Aspect of thrombolytic therapy: a review.
Ontology highlight
ABSTRACT:
SUBMITTER: Ali MR
PROVIDER: S-EPMC4276353 | biostudies-other | 2014
REPOSITORIES: biostudies-other
Similar Datasets
Project description: Not available
| S-EPMC6516871 | biostudies-literature
Project description: Not available
| S-EPMC6710099 | biostudies-literature
Project description: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.
| S-EPMC5954957 | biostudies-literature
Project description:BACKGROUND:Previous animal studies by us and others have indicated that catheter-administered plasmin or its des-kringle derivatives may be more appropriate alternatives to plasminogen activators for treating thrombolytic diseases, since it has a very short serum half-life and therefore does not result in hemorrhaging. We have previously produced recombinant miniPlasmin (mPlasmin) that was proven suitable for treating peripheral arterial occlusion in animal models. However, our previous results showed that non-specific cleavage at position K698 of mPlasmin during activation hindered the further development of this promising therapeutic candidate. In order to minimize or eliminate the non-specific cleavage problem, we performed saturation mutagenesis at the K698 position to develop a mutant form of mPlasmin for thrombolytic therapy. METHODS:We changed K698 to 16 other amino acids, with preferred E. coli codons. Each of these mutants were expressed in E. coli as inclusion bodies and then refolded, purified, and subsequently characterized by detailed kinetic assays/experiments/studies which identified highly active mutants devoid of non-specific cleavage. RESULTS:Activation studies indicated that at those conditions in which the wild type enzyme is cut at the non-specific position K698, the active mutants can be activated without being cleaved at this position. CONCLUSIONS:From the above results, we selected two mutants, K698Q and K698N, as our lead candidates for further thrombolytic drug developments. The selected mutants are potentially better therapeutic candidates for thrombolytic therapy.
| S-EPMC3724493 | biostudies-literature
Project description:Ischaemic stroke can occur when an artery to the brain is blocked by a blood clot. The use of thrombolytic agents, such as tissue plasminogen activator (tPA), to dissolve the occluding clot is limited by the risk of intracerebral haemorrhage (ICH), a known side effect associated with tPA. We developed a computational thrombolysis model for a 3D patient-specific artery coupled with a compartmental model for temporal concentrations of tPA and lysis proteins during intravenous infusion of tPA, in order to evaluate the effects of tPA dose on the efficacy of thrombolytic therapy and the risk of ICH. The model was applied to a 3-mm-long fibrin clot with two different fibrin fibre radii in the middle cerebral artery (MCA) - a setting relevant to ischaemic stroke, and results for different tPA dose levels and fibrin fibre radii were compared. Our simulation results showed that clot lysis was accelerated at higher tPA doses at the expense of a substantial increase in the risk of ICH. It was also found that a fine clot with a smaller fibre radius dissolved much slowly than a coarse clot due to a slower tPA penetration into the clots.
| S-EPMC6202379 | biostudies-literature
Project description:Background and Purpose- We aim to determine the potential impact on stroke thrombolysis of drip-and-ship helicopter flights and specifically of their low-frequency vibrations (LFVs). Methods- Mice with a middle cerebral artery autologous thromboembolic occlusion were randomized to receive rtPA (recombinant tissue-type plasminogen activator; or saline) 90 minutes later in 3 different settings: (1) a motion platform simulator that reproduced the LFV signature of the helicopter, (2) a standardized actual helicopter flight, and (3) a ground control. Results- Mice assigned to the LFV simulation while receiving tPA had smaller infarctions (31.6 versus 54.9 mm3; P=0.007) and increased favorable neurological outcomes (86% versus 28%; P=0.0001) when compared with ground controls. Surprisingly, mice receiving tPA in the helicopter did not exhibit smaller infarctions (47.8 versus 54.9 mm3; P=0.58) nor improved neurological outcomes (37% versus 28%; P=0.71). This could be due to a causative effect of the 20- to 30-Hz band, which was inadvertently attenuated during actual flights. Mice using saline showed no differences between the LFV simulator and controls with respect to infarct size (80.9 versus 95.3; P=0.81) or neurological outcomes (25% versus 11%; P=0.24), ruling out an effect of LFV alone. There were no differences in blood-brain barrier permeability between LFV simulator or helicopter, compared with controls (2.45-3.02 versus 4.82 mm3; P=0.14). Conclusions- Vibration in the low-frequency range (0.5-120 Hz) is synergistic with rtPA, significantly improving the effectiveness of thrombolysis without impairing blood-brain barrier permeability. Our findings reveal LFV as a novel, safe, and simple-to-deliver intervention that could improve the outcomes of patients. Visual Overview- An online visual overview is available for this article.
