Journal articles on the topic 'Thrombolytic Agent'
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1
Madonov, Pavel, Stanialav Leont’ev, Sergey Zotov, Maksim Ufimtsev, Svetlana Mishenina, and Dmitrii Kinsht. "Initial Results of Oral Thrombolytic Agent Clinical Application." Proceedings 2, no. 9 (July 20, 2018): 530. http://dx.doi.org/10.3390/proceedings2090530.
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At the moment, there is no oral thrombolytic drug on the world pharmaceutical market. The drug Trombovazim, which has a thrombolytic effect under oral administration, has been registered in Russia. It differs from all thrombolytics—it has a fundamentally different mechanism of action. It is not an activator of plasminogen. It independently dissolves a thrombus. It is a direct thrombolytic. The article presents the materials of the initial studies of the drug Trombovazim.
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Agnelli, G., MR Buchanan, F. Fernandez, J. Van Ryn, and J. Hirsh. "Sustained thrombolysis with DNA-recombinant tissue type plasminogen activator in rabbits." Blood 66, no. 2 (August 1, 1985): 399–401. http://dx.doi.org/10.1182/blood.v66.2.399.399.
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Abstract Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular veins at different times after a bolus injection of the fibrinolytic agents. The pharmacodynamics of both thrombolytic agents were determined in rabbits using a sensitive ex vivo fibrinolytic assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg. There was no detectable circulating fibrinolytic activity 30 minutes after the bolus dose of t- PA and 120 minutes after the bolus dose of streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes, 90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120 minutes, and 34% at 240 minutes. These observations indicate that the thrombolytic effect of t-PA is sustained beyond its time of clearance from the circulation whereas the thrombolytic effect of streptokinase closely parallels its activity in the circulation.
3
Agnelli, G., MR Buchanan, F. Fernandez, J. Van Ryn, and J. Hirsh. "Sustained thrombolysis with DNA-recombinant tissue type plasminogen activator in rabbits." Blood 66, no. 2 (August 1, 1985): 399–401. http://dx.doi.org/10.1182/blood.v66.2.399.bloodjournal662399.
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Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular veins at different times after a bolus injection of the fibrinolytic agents. The pharmacodynamics of both thrombolytic agents were determined in rabbits using a sensitive ex vivo fibrinolytic assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg. There was no detectable circulating fibrinolytic activity 30 minutes after the bolus dose of t- PA and 120 minutes after the bolus dose of streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes, 90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120 minutes, and 34% at 240 minutes. These observations indicate that the thrombolytic effect of t-PA is sustained beyond its time of clearance from the circulation whereas the thrombolytic effect of streptokinase closely parallels its activity in the circulation.
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Qu, Shu, and Xingwei Ding. "Shear-, Sound-, and Light-Sensitive Nanoparticles for Thrombolytic Drug Delivery." Seminars in Thrombosis and Hemostasis 46, no. 05 (May 16, 2019): 587–91. http://dx.doi.org/10.1055/s-0039-1688490.
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AbstractThrombotic diseases, as potentially induced by blood clots or vascular embolization, frequently occur with high rates of mortalities worldwide. Current drug thrombolysis, a primary clinical therapy, may increase fatal risk of hemorrhage when thrombolysis agents become systemically distributed. Given current thrombolysis limitations, some novel drug delivery systems based on nanoparticles have been recently exploited to achieve a more controlled release of loaded thrombolytic agents, able to respond to environmental changes, and resulting in a safer thrombolysis. In this review, the authors outline and discuss some prominent examples of early and recent thrombolytic agent delivery systems using controlled release by physical stimuli (shear, sound and light). Shear-sensitive systems are designed to exploit the specific biomechanical feature of thrombosis, that is, the increased blood shear stress. Sound- and light-sensitive systems reflect “remote control” of drug release by responding to external ultrasound or light stimulus. These smart thrombolytic drug delivery systems hold promise for more effective and safer future thrombolytic therapy.
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Bizjak, Eric D., and Vincent F. Mauro. "Thrombolytic Therapy: A Review of Its Use in Acute Myocardial Infarction." Annals of Pharmacotherapy 32, no. 7-8 (July 1998): 769–84. http://dx.doi.org/10.1345/aph.17350.
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OBJECTIVE: To review the literature on the use of thrombolytic agents in the pharmacotherapeutic management of acute myocardial infarction (AMI). DATA SOURCE: English-language clinical trials, reviews, and editorials derived from MEDLINE (January 1966–September 1997) and/or cross-referencing of selected articles. STUDY SELECTION: Articles that were selected best represent the clinical trials researching the role for thrombolytics in the therapy of AMI to improve morbidity and mortality. DATA SYNTHESIS: AMI is one of the leading causes of mortality in the US. Following supportive data that the most common cause of an AMI is an intracoronary thrombus, clinical investigation has demonstrated that intravenous thrombolytic agents improve survival rates in patients who experience an AMI. Several clinical trials have been conducted to determine whether one thrombolytic agent is superior to others with respect to improving mortality. At present, only the first Global Use of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial has reported any statistically significant difference in mortality rate. In this trial, “front-loaded” alteplase induced a statistically significant (p < 0.001) 1% absolute reduction in 30-day and 1-year mortality compared with streptokinase. This has led to alteplase being the preferred thrombolytic at many US institutions. However, the results of GUSTO-I have been questioned by some on the basis of either study design or clinical significance. CONCLUSIONS: Thrombolytic agents have secured a place in the treatment of AMI due to their well-proven reduction in mortality rates. In general, comparative trials have demonstrated minimal differences in efficacy among these agents. Probably just as important as choosing which thrombolytic agent to use is ensuring that a patient experiencing an AMI is administered thrombolytic therapy unless a contraindication to receive such therapy exists in the patient and/or the patient is a candidate to receive an emergent intracoronary procedure. Trials also indicate that the sooner thrombolytics can be administered, the greater the benefit to the patient.
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Nikitin, Dmitri, Seungbum Choi, Jan Mican, Martin Toul, Wi-Sun Ryu, Jiri Damborsky, Robert Mikulik, and Dong-Eog Kim. "Development and Testing of Thrombolytics in Stroke." Journal of Stroke 23, no. 1 (January 31, 2021): 12–36. http://dx.doi.org/10.5853/jos.2020.03349.
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Despite recent advances in recanalization therapy, mechanical thrombectomy will never be a treatment for every ischemic stroke because access to mechanical thrombectomy is still limited in many countries. Moreover, many ischemic strokes are caused by occlusion of cerebral arteries that cannot be reached by intra-arterial catheters. Reperfusion using thrombolytic agents will therefore remain an important therapy for hyperacute ischemic stroke. However, thrombolytic drugs have shown limited efficacy and notable hemorrhagic complication rates, leaving room for improvement. A comprehensive understanding of basic and clinical research pipelines as well as the current status of thrombolytic therapy will help facilitate the development of new thrombolytics. Compared with alteplase, an ideal thrombolytic agent is expected to provide faster reperfusion in more patients; prevent re-occlusions; have higher fibrin specificity for selective activation of clot-bound plasminogen to decrease bleeding complications; be retained in the blood for a longer time to minimize dosage and allow administration as a single bolus; be more resistant to inhibitors; and be less antigenic for repetitive usage. Here, we review the currently available thrombolytics, strategies for the development of new clot-dissolving substances, and the assessment of thrombolytic efficacies <i>in vitro</i> and <i>in vivo</i>.
7
Verhaeghe, Raymond. "Thrombolysis in Arterial Occlusion." Thrombosis and Haemostasis 82, S 01 (1999): 109–11. http://dx.doi.org/10.1055/s-0037-1615565.
