Pharmacological and clinical application of heparin progress: An essential drug for modern medicine

Qiu, Min; Huang, Shengjie; Luo, Chuanhong; Wu, Zhenfeng; Liang, Binzhu; Huang, Haozhou; Ci, Zhimin; Zhang, Dingkun; Han, Li; Lin, Junzhi

doi:10.1016/j.biopha.2021.111561

Cited by 74 publications

(43 citation statements)

References 196 publications

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“…The study also increases the understanding of 3-O-sulfated motifs that lack anticoagulant activity, which may be desirable in the development of tailor-made GAG-based therapeutics where anticoagulant effects are unwanted. This may include GAG designs with anti-inflammatory, antitumor, antioxidant, and antiviral properties ( 59 ). Furthermore, the library of HS3ST KI cells can be applied beyond dissection of binding to ATIII and PF4 for determining binding specificities for known 3-O-sulfate–binding proteins such as neuropilin-1, cyclophilin B, stabilin, receptor for advanced glycation endproducts (RAGE), fibroblast growth factor–7 (FGF-7), FGF-9, FGF receptor–1 (FGFR-1), and bone morphogenetic protein 2 and 4 (BMP-2/4) ( 17 , 60 ).…”

Section: Discussionmentioning

confidence: 99%

Dissecting structure-function of 3-O-sulfated heparin and engineered heparan sulfates

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Dissecting structure-function of 3-O-sulfated heparin and engineered heparan sulfates

et al. 2021

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“…Максимальную анти-Ха активность в плазме крови наблюдали через 3-5 ч после введения препарата, максимальную концентрацию TFPI -через 1-4 ч после введения, далее наблюдали постепенное снижение регистрируемых значений (рис. 3a По данным литературы, анти-Ха активность надропарина кальция приблизительно в 4 раза превосходит его анти-IIа активность [9][10][11] 16 ; фармакокинетические свойства препарата «Фраксипарин форте» определяются его анти-Хафакторной активностью, поскольку активность данного фактора выше, чем анти-IIа фактора 17 ; низкомолекулярные гепарины, к которым относят дальтепарин натрия, надропарин кальция и эноксапарин натрия, сильнее влияют на фактор Ха, чем на фактор IIа, что приводит к более выраженному подавлению образования тромбина, а также сильнее влияют на фактор ингибитора активатора плазминогена [12]. Авторы [13, 14] отмечают, что избирательность действия в отношении анти-Ха активности падает в ряду эноксапарин → надропарин → далтепарин → тинзапарин.…”

Section: материалы и методыunclassified

Considerations for the Bioanalytical Part of Equivalence Studies of Biosimilar Nadroparin Calcium

Косман¹,

Karlina²,

Фаустова³

et al. 2023

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

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According to current regulatory views, a comparative study of the pharmacodynamics (PD) of low molecular weight heparin (LMWH) products and confirmation of their equivalence require comparing three PD markers: the anti-Xa activity, the anti-IIa activity, and the tissue factor pathway inhibitor (TFPI) concentration.The aim of this study was to analyse the features specific to the bioanalytical part of an equivalence study of a nadroparin calcium biosimilar after single subcutaneous administration.Material and methods: the anti-Xa and anti-IIa activity values and TFPI content were determined in human plasma samples obtained after single subcutaneous administration of the test and the reference product in the same dose, using commercially available reagent kits and pre-validated assays. The authors calculated the main PD parameters (surrogate pharmacokinetic markers), namely the maximum activity or concentration (Amax or Cmax), time to maximum activity or concentration (Tmax), area under the activity–time (or concentration–time) curve (AUC), and half-life period (T1/2), by means of the model-independent statistical moment analysis and carried out further statistical testing of the parameters.Results: the anti-Xa activity and TFPI concentration results provided for the possibility of calculating and comparing the PD parameters (Amax or Cmax, AUC0-24, AUC0-∞, Tmax, T1/2) and estimating the confidence intervals that are necessary to confirm the bioequivalence of the studied products. The anti-IIa activity data had a characteristic pattern of slight fluctuations around one level, which prevented the calculation and comparison of PD parameters.Conclusion: the study identified specific features to consider when planning comparative PD studies of nadroparin calcium products. Firstly, it is feasible to divide samples into two test aliquots (one for anti-Xa and anti-IIa activity determination, the other for TFPI analysis) at the moment of collection in order to perform the analytical step correctly. Secondly, there is no need in full validation for the bioanalytical assays of the anti-Xa and anti-II activity and TFPI content in human plasma validated in the concentration ranges of 0.024–0.182 IU/mL, 0.0069–0.052 IU/mL and 1.56–100 ng/mL, respectively; a confirmation that the active ingredient does not interfere with the analytical procedure is adequate for the purpose. Finally, the data obtained may not allow for calculating PD parameters and comparing confidence intervals for all three markers. The listed considerations may be relevant for other LMWH products as well.

