation was detected in a minority of intensive care patients receiving CVVH without anticoagulation. Systemic concentrations of markers of the tissue factor system and of the contact system did not change during CVVH. To elucidate the mechanism of clot formation during CVVH we suggest that future studies are needed that investigate the activation of coagulation directly at the site of the filter. Early coagulation during CVVH may be related to lower baseline levels of markers of contact activation

Effect of Puumala hantavirus infection on human umbilical vein endothelial cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release

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Identification and Characterization of Ixodes scapularis Antigens That Elicit Tick Immunity Using Yeast Surface Display

Repeated exposure of rabbits and other animals to ticks results in acquired resistance or immunity to subsequent tick bites and is partially elicited by antibodies directed against tick antigens. In this study we demonstrate the utility of a yeast surface display approach to identify tick salivary antigens that react with tick-immune serum. We constructed an Ixodes scapularis nymphal salivary gland yeast surface display library and screened the library with nymph-immune rabbit sera and identified five salivary antigens. Four of these proteins, designated P8, P19, P23 and P32, had a predicted signal sequence. We generated recombinant (r) P8, P19 and P23 in a Drosophila expression system for functional and immunization studies. rP8 showed anti-complement activity and rP23 demonstrated anti-coagulant activity. Ixodes scapularis feeding was significantly impaired when nymphs were fed on rabbits immunized with a cocktail of rP8, rP19 and rP23, a hall mark of tick-immunity. These studies also suggest that these antigens may serve as potential vaccine candidates to thwart tick feeding

Laboratory investigation in normal and pathologic coagulation

Kamran Bakhtiari deed onderzoek naar het gebruik en het belang van hemostase-testen in verschillende situaties, bij gezonde personen en patiënten met bloedingen of trombose. Hemostase is het proces dat zorgt voor de vloeibaarheid van het bloed en het voorkomen van bloedverlies na beschadiging van een bloedvat. Verstoring van dit delicate proces kan leiden tot bloedingen of trombose (bloedklontering). Voor het vaststellen van afwijkingen in de hemostase zijn er veel laboratoriumtesten beschikbaar. Globale testen brengen een deel van het proces in kaart, specifiekere testen meten functie of concentratie van een enkel eiwit

Integration of foreign-born women into the labor market : A qualitative study of how social workers and foreign-born women experience integration

The purpose of the study was to investigate what the social work behind the integration of foreign-born women in the labor market looks like and how social workers experience integration. The second purpose was also to investigate how foreign-born women themselves experience integration in a country that is new to them. For the purpose of the study and questions, six interviews were conducted, three with social workers and three with foreign-born women. The theory applied in this study is intersectional perspective with a focus on gender and ethnicity. The data collection was analyzed with the help of qualitative content analysis and interpreted through an intersectional perspective and through the study's knowledge overview, in order to contribute to understanding where both individual and structural factors can create exclusion in the labor market for foreign-born women. The results showed that integration work is carried out aimed at foreign-born women, in the form of locally and internationally sponsored integration projects that are to contribute to employment in society. Regarding promoting factors, the results showed that both the professional respondents and the foreign-born respondents considered that, among other things, language education and social interaction are a central part of the integration. Finally, the results showed that the experience of integration among social workers and foreign-born women is a collaborative relationship, where both groups contribute to consistent notions of obstacles and opportunities for integration. In summary, the conclusions were that the design of integration policy is a contributing factor to how social integration work is conducted and how integration is perceived and practiced by those affected by the phenomenon

Integration of foreign-born women into the labor market : A qualitative study of how social workers and foreign-born women experience integration

The purpose of the study was to investigate what the social work behind the integration of foreign-born women in the labor market looks like and how social workers experience integration. The second purpose was also to investigate how foreign-born women themselves experience integration in a country that is new to them. For the purpose of the study and questions, six interviews were conducted, three with social workers and three with foreign-born women. The theory applied in this study is intersectional perspective with a focus on gender and ethnicity. The data collection was analyzed with the help of qualitative content analysis and interpreted through an intersectional perspective and through the study's knowledge overview, in order to contribute to understanding where both individual and structural factors can create exclusion in the labor market for foreign-born women. The results showed that integration work is carried out aimed at foreign-born women, in the form of locally and internationally sponsored integration projects that are to contribute to employment in society. Regarding promoting factors, the results showed that both the professional respondents and the foreign-born respondents considered that, among other things, language education and social interaction are a central part of the integration. Finally, the results showed that the experience of integration among social workers and foreign-born women is a collaborative relationship, where both groups contribute to consistent notions of obstacles and opportunities for integration. In summary, the conclusions were that the design of integration policy is a contributing factor to how social integration work is conducted and how integration is perceived and practiced by those affected by the phenomenon

The Iranian patenting system: An introduction

Abstract The history of the Iranian patent law and its up coming changes are described. A short description of the official structure of the Iranian patent office and the procedures for getting an Iranian patent are also described. The status of patenting in Iran is discussed using some recent statistics on the number of filed and granted Iranian patents to resident and non-resident applicants. The accessibility of Iranian patent information and the status of the patent professions are reviewed. Finally, the changes that are currently taking place, and which are expected to change the overall picture of intellectual property rights (IPRs), in Iran, are outlined. IP-considerations in Iran's Development Plans have been presented in this respect, to show the orientation of the Iranian officials in IPRs policy making