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SummaryIntra-arterial thrombolytic therapy has replaced systemic intravenous infusion of thrombolytic agents as a treatment modality for arterial occlusion in the limbs. Several catheter-guided techniques and various infusion methods and schemes have been developed. At present there is no scientific proof of definite superiority of any agent in terms of efficacy or safety but clinical practice favours the use of urokinase or alteplase. Studies which compared thrombolysis to surgical intervention suggest that thrombolytic therapy is an appropriate initial management in patients with acute occlusion of a native leg artery or a bypass graft. Underlying causative lesions are treated in a second step by endovascular or open surgical techniques. Severe bleeding is the most feared complication: the risk of hemorrhagic stroke is 1-2%.
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Ringleb, Peter, Robert Stingele, and Werner Hacke. "Thrombolysis in Acute Cerebrovascular Disease: Indications and Limitations." Thrombosis and Haemostasis 82, no. 08 (1999): 983–86. http://dx.doi.org/10.1055/s-0037-1615942.
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IntroductionLarge-scale trials have shown that thrombolytic therapy reduces mortality and preserves left ventricular function in patients with acute myocardial infarction (AMI). As most ischemic strokes are thromboembolic in origin,1 there appears to be a rationale for the use of thrombolytic agents in the management of ischemic stroke.Thrombolytic agents differ in their mechanisms of action, but in general, they act by promoting the conversion of plasminogen into plasmin, resulting in fibrin degradation and clot dissolution. Streptokinase and recombinant tissue plasminogen activator (rt-PA) are the agents that have been the most widely investigated in stroke studies. Ancrod, the active agent in the venom of the Malayan pit viper, is primarily considered an anticoagulant, although it does stimulate endogenous t-PA release from the vascular endothelium and may enhance local thrombolysis. Urokinase is used in local, intra-arterial thrombolysis but has not been subjected to large clinical trials since computed tomography (CT) diagnosis became widely available.
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Perkins, W. R., D. E. Vaughan, S. R. Plavin, W. L. Daley, J. Rauch, L. Lee, and A. S. Janoff. "Streptokinase Entrapment in Interdigitation-Fusion Liposomes Improves Thrombolysis in an Experimental Rabbit Model." Thrombosis and Haemostasis 77, no. 06 (1997): 1174–78. http://dx.doi.org/10.1055/s-0038-1656133.
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SummaryThe successful design of new thrombolytic agents depends on providing these agents with increased clot selectivity. As recently demonstrated (10), entrapment of tissue plasminogen activator into liposomes apparently provided the selective targeting needed to improve the efficacy of this fibrinolytic agent. To test whether liposomal entrapment would benefit streptokinase, a fibrinolytic agent with a different mode of action and inactivation, we compared liposomal streptokinase with free streptokinase in an experimental rabbit model of thrombolysis.First we adapted a new method to produce liposomes of high entrapment efficiency, termed interdigitation-fusion (IF) liposomes, for the encapsulation of streptokinase. This system was then tested in an in vivo rabbit model of thrombolysis where animals with established clots were infused with either free streptokinase (40,000 U/kg), liposomally entrapped streptokinase, free streptokinase + empty liposomes, or the corresponding amount of empty liposomes or saline. Significant differences (p <0.05) in the percent clot lysis were observed between saline control (22.4 ± 3.3%; mean ± S.E.), free streptokinase (36.3 ± 3.4%), and liposomal streptokinase (47.4 ± 1.4%). Importantly, animals treated with empty liposomes experienced a level of thrombolysis (32.4 ± 2.8%) not different to that produced by free streptokinase or empty liposomes plus free streptokinase (38.0 ± 2.0%). We believe the effect of liposomes alone is due to a transient redistribution or margination of circulating platelets.When tested in rabbits immunized against streptokinase, liposomal (33.8 ± 1.5%) but not free streptokinase (29.3 ± 2.1%) showed significant thrombolytic activity compared to saline (22.4 ± 3.3%) (p <0.05). The thrombolytic activity was comparable to free streptokinase in nonimmunized rabbits. This suggests liposomal streptokinase would have better thrombolytic activity than streptokinase alone and still provide to those patients possessing high levels of anti-streptokinase antibodies (5% of the population) the equivalent degree of therapy expected from free streptokinase.
10
Kim, Dongjune, Susan M. Shea, and David N. Ku. "Lysis of arterial thrombi by perfusion of N,N’-Diacetyl-L-cystine (DiNAC)." PLOS ONE 16, no. 2 (February 25, 2021): e0247496. http://dx.doi.org/10.1371/journal.pone.0247496.
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The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi. We have developed an in vitro system to study the efficacy of known and proposed thrombolytic agents on white clots formed from whole blood in a stenosis with arterial conditions. The agents and adjuncts tested were tPA, ADAMTS-13, abciximab, N-acetyl cysteine, and N,N’-Diacetyl-L-cystine (DiNAC). Most of the agents, including tPA, had little thrombolytic effect on the white clots. In contrast, perfusion of DiNAC lysed thrombi as quickly as 1.5 min, which ranged up to 30 min at lower concentrations, and resulted in an average reduction in surface area of 71 ± 20%. The clot burden was significantly reduced compared to both tPA and a saline control (p<0.0001). We also tested the efficacy of all agents on red fibrinous clots formed in stagnant conditions. DiNAC did not lyse red clots, whereas tPA significantly lysed red clot over 48 h (p<0.01). These results lead to a novel use for DiNAC as a possible thrombolytic agent against acute arterial occlusions that could mitigate the risk of hyper-fibrinolytic bleeding.
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Latfullin, I. A., A. V. Bondarev, A. A. Podolskaya, and E. I. Aglullina. "Thrombolytic therapy of the acute myocardial infarction by cabicinase." Kazan medical journal 79, no. 4 (July 15, 1998): 251–54. http://dx.doi.org/10.17816/kazmj64386.
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The necessity to perform the systemic thrombolysis to patients with acute myocardial infarction is emphasized. The most effective and save thrombolytic agent is cabicanase. The recommendations for practical physicians are worthy of notice. The control of blood coagulability velocity and hemorrhage lingering is obligatory in the performance of thrombolysis; if it is possible, thrombelastograms are to be studied. It is essential to know well the contradictions to thrombolysis.
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Dar, Mohammad Arif, and Nahida Tabassum. "Rutin- potent natural thrombolytic agent." International Current Pharmaceutical Journal 1, no. 12 (November 1, 2012): 431–35. http://dx.doi.org/10.3329/icpj.v1i12.12454.
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Thrombosis, the formation of blood clots, is a cause not only of heart attacks and strokes, but of deep venous thrombosis (DVT) and pulmonary embolism as well. The number one killer of Americans is a blood clot that blocks blood flow to the heart or to the brain and approximately half of all morbidity and mortality in the United States can be attributed to heart attack or stroke. All the blood clot related conditions are life-threatening, and so there is a need for safe, effective and preventive treatment. A natural substance rutin, also called rutoside, is a citrus flavonoid glycoside found in Fagopyrum esculentum (buckwheat), the leaves and petioles of Rheum species, and Asparagus. This flavonoid compound has shown effective thrombolytic activity (prevents the formation of blood clots) by blocking the enzyme protein disulfide isomerase (PDI) found in all cells involved in blood clotting. Food and Drug Administration (FDA) has established that rutin is safe and, thus provides a safe and inexpensive drug that could reduce recurrent clots and help save thousands of lives.DOI: http://dx.doi.org/10.3329/icpj.v1i12.12454 International Current Pharmaceutical Journal 2012, 1(12): 431-435
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White, Roger L. "Thrombolytic Therapy in Acute Myocardial Infarction: A Review with Current Recommendations." Asian Cardiovascular and Thoracic Annals 1, no. 4 (December 1993): 145–51. http://dx.doi.org/10.1177/021849239300100402.
