Methods available to assess therapeutic potential of fibrinolytic enzymes of microbial origin: a review

Krishnamurthy, Anusha; Belur, Prasanna D.; Subramanya, Sandeep B.

doi:10.1186/s40543-018-0143-3

Cited by 21 publications

(21 citation statements)

References 66 publications

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“…However, some of the older global tests are considered to have poor reproducibility, to the extent of possibly affecting the outcome of trials. 63,70 The evidence for underlying changes in specific components of fibrinolysis is also weaker. There is some indication that tPA activity may increase, 52 but it has also been shown to increase in healthy controls after 2 hours' rest.…”

Section: Discussionmentioning

confidence: 99%

Haematological Effects of Intermittent Pneumatic Compression for Deep Vein Thrombosis Prophylaxis

Morris

Roberts

2020

Thromb Haemost

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Intermittent pneumatic compression (IPC) is a widely used and recommended method to prevent deep vein thrombosis. While the haemodynamic effects of IPC are well understood, the objective of this systematic review was to analyse the evidence for additional haematological changes. Forty-eight studies were identified where the haematological effects of IPC were measured. The many differences between the studies prevented meta-analysis, but there was a significant amount of evidence that global fibrinolytic activity was increased by IPC, and that levels of D-dimer and tissue factor pathway inhibitor in the blood also increased. There was less consistent evidence for changes in tissue plasminogen activator, plasminogen activator inhibitor and other fibrinolytic parameters. The evidence for changes in pro-coagulant factors and many measures of platelet activation was weak, but there was evidence for increases in prostacyclin. There is sufficient evidence to conclude that IPC does produce haematological changes, but not enough data to clarify the detail of those changes or to determine if it is mediated more by direct compression of the blood vessels, or by the flow changes.

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Section: Discussionmentioning

confidence: 99%

Haematological Effects of Intermittent Pneumatic Compression for Deep Vein Thrombosis Prophylaxis

Morris

Roberts

2020

Thromb Haemost

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“…In vitro testing of thrombolytics is typically based on the physiological fibrinolytic pathway (Figure 3A); however, individual assays differ in the level of their complexity, analysis time, reproducibility, and the targeted property. 133,134 Since none of these methods is superior, it is necessary to always choose the most relevant ones for a given purpose. To obtain a complex understanding of the studied thrombolytics, a combination of different methods may need to be used.…”

Section: In Vitro Testing Of Novel Thrombolyticsmentioning

confidence: 99%

Development and Testing of Thrombolytics in Stroke

Nikitin¹,

Choi

Mičan³

et al. 2021

J Stroke

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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>.

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“…Fibrinolytic enzymes are involved in the degradation of fibrin clots, by either catalyzing fibrin degradation process or by transforming the inactive plasminogen into active plasmin, thus re-establishing the normal blood vascular architecture (Krishnamurthy et al, 2018). They are largely proteases, which are involved in the total hydrolysis of proteins, and can be produced from all living cells especially bacteria.…”

Section: Introductionmentioning

confidence: 99%

Role of Fibrinolytic Enzymes in Anti-Thrombosis Therapy

Altaf

Kasim

2021

Front. Mol. Biosci.

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Thrombosis, a major cause of deaths in this modern era responsible for 31% of all global deaths reported by WHO in 2017, is due to the aggregation of fibrin in blood vessels which leads to myocardial infarction or other cardiovascular diseases (CVDs). Classical agents such as anti-platelet, anti-coagulant drugs or other enzymes used for thrombosis treatment at present could leads to unwanted side effects including bleeding complication, hemorrhage and allergy. Furthermore, their high cost is a burden for patients, especially for those from low and middle-income countries. Hence, there is an urgent need to develop novel and low-cost drugs for thrombosis treatment. Fibrinolytic enzymes, including plasmin like proteins such as proteases, nattokinase, and lumbrokinase, as well as plasminogen activators such as urokinase plasminogen activator, and tissue-type plasminogen activator, could eliminate thrombi with high efficacy rate and do not have significant drawbacks by directly degrading the fibrin. Furthermore, they could be produced with high-yield and in a cost-effective manner from microorganisms as well as other sources. Hence, they have been considered as potential compounds for thrombosis therapy. Herein, we will discuss about natural mechanism of fibrinolysis and thrombus formation, the production of fibrinolytic enzymes from different sources and their application as drugs for thrombosis therapy.

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Methods available to assess therapeutic potential of fibrinolytic enzymes of microbial origin: a review

Cited by 21 publications

References 66 publications

Haematological Effects of Intermittent Pneumatic Compression for Deep Vein Thrombosis Prophylaxis

Haematological Effects of Intermittent Pneumatic Compression for Deep Vein Thrombosis Prophylaxis

Development and Testing of Thrombolytics in Stroke

Role of Fibrinolytic Enzymes in Anti-Thrombosis Therapy

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