Sickle cell disease: Hemostatic and inflammatory changes, and their interrelation

Toledo, Sílvia Letícia de Oliveira; Guedes, João Victor Marques; Alpoim, Patrícia Nessralla; Rios, Danyelle Romana Alves; Pinheiro, Melina de Barros

doi:10.1016/j.cca.2019.02.026

Cited by 17 publications

(18 citation statements)

References 164 publications

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“…Hypercoagulability may pre-dispose to cerebral thromboembolism and is also a feature of SCD. Activation of the coagulation cascade and fibrinolysis are favored (122) and there is a high risk of venous thromboembolism (123). Risk factors may include genetic predisposition (124), inflammation (122), and splenectomy (125).…”

Section: Hypercoagulability and Embolic Eventsmentioning

confidence: 99%

“…Activation of the coagulation cascade and fibrinolysis are favored (122) and there is a high risk of venous thromboembolism (123). Risk factors may include genetic predisposition (124), inflammation (122), and splenectomy (125). Phosphotidylserine exposure on red cells and microparticles may play a role, related in part to acquired protein S deficiency (126).…”

Section: Hypercoagulability and Embolic Eventsmentioning

confidence: 99%

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Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

et al. 2019

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It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies.

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Section: Hypercoagulability and Embolic Eventsmentioning

confidence: 99%

Section: Hypercoagulability and Embolic Eventsmentioning

confidence: 99%

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

et al. 2019

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“…Massive blood loss can be a consequence of a transport accident or may occur on the battlefield [1,2,3]. Hemorrhage appears also during surgeries and as a result of certain diseases [4,5,6,7]. Despite modern surgical techniques and new hemostatic materials, bleeding is one of the most common causes of death in surgery [2].…”

Section: Introductionmentioning

confidence: 99%

“…Currently there are a few types of hemostatic agents, such as physical agents, resorbable agents, biological agents, synthetic agents and dressings [1,2]. The most popular ones are biodegradable gelatin and collagen foams, fibrin sealants as well as chitosan granules, sponges and dressings [1,2,3,4,5,6,7]. Hemostatic agents may be used in hospitals and by individuals.…”

Section: Introductionmentioning

confidence: 99%

Chitosan-Based Bioactive Hemostatic Agents with Antibacterial Properties—Synthesis and Characterization

et al. 2019

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Massive blood loss is responsible for numerous causes of death. Hemorrhage may occur on the battlefield, at home or during surgery. Commercially available biomaterials may be insufficient to deal with excessive bleeding. Therefore novel, highly efficient hemostatic agents must be developed. The aim of the following research was to obtain a new type of biocompatible chitosan-based hemostatic agents with increased hemostatic properties. The biomaterials were obtained in a quick and efficient manner under microwave radiation using l-aspartic and l-glutamic acid as crosslinking agents with no use of acetic acid. Ready products were investigated over their chemical structure by FT-IR method which confirmed a crosslinking process through the formation of amide bonds. Their high porosity above 90% and low density (below 0.08 g/cm3) were confirmed. The aerogels were also studied over their water vapor permeability and antioxidant activity. Prepared biomaterials were biodegradable in the presence of human lysozyme. All of the samples had excellent hemostatic properties in contact with human blood due to the platelet activation confirmed by blood clotting tests. The SEM microphotographs showed the adherence of blood cells to the biomaterials’ surface. Moreover, they were biocompatible with human dermal fibroblasts (HDFs). The biomaterials also had superior antibacterial properties against both Staphylococcus aureus and Escherichia coli. The obtained results showed that proposed chitosan-based hemostatic agents have great potential as a hemostatic product and may be applied under sterile, as well as contaminated conditions, by both medicals and individuals.

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“…Previous studies have shown that increasing levels of HO-1 with heme arginate can improve inflammation and viral infections [ 145 , 146 , 147 , 148 ]. Sickle cell patients, for example, are in a pro-inflammatory state [ 149 ]. HO-1 upregulation reduced oxidative stress in the kidney in sickle cell disease [ 150 ].…”

Section: Heme Arginate-ho-1 Levels—inflammationmentioning

confidence: 99%

Genetic Polymorphisms Complicate COVID-19 Therapy: Pivotal Role of HO-1 in Cytokine Storm

et al. 2020

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Coronaviruses are very large RNA viruses that originate in animal reservoirs and include severe acute respiratory distress syndrome (SARS) and Middle East respiratory syndrome (MERS) and other inconsequential coronaviruses from human reservoirs like the common cold. SARS-CoV-2, the virus that causes COVID-19 and is believed to originate from bat, quickly spread into a global pandemic. This RNA virus has a special affinity for porphyrins. It invades the cell at the angiotensin converting enzyme-2 (ACE-2) receptor and binds to hemoproteins, resulting in a severe systemic inflammatory response, particularly in high ACE-2 organs like the lungs, heart, and kidney, resulting in systemic disease. The inflammatory response manifested by increased cytokine levels and reactive oxygen species results in inhibition of heme oxygenase (HO-1), with a subsequent loss of cytoprotection. This has been seen in other viral illness like human immunodeficiency virus (HIV), Ebola, and SARS/MERS. There are a number of medications that have been tried with some showing early clinical promise. This illness disproportionately affects patients with obesity, a chronic inflammatory disease with a baseline excess of cytokines. The majority of the medications used in the treatment of COVID-19 are metabolized by cytochrome P450 (CYP) enzymes, primarily CYP2D6. This is further complicated by genetic polymorphisms of CYP2D6, HO-1, ACE, and ACE-2. There is a potential role for HO-1 upregulation to treat/prevent cytokine storm. Current therapy must focus on antivirals and heme oxygenase upregulation. Vaccine development will be the only magic bullet.

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Sickle cell disease: Hemostatic and inflammatory changes, and their interrelation

Cited by 17 publications

References 164 publications

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

Chitosan-Based Bioactive Hemostatic Agents with Antibacterial Properties—Synthesis and Characterization

Genetic Polymorphisms Complicate COVID-19 Therapy: Pivotal Role of HO-1 in Cytokine Storm

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