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Thrombolytic therapy has clearly become an established therapeutic modality to treat patients with acute myocardial infarction. Since there is no ideal agent at this time, we must evaluate the advantages and disadvantages of current therapy based on major clinical studies. Thrombolysis is the body's natural response to dissolving clots after they have served their purpose. Thrombolytic agents accelerate fibrinolysis by overwhelming the system. There are 4 thrombolytic agents currently available: streptokinase urokinase, anistreplase (APSAC), and rt-PA. Tissue plasminogen activator is a naturally occurring protein that can be created with genetic recombinant technology (rt-PA). It establishes higher patency rates (70–90%) than the other available thrombolytic agents. Recently published results of accelerated rt-PA infusion during acute myocardial infarction demonstrate that the infarct-related artery seems to open more quickly and provide greater blood flow. The use of intravenous heparin as adjunctive therapy along with aspirin seems to maintain patency at comparable levels to streptokinase. Not only is mortality reduced in the accelerated rt-PA group, but complications from myocardial infarction such as arrhythmia and heart failure are significantly reduced. rt-PA remains the drug of choice in the hypotensive patient and, because of potential allergy, in patients with previous exposure to streptokinase. Percutaneous transluminal coronary angioplasty is frequently needed to improve long-term patency and reduce ischemic episodes. Recent studies show that it may provide some advantage over thrombolytic therapy, because the artery can be opened faster, with higher flow rates.
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Stankiewicz, Adrian, Wioletta Rozmyslowicz-Szermńska, Andrzej Mogielnicki, Anna Gromotowicz, Wlodzimierz Buczko, Katarzyna Oszajca, Jacek Bartkowiak, Ewa Chabielska, and Janusz Szemraj. "A new recombinant thrombolytic and antithrombotic agent with higher fibrin affinity – a staphylokinase variant." Thrombosis and Haemostasis 97, no. 06 (2007): 1037–45. http://dx.doi.org/10.1160/th06-10-0562.
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SummaryThe recombinant protein SAK-RGD-K2-Hir is characterized by its fibrin-specific properties of plasminogen activation combined with antithrombin and antiplatelet activities. It was previously shown in our in-vitro studies to be a more potent and faster-acting thrombolytic agent compared with standard r-SAK. In order to document the effects of the thrombolytic potential of SAKRGD- K2-Hir we examined this protein in an electrically induced carotid artery thrombosis model and stasis-induced venous model in rats. In the arterial thrombosis model, a bolus injection of SAK-RGD-K2-Hir was less effective than rt-PA and r-SAK. However, the most effective in the improvement and maintenance of carotid patency and in arterial thrombus mass reduction was SAK-RGD-K2. In contrast, all r-SAK derivatives reduced venous thrombus weight significantly in comparison to r-SAK and r-Hir. However, the most observable decrease in thrombus weight was obtained after application of recombinant proteins containing the r-Hir.The bleeding time was significantly prolonged in the animals treated with proteins containing r-Hir at a dose of 1.0 mg/kg.There were no observable changes in plasma fibrinogen concentration.In conclusion,our findings show thrombolytic activity in intravenous bolus injection of the novel thrombolytic agent SAK-RGD-K2-Hir in rats.Although this protein compares favourably with r-SAK in rat venous thrombolysis, we were unable to confirm the beneficial effects of SAK-RGDK2- Hir over r-SAK and rt-PA in the carotid artery thrombolysis model. Furthermore, our results also suggest that SAKRGD- K2-Hir bears a risk of bleeding, but this may be true for higher doses.
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Comeau-Luis, OY, SW Corbett, WA Wittlake, KR Jutzy, and BL Huiskes. "Case report: reversal of an evolving myocardial infarction with intravenous thrombolysis." American Journal of Critical Care 8, no. 4 (July 1, 1999): 246–49. http://dx.doi.org/10.4037/ajcc1999.8.4.246.
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This case, in many ways, represents the ideal: a timely and effective administration of thrombolytic agents. The rarity of this situation reinforces the need for earlier recognition and treatment of infarction. In an analysis of time delays in thrombolytic therapy, 38% were attributed to in-hospital issues, 22% to patients' delays, 21% to problems with transportation, and 19% to reperfusion time. The National Heart Attack Alert Program calls for treatment within 1 hour of the development of signs and symptoms, including administration of thrombolytic agents within 30 minutes of the patient's arrival in the emergency department. That program seeks heightened awareness among hospital and prehospital providers and public education about seeking immediate treatment for chest pain. The prompt acquisition of additional ECGs and the subsequent rapid administration of a thrombolytic agent were the clinical essentials. This fact suggests the need to look for measures of quality other than simple "door to drug" times. "Data to drug" times may be another indicator of quality to address cases in which the initial ECG findings are not diagnostic. Furthermore, emergency departments may see more patients with impending infarction if public education campaigns are successful. This case emphasizes the need to obtain follow-up ECGs in light of the potential benefits from thrombolysis.
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Hong, Ting-Ting, Jinbao Huang, and Benedict R. Lucchesi. "Effect of thrombolysis on myocardial injury: recombinant tissue plasminogen activator vs. alfimeprase." American Journal of Physiology-Heart and Circulatory Physiology 290, no. 3 (March 2006): H959—H967. http://dx.doi.org/10.1152/ajpheart.00649.2005.
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Plasmin-dependent thrombolytic agents are potentially prothrombotic and proinflammatory. Alfimeprase, a zinc-containing metalloproteinase, degrades fibrin directly and achieves thrombolysis independent of plasmin formation. This study examines the hypothesis that thrombolysis in the absence of plasmin generation results in improved myocardial salvage on reperfusion. The thrombolytic effects of recombinant tissue plasminogen activator [rt-PA; 0.022 mg/kg, 1/10 of which was administered as a loading dose; the rest (9/10) was infused over 60 min by intracoronary (ic) administration] or alfimeprase (0.5 mg/kg over 1 min ic) were evaluated in a canine model of arterial thrombosis involving electrolytic injury of the left circumflex (LCX) coronary artery. Both agents induced thrombolysis, with onset of reperfusion being more rapid after alfimeprase compared with rt-PA (1.5 ± 0.6 vs. 10.1 ± 2.1 min). In the absence of adjunctive therapy, time to reocclusion after alfimeprase was 3.2 ± 0.5 min compared with 77.5 ± 31.9 min with rt-PA. The glycoprotein IIb/IIIa platelet receptor antagonist CRL-42796 prolonged reperfusion time after thrombolysis with alfimeprase or rt-PA. The effect of each lytic agent on myocardial infarct size was examined in a separate group of dogs subjected to 60 min of LCX coronary artery ligation and 4 h of reperfusion. Myocardial infarct size, expressed as percentage of the risk region, was larger (32.16 ± 3.95%) after rt-PA compared with alfimeprase (19.85 ± 3.61%) or that of the saline control group (18.46 ± 3.34%). rt-PA in contrast to alfimeprase, a direct-acting fibrinolytic agent, is associated with an increase in myocyte reperfusion injury.
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Bakhtawer, Muhammad Faheem malik, and Sumera Afsheen. "Isolation and Purification of Thrombolytic Enzyme Extracted from Earthworm Punjab, Pakistan." Volume 4 Issue 1, Volume 4 Issue 1 (September 11, 2021): 127–35. http://dx.doi.org/10.34091/ajls.4.1.15.
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The Cardiovascular disease due to thrombus (clot) formation is the major factor of death throughout the world. Earthworms being the eco engineers has thrombolytic enzyme that can be used for thrombolysis. The thrombolytic enzyme was isolated and purified from supernatant of earthworm Apporectodea longa by column chromatography. Six Strain BKT 11, BKT 15, BKT 17, BKT 26, BKT 27 and BKT 28 shows the thrombolytic activity 791.64 U/mg, 1362.39 U/mg, 1205.4 U/mg, 710.63 U/mg, 529.66 U/mg and 625.00 U/mg respectively. Thrombolytic activity was confirmed by blood clot lysis method. Different concentrations 50 ?l,100 ?l, 150 ?l, 200 ?l and 250 ?l of extracted enzyme were applied on 25mg of wet blood clot along with control where distill water used. These fractions of extracted enzymes represent the dissolution of clot (thrombolysis). The molecular weight 32 KDa was determined by sodium dodecyl sulphate gel electrophoresis (SDS-PAGE). Results show that extracted elute have potential of fibrinolytic activity in this specie of earthworm and it can serve as a suitable therapeutic agent. Keywords: Thrombolytic activity, Casein plate assay, Blood clot lysis, spectrophotometry, Gel electrophoresis.
