Non-anticoagulant effects of low molecular weight heparins in inflammatory disorders: A review

Yan, Yishu; Yang, Jing; Su, Nan; Xiang, Ming; Wang, Yi; Du, Shanshan; Zhu, Wenming; Zhang, Chong; Lu, Yuan; Xing, Xin‐Hui

doi:10.1016/j.carbpol.2016.12.037

Cited by 51 publications

(29 citation statements)

References 97 publications

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“…This effect may instead be due to the non-anticoagulant effects of lMWH (40). according to previous studies, nadroparin, which was used in the present study, has anti-inflammatory, anti-metastatic and anti-fibrotic activities (41)(42)(43)(44). Yalniz et al (44) reported that nadroparin exerts anti-oxidative and anti-inflammatory effects by regulating the nF-κB and nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathways.…”

Section: Discussionmentioning

confidence: 60%

Low molecular weight heparin (nadroparin) improves placental permeability in rats with gestational diabetes mellitus via reduction of tight junction factors

et al. 2019

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Section: Discussionmentioning

confidence: 60%

Low molecular weight heparin (nadroparin) improves placental permeability in rats with gestational diabetes mellitus via reduction of tight junction factors

et al. 2019

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“…Many of the applications of heparin may stem, at least in part, from the ability of heparin to moderate inflammation (see [19,79]). In general, heparin is perceived as acting via several routes, among them interaction with cytokines [80].…”

Section: Discussionmentioning

confidence: 99%

Heparin as an Anti-Inflammatory Agent

Litov

Petkov

Rangelov

et al. 2020

Preprint

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Timely control of the cytokine release syndrome (CRS) at the severe stage of COVID-19 is key to improving the treatment success and reducing the mortality rate. The inhibition of the activity of the two key cytokines, IFNγ and IL-6, can significantly reduce or even reverse the development of the cytokine storm. The objective of our investigations is to reveal the anti-inflammatory potential of heparin for prevention and suppression of the development of CRS in acute COVID-19 patients.The effect of low-molecular-weight heparin (LMWH) on IFNγ signalling inside the stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. The mechanism of heparin binding to IFNγ and IL-6 and therefore inhibition of their activity was studied by means of extensive molecular-dynamics simulations. We find that LMWH binds with high affinity to IFNγ and is able to inhibit fully the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Rα thus preventing the formation of the IL-6/IL-6Rα/gp130 signaling complex. Our conclusion is that heparin is a potent anti-inflammatory agent that can be used in acute inflammatory conditions, due to its potential to inhibit both IFN γ and IL-6 signalling pathways. Based on our results and available clinical observations, we suggest the administration of LMWH to COVID-19 patients in the initial stages of the acute phase. The beginning of the treatment and the dosage should be based on a careful follow-up of the platelet count and the D-dimer, IL-6, IFN, T-cells, and B-cells levels.

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“…LMWH, an effective anticoagulation agent, can inhibit blood coagulation cascade through indirect interaction with antithrombin III so as to reduce blood viscosity and improve microcirculation . Besides its anticoagulation effect, LMWH could also inhibit inflammation during the progression of disease . It has also been demonstrated that LMWH can downregulate proinflammatory cytokine production, induce a profound change in human neutrophils to generate neutrophil extracellular traps to control inflammation, and reduce the occurrence of pancreatic encephalopathy through inhibition of inflammatory activation in animal experiment .…”

Section: Discussionmentioning

confidence: 99%

“…34 Besides its anticoagulation effect, LMWH could also inhibit inflammation during the progression of disease. 35,36 It has also been demonstrated that LMWH can downregulate proinflammatory cytokine production, induce a profound change in human neutrophils to generate neutrophil extracellular traps to control inflammation, 36 and reduce the occurrence of pancreatic encephalopathy through inhibition of inflammatory activation in animal experiment. 37 Our meta-analysis showed the levels of WBC and CRP were lower in LMWH treatment group than in the conventional treatment group, supporting that LMWH had anti-inflammatory effect.…”

Section: Discussionmentioning

confidence: 99%

The efficacy of low molecular weight heparin in severe acute pancreatitis: A systematic review and meta‐analysis of randomized controlled trials

Qiu

Tang

et al. 2019

J of Digest Diseases

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Objective The effects of low molecular weight heparin (LMWH) on severe acute pancreatitis (SAP) have been controversial. We aimed to evaluate the efficacy of LMWH on prognosis of SAP by systematic review and meta‐analysis. Methods We searched relevant studies published up to March 2019 in five databases (MEDLINE/PubMed, EMBASE, the Cochrane Central Register of Controlled Trials in Cochrane Library, China National Knowledge Infrastructure, and the Chinese Journal of Science and Technology of VIP database). Results Sixteen randomized controlled trials with 1625 patients were included in the final analysis. Most studies were from China. In analysis of laboratory parameters and clinical scores, SAP patients receiving LMWH treatment had lower white blood cell counts, C‐reactive protein level, Acute Physiology and Chronic Health Evaluation II score, and computed tomography severity index. In clinical outcomes, SAP patients who received LMWH treatment had shorter hospital stay (pooled mean difference [95% confidence interval; CI] −8.79 [−11.18, −6.40], P < .01), lower mortality (pooled risk ratio [RR] [95% CI] 0.33 [0.24‐0.44], P < .01), lower incidences of multiple organ failure (pooled RR [95% CI] 0.34 [0.23‐0.52], P < .01), pancreatic pseudocyst (pooled RR [95% CI] 0.49 [0.27‐0.90], P = .02), and operation rate (pooled RR [95% CI] 0.39 [0.31‐0.50], P < .01). Conclusions LMWH could improve the prognosis of SAP, and has a potential role in reducing hospital stay, mortality, incidences of multiple organ failure, pancreatic pseudocyst, and operation rate.

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Non-anticoagulant effects of low molecular weight heparins in inflammatory disorders: A review

Cited by 51 publications

References 97 publications

Low molecular weight heparin (nadroparin) improves placental permeability in rats with gestational diabetes mellitus via reduction of tight junction factors

Low molecular weight heparin (nadroparin) improves placental permeability in rats with gestational diabetes mellitus via reduction of tight junction factors

Heparin as an Anti-Inflammatory Agent

The efficacy of low molecular weight heparin in severe acute pancreatitis: A systematic review and meta‐analysis of randomized controlled trials

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