Inhaled nebulised unfractionated heparin improves lung function in moderate to very severe COPD: A pilot study

Shute, Janis K.; Calzetta, Luigino; Cardaci, Vittorio; Toro, Stefania Di; Page, Clive; Cazzola, Mario

doi:10.1016/j.pupt.2017.10.001

Cited by 41 publications

(35 citation statements)

References 55 publications

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“…Also, Shute et al, proved that neulised heparin in 75,000 or 150,000 IU/day for 21 days in moderate to very severe COPD patients significantly increased FVC following 7 days of treatment [28] . These results might be explained by an earlier study on the intrapulmonary administered heparin that proved that it was absorbed rapidly by the alveolar membrane and released gradually into the blood and the study done by Bendstrup et.al, that concluded that nebulised heparin was cleared slowly form the lungs, and that 39% of it was still present in the lungs 24 h after nebulisation [29,30] .…”

Section: Discussionmentioning

confidence: 98%

Nebulized heparin and salbutamol versus salbutamol alone in acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation: a double-blind randomized controlled trial

Ashoor

Hasseb

Esmat

2020

Korean J Anesthesiol

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Section: Discussionmentioning

confidence: 98%

Nebulized heparin and salbutamol versus salbutamol alone in acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation: a double-blind randomized controlled trial

Ashoor

Hasseb

Esmat

2020

Korean J Anesthesiol

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“… 39 Other reports on nebulized heparins have demonstrated improved outcomes in chronic obstructive pulmonary disease and other lung diseases such as inhalation injury. 40 – 42 As the COVID-19 viral infection results in significant pulmonary injury, the inhaled forms of heparins that reach lung tissue may be effective in through anti-inflammatory and antiviral effects.…”

Section: Covid-19-associated Viral Coagulopathymentioning

confidence: 99%

Viral Coagulopathy in Patients With COVID-19: Treatment and Care

Kipshidze

Dangas

White

et al. 2020

Clin Appl Thromb Hemost

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COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation–like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.

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“…Importantly, previous studies have shown that following nebulisation, UFH does not enter the systemic circulation significantly which means it can be used in addition to systemic therapeutic or prophylactic anti-coagulation without concerns of furthering systemic anti-coagulation. The use of nebulised UFH in other respiratory settings was not associated with local side effects in the lung including bleeding [ 85 – 89 ].…”

Section: Biological Rationale: Effects Of Nebulised Ufhmentioning

confidence: 99%

Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence

et al. 2020

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Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes. The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low-and middle-income countries. These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.

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Inhaled nebulised unfractionated heparin improves lung function in moderate to very severe COPD: A pilot study

Abstract: Inhaled nebulised UFH is safe and provides additional clinical benefit for patients with moderate to very severe COPD through effects that are independent of its anticoagulant activity.

Cited by 41 publications

References 55 publications

Nebulized heparin and salbutamol versus salbutamol alone in acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation: a double-blind randomized controlled trial

Nebulized heparin and salbutamol versus salbutamol alone in acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation: a double-blind randomized controlled trial

Viral Coagulopathy in Patients With COVID-19: Treatment and Care

Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence

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