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Vaughan, DE, SR Plavin, AI Schafer, and J. Loscalzo. "PGE1 accelerates thrombolysis by tissue plasminogen activator." Blood 73, no. 5 (April 1, 1989): 1213–17. http://dx.doi.org/10.1182/blood.v73.5.1213.1213.
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Abstract Platelets are an active element in the generation of thrombus and may influence rates of thrombolysis during the administration of plasminogen activators. To assess the potential importance of platelet aggregation in the thrombolytic response to plasminogen activators, we measured rates of thrombolysis induced by tissue plasminogen activator in the presence and absence of a coinfusion of prostaglandin E1 in a rabbit jugular vein model of thrombosis. Rates of lysis were quantified by measuring the half-time for lysis of the thrombus. At all concentrations of tissue plasminogen activator used, prostaglandin E1 markedly reduced the half-time for clot lysis and enhanced somewhat the overall extent of thrombolysis, without affecting significantly either the degree of fibrinogen depletion or the animals' mean arterial pressures. These effects on thrombolytic efficacy were accompanied by ex vivo evidence of platelet inhibition. These data suggest that the antiplatelet prostaglandin E1 may be a very useful adjunctive agent in thrombolytic therapy primarily by virtue of the significant improvement in the rate of thrombolysis that its use affords.
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Vaughan, DE, SR Plavin, AI Schafer, and J. Loscalzo. "PGE1 accelerates thrombolysis by tissue plasminogen activator." Blood 73, no. 5 (April 1, 1989): 1213–17. http://dx.doi.org/10.1182/blood.v73.5.1213.bloodjournal7351213.
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Platelets are an active element in the generation of thrombus and may influence rates of thrombolysis during the administration of plasminogen activators. To assess the potential importance of platelet aggregation in the thrombolytic response to plasminogen activators, we measured rates of thrombolysis induced by tissue plasminogen activator in the presence and absence of a coinfusion of prostaglandin E1 in a rabbit jugular vein model of thrombosis. Rates of lysis were quantified by measuring the half-time for lysis of the thrombus. At all concentrations of tissue plasminogen activator used, prostaglandin E1 markedly reduced the half-time for clot lysis and enhanced somewhat the overall extent of thrombolysis, without affecting significantly either the degree of fibrinogen depletion or the animals' mean arterial pressures. These effects on thrombolytic efficacy were accompanied by ex vivo evidence of platelet inhibition. These data suggest that the antiplatelet prostaglandin E1 may be a very useful adjunctive agent in thrombolytic therapy primarily by virtue of the significant improvement in the rate of thrombolysis that its use affords.
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Rehman, Ayesha, Shabbir Hussain, Muhammad Ahmad, Muhammad Riaz, Muhammad Amin Abid, and Tanzeela Gulab Shazady. "Evaluation of Thrombolytic Potential of Elaeagnus rhamnoides (L.) A. Nelson." Scientific Inquiry and Review 6, no. 3 (September 15, 2022): 94–110. http://dx.doi.org/10.32350/sir.63.06.
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Plants find a special significance in the field of medicine due to their therapeutic value. Thrombolytic agents play a crucial role in the treatment of numerous human diseases including atherothrombotic diseases, pulmonary embolism, and myocardial infarction. The current study was performed to evaluate the thrombolytic potential of Elaeagnus rhamnoides (L.) A. Nelson (Sea buckthorn or SBT). The extract of leaves, stems, and berries of the investigated plant displayed 28%, 26%, and 44% blood clot lysis, respectively as compared to that of a standard thrombolytic agent namely streptokinase (59% lysis). The fruit extract of sea buckthorn was found to display higher thrombolytic potential as compared to that of its leaves and stem. It was concluded that the extract of leaves, stem, and berries of SBT may find applications in the future as a thrombolytic agent. The presence of important functional groups for instance, alcohol, aldehyde, alkyne, alkene, amines, and ester in different ariel parts of SBTwere verified by FTIR spectroscopy.
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Ghandehari, Kavian. "Barriers of Thrombolysis Therapy in Developing Countries." Stroke Research and Treatment 2011 (2011): 1–4. http://dx.doi.org/10.4061/2011/686797.
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The developing world carries the highest burden of stroke mortality and stroke-related disability. The number of stroke patients receiving r-tPA in the developing world is extremely low. Prehospital delay, financial constraints, and lack of infrastructure are main barriers of thrombolysis therapy in developing countries. Until a cheaper thrombolytic agent and the proper infrastructure for utilization of thrombolytic therapy is available, developing countries should focus on primary and secondary stroke prevention strategies. However, governments and health systems of developing countries should efforts exerb for promotion of their infrastructure of stroke care.
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Erickson, Laurence A., and Keith R. Marotti. "Design of Novel Thrombolytic Agents via Domain Modifications*." Toxicologic Pathology 18, no. 4a (January 1990): 597–602. http://dx.doi.org/10.1177/019262339001804a09.
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Generation of plasmin in the vicinity of a blood clot has proven to be an effective approach for treating thrombotic disorders, particularly myocardial infarction. Conceptually, the ideal thrombolytic agent would initiate the formation of plasmin, primarily in association with fibrin incorporated into the occlusive thrombus. Thus, thrombolytic agents that exhibit relative fibrin specificity and, thus, presumably clot selectivity (e.g., tissue plasminogen activator) were expected to have a marked clinical benefit compared to agents that do not display affinity for fibrin (e.g., streptokinase). However, results obtained recently from clinical trials indicate that these 2 agents essentially were equally effective in treating myocardial infarction. With these findings in mind, efforts are being made to develop novel thrombolytic agents that might achieve more rapid and specific thrombolysis than that achieved by presently available agents and, thus, could be administered earlier because of an improved margin of safety. The available data suggest that tissue-type PA (tPA) mutants possessing resistance to endogenous inhibitors, altered fibrin affinity, and/or slower rates of clearance may prove beneficial in this regard. In addition, adjunctive therapies (i.e., anti-platelet and anti-thrombin compounds) have been found to decrease the time necessary to achieve reperfusion and have reduced rates of reocclusion. These efforts are expected to yield therapeutic agents in the 1990s and beyond that, when administered in combination, would exhibit increased efficacy in the treatment of myocardial infarction and other thrombotic disorders.
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Shahzadi, Irum, Ameer Fawad Zahoor, Burak Tüzün, Asim Mansha, Muhammad Naveed Anjum, Azhar Rasul, Ali Irfan, Katarzyna Kotwica-Mojzych, and Mariusz Mojzych. "Repositioning of acefylline as anti-cancer drug: Synthesis, anticancer and computational studies of azomethines derived from acefylline tethered 4-amino-3-mercapto-1,2,4-triazole." PLOS ONE 17, no. 12 (December 15, 2022): e0278027. http://dx.doi.org/10.1371/journal.pone.0278027.
