Heparin, Low Molecular Weight Heparin, and Non-Anticoagulant Derivatives for the Treatment of Inflammatory Lung Disease

Shute, Janis K.

doi:10.3390/ph16040584

Cited by 16 publications

(5 citation statements)

References 199 publications

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“…In addition, it is noteworthy that our patients have received unfractionated heparin. Even though its antimicrobial, anti-inflammatory, and mucoactive activities are shared by low molecular weight heparin (LMWH), unfractionated heparin appears more potent than low molecular heparin regarding, for example, anti-viral effects [ 37 , 38 ]. Further research is needed to explore these topics (lower cardiovascular risk under RCA and differences between unfractionated and LMW heparin) more extensively.…”

Section: Discussionmentioning

confidence: 99%

Monocytes as Targets for Immunomodulation by Regional Citrate Anticoagulation

Di Marco,

Chasan,

Boeckel

et al. 2024

IJMS

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Immune alterations in end-stage renal patients receiving hemodialysis are complex and predispose patients to infections. Anticoagulation may also play an immunomodulatory role in addition to the accumulation of uremic toxins and the effects of the dialysis procedure. Accordingly, it has been recently shown that the infection rate increases in patients under regional citrate anticoagulation (RCA) compared with systemic heparin anticoagulation (SHA). We hypothesized that RCA affects the immune status of hemodialysis patients by targeting monocytes. In a cohort of 38 end-stage renal patients undergoing hemodialysis, we demonstrated that whole blood monocytes of patients receiving RCA—but not SHA—failed to upregulate surface activation markers, like human leukocyte antigen class II (HLA-DR), after stressful insults, indicating a state of deactivation during and immediately after dialysis. Additionally, RNA sequencing (RNA-seq) data and gene set enrichment analysis of pre-dialysis monocytes evidenced a great and complex difference between the groups given that, in the RCA group, monocytes displayed a dramatic transcriptional change with increased expression of genes related to the cell cycle regulation, cellular metabolism, and cytokine signaling, compatible with the reprogramming of the immune response. Transcriptomic changes in pre-dialysis monocytes signalize the lasting nature of the RCA-related effects, suggesting that monocytes are affected even beyond the dialysis session. Furthermore, these findings demonstrate that RCA—but not SHA—impairs the response of monocytes to activation stimuli and alters the immune status of these patients with potential clinical implications.

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Section: Discussionmentioning

confidence: 99%

Monocytes as Targets for Immunomodulation by Regional Citrate Anticoagulation

Di Marco,

Chasan,

Boeckel

et al. 2024

IJMS

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“…Early intervention with heparin is crucial for ARDS treatment strategies, possibly due to its impact on the inflammatory response and the progression of secondary injury, as well as its role in reducing the risk of microvascular thrombosis, thereby helping to maintain the stability of the pulmonary microcirculation and improve clinical outcomes for patients [ 25 ]. Our findings echo those of existing studies.…”

Section: Discussionmentioning

confidence: 99%

“…In the current literature, studies exploring the impact of subcutaneously administered prophylactic heparin on acute respiratory distress syndrome (ARDS) are relatively scarce. The majority of related research has focused on the effects of therapeutically dosed heparin, administered via nebulization or intravenous injection, on ARDS patients, particularly in those studies concerning COVID-19 patients [ 25 , 44 ]. In contrast, our study delves into the potential benefits of early subcutaneous administration of prophylactic heparin in non-COVID-19 ARDS patients.…”

Section: Discussionmentioning

confidence: 99%

Exploring the therapeutic role of early heparin administration in ARDS management: a MIMIC-IV database analysis

Xiao,

Zhu,

Chen

et al. 2024

j intensive care

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Background Acute respiratory distress syndrome (ARDS) is a severe respiratory condition characterized by a high mortality rate, the management of which relies on supportive care and a profound understanding of its pathophysiology. Heparin, with its anticoagulant and potential anti-inflammatory properties, offers a new therapeutic opportunity for the treatment of ARDS. Methods In this retrospective cohort study, we examined the MIMIC-IV database for ARDS patients who received prophylactic heparin within the first 72 h of ICU admission. Employing propensity score matching and inverse probability weighting (IPW) analysis, we evaluated the impact of early heparin use on patient outcomes, focusing on mortality rates. Results Patients who received prophylactic heparin had a significantly lower in-hospital mortality rate compared to those who did not (13.55% vs 17.93%, HR = 0.71, 95% CI: 0.54–0.93, P = 0.012). This result remained significant after propensity score matching (12.75% vs 17.93%, HR = 0.65, 95% CI 0.47–0.90, P = 0.010). Analysis using five different statistical models indicated that early use of heparin significantly reduced the in-hospital mortality rate, with HR = 0.669 (95% CI 0.487–0.919, P = 0.013) in the doubly robust model without balanced covariates; HR = 0.705 (95% CI 0.515–0.965, P = 0.029) with all covariates considered; HR = 0.660 (95% CI 0.491–0.888, P = 0.006) in the propensity score (IPW) model; HR = 0.650 (95% CI 0.470–0.900, P = 0.010) in the propensity score matching model; and HR = 0.706 (95% CI 0.536–0.930, P = 0.013) in the multivariate Cox regression model. Secondary outcomes indicated that heparin use was also associated with reduced mortality rates at 60 days, and 90 days. Conclusion This research highlights that early prophylactic administration of heparin may substantially lower mortality in ARDS patients. These findings underscore the potential of heparin as a key component in the management of ARDS, offering a new perspective and novel strategies for clinical treatment.

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“…Clinical studies have shown that it can prevent SARS-CoV-2 from adhering to nasal epithelial cells, effectively preventing infection by the virus [ 128 ]. In addition, this dosage form of LMWHs is easy to apply and carry and has potential use for possible lung diseases such as acute lung injury, chronic obstructive pulmonary disease, cystic fibrosis, and asthma [ 129 ].…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

Non-Anticoagulant Activities of Low Molecular Weight Heparins—A Review

Feng,

Wang,

Zhou

et al. 2023

Pharmaceuticals

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Low molecular weight heparins (LMWHs) are derived from heparin through chemical or enzymatic cleavage with an average molecular weight (Mw) of 2000–8000 Da. They exhibit more selective activities and advantages over heparin, causing fewer side effects, such as bleeding and heparin-induced thrombocytopenia. Due to different preparation methods, LMWHs have diverse structures and extensive biological activities. In this review, we describe the basic preparation methods in this field and compare the main principles and advantages of these specific methods in detail. Importantly, we focus on the non-anticoagulant pharmacological effects of LMWHs and their conjugates, such as preventing glycocalyx shedding, anti-inflammatory, antiviral infection, anti-fibrosis, inhibiting angiogenesis, inhibiting cell adhesion and improving endothelial function. LMWHs are effective in various diseases at the animal level, including cancer, some viral diseases, fibrotic diseases, and obstetric diseases. Finally, we briefly summarize their usage and potential applications in the clinic to promote the development and utilization of LMWHs.

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Heparin, Low Molecular Weight Heparin, and Non-Anticoagulant Derivatives for the Treatment of Inflammatory Lung Disease

Cited by 16 publications

References 199 publications

Monocytes as Targets for Immunomodulation by Regional Citrate Anticoagulation

Monocytes as Targets for Immunomodulation by Regional Citrate Anticoagulation

Exploring the therapeutic role of early heparin administration in ARDS management: a MIMIC-IV database analysis

Non-Anticoagulant Activities of Low Molecular Weight Heparins—A Review

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