| S-EPMC7263385 | biostudies-literature
Project description:BackgroundSpecific clinical risk factors may contribute to improving or worsening neurological functions in acute ischemic stroke (AIS) patients pre-treated with a combined cholesterol reducer and recombinant tissue plasminogen activator (rtPA) therapy. In this study, clinical risk factors associated with good or poor presenting neurological symptoms in ischemic stroke patients with prior cholesterol reducer use, specifically a statin and rtPA therapy was investigated.MethodsRetrospective data for baseline clinical and demographic data for patients with AIS taking cholesterol reducers prior to rtPA treatment from January 2010 to June 2016 in a regional stroke center was analyzed. Improving (NIHSS score ≤ 7) or worsening (NIHSS score > 7) of neurologic functions were the determined measures of treatment outcome. Multivariate logistic regression models identified demographic and clinical factors associated with worsening or improving neurologic functions.ResultsAdjusted multivariate analysis showed that in an AIS population with a combined rtPA and cholesterol reducer medication history, increasing age (OR = 1.032, 95% CI, 1.015-1.048, P < 0.001) and atrial fibrillation (OR = 1.859, 95% CI, 1.098-3.149, P = 0.021) demonstrated a likely association with worsening neurologic functions, while direct admission (OR = 0.411, 95% CI, 0.246-0.686, P = 0.001) and being Caucasian (OR = 0.496, 95% CI, 0.297-0.827, P = 0.007) showed an association with improving or progressing neurologic functions.ConclusionA prior cholesterol reducer, namely a statin, plus rtPA combination may be associated with worsening neurological function for elderly AIS patients with atrial fibrillation, while Caucasians directly admitted to a neurology unit are more likely to show an association with progress or improvements in neurologic functions. While combining statin with rtPA treatment may facilitate worsening neurologic functions in elderly AIS patients with atrial fibrillation, they should not be denied of this therapy. The decision to combine statin and rtPA for AIS patients with atrial fibrillation can be done after clinical stabilization following appropriate clinical management.
| S-EPMC7201805 | biostudies-literature
Project description:Mechanical heart valves require long-term anticoagulation strategies to prevent valve thrombosis. Pregnant women with mechanical heart valves are especially susceptible to valve thrombosis, given their procoagulant state and the complexity of anticoagulation strategies during pregnancy. We describe a case of prosthetic valve thrombosis in a pregnant woman treated successfully with low-dose slow infusion of thrombolytic therapy. A 23-year-old pregnant woman with a mechanical aortic valve on subcutaneous enoxaparin presented to the maternal cardiac clinic for a follow-up visit. Her physical exam was notable for a loud grade three crescendo decrescendo murmur and follow-up transthoracic echocardiography revealed peak and mean gradients of 87 and 58 mmHg, respectively. The Doppler velocity index (DVI) was 0.24 with an acceleration time of 130 ms. Fluoroscopy confirmed a stuck leaflet disk. Thrombolysis was performed using a low-dose ultra-slow infusion of thrombolytic therapy (1 mg/h of tissue-type plasminogen activator) with the restoration of normal valve function after 8 days. A repeat transthoracic echocardiography showed a decrease in the peak and mean gradients to 37 and 21 mmHg, respectively, with an improvement in the DVI to 0.53. Repeat fluoroscopy confirmed the opening of both leaflet disks. Treatment options for mechanical aortic valve thrombosis are either slow-infusion, low-dose thrombolytic therapy or emergency surgery. The hypercoagulable state of pregnancy makes adequate anticoagulation, proper monitoring, and medication adherence even more critical to prevent valve thrombosis. Physicians should educate pregnant patients on anticoagulation strategies and participate in shared decision-making.
| S-EPMC9757675 | biostudies-literature
Project description:In recent years, pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose. Indeed, pharmacogenetics may exert its action on immunosuppressant drugs at three levels. Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation. Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants. Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways. Of course, not all genes have been discovered and studied, but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined. Other genes on the basis of relevant studies have been proposed as good candidates for future studies. Unfortunately, to date, clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney, heart and lung transplantation is recommended. The conclusions of the studies on the recommended candidate genes, together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.
| S-EPMC7428791 | biostudies-literature
Project description:Background and Purpose- Dual antiplatelet treatment poses a risk for increased hemorrhagic transformation (HT) following intravenous thrombolysis and mechanical thrombectomy. The aim of this study was to implement a model of experimental stroke with tissue-type plasminogen activator (tPA)-associated HT in mice on dual antiplatelet treatment to enable mechanistic studies and also to allow for an initial assessment of therapeutic approaches to limit HT. Methods- Male C57BL6 mice were fed with Aspirin and Clopidogrel via drinking water for 3 days. Subsequently, mice were subjected to 2-hour transient middle cerebral artery occlusion, and tPA was infused when indicated. HT was quantified by measuring hemorrhaged areas in brain sections with ImageJ. TTC staining was used to determine infarct size. Platelet function was tested in vitro using flow cytometry and in vivo with standard tail bleeding tests. Results- Both flow cytometry and tail bleeding volumes indicated significantly reduced platelet function following Aspirin and Clopidogrel treatment. While tPA administered 2 hours after onset of middle cerebral artery occlusion did not cause bleeding in control mice (0.51±0.13 mm2), HT significantly increased by 18.9±5.4 mm2 (P=0.0045) in Aspirin and Clopidogrel mice treated with tPA. HT in aspirin and clopidogrel mice not treated with tPA was nonsignificantly elevated by 8.0±4.6 mm2 (P=0.3784) compared with controls. Infarct sizes did not differ between groups. The HT persisted when the tPA dosage was reduced. Conclusions- We successfully established a translational stroke model of tPA treatment under dual antiplatelet treatment. The impaired platelet function led to an increased risk for HT in tPA-treated mice. Reducing the dosage of tPA did not prevent this hemorrhagic complication.
| S-EPMC6878181 | biostudies-literature