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Novel azomethines derived from acefylline tethered triazole hybrids (7a-k) have been synthesized and evaluated against human liver cancer cell line (Hep G2) using MTT assay. The synthesized series of azomethines exhibited promising efficacy against liver cancer cell line. Screening of the synthesized series identified compound 7d with the least cell viability value (11.71 ± 0.39%) as the most potent anticancer agent in contrast to the reference drug acefylline (cell viability = 80 ± 3.87%). In this study, the potentials of the novel agents (7a-k) to inhibit liver cancer proteins were assessed. Subsequently, the structure-activity relationship of the potential drug candidates was assessed via ADME/T molecular screening. The cytotoxic potential of these derivatives was also investigated by hemolysis and thrombolysis. Their hemolytic and thrombolytic studies showed that all of these drugs had very low cytotoxicity and moderate clot lysis activity. Compound 7g (0.26% hemolysis) and 7k (52.1% clot lysis) were the least toxic and moderate thrombolytic agents respectively.
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MATSUO, O. "An ideal thrombolytic and antithrombotic agent?" Journal of Thrombosis and Haemostasis 3, no. 10 (September 29, 2005): 2154–55. http://dx.doi.org/10.1111/j.1538-7836.2005.01599.x.
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Razavi, Mahmood. "Selecting a Thrombolytic Agent and Regimen." Journal of Vascular and Interventional Radiology 14, no. 2 (February 2003): P245. http://dx.doi.org/10.1016/s1051-0443(03)70199-7.
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Banerjee, Anirban, Yusuf Chisti, and U. C. Banerjee. "Streptokinase—a clinically useful thrombolytic agent." Biotechnology Advances 22, no. 4 (February 2004): 287–307. http://dx.doi.org/10.1016/j.biotechadv.2003.09.004.
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Topol, Eric J. "Which thrombolytic agent should one choose?" Progress in Cardiovascular Diseases 34, no. 3 (November 1991): 165–78. http://dx.doi.org/10.1016/0033-0620(91)90011-a.
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Leebeek, Frank W. G. "A novel VWF-associated thrombolytic agent." Blood 140, no. 26 (December 29, 2022): 2770–71. http://dx.doi.org/10.1182/blood.2022018024.
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Stewart, Daphne, Mansze Kong, Valery Novokhatny, Gary Jesmok, and Victor J. Marder. "Distinct dose-dependent effects of plasmin and TPA on coagulation and hemorrhage." Blood 101, no. 8 (April 15, 2003): 3002–7. http://dx.doi.org/10.1182/blood-2002-08-2546.
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AbstractAll thrombolytic agents in current clinical usage are plasminogen activators. Although effective, plasminogen activators uniformly increase the risk of bleeding complications, especially intracranial hemorrhage, and no laboratory test is applicable to avoid such bleeding. We report results of a randomized, blinded, dose-ranging comparison of tissue-type plasminogen activator (TPA) with a direct-acting thrombolytic agent, plasmin, in an animal model of fibrinolytic hemorrhage. This study focuses on the role of plasma coagulation factors in hemostatic competence. Plasmin at 4-fold, 6-fold, and 8-fold the thrombolytic dose (1 mg/kg) induced a dose-dependent effect on coagulation, depleting antiplasmin activity completely, then degrading fibrinogen and factor VIII. However, even with complete consumption of antiplasmin and decreases in fibrinogen and factor VIII to 20% of initial activity, excessive bleeding did not occur. Bleeding occurred only at 8-fold the thrombolytic dose, on complete depletion of fibrinogen and factor VIII, manifest as prolonged primary bleeding, but with minimal effect on stable hemostatic sites. Although TPA had minimal effect on coagulation, hemostasis was disrupted in a dose-dependent manner, even at 25% of the thrombolytic dose (1 mg/kg), manifest as rebleeding from hemostatically stable ear puncture sites. Plasmin degrades plasma fibrinogen and factor VIII in a dose-dependent manner, but it does not disrupt hemostasis until clotting factors are completely depleted, at an 8-fold higher dose than is needed for thrombolysis. Plasmin has a 6-fold margin of safety, in contrast with TPA, which causes hemorrhage at thrombolytic dosages.
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Kumar, Anil, Abdul Wadood Kakar, Javed Khurshed Shaikh, Muhammad Hassan Butt, Muhammad Hashim Kalwar, and Nadeem Hassan Rizvi. "Post Thrombolytic Angiographic Profile and TIMI Flow in Patients with ST-Elevation Myocardial Infarction." Pakistan Journal of Medical and Health Sciences 16, no. 5 (May 29, 2022): 1054–56. http://dx.doi.org/10.53350/pjmhs221651054.
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Background: Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide. Primary Percutaneous coronary intervention (PPCI) is recommended as a treatment of choice in patients with STEMI but fibrinolysis also remains prevalent as a reperfusion strategy in most of the patients with STEMI presenting to non-PCI capable hospitals where timely PPCI cannot be performed. Objectives: To assess the angiographic characteristics and angiographic success of thrombolysis in terms of TIMI 3 flow in patients who underwent angiography after thrombolysis for STEMI and the factors most commonly associated with unsuccessful thrombolysis. Methods: All 130 hospitalized patients in the department of Cardiology, at Bolan Medical Complex Hospital, Quetta from 31st July 2021 to 30th November 2021 with an acute ST-segment elevation MI (STEMI) diagnosis who received thrombolytics were included in this observational study. We didn't include patients who couldn't benefit from thrombolysis e.g. NSTEMI, contraindication to thrombolytics, and refused fibrinolysis. A 12-lead electrocardiogram (ECG) was performed when the patient arrived in ER and a repeat ECG was done 90 minutes after the administration of a thrombolytic agent (streptokinase). To assess the angiographic success of thrombolysis, coronary anatomy, and TIMI flow, we performed coronary angiography in all patients included in this study. Results: The study included 130 patients, 72 of whom had successful thrombolysis and 58 who had unsuccessful thrombolysis. Angiography reported TIMI 3 flow rates of 48(36.9%). Subjects in the unsuccessful thrombolysis group had the single-vessel disease in 29 (50%) and a multi-vessel disease was found in 19 (32.75%) of the patients. Patients with successful thrombolysis had Single vessel disease 6 (19.3%), Multivessel disease 1 (3.2) It was observed that patients with diabetes mellitus had a significant rise in the number of failed thrombolysis compared to those without diabetes mellitus (p<0.005). It was also observed that anterior wall MI was significantly at risk for a failure in thrombolysis (82.1%) compared to inferior wall MI (17.8%). Conclusions: Effective thrombolysis was more prevalent than failed thrombolysis in our study. This data reiterates the utility of thrombolysis in resource-limited settings. Patients with diabetes, anterior wall MI, and delay in the presentations of the patients have a higher risk of thrombolysis failure. Type B lesions and multivessel disease were also prevalent in subjects with unsuccessful thrombolysis. According to the findings of this study, screening for risk factors before starting thrombolysis can aid in the development of alternative treatment methods that reduce failure rates and redirect resources to more successful treatment options. Keywords: Post thrombolytic; Angiographic Profile, TIMI flow; St-elevation; Myocardial Infarction
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Qureshi, Adnan I., Amir M. Siddiqui, M. Fareed K. Suri, Stanley H. Kim, Zulfiqar Ali, Abutaher M. Yahia, Demetrius K. Lopes, et al. "Aggressive Mechanical Clot Disruption and Low-dose Intra-arterial Third-generation Thrombolytic Agent for Ischemic Stroke: A Prospective Study." Neurosurgery 51, no. 5 (November 1, 2002): 1319–29. http://dx.doi.org/10.1097/00006123-200211000-00040.
