Key result
Targeting endogenous fibrinolytic inhibitors and clot architecture shows promise for improving stroke thrombolysis.
Why the study?
Detailed understanding of the modulation of clot formation and fibrinolysis is required to explain the variable response to current stroke fibrinolytics and to develop new and improved acute ischaemic stroke therapeutics.
Answers are grounded in this paper and cite their sources.
This narrative review synthesizes the mechanisms of clot formation and endogenous fibrinolytic inhibition in acute ischaemic stroke, highlighting emerging thrombolytics and novel adjunctive targets (such as NETs, vWF, and alpha-2-antiplasmin) to overcome thrombolytic resistance.
The processes of clot formation and clot dissolution with fibrinolysis underpin the pathophysiological mechanisms of acute ischaemic stroke (AIS) and its treatment. Detailed understanding of the modulation of this system is required to develop effective and safe stroke therapeutics. Clot formation occurs with the interaction of the coagulation cascade, along with platelets and fibrin meshwork. Conversely, fibrinolysis involves the serine protease plasmin, its zymogen, plasminogen and its enzymatic conversion by tissue plasminogen activator. The regulators and inhibitors that modulate the interactions in clot formation and fibrinolysis can be potential targets for new and emerging stroke therapies. The aim of this narrative review is to help inform stroke clinicians and researchers about the role of the fibrinolytic system and its inhibitors in AIS and the potential for new therapeutic targets. We outline the processes involved in clot formation and dissolution, the role of endogenous inhibitors of the fibrinolytic system, followed by potential therapeutic targets including tissue plasminogen activators as well as novel therapies and adjuncts. Better understanding of these processes will provide insight into the variable response to current stroke fibrinolytics amongst AIS patients and help to develop new and improved AIS therapeutics in future.
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Swarup et al. (2026) conducted a review in Acute ischaemic stroke (AIS). Fibrinolytic agents (tissue plasminogen activators including alteplase, tenecteplase, reteplase, pro-urokinase, desmoteplase, staphylokinase) and novel thrombolytic adjuncts (tirofiban, dornase alfa, ADAMTS13, N-acetylcysteine, TS23, DS-1040, BB-031) was evaluated. Endogenous fibrinolytic inhibitors (PAI-1, alpha-2-antiplasmin, TAFI) and structural clot elements (NETs, vWF, FXIIIa) represent promising adjunctive therapeutic targets to improve thrombolysis efficacy in acute ischaemic stroke.
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