Thromb Haemostasis
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Review Practice Guideline Guideline
Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen.
Approximately 250 cases of dysfibrinogenemia have been reported; 55% were asymptomatic (detected by chance), 25% had a tendency to bleeding, and 20% were reported to have a tendency to thrombosis. To establish a possible association between familial dysfibrinogenemia and thrombophilia, data on cases with both affections were collected in a study within the framework of the SSC Subcommittee on Fibrinogen of the International Society on Thrombosis and Haemostasis. Registry forms of 51 cases were received. ⋯ Analysis of 187 investigated family members showed that thrombophilia affected 20 persons exclusively in the group of 99 relatives with dysfibrinogenemia, no thrombosis was reported in the group of 88 relatives without the defect. Convincing evidence for such an association became apparent for only 5 individual propositi of whom 2 or more family members had both the defect and thrombotic episodes at a young age (Caracas V, Frankfurt IV/Vlissingen, Melun, Naples and Paris V, also named Dusart). Mainly two mechanisms to explain thrombosis as a consequence of malfunctioning fibrinogen have been suggested: a) A defective binding of thrombin to abnormal fibrin which leads to increased thrombin levels (Malmö, Naples, New York I, Pamplona II, Poitiers), b) A defective stimulatory function of abnormal fibrin in the t-PA mediated fibrinolysis (Argenteuil, Chapel Hill III, Date, New York I, Nijmegen, Pamplona II, Paris V).(ABSTRACT TRUNCATED AT 400 WORDS)
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Clinical Trial
Application of a novel and rapid whole blood assay for D-dimer in patients with clinically suspected pulmonary embolism.
To determine the clinical utility of a novel whole blood assay for D-dimer (SimpliRED) in patients with clinically suspected pulmonary embolism (PE). ⋯ This study demonstrates that the SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within five minutes, has potential clinical utility as an exclusionary test in patients with clinically suspected PE. The assay should be evaluated in large clinical management studies.
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Conformational changes in platelet membrane glycoprotein (GP) IIb-IIIa, whose nature is not defined, lead to exposure of fibrinogen binding sites. We have reported previously that F(ab')2 fragments of a monoclonal antibody, PMA4, directed against the GPIIb-IIIa complex-specific domain, induced binding of fibrinogen to platelets without causing intracellular activation, whereas Fab did not. In this study, we examined the mechanism responsible for the difference in the ability of PMA4 F(ab')2 and Fab to expose fibrinogen binding sites. ⋯ There was a direct correlation between the number of molecules of PMA4 F(ab')2 and the amount of fibrinogen bound. PMA4 did not recognize ligand-induced binding sites (LIBS). These results suggest that the cross-linking of special sites on the GPIIb-IIIa complex-specific domain by bivalent antibody alters the conformation of GPIIb-IIIa to a state competent to bind soluble fibrinogen and that conformational changes in non-LIBS are involved in the mechanism for exposing fibrinogen binding sites on GPIIb-IIIa.