Since the discovery of TAFI [38] its anti-fibrinolytic action has been largely attributed to the removal of plasmin-generated C-terminal lysines in the fibrin matrix, but it has been difficult to show convincingly that TAFI levels affect myocardial infarction or stroke outcomes at a population level or to explain the different anti-fibrinolytic impact of TAFI and plasma CPN. This evidence concerns the gene PLG and stroke disorder.