The fibrinolytic system plays a pivotal role in the regulation of hemostasis and the prevention of thrombosis. There are no drugs that will increase the plasma fibrinolytic activity for a lasting duration to prevent thrombotic events effectively. Despite the ability of vasoactive agents such as nicotinic acid and metformin to release PA from the vessel wall, this therapeutic effect has not been evaluated adequately. The PAs are short-acting and indicated only for thrombolysis and not for prophylaxis. Future directions are directed at finding agents that can enhance plasminogen activator release or inhibit PAI-1 activity. As there are multiple factors involved in the pathogenesis of thrombosis, there are a number of conditions in which abnormal fibrinolysis is only a contributory factor. Examples are seen in pregnancy, especially during puerperium, when the thromboembolic risk is at its highest. The levels of inhibitors of fibrinolysis, both PAI-1 and PAI-2, are also at their highest. Another example was seen recently in the antiphospholipid syndrome, where antibodies against Annexin II, a receptor for tPA, were found to be higher than in healthy controls . Thus, a thorough investigation into other hereditary and acquired risk factors for thrombosis is recommended.
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