Heparin Therapy Improving Hypoxia in COVID-19 Patients – A Case Series

Abstract

Introduction: Elevated D-dimer is a predictor of severity and mortality in COVID-19 patients, and heparin use during in-hospital stay has been associated with decreased mortality. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting that hypercoagulability is a prominent feature of organ failure in these patients. Interestingly, in COVID-19, pulmonary compliance is preserved despite severe hypoxemia corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure. Methods: We describe a series of 27 consecutive COVID-19 patients admitted to Sirio-Libanes Hospital in São Paulo-Brazil and treated with heparin in therapeutic doses tailored to clinical severity. Results: PaO2/FiO2 ratio increased significantly over the 72 h following the start of anticoagulation, from 254(±90) to 325(±80), p = 0.013, and 92% of the patients were discharged home within a median time of 11 days. There were no bleeding complications or fatal events. Discussion: Even though this uncontrolled case series does not offer absolute proof that micro thrombosis in the pulmonary circulation is the underlying mechanism of respiratory failure in COVID-19, patient's positive response to heparinization contributes to the understanding of the pathophysiological mechanism of the disease and provides valuable information for the treatment of these patients while we await the results of further prospective controlled studies.

The Use of the Anticoagulant Heparin and Corticosteroid Dexamethasone as Prominent Treatments for COVID-19

“…Moreover, the appearance of neurological alterations caused by cerebral venous thrombosis was also reported (34,35). In this context, early anticoagulant treatment was applied and it was observed a decrease of D dimer levels, mechanical ventilation urgency, and a decrease of 24.2% in the mortality rate of patients presenting sepsis-induced coagulopathy (30,32,36,37). The use of a high dose of UFH, such as 5,000 U, showed important protection against sepsis-induced VTE, a complication that presents a major impact on a patient's prognosis (32).…”

“…Reports have shown that COVID-19 patients presented increased levels of procoagulation biomarkers and severe immune dysfunction that can lead to disseminated intravascular coagulation (DIC), increased risk for venous thromboembolism (VTE), and organ failure, which reflects in a high hospital mortality rate of 1:31 with a confidence interval (CI) of 95% (30)(31)(32). Using an animal model, the increased deposition of collagen, fibrin, and von Willebrand factor was linked to augmented thrombi formation and endothelialits establishment during COVID-19 (33).…”

“…In this context, early anticoagulant treatment was applied and it was observed a decrease of D dimer levels, mechanical ventilation urgency, and a decrease of 24.2% in the mortality rate of patients presenting sepsis-induced coagulopathy (30,32,36,37). The use of a high dose of UFH, such as 5,000 U, showed important protection against sepsis-induced VTE, a complication that presents a major impact on a patient's prognosis (32). Besides, ongoing clinical trials have been focusing on inhalational heparin treatment for hospitalized patients with or without mechanical ventilation urgency, especially due to several reports that addressed the protective role of nebulized UFH against intrapulmonary fibrin deposition and lung injury (38,39).…”

Comparative Genomics and Integrated Network Approach Unveiled Undirected Phylogeny Patterns, Co-mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2

“…It was found that inhibition of MYO5A, MYO5B, and MYO5C was efficient in blocking the internalization pathway, thus this target can be used for the development of a new treatment for SARS-CoV-2 (60). Patients suffering from COVID-19 undergo two major condition in the severe stage, thrombotic phenomenon and hypoxia, that are acting as silent killers (61, 62). Hypoxia, condition where oxygen level of the body reduces drastically results in the elevated expression of T protein in the body (63).…”

Molecular Mechanism of the Anti-Inflammatory Action of Heparin

“…GAGs and heparin, in particular, have been suggested as playing a protective role in the inflammation response [ 39 ], which has been interpreted as involving (among other things) the inhibition of elastase and the interaction with several cytokines [ 3 , 40 ]. Thus, a number of heparin applications may be rooted in its ability to moderate inflammation (see [ 4 , 41 ]).…”