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Abstract OBJECTIVE We prospectively evaluated the safety and effectiveness of aggressive mechanical disruption of clot in conjunction with intra-arterial administration of a low-dose third-generation thrombolytic agent (reteplase) to treat ischemic stroke in patients who were considered poor candidates for intravenous alteplase therapy or who failed to improve after intravenous thrombolysis. Mechanical clot disruption was used if low-dose pharmacological thrombolysis was ineffective. This strategy was adopted to increase the recanalization rate without increasing the risk of intracerebral hemorrhage. METHODS Patients were considered poor candidates for intravenous therapy because of severity of neurological deficits, interval from symptom onset to presentation of at least 3 hours, or recent major surgery. We administered a maximum total dose of 4 U of reteplase intra-arterially in 1-U increments via superselective catheterization. After the initial doses were administered, we performed mechanical angioplasty (for proximal occlusion) or snare manipulation (for distal occlusion) at the occlusion site if recanalization had not occurred. The remaining doses of thrombolytics were subsequently administered if required for further recanalization. Angiographic responses were graded using modified Thrombolysis in Myocardial Infarction (TIMI) criteria. Clinical evaluations were performed before and 24 hours, 7 to 10 days, and 1 to 3 months after treatment. RESULTS Nineteen consecutive patients were treated (mean age, 64.3 ± 16.2 yr; 10 were men). Initial National Institutes of Health Stroke Scale scores ranged from 11 to 42. Time from onset to treatment ranged from 1 to 9 hours. Occlusion sites were in the following arteries: cervical internal carotid (n = 7), intracranial internal carotid (n = 1), middle cerebral (n = 9), and basilar (n = 2). Of the 19 patients, thrombolysis alone was used in 5 patients, angioplasty was performed in 11 patients, and snare maneuvers were used in 5 patients. Complete restoration of blood flow (modified TIMI Grade 4) was observed in 12 patients, near-complete restoration of flow (modified TIMI Grade 3) in 4 patients, minimal response (modified TIMI Grade 1) in 1 patient, and no response in 2 patients (modified TIMI Grade 0). Neurological improvement at 24 hours (decline of at least 4 points in National Institutes of Health Stroke Scale score) was observed in seven patients. Five other patients experienced further improvement in National Institutes of Health Stroke Scale score at 7 to 10 days. No vessel rupture, dissection, or symptomatic intracranial hemorrhages were observed. At the time of follow-up evaluation, 7 of 19 patients were functionally independent. CONCLUSION A high rate of recanalization and clinical improvement can be observed in patients with ischemic stroke using low-dose thrombolytic agents with adjunctive mechanical disruption of clot. Moreover, this strategy may reduce the risk of intracerebral hemorrhage observed with thrombolytics.
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Zaman, Md Asad Uz, Md Arafat Al Mamun, Shakila Nargis Khan, Md Mozammel Hoq, and Md Abdul Mazid. "Partial Purification of Alkaline Protease as Thrombolytic Agent from Mutant Strain Bacillus licheniformis EMS250-O-1." Dhaka University Journal of Pharmaceutical Sciences 15, no. 2 (January 2, 2017): 135–41. http://dx.doi.org/10.3329/dujps.v15i2.30926.
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Thrombosis leads to myocardial infarction, stroke and other cardiovascular complications. Microbial thrombolytic agents such as urokinase, streptokinase etc. are used to treat complications related to thrombosis. To search for new microbial enzymes as thrombolytics having better efficacy and specificity, Bacillus licheniformis EMS-O-1 mutant strain was cultured in modified urea-molasses media followed by purification using ammonium sulphate precipitation and ultrafiltration through centricon tube of 100 MWCO value. The yield of crude enzyme was 11129.14 U/mg and after purification 40180.46 U/mg. Purification process increased the specific activity of purified enzyme to 12.28 fold with a recovery of 17.79%. The purified enzyme was a serine protease with molecular weight of 25.5 kDa as confirmed by irreversible inhibition of activity with phenylmethylsulfonyl fluoride (PMSF) followed by SDS-PAGE gel image and by LC-MS analyses. In vitro clot lysis assay of the purified enzyme exhibited 38.30% thrombolytic activity. The crude enzymes from the mutant strain EMS-O-1 were found to be stable up to 50oC and showed maximum stability between pH range 7.5 to 8.5. These findings signify that proteases produced by B. licheniformis mutant have the potential to be developed as a viable thrombolytic agent.Dhaka Univ. J. Pharm. Sci. 15(2): 135-141, 2016 (December)
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Poredoš, Pavel, Peter Poredoš, and Mateja Kaja Jezovnik. "Factors influencing recanalization of thrombotic venous occlusions." Vasa 49, no. 1 (January 1, 2020): 17–22. http://dx.doi.org/10.1024/0301-1526/a000800.
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Summary. The outcome of a thrombotic vessel occlusion is related to the resolution of thrombus and restitution of blood flow. Thrombus formation simultaneously activates an enzymatic process that mediates endogenous fibrinolysis to maintain vessel patency. The balance between coagulation and fibrinolysis determines the extent of thrombus formation, its resolution, and clinical outcome. Endogenic fibrinolysis is frequently unable to overcome coagulation and to resolve the thrombus. Therefore, for a complete resolution of thrombus in an acute phase, exogenic fibrinolytic agents are needed. Currently, tissue plasminogen activator (tPA) is most frequently used for therapeutic thrombolysis. Also, heparins, particularly low-molecular-weight heparins and direct oral anticoagulants which are known as anticoagulant drugs, have some pro-fibrinolytic properties. Besides the extent and age of a clot, different other factors influence the lysis of thrombus. Thrombus structure is one of the most important determinants of thrombus lysis. The concentration of thrombolytic agent (tPA) around and inside of thrombus importantly determines clot lysis velocity. Further, flow-induced mechanical forces which stimulate the transport of thrombolytic agent into the clot influence thrombolysis. Inflammation most probably represents a basic pathogenetic mechanism of activation of coagulation and influences the activity of the fibrinolytic system. Inflammation increases tissue factor release, platelet activity, fibrinogen concentration and inhibits fibrinolysis by increasing plasminogen activator inhibitor 1. Therefore, recanalization of a thrombotic vessel occlusion is inversely related to levels of some circulating inflammatory agents. Consequently, inhibition of inflammation with anti-inflammatory drugs may improve the efficacy of prevention of thromboembolic events and stimulate recanalization of thrombotic occlusions of veins.
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Kasirajan, Karthikeshwar, Venkatesh G. Ramaiah, and Edward B. Diethrich. "The Trellis Thrombectomy System in the Treatment of Acute Limb Ischemia." Journal of Endovascular Therapy 10, no. 2 (April 2003): 317–21. http://dx.doi.org/10.1177/152660280301000223.
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Purpose: To report the use of a new percutaneous mechanical thrombectomy device in the treatment of acute limb-threatening ischemia. Technique: The Trellis Thrombectomy System is a 7-F drug dispersion catheter that features a treatment segment isolated by proximal and distal occlusion balloons, which help prevent distal embolization and systemic release of the infused thrombolytic agent. After inflating the distal balloon, the thrombolytic agent is infused and held at the target site by inflation of the proximal balloon. An oscillating dispersion wire optimizes dispersal of the thrombolytic agent as the thrombus is mechanically fragmented. The liquefied thrombus is then aspirated. Four consecutive patients with acute lower extremity ischemia secondary to bypass graft thrombosis were treated with the Trellis thrombectomy catheter. Overall, 95% of thrombus was successfully removed from the treatment zone, with no device-related complications. Only one patient required adjunctive thrombolytic therapy after thrombectomy with the Trellis device. Conclusions: The Trellis thrombectomy device is a safe and effective technique to isolate the infused thrombolytic agent in association with mechanical fragmentation for rapid blood flow restoration.
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Kartik Soni, Rajesh Asija, and Rashmi Khanijau. "Management of acute ischemic stroke." World Journal of Biology Pharmacy and Health Sciences 12, no. 3 (December 30, 2022): 210–15. http://dx.doi.org/10.30574/wjbphs.2022.12.3.0231.
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Stroke is a major cause of mortality and morbidity, and thrombolysis has served as a catalyst for major changes in the management of acute ischaemic stroke. Intravenous alteplase (recombinant tissue plasminogen activator) is the only approved thrombolytic agent at present indicated for acute ischaemic stroke. Recombinant tissue plasminogen activator (rt-PA) therapy is effective in reducing early and long-term neurologic disabilities if it is started quickly. This article summarizes the recent advances in thrombolysis for acute ischaemic stroke.
