Model thrombi formed under flow reveal the role of factor XIII-mediated cross-linking in resistance to fibrinolysis

Background: Activated factor XIII (FXIIIa), a transglutaminase, introduces fibrin-fibrin and fibrin-inhibitor cross-links, resulting in more mechanically stable clots. The impact of cross-linking on resistance to fibrinolysis has proved challenging to evaluate quantitatively. Methods: We used a whole blood model thrombus system to characterize the role of cross-linking in resistance to fibrinolytic degradation. Model thrombi, which mimic arterial thrombi formed in vivo, were prepared with incorporated fluorescently labeled fibrinogen, in order to allow quantification of fibrinolysis as released fluorescence units per minute. Results: A site-specific inhibitor of transglutaminases, added to blood from normal donors, yielded model thrombi that lysed more easily, either spontaneously or by plasminogen activators. This was observed both in the cell/platelet-rich head and fibrin-rich tail. Model thrombi from an FXIII-deficient patient lysed more quickly than normal thrombi; replacement therapy with FXIII concentrate normalized lysis. In vitro addition of purified FXIII to the patient's preprophylaxis blood, but not to normal control blood, resulted in more stable thrombi, indicating no further efficacy of supraphysiologic FXIII. However, addition of tissue transglutaminase, which is synthesized by endothelial cells, generated thrombi that were more resistant to fibrinolysis; this may stabilize mural thrombi in vivo. Conclusions: Model thrombi formed under flow, even those prepared as plasma 'thrombi', reveal the effect of FXIII on fibrinolysis. Although very low levels of FXIII are known to produce mechanical clot stability, and to achieve ?-dimerization, they appear to be suboptimal in conferring full resistance to fibrinolysis

Improving uptake and adherence in cardiac rehabilitation: literature review.

AIMS: This paper presents a comprehensive systematic review of literature carried out to identify studies of interventions to improve uptake, adherence and professional compliance in cardiac rehabilitation. BACKGROUND: Guidelines recommend that cardiac rehabilitation should be offered to patients following acute myocardial infarction and revascularization. Uptake and adherence are low, particularly in women, older people, and socially deprived and ethnic minority patients. Although patient, service and professional barriers to rehabilitation uptake have been described, no attempt has been made to evaluate systematically interventions aimed at improving uptake and adherence in cardiac rehabilitation. METHODS: A comprehensive search strategy identified studies of cardiac rehabilitation, using the terms uptake, adherence and compliance. The search included grey literature, hand searching of specialist journals and conference abstracts. No language restriction was applied. Studies were summarized in three qualitative overviews and assessed by quality of evidence. RESULTS: From 3261 publications identified, 957 were acquired on the basis of title or abstract. Few studies were of sufficient quality to make specific recommendations. Six, 12 and five studies, respectively, provided adequate information on methods to improve uptake, adherence or professional compliance. A minority of studies were randomized controlled trials. Studies of motivational and self-management strategies and use of lay volunteers showed some promise in improving rehabilitation uptake or lifestyle change. Nurse-led coordination of care after hospital discharge may have a role in improving rehabilitation uptake. Limited information was provided on resource implications, and there was a lack of studies with under-represented groups. The literature contained numerous suggested interventions which merit evaluation in appropriately designed studies. CONCLUSIONS: Little research has been reported evaluating interventions to improve uptake, adherence and professional compliance in cardiac rehabilitation. A wide range of possible interventions was identified and further evaluations of methods are indicated