Heparin: Physiology, Pharmacology, and Clinical Application

Lee, Michael S.; Kong, Jeremy

doi:10.3909/ricm0778

Cited by 17 publications

(13 citation statements)

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“…Basophil cytokine responses to COVID-19 might help reducing the inflammation and also promoting antibody responses to the virus. Furthermore, basophils store the secretory granules of heparin that is only released into the vasculature at sites of injury [29], therefore helping maintaining a proper blood flow by balancing the active anticoagulant and procoagulant processes in pato-fisological condition. This property could be hypothesized also during the Table 3 Explorative mediation analysis of the direct and indirect effects of glucose on mortality; the average causal mediation effect (ACME) and the average direct effect (ADE) represent the estimated averages of the mediation and direct effects, respectively COVID-19 infection of diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Predictive markers for clinical outcomes in a cohort of diabetic patients hospitalized for COVID-19

Madaschi

Resmini

Bonfadini

et al. 2022

Diabetol Metab Syndr

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Introduction The role of glycemic control, both prior and during hospitalization, on mortality from COVID-19 in diabetic patients is debated. Furthermore, it is not clear whether hyperglycemia has a direct effect or requires inflammatory mechanisms. Objective To identify predictors of clinical outcomes (in-hospital mortality, length of hospitalization, respiratory failure, need for intensive care), considering hyperglycemia, inflammation markers and clinical history. Methods Retrospective observational study of 291 diabetic patients hospitalized with COVID-19 in the Spedali Civili di Brescia from February 1th 2020 to March 31th 2021, with also outpatient electronic records. Glucose, inflammatory parameters, creatinine were collected within 24 h after admission to the hospital. A causal mediation analysis allowed the estimation of the direct and indirect effects of hyperglycemia on mortality. Results Glucose at admission ≥ 165 mg/dL and reduced renal function were associated with an increased risk of in-hospital mortality and length of hospitalization (all p < 0.001), while an increase in inflammatory parameters was significantly associated with an increased risk of all outcomes. High basophil count was associated with reduced mortality (p < 0.001). Hyperglycemia had a direct effect on mortality (p < 0.001); the indirect, through inflammatory markers, was significant only for absolute neutrophil count, C-Reactive protein and procalcitonin (p = 0.007, p = 0.029, p = 0.042). Patients with microvascular complications and with chronic kidney disease showed higher mortality (p = 0.03, p = 0.01). Conclusions Hyperglycemia at admission, renal function and inflammatory parameters were found to be predictors of in-hospital mortality, while an increased basophil count was protective. Hyperglycemia had a direct effect on mortality, the indirect effect was only through few markers and markedly lower than the direct one.

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Section: Discussionmentioning

confidence: 99%

Predictive markers for clinical outcomes in a cohort of diabetic patients hospitalized for COVID-19

Madaschi

Resmini

Bonfadini

et al. 2022

Diabetol Metab Syndr

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“…Heparin (HEP) is an anticoagulant and antithrombotic agent with many pharmaceutical applications, including the treatment of acute coronary syndrome, atrial fibrillation, pulmonary embolism, and arterial thrombosis [ 1 , 2 ]. In addition, the antiangiogenesis, antimetastasis, and antitumor cell proliferation properties of HEP make it an extremely valuable commercial biomolecule.…”

Section: Introductionmentioning

confidence: 99%

“…HEP is typically extracted from the intestinal mucosa of pigs, even though there exist other such viable sources [ 9 ]. It is isolated through multi-step adsorption–desorption cycles after the digestion process, which depend on the adsorbent surface properties, porosity, as well as its thermodynamic and chemical stability, in order to extract the maximum possible HEP as the outcome [ 1 , 10 , 11 , 12 ]. However, the amount of recovery is very low and often requires multiple purifications to selectively separate HEP from other components, such as proteins, nucleic acids, etc., found in the digestion mixture, thus making the entire process laborious and unsustainable [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Efficient and Economic Heparin Recovery from Porcine Intestinal Mucosa Using Quaternary Ammonium-Functionalized Silica Gel