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Witt, W., B. Baldus, P. Bringmann, L. Cashion, P. Donner, and WD Schleuning. "Thrombolytic properties of Desmodus rotundus (vampire bat) salivary plasminogen activator in experimental pulmonary embolism in rats." Blood 79, no. 5 (March 1, 1992): 1213–17. http://dx.doi.org/10.1182/blood.v79.5.1213.1213.
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Abstract rDSPA alpha 1 (recombinant Desmodus salivary plasminogen activator alpha 1) is a recombinant protein corresponding to a natural plasminogen activator from the vampire bat Desmodus rotundus. The thrombolytic properties of rDSPA alpha 1 and tissue-type plasminogen activator (t-PA) were compared in a rat model of pulmonary embolism. Whole blood clots, produced in vitro and labeled with 125I-fibrinogen, were embolized into the lungs of anesthetized rats. Thrombolysis was calculated from the difference between initial clot radioactivity and that remaining in the lungs at 60 minutes. Blood was sampled for gamma counting, measurement of hemostatic factors, and plasminogen activator antigen levels. Thrombolysis at 3, 10, 30, and 100 nmol/kg intravenously (10% bolus, 90% over 60 minutes) amounted to 30% +/- 2%, 51% +/- 4%, 85% +/- 4%, 98% +/- 0% for rDSPA alpha 1 and 30% +/- 3%, 41% +/- 3%, 57% +/- 6%, 93% +/- 2% for t-PA (controls: 29% +/- 2%; mean +/- SEM, n greater than or equal to 6). t-PA at 100 nmol/kg significantly decreased fibrinogen, plasminogen, and alpha 2- antiplasmin levels by 33% +/- 7%, 38% +/- 8%, and 61% +/- 9%, whereas rDSPA alpha 1 at 100 nmol/kg only lowered alpha 2-antiplasmin significantly (by 29% +/- 6%). Compared with t-PA, rDSPA alpha 1 is the more potent and more clot selective (fibrin specific) thrombolytic agent. These results suggest that rDSPA alpha 1 may be safer and more efficacious than currently used thrombolytics.
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Witt, W., B. Baldus, P. Bringmann, L. Cashion, P. Donner, and WD Schleuning. "Thrombolytic properties of Desmodus rotundus (vampire bat) salivary plasminogen activator in experimental pulmonary embolism in rats." Blood 79, no. 5 (March 1, 1992): 1213–17. http://dx.doi.org/10.1182/blood.v79.5.1213.bloodjournal7951213.
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rDSPA alpha 1 (recombinant Desmodus salivary plasminogen activator alpha 1) is a recombinant protein corresponding to a natural plasminogen activator from the vampire bat Desmodus rotundus. The thrombolytic properties of rDSPA alpha 1 and tissue-type plasminogen activator (t-PA) were compared in a rat model of pulmonary embolism. Whole blood clots, produced in vitro and labeled with 125I-fibrinogen, were embolized into the lungs of anesthetized rats. Thrombolysis was calculated from the difference between initial clot radioactivity and that remaining in the lungs at 60 minutes. Blood was sampled for gamma counting, measurement of hemostatic factors, and plasminogen activator antigen levels. Thrombolysis at 3, 10, 30, and 100 nmol/kg intravenously (10% bolus, 90% over 60 minutes) amounted to 30% +/- 2%, 51% +/- 4%, 85% +/- 4%, 98% +/- 0% for rDSPA alpha 1 and 30% +/- 3%, 41% +/- 3%, 57% +/- 6%, 93% +/- 2% for t-PA (controls: 29% +/- 2%; mean +/- SEM, n greater than or equal to 6). t-PA at 100 nmol/kg significantly decreased fibrinogen, plasminogen, and alpha 2- antiplasmin levels by 33% +/- 7%, 38% +/- 8%, and 61% +/- 9%, whereas rDSPA alpha 1 at 100 nmol/kg only lowered alpha 2-antiplasmin significantly (by 29% +/- 6%). Compared with t-PA, rDSPA alpha 1 is the more potent and more clot selective (fibrin specific) thrombolytic agent. These results suggest that rDSPA alpha 1 may be safer and more efficacious than currently used thrombolytics.
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Karahan, Oguz, H. Barıs Kutas, Orcun Gurbuz, Orhan Tezcan, Ahmet Caliskan, Celal Yavuz, Sinan Demirtas, and Binali Mavitas. "Pharmacomechanical thrombolysis with a rotator thrombolysis device in iliofemoral deep venous thrombosis." Vascular 24, no. 5 (July 10, 2016): 481–86. http://dx.doi.org/10.1177/1708538115612637.
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Objective Deep venous thrombosis (DVT) is a life-threatening and morbid pathology. This study aimed to investigate the efficacy of an early thrombolysis procedure using a rotator thrombolysis device. Methods Sixty-seven patients with acute proximal DVT were enrolled in the study. Patients’ data were recorded retrospectively. Initially, an infrarenal retrievable vena cava filter was placed through the femoral vein. Then, a rotator thrombolysis device and a thrombolytic agent injection were applied to the occluded segments of the deep veins by puncturing the popliteal vein. Results The identified reasons were trauma (43.3%), pregnancy (20.9%), undiagnosed (11.9%), major surgical operation (10.5%), immobilization (7.5%), and malignancy (5.9%). Immediate total recanalization was conducted in all patients, and the leg diameters returned to normal ranges in the early postoperative period. Hospital mortality or severe complications were not detected. Conclusion New thrombolytic devices seem to reduce in-hospital mortality risks and may potentially decrease post-thrombotic morbidity.
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Akhtar, Taqiyah, Md Mozammel Hoq, and Md Abdul Mazid. "Bacterial Proteases as Thrombolytics and Fibrinolytics." Dhaka University Journal of Pharmaceutical Sciences 16, no. 2 (January 10, 2018): 255–69. http://dx.doi.org/10.3329/dujps.v16i2.35265.
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Proteases regulate important pathophysiological processes in human body such as homeostasis, blood coagulation, fibrinolysis, tumor progression, etc. These biological effects of proteases largely attribute to their applicability as therapeutic agents. Imbalance in blood coagulation and fibrinolysis, two important physiological processes in human body, leads to thrombosis, a leading cause of cardiovascular complications including myocardial infarction, stroke, etc. The enzymes used to dissolve thrombus (blood clot) are known as thrombolytic agents and among them, the enzymes involving hydrolysis of fibrin called fibrinolytic agents. Thrombolytic agents can be classified according to generation, mechanism of action, source and active site of the enzymes. Among the commercially available thrombolytic agents, uPA and tPA are generally safe but are very expensive. On the other hand, the bacterial streptokinase is a relatively cheap thrombolytic agent but causes undesirable side effects such as bleeding complications. For this reason, worldwide research for potent thrombolytic agents to prevent and treat cardiovascular diseases have been continuing. Microbes are considered as a potential source of as well as safe vectors for expressing thrombolytic and fibrinolytic enzymes. Bacilli are one of the largest groups for this purpose. They have been collected from different traditional fermented foods or have been produced by solid state fermentation using appropriate nutrient substrates including different agro-industrial wastes such as rice straw, molasses, soybean curd residues, etc. This review focuses on different bacterial proteases reported to have potential thrombolytic and fibrinolytic activities.Dhaka Univ. J. Pharm. Sci. 16(2): 255-269, 2017 (December)
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Karakurt, Ahmet. "New Thrombolytic Infusion Application of Dissolving Renal Artery Embolic Thrombosis: Low-Dose Slow-Infusion Thrombolytic Therapy." Case Reports in Nephrology 2018 (2018): 1–4. http://dx.doi.org/10.1155/2018/1609025.
