The objective of the present study was to systematically evaluate the impact of methodology on thromboelastometry with canine whole blood. Thromboelastometry was performed on citrated blood using a variety of combinations of clotting activators [ex-tem (tissue factor or TF), in-tem (ellagic acid), diluted TF from Innovin, or Ca (recalcification only)] and storage times. Thromboelastometry was also performed using diluted TF from Innovin on blood collected into a contact inhibitor. Ex-vivo contact activation was compared between canine and human blood. Clotting activator had a marked impact on coagulation time, a minor impact on alpha angle, and no impact on clot formation time or maximum clot firmness. When ex-tem or in-tem was the clotting activator, sample storage up to 30 min did not affect results. With diluted TF from Innovin or Ca, sample storage was associated with the development of increased coagulability (as indicated by shorter coagulation time and clot formation time and higher alpha angle) due to ex-vivo contact activation. Canine blood underwent markedly more ex-vivo contact activation than did human blood. Canine blood undergoes significant ex-vivo contact activation during and after collection, which influences thromboelastometry results when a weak clotting activator (such as low TF or recalcification) is used. Thromboelastometry with a strong activator (such as ex-tem or in-tem) is less influenced by ex-vivo changes, and, therefore, likely to be more reflective of in-vivo hemostatic capabilities and to provide consistently interpretable and comparable results.

<p>The newly established Swedish Apheresis Registry makes it possible to do national inter-center comparisons. This study was undertaken to describe and analyze the use of therapeutic apheresis and the adverse effects in such therapy. The special case of plasma exchange as rescue therapy in multi-organ failure, including renal failure, was also studied. In Sweden, plasma for transfusion is prepared and stored to ensure rapid availability. Due to new EU legislation, validation of such plasma was performed. </p><p>The analysis indicated that the use of therapeutic apheresis was in line with recommendations of other international societies. The frequency and types of adverse effects were comparable to those reported in other studies from analogous time periods. Compared with other countries, it appears that more therapeutic resources are available in Sweden and that there is a lower frequency of adverse effects in specific procedures. No fatalities were reported. The unique comparison of differences between centers regarding plasma exchange identified areas for further improvement.</p><p>The study on plasma exchange as rescue therapy in severe sepsis or septic shock is the second largest reported. The result was promising, with a survival rate of 82%. The rapid availability of plasma for transfusion appears to be of clinical importance in patients with early coagulopathy and severe trauma but the present selection and storage procedures for plasma lead to a time-dependent increase of the number of units with cold-induced activation of the contact system and C1 inhibitor consumption before day 14. Improvements of plasma quality can be attained by using plasma from male donors only and by reducing the storage time from 14 to 7 days. </p><p>Further studies are needed to define the role of plasma exchange in severe sepsis/septic shock, to evaluate the outcome of each patient’s treatment and to establish the indications for the transfusion of plasma.</p>

The newly established Swedish Apheresis Registry makes it possible to do national inter-center comparisons. This study was undertaken to describe and analyze the use of therapeutic apheresis and the adverse effects in such therapy. The special case of plasma exchange as rescue therapy in multi-organ failure, including renal failure, was also studied. In Sweden, plasma for transfusion is prepared and stored to ensure rapid availability. Due to new EU legislation, validation of such plasma was performed. The analysis indicated that the use of therapeutic apheresis was in line with recommendations of other international societies. The frequency and types of adverse effects were comparable to those reported in other studies from analogous time periods. Compared with other countries, it appears that more therapeutic resources are available in Sweden and that there is a lower frequency of adverse effects in specific procedures. No fatalities were reported. The unique comparison of differences between centers regarding plasma exchange identified areas for further improvement. The study on plasma exchange as rescue therapy in severe sepsis or septic shock is the second largest reported. The result was promising, with a survival rate of 82%. The rapid availability of plasma for transfusion appears to be of clinical importance in patients with early coagulopathy and severe trauma but the present selection and storage procedures for plasma lead to a time-dependent increase of the number of units with cold-induced activation of the contact system and C1 inhibitor consumption before day 14. Improvements of plasma quality can be attained by using plasma from male donors only and by reducing the storage time from 14 to 7 days. Further studies are needed to define the role of plasma exchange in severe sepsis/septic shock, to evaluate the outcome of each patient’s treatment and to establish the indications for the transfusion of plasma.

The physiological role of the plasma contact system still remains a partial enigma. The aim of the presented work was to expand our understanding of the plasma contact system, focusing on its physiological activation and function, principally from a hemostatic perspective. It also explored contact system activation under pathological conditions. We found that when human platelets become activated in blood, plasma proteins of the contact system bind to platelets and initiate contact activation. The platelet-triggered contact activation contributed to clot formation by shortening the clotting time and enhancing clot stability. We demonstrated that the regulation of contact activation elicited by activated platelets differed from the previously described contact activation elicited by negatively charged material surfaces. Platelet-triggered contact activation and activation propelled by clotting blood were found to be regulated by antithrombin, whereas material-induced activation was regulated by C1 inhibitor. We also showed that the fibrin fibers that are formed during the clot process further enhance and propagate the contact activation initially induced by activated platelets. Fibrin not only activated factor XII but also seemed to increase the affinity of antithrombin for the proteases of the contact system, leading to the generation of contact enzyme-antithrombin complexes during clot formation. To determine whether the contact system might be involved in the inflammation and vascular disease associated with systemic lupus erythematosus (SLE), we analyzed plasma samples from SLE patients. These patients were found to have altered levels of contact enzyme-serpin complexes, supporting the concept that the contact system may be involved in the pathophysiology of SLE. The contact enzyme-antithrombin complexes were clearly linked to platelet activation in vivo. Altered levels of both FXIIa-antithrombin and FXIIa-C1 inhibitor were found to be correlated with previous vascular disease and may therefore be potential biomarkers for assessing the risk of thrombotic events in SLE patients. These findings add to our knowledge of how the plasma contact system is activated and functions in vivo and will help us to understand the role of the contact system, not only in hemostasis but also in vascular disease and thrombotic conditions.

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