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Removing plasmin from the equation: something to chew on…

Morrow, Gael B.; Mutch, Nicola J.


Nicola J. Mutch


Thrombolytics or fibrinolytics are a group of pharmacological agents used to target and dissolve occlusive intravascular thrombi. Thrombi form a haemostatic plug at the site of injury to arrest bleeding and are essential for wound healing. However, intravascular thrombi that aberrantly form in pathophysiological settings block blood vessels lead to disturbed blood flow, thereby promoting thromboembolic events. Degradation of a thrombus occurs when the circulating zymogen, plasminogen, is cleaved to an active serine protease, plasmin. This process, termed fibrinolysis, is dependent on the presence of plasminogen activators; namely tissue plasminogen activator or urokinase (tPA or uPA, respectively). The differences in the mechanism of action of tPA and uPA are also important, tPA requires fibrin as a co‐factor to form a tertiary complex with plasmin, however, uPA does not and can promote plasmin generation in solution or on the cell surface. tPA is also more susceptible to plasminogen activator inhibitor 1 (PAI‐1) inhibition, as demonstrated by their second order rate constants, which differ by an order of magnitude; 12.6 × 107 vs. 4.8 × 106 M−1s−1 for tPA and uPA, respectively.


MORROW, G.B. and MUTCH, N.J. 2022. Removing plasmin from the equation: something to chew on… Journal of thrombosis and haemostasis [online], 20(2), pages 280-284. Available from:

Journal Article Type Commentary
Acceptance Date Nov 10, 2021
Online Publication Date Jan 21, 2022
Publication Date Feb 28, 2022
Deposit Date Jul 25, 2023
Publicly Available Date Jul 25, 2023
Journal Journal of thrombosis and haemostasis
Print ISSN 1538-7933
Electronic ISSN 1538-7836
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 20
Issue 2
Pages 280-284
Keywords Fibrin; HtrA1; Plasminogen; Tissue plasminogen activator; Thrombolytic therapy
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