Alterations in markers of coagulation and fibrinolysis in XXXX with @entity7965 before and during treatment with eculizumab.

@entity1 @entity7965 @entity1351 @entity2142 @entity715
BACKGROUND: @entity7965 is characterized by complement-mediated @entity2142 and an increased @entity715 risk. Eculizumab, an antibody to complement factor C5, reduces @entity715 risk via unknown mechanisms. Clinical observations suggest that eculizumab has an immediate effect. OBJECTIVES: A better understanding of the mechanism via which eculizumab reduces @entity715 risk by studying its pharmacodynamic effect on coagulation and fibrinolysis. METHODS: We measured microparticles (MP), tissue factor (TF) activity, prothrombin fragment 1+2 (F1+2), D-dimer and simultaneously thrombin and @entity1351 generation in 55 PNH @entity1 . In 20 @entity1 , parameters were compared before and during eculizumab treatment (at 1 and 2hours, 1, 4 and>= 12weeks after commencement). RESULTS: @entity1 with a history of @entity715 had elevated D-dimers (p=0.02) but not MP. Among patients on anticoagulants, those with @entity715 had higher F1+2 concentrations (p=0.003). TF activity was undetectable in plasma MP. Unexpectedly, thrombin peak height and thrombin potential were significantly lower in PNH @entity1 than in healthy controls. Fibrinolysis parameters were normal. During eculizumab treatment D-dimer levels significantly decreased after 1hour (p=0.008) and remained decreased at>= 12weeks (p=0.03). F1+2 (p=0.03) and thrombin peak height (p=0.02) in @entity1 not on anticoagulants significantly decreased at>= week 12. MP remained unchanged. CONCLUSIONS: Eculizumab induces an immediate decrease of D-dimer levels but not of other markers. The decrease in thrombin peak height and F1+2 suggests that eculizumab reduces thrombin generation. Elevated D-dimer levels in untreated PNH @entity1 with a history of @entity715 suggest possible value in predicting @entity715 risk.