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Renal artery thromboembolism (RATE) is an uncommon complication of renal arteries from heart chamber. Although there is no treatment protocol prescribed with guidelines, thrombolytic agents such as rt-PA are frequently used. Unfortunately, current thrombolytic agent application protocol in treatment for the RATE is used in acute myocardial infarction or acute pulmonary embolism. In this protocol, 0.9–1.0% cerebral and 4–13% noncerebral hemorrhages are seen. In contrast to this protocol, we aimed to present a case of RATE, in which we applied low-dose, slow-infusion thrombolytic therapy, and we have not observed any complication such as cerebral and noncerebral hemorrhage.
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Shah, R. Nisha, and P. Farida Minocheherhomji. "NATTOKINASE: ARMOUR AGAINST THROMBOSIS." Journal of Advanced Scientific Research 13, no. 05 (June 30, 2022): 34–37. http://dx.doi.org/10.55218/jasr.202213504.
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In this review paper, an emphasis is made to focus on the history, source, structure, mode of action, and application of Nattokinase. The review reveals that Nattokinase can act as a potent thrombolytic agent as compared to other agents which are commercially available. Studies on NK as a thrombolytic agent have also be proved it as an useful for dissolving blood clots by converting plasminogen to plasmin, which further act on fibrin clots. Nattokinase is been isolated from Bacillus subtilis varnatto. Various studies been done on the application of NK has shown to overcome the undesirable effects caused by other tissue plasminogen activator, Streptokinase, Staphylokinaseetc and increased its area of application.
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Prasad, Krishna, Parminder Singh, Kewal Kanabar, and Rajesh Vijayvergiya. "Pulmonary haemorrhage following thrombolysis with streptokinase in myocardial infarction." BMJ Case Reports 13, no. 1 (January 2020): e232308. http://dx.doi.org/10.1136/bcr-2019-232308.
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Pulmonary haemorrhage is a rare but a life-threatening complication of thrombolytic therapy in patients with acute ST-elevation myocardial infarction (MI). It usually presents with anaemia, massive haemoptysis, acute-onset respiratory distress and diffuse bilateral lung infiltrates on imaging. We hereby describe two patients, who had pulmonary haemorrhage following streptokinase therapy for acute MI. The first patient improved with conservative treatment, while the second patient died due to respiratory failure. Streptokinase, a fibrin non-specific agent, is a widely used thrombolytic in low-income and middle-income countries. Pulmonary haemorrhage should be suspected in patients who develop sudden respiratory compromise after receiving thrombolytics, especially streptokinase. The management issues related to this uncommon life-threatening complication have been discussed in this article.
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Hanna, G. P., and R. W. Smalling. "Reteplase, a new third generation thrombolytic agent." Drugs of Today 33, no. 9 (1997): 627. http://dx.doi.org/10.1358/dot.1997.33.9.444768.
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Marder, V. "ID: 357 Plasmin: a Direct Thrombolytic Agent." Journal of Thrombosis and Haemostasis 4, s1 (October 2006): 52. http://dx.doi.org/10.1111/j.1538-7836.2006.00357.x.
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Crabbe, Sarah J., and Cynthia C. Cloninger. "Tissue plasminogen activator: A new thrombolytic agent." American Journal of Health-System Pharmacy 44, no. 6 (June 1, 1987): 1462–74. http://dx.doi.org/10.1093/ajhp/44.6.1462.
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Verstraete, Marc. "The search for the ideal thrombolytic agent." Journal of the American College of Cardiology 10, no. 5 (November 1987): 4B—10B. http://dx.doi.org/10.1016/s0735-1097(87)80421-7.
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Kellett, J. G., and J. O’Riordan. "Whither the rationale for thrombolytic agent administration?" Irish Journal of Medical Science 162, no. 4 (April 1993): 133–39. http://dx.doi.org/10.1007/bf02942102.
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Bajka, Balázs, Edvin Benedek, Alexandra Stănescu, Emese Rapolti, Monica Chițu, and István Kovács. "Treatment Difficulties in High Risk Pulmonary Embolism. A Case Report." Journal Of Cardiovascular Emergencies 2, no. 1 (March 1, 2016): 37–42. http://dx.doi.org/10.1515/jce-2016-0007.
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Abstract Pulmonary embolism (PE) remains a common and potentially life-threatening cardiovascular emergency. Systemic thrombolysis with intravenous infusion of a thrombolytic agent is generally recommended for treatment of high risk PE. However, this method has known limitations in the presence of high bleeding risk. Catheter-directed thrombolysis has the potential to achieve the same benefits as systemic thrombolysis, with a lower risk of haemorrhage. The case presented is of a 67-year-old male patient with a high risk of pulmonary embolism and contraindications for systemic thrombolysis, in whom the presence of severe comorbidities presented an increased risk of surgical embolectomy, who was successfully treated by catheter-directed thrombolysis.
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Mavrogeni, S. I., M. Tsirintani, C. Kleanthous, K. Vranakis, E. Secheta, D. Mihelakis, D. Sotiriou, et al. "Supervision of thrombolysis of acute myocardial infarction using telemedicine." Journal of Telemedicine and Telecare 6, no. 1 (February 2, 2000): 54–58. http://dx.doi.org/10.1258/1357633001933853.
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The treatment of acute myocardial infarction (MI) constitutes a significant problem in remote geographical areas of Greece. Furthermore, thrombolysis, the treatment of choice in the early phase of acute MI, requires the supervision of an expert. We have used thrombolytic treatment, using telemedicine, in remote medical centres. The Onassis Cardiac Surgery Centre was linked to six remote Aegean islands via telemedicine systems which permitted the transmission of 12-lead electrocardiograms (ECGs). The thrombolytic agent anistreplase was administered to patients with acute MI. Supervision, including consultation for treatment of complications, was achieved using the telemedicine system. One hundred and fifty-two ECGs were transmitted during 24 months, of which 108 (71%) indicated specific treatment of a cardiac condition. Ten cases were diagnosed as having acute MI and eight of these were treated with anistreplase. All patients survived acute MI and complications were treated locally. The application of thrombolytic treatment in acute MI is feasible in remote areas, with the use of a telemedicine system.
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Jovic, Zoran, Slobodan Obradovic, Nemanja Djenic, Zorica Mladenovic, Predrag Djuric, Marijan Spasic, and Dragan Tavciovski. "Does thrombolytic therapy harm or help in ST elevation myocardial infarction (STEMI) caused by the spontaneous coronary dissection?" Vojnosanitetski pregled 72, no. 6 (2015): 536–40. http://dx.doi.org/10.2298/vsp1506536j.
Full textAbstract:
Introduction. Spontaneous coronary artery dissection (SCAD) is a very rare disease with poor prognosis. It mainly affects young women free of risk factors for coronary artery disease (CAD) and women during the peripartum period. The prognosis for myocardial infarction caused by SCAD is poor, management is often difficult and guidelines still missing. Case report. We presented a woman with acute myocardial infarction of anterior wall of the left ventricle, caused by spontaneous dissection of medial segment of the left anterior descending coronary artery. We treated the patient with thrombolytic therapy and performed coronary angiography after that. Finally we decided to do nothing more. Two years later we performed coronary angiography again and founded the coronary artery normal. We also analyzed 19 cases publiched from 1996 to 2012 when coronary artery dissection had been treated with thrombolytic agent. Analysis revealed only one case of 19, with complication after treating SCAD with thrombolysis. Conclusion. Sometimes, regarding myocardial infarction in young women with no risk factors for CAD, especially in young women in peripartum, we should think about SCAD. The presented case, like eight others, demonstrates that good clinical outcomes can be achieved with thrombolysis. In spite of all this, we still need more data to verify that thrombolysis does not have to harm the therapy for SCAD. For the time being thrombolytic therapy could be an option.