Half-life of single-chain urokinase-type plasminogen activator (scu-PA) and two-chain urokinase-type plasminogen activator (tcu-PA) in patients with acute myocardial infarction

Köhler, Michael; Sen, Semi; Miyashita, C.; Hermes, Ricardo; Pindur, G.; Heiden, Matthew G. Vander; Berg, Günter; Mörsdorf, S.; Leipnitz, Guilhian; Zeppezauer, Michael; Schieffer, Hermann; Wenzel, E.; Schönberger, A; Hollemeyer, Klaus

doi:10.1016/0049-3848(91)90670-r

Cited by 29 publications

(12 citation statements)

References 18 publications

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“…The circulating half-life of this scFv/CD39 chimera PLT/uPA-T binds to both quiescent and activated human (and baboon) platelets in vitro and in vivo and neither induces nor inhibits platelet activation, thereby maintaining normal hemostatic pathways that drive platelets into clots. When injected into hαIIb + mice that expressed hαIIb/mβ3 on their platelets (15), the half-life of PLT/uPA-T was approximately 2 hours ( Figure 5A), which is approximately 100-fold longer than that of nontargeted uPA (20). This combination of high affinity for platelets and a prolonged half-life of PLT/uPA-T translated into an approximately 30-fold greater inhibition of clot growth than was seen with uPA-T alone using a bolus infusion approach (Figure 7), and an even greater difference if only a bolus was given ( Figure 6).…”

Section: Discussionmentioning

confidence: 99%

A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation

Fuentes

Зайцев

Ahn

et al. 2015

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 99%

A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation

Fuentes

Зайцев

Ahn

et al. 2015

Journal of Clinical Investigation

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“…The two-chain u-PA does not exhibit fibrin affinity, but scu-PA has a weak fibrin affinity that is considerably lower than that of t-PA [20]. The initial half-life of scu-PA was 6-9 min, when it was administrated to the patients with acute myocardial infarction ( Table 2) [21].…”

Section: The First Generation Of the Fibrin-specific Thrombolytic Agementioning

confidence: 99%

Development of New Fibrinolytic Agents

Ueshima¹,

Matsuo²

2006

CPD

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Since the activation of coagulation system and platelets triggers the thrombosis, the agents possessing anticoagulation or anti-platelet function have been used for the antithrombotic procession actions. However, in the physiological condition, the fibrinolytic system serves as antithrombotic, which removes the thrombus from the circulation. The fibrinolytic system plays an important role in the dissolution of fibrin, which is the main component of thrombus. So that, the balance between the coagulation and fibrinolytic system regulates the formation of thrombus. Now, the new agents that activate the fibrinolytic system have been clinically applied for the thrombolytic therapy. The main factor in fibrinolytic system is the plasmin, which is activated from the plasminogen by the plasminogen activator (PA). The plasminogen activator is mainly used for the thrombolytic therapy. There are two types of PA. One is the non fibrin-specific PA such as streptokinase (SK) and two-chain urokinase-type PA (tcu-PA, urokinase), and another is the fibrin-specific PA such as tissue-type PA (t-PA) and single-chain urokinase-type PA (scu-PA). Recently, some derivatives of t-PA have been developed to obtain the longer half-life than native t-PA and allowed to administrate as the single-bolus. Further, the new fibrin-specific PA such as staphylokinase and bat-PA has been developed. Many attempts have been made to develop the agents that would induce the release of t-PA from endothelial cells. In this review, the development of new fibrinolytic agents is summarized.

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“…34 Single-chain urokinase-type plasminogen activator is rapidly metabolized in the liver with a half-life of 7 to 8 minutes in humans, but like t-PA, has been shown to have a longer than expected thrombolytic effect. 36,37 Single-chain urokinase-type plasminogen activator has been shown to have comparable coronary patency rates compared with t-PA or streptokinase in myocardial infarction. [38][39][40][41] • Anisoylated Plasminogen-streptokinase Activator Complex Anisoylated plasminogen-streptokinase activator complex (APSAC) is a third generation plasminogen activator derived from a chemical modification of streptokinase that has increased fibrin specificity and a prolonged half-life in plasma.…”

Section: • Single Chain Urokinase-type Plasminogen Activatormentioning

confidence: 99%

Thrombolytic Therapy in Dogs and Cats

Thompson

Scott‐Moncrieff

Hogan

2001

J Vet Emergen Crit Care

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Objective: To review the thrombolytic agents most commonly used in humans, their mechanisms of action, potential uses, adverse effects, and reports of their use in dogs and cats. Human data synthesis: Thrombolytic agents available in human medicine include streptokinase, urokinase, tissueplasminogen activator (t-PA), single-chain urokinase plasma activator (scu-PA) and anisoylated plasminogen-streptokinase activator complex (APSAC). These agents were originally used for the management of proximal deep vein thrombosis and severe pulmonary embolism but more recently, use of these drugs has been extended to include the treatment of acute peripheral arterial disease, cerebrovascular disease (stroke) and acute coronary thrombosis. The most predictable side effect associated with the use of thrombolytic therapy is hemorrhage. Veterinary data synthesis: Clinical experience with thrombolytic agents in small animals is limited to streptokinase and t-PA. It is possible, that as in humans, canine and feline patients with PTE and right ventricular dysfunction may benefit from thrombolytic therapy but there are no veterinary studies to support this theory to date. Successful use of streptokinase has been documented in a small number of canine patients with systemic thromboembolism. 63 Thrombolytic therapy is relatively efficacious in cats with aortic thromboemboli but is associated with a high mortality rate. 59,60,64 With regard to use of t-PA in veterinary medicine, the small number of animals treated with varying protocols makes it impossible to provide safe and effective dose recommendations at this time. Conclusions: Future goals for thrombolytic therapy in veterinary medicine include determination of more specific clinical indications, as well as design of effective protocols that minimize mortality and morbidity. (J Vet Emerg Crit Care 2001; 11(2): 111-121)

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Half-life of single-chain urokinase-type plasminogen activator (scu-PA) and two-chain urokinase-type plasminogen activator (tcu-PA) in patients with acute myocardial infarction

Cited by 29 publications

References 18 publications

A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation

A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation

Development of New Fibrinolytic Agents

Thrombolytic Therapy in Dogs and Cats

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