et al. 2022

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Heparin, usually isolated from porcine intestinal mucosa, is an active pharmaceutical ingredient of great material value. Traditionally, diverse types of commercial resins were employed as an adsorbent for heparin retrieval from biological samples. However, more recent years have encouraged the advent of new cost-effective adsorbents to achieve enhanced heparin retrieval. Inexpensive cationic ammonium-functionalized silica gels, monodispersed with larger surface area, porosity, and higher thermal stability, were chosen to evaluate the heparin recovery yield from porcine intestinal mucosa. We demonstrated that higher positively charged and less bulky quaternary modified silica gel (e.g., QDASi) could adsorb ~28% (14.7 mg g−1) heparin from the real samples. In addition, we also determined suitable surface conditions for the heparin molecule adsorption by mechanistic studies and optimized different variables, such as pH, temperature, etc., to improve the heparin adsorption. This is going to be the first reported study on the usage of quaternary amine-functionalized silica gel for HEP uptake.

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“…Heparin is a polysaccharide biomacromolecule featuring a linear long-chain, sulfur-rich glycosaminoglycan with a high density of negative charges (Scheme ). As a drug, heparin has many applications for the treatment of arterial thrombosis, atrial fibrillation, acute coronary syndrome, and pulmonary embolism due to its antithrombotic property that makes it the main injectable anticoagulant used today . Beside this main application, heparin also shows antitumor cell proliferation, anti-inflammation, antimetastasis, and antiangiogenesis properties , and has also been used extensively in a variety of applications and technologies related to drug delivery and tissue engineering. − …”

Section: Introductionmentioning

confidence: 99%

One-Pot Synthesis of Cross-Linked Polymer Networks as a Hydrophilic Super-Adsorbent for Efficient Recovery of Heparin

Enayati

Eskandarloo

Abbaspourrad

2019

ACS Appl. Polym. Mater.

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Heparin is a naturally occurring sulfated glycosaminoglycan polysaccharide often used as an anticoagulant agent. In this work, a series of water swellable cross-linked polymer networks consisting of acrylamide (AAm) as a support, N,N′methylene bis(acrylamide) (BisAAm) as a cross-linker, and (3-acrylamidopropyl)-trimethylammonium chloride) (APTMAC) as a heparin adsorbent was synthesized in water at different ratios of AAm to APTMAC in one-pot. A two-step polymerization process was used to incorporate APTMAC as an adsorbent primarily on the surface of the preformed but still growing crosslinked AAm support (X-AAm). Heparin adsorption results showed that the sample with 15 mol % APTMAC incorporated into the X-AAm core demonstrated efficiency as high as the 100% APTMAC resin, with a high adsorption capacity of 223.36 mg g −1 , which makes it the sample of choice for industrial application and cost-effectiveness. The adsorption efficiency of the optimized sample, X-AAm-APTMAC-(85−15) (that contains 15 mol % APTMAC), was evaluated versus some of the operational variables, including adsorbent dosage, initial heparin concentration, temperature, pH, and time as well as the stability and reusability of the resin, which showed satisfying performance in a wide range of operational parameters with suitable stability and reusability. Heparin was efficiently adsorbed by the X-AAm-APTMAC-(85−15) from a biological sample containing enzymatically digested heparin. The calculated bioactivity of heparin eluted from X-AAm-APTMAC-(85−15) beads and Amberlite FPA98 Cl, an industrially available adsorbent for heparin recovery, was 3430 and 2623 units, respectively. Therefore, the eluted heparin that adsorbed from the biological mixture using synthesized resin complies with the requirement of the United States Pharmacopeia.

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Heparin: Physiology, Pharmacology, and Clinical Application

Cited by 17 publications

References 0 publications

Predictive markers for clinical outcomes in a cohort of diabetic patients hospitalized for COVID-19

Predictive markers for clinical outcomes in a cohort of diabetic patients hospitalized for COVID-19

Efficient and Economic Heparin Recovery from Porcine Intestinal Mucosa Using Quaternary Ammonium-Functionalized Silica Gel

One-Pot Synthesis of Cross-Linked Polymer Networks as a Hydrophilic Super-Adsorbent for Efficient Recovery of Heparin

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