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“…PLTs are implicated in the pathogenesis of venous thrombosis ( Qiu et al, 2021 ). Evidence of PLTs activation in patients with acute VTE demonstrates that PLTs play an essential role in the amplification and propagation of venous thrombosis.…”

Section: Introductionmentioning

confidence: 99%

The Central Role of Extracellular Vesicles in the Mechanisms of Thrombosis in COVID-19 Patients With Cancer and Therapeutic Strategies

Jing

Zuo

Novakovic

et al. 2022

Front. Cell Dev. Biol.

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Cancer patients have increased SARS-CoV-2 susceptibility and are prone to developing severe COVID-19 infections. The incidence of venous thrombosis is approximately 20% in COVID-19 patients with cancer. It has been suggested that thrombus formation has been suggested to correlate with severe clinical manifestations, mortality, and sequelae. In this review, we primarily elaborate on the pathophysiological mechanisms of thrombosis in COVID-19 patients with cancer, emphasize the role of microparticles (MPs) and phosphatidylserine (PS) in coagulation, and propose an antithrombotic strategy. The coagulation mechanisms of COVID-19 and cancer synergistically amplify the coagulation cascade, and collectively promotes pulmonary microvascular occlusion. During systemic coagulation, the virus activates immune cells to release abundant proinflammatory cytokines, referred to as cytokine storm, resulting in the apoptosis of tumor and blood cells and subsequent MPs release. Additionally, we highlight that tumor cells contribute to MPs and coagulation by apoptosis owing to insufficient blood supply. A positive feedback loop of cytokines storm and MPs storm promotes microvascular coagulation storm, leading to microthrombi formation and inadequate blood perfusion. Microthrombi-damaged endothelial cells (ECs), tumor, and blood cells further aggravate the apoptosis of the cells and facilitate MPs storm. PS, especially on MPs, plays a pivotal role in the blood coagulation process, contributing to clot initiation, amplification, and propagation. Since coagulation is a common pathway of COVID-19 and cancer, and associated with mortality, patients would benefit from antithrombotic therapy. The above results lead us to assert that early stage antithrombotic therapy is optimal. This strategy is likely to maintain blood flow patency contributing to viral clearance, attenuating the formation of cytokines and MPs storm, maintaining oxygen saturation, and avoiding the progress of the disease.

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Pharmacological and clinical application of heparin progress: An essential drug for modern medicine

Cited by 74 publications

References 196 publications

Dissecting structure-function of 3-O-sulfated heparin and engineered heparan sulfates

Dissecting structure-function of 3-O-sulfated heparin and engineered heparan sulfates

Considerations for the Bioanalytical Part of Equivalence Studies of Biosimilar Nadroparin Calcium

The Central Role of Extracellular Vesicles in the Mechanisms of Thrombosis in COVID-19 Patients With Cancer and Therapeutic Strategies

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