Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: Initial patency and influence of maintained infusion on reocclusion rate

Verstraete, Marc; Arnold, Alfred; Brower, R. W.; Collen, D.; Bono, David P. de; Zwaan, Chris de; R, Erbel; Hillis, W.Stuart; Lennane, R. J.; Lubsen, Jacobus; Mathey, D; Reid, D S; Rutsch, Wolfgang; Schartl, M.; Schofer, Joachim; Serruys, Patrick W.; Simoons, Maarten L.; Uebis, R.; Vahanian, Alec; Verheugt, Freek W.A.; Essen, R. von

doi:10.1016/0002-9149(87)90219-0

Cited by 111 publications

(16 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Reocclusion of coronary arteries following t-PA thrombolytic therapy occurs frequently despite administration of heparin [1,2]. Because heparin promotes binding of thrombin to fibrin polymer by forming a ternary complex, its efficacy in preventing coronary reocclusion is limited [3,4].…”

Section: Introductionmentioning

confidence: 99%

Algal fucoidan, unlike heparin, has thrombolytic activity in a murine arterial thrombosis model

Min¹,

Han²,

Kim³

et al. 2012

Blood Coagulation &Amp; Fibrinolysis

View full text Add to dashboard Cite

Thrombolytic effects of fucoidans were investigated in the FeCl3-induced arterial thrombus mouse model and compared with heparin and tissue plasminogen activator (t-PA). Thrombosis model was made by applying 5% FeCl3 on the carotid artery of a Balb/c mouse. Twenty minutes after complete occlusion, a couple of test agents including fucoidan were infused into each mouse group with various doses intravenously, before measuring the time to reperfusion. The occluded arteries were reperfused 37.5 ± 12.4 min after administration of unfractionated fucoidan from Undaria pinnatifida sporophylls (UPS-UF) with a dose of 100 mg/kg. In the mice given either a low-molecular-weight UPS fucoidan or fucoidan source from Fucus vesiculosus (FV-UF), reperfusion was delayed at 55.0 ± 8.0 min with a higher reperfusion effective dose (RED) of 1 g/kg or at 63.3 ± 7.2 at RED of 200 mg/kg, respectively. In the control mice given t-PA of 15 mg/kg, reperfusion occurred at 24.8 ± 6.5 min after administration. In contrast, reperfusion was not observed in the occluded mice given heparin (P < 0.001) in the range of 60-1000 mg/kg. Minimal injection of fucoidan in addition to a given t-PA-enabled restoration of blood flow in the blocked artery without reocclusion at 17.2 ± 2.3 min postinjection (P < 0.002). In conclusion, algal fucoidan has both thrombolytic activity and a stimulatory effect on the thrombolytic activity of t-PA in a dose-dependent manner at an arterial thrombosis model.

show abstract

Section: Introductionmentioning

confidence: 99%

Algal fucoidan, unlike heparin, has thrombolytic activity in a murine arterial thrombosis model

Min¹,

Han²,

Kim³

et al. 2012

Blood Coagulation &Amp; Fibrinolysis

View full text Add to dashboard Cite

show abstract

“…7–9 TNK-tPA has the same amino acid sequence as natural human t-PA except with the three substitutions, at T103 to N, at N117 to Q, and at KHRR (296–299) to AAAA. These substitutions lead to a longer half life and higher fibrin specificity than t-PA. 10–11 In this study, differences in glycosylation occupancy and chain cleavage at the activation site of the enzyme have been observed between the innovator and follow-on products.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Glycosylation Occupancy and the Active Site in the Follow-on Protein Therapeutic: TNK-Tissue Plasminogen Activator

Jiang

Karger

et al. 2010

Anal. Chem.

View full text Add to dashboard Cite

Summary TNK-tPA products from the innovator and follow-on manufacturers were characterized and compared. All tryptic peptides including N-terminal, C-terminal and mutated peptides as well as the disulfide linked peptides were identified, with the demonstration of the same primary sequence and disulfide linkages between the innovator and follow-on products. The three N-linked and one O-linked fucose glycosylation sites were identified. The two N-linked (N103 and N448) and one O-linked fucose (T61) sites were fully glycosylated in both innovator and follow-on products. The other N-linked site (N184) was partially glycosylated and exhibited a ~2.5 fold difference between the innovator (60% occupancy) and follow-on (25% occupancy) products. Since the glycosylation occupancy at this site is known to affect biological activity in the clot lysis assay, this observed difference could cause a concern as to their bioequivalence. The cleavage site for the conversion of the zymogen form to active enzyme was also identified between R275 and I276, with a cleavage of 40% for the innovator and 10% for the follow-on products. Both the % glycosylation occupancy and the chain cleavage were determined by two independent approaches, starting from either the peptide or intact protein separation, with consistent results by both methods. Subtle differences of modifications such as deamidation and oxidation between innovator and biosimilar were shown at M207, M445, M490 and N58, N184. The observation of different extent of oxidation at M207 and deamidation at N184, which could influence the clot lysis activity, were also of potential concern in drug efficacy between the follow-on and innovator products.

show abstract

“…Verstraete et al [11] reported reperfusion of the infarct-related artery in 78 of 119 patients administered 40 mg of rt-PA for 90 minutes. Half of these patients had received an additional 30 mg over 6 hours: the other half received a placebo.…”

Section: Discussionmentioning

confidence: 99%

Influence of the rt-PA dose (1 mg/kg versus 1.5 mg/kg) and duration of administration on the patency of infarct-related coronary arteries in 81 patients

Gibelin

Tiger

Moles

et al. 1992

Cardiovasc Drug Ther

View full text Add to dashboard Cite

This open study compared the efficacy and side effects of two dose regimens of intravenous rt-PA initiated before the fifth hour after the onset of myocardial infarction. The first 40 patients (group A) received 1 mg/kg of rt-PA infused over 90 minutes, including a 10-mg initial bolus. The following 41 patients (group B) received 1.5 mg/kg (20-mg initial bolus, 60% over 60 minutes and 40% over 120 minutes). Noninvasive clinical, electrocardiographic, and biochemical parameters of reperfusion were recorded systematically, along with serial measurements of fibrinogen and hemoglobin levels. Coronary arteriography and left ventriculography were performed at the 48th hour or earlier, on an emergency basis, in the absence of signs of reperfusion, or if there were clinical and ECG signs of rethrombosis. Patency of the infarct-related artery (TIMI grades 2 and 3) was achieved in 55% of the group A patients vs. 83% of the group B patients (p less than .01). Twelve emergency coronary arteriographies were performed in each group. No significant difference was observed in the ejection fraction (48% in group A vs. 52% in group B). The peak CPK level was similar in both groups, but the peak occurred earlier in group B (p less than .001). There was no statistically significant difference between the two dose regimens in terms of reduction in fibrinogen or plasminogen levels. Two deaths occurred in group A vs. one death in group B. No cerebrovascular accidents occurred in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: Initial patency and influence of maintained infusion on reocclusion rate

Cited by 111 publications

References 29 publications

Algal fucoidan, unlike heparin, has thrombolytic activity in a murine arterial thrombosis model

Algal fucoidan, unlike heparin, has thrombolytic activity in a murine arterial thrombosis model

Characterization of the Glycosylation Occupancy and the Active Site in the Follow-on Protein Therapeutic: TNK-Tissue Plasminogen Activator

Influence of the rt-PA dose (1 mg/kg versus 1.5 mg/kg) and duration of administration on the patency of infarct-related coronary arteries in 81 patients

Contact Info

Product

Resources

About