Interplay between coagulation and vascular inflammation in sickle cell disease

Sparkenbaugh, Erica; Pawliński, Rafał

doi:10.1111/bjh.12336

Cited by 140 publications

(128 citation statements)

References 154 publications

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“…24,25 Similarly to observations in SCA, the hypercoagulability state encountered in HbSC disease seems to be associated with inflammation and hemolysis. 17,19,26 Thus, our results demonstrate similarities between the pathophysiological mechanisms involved in the activation of coagulation in HbSC disease and SCA. However,…”

Section: Controlssupporting

confidence: 61%

Elevated hypercoagulability markers in hemoglobin SC disease

et al. 2015

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ABSTRACTincluded in the study was being treated with hydroxyurea. Patients who were on anticoagulation were excluded. A total of 56 HbSC patients were compared to a population of 39 HbSS patients, of whom 15 were described in a previous study. 17 We also selected 27 healthy age-matched HbAA controls. The University's ethics committee approved the study and all of the patients included signed a written informed consent form.Venous blood samples for all of the study analyses, including peripheral blood counts and hemolysis markers, were obtained simultaneously.

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Section: Controlssupporting

confidence: 61%

Elevated hypercoagulability markers in hemoglobin SC disease

et al. 2015

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“…Patients with SCD have a chronic low-grade pro-inflammatory state, even at a steady state condition [7,20]. They have elevated levels of circulating cytokines and vascular adhesion molecules (e.g., VCAM-1), hypercoagulable state and endothelial dysfunction, which all can contribute to vascular inflammation [36][37][38][39][40][41][42][43][44][45][46]. Sickle red cells, and in particular sickle reticulocytes, express a number of adhesion receptors that can mediate adherence to vascular endothelial cells and consequently contribute to endothelial dysfunction [47].…”

Section: Coronary Artery Ectasia In Sickle Cell Diseasementioning

confidence: 99%

Coronary Artery Ectasia in Atherosclerotic Coronary Artery Disease, Inflammatory Disorders, and Sickle Cell Disease

Dahhan

2015

Cardiovascular Therapeutics

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SUMMARYCoronary artery ectasia (CAE) or aneurysm is usually defined as dilation ≥1.5-fold the normal vessel diameter. It has an incidence of 1.4-5.3% and is associated with a wide variety of etiologies-mainly congenital, atherosclerotic, and inflammatory ones. CAE is very common in sickle cell disease, and possibly sickle cell trait, with an incidence of 17.7%. It is likely related to the inflammatory process associated with hemoglobin S. Prognosis depends mainly on the underlying etiology. Atherosclerotic CAE does not carry additional risks compared to atherosclerotic coronary artery disease (ACAD) without ectasia. However, isolated CAE in the absence of ACAD carries an increased risk of myocardial infarction (MI) due to vasospasm, slower coronary blood flow, and thrombosis, typically within the dilated segments. Due to lack of studies and guidelines, management recommendations are based on personal experiences. Therapy should be tailored to each individual case after assessment of severity, history of complications, underlying etiology, and comorbidities. Treatment of underlying condition and avoidance of exacerbating factors are essential. Medical therapy in general may include antiplatelets, b-blockers, angiotensin-converting enzyme inhibitors statins, and dihydropyridine calcium channel blockers. In severe CAE or history of MI, the addition of anticoagulation therapy after assessing bleeding risk may be warranted. In acute MI, the large thrombus burden in the dilated segment makes the percutaneous approach very challenging. Aspiration attempts can result in distal thromboembolization. Survival is better in bypass grafting than with medical therapy. Nonetheless, bypass grafting does not improve survival in atherosclerotic CAE. Depending on the physical characteristics of aneurysm, different surgical approaches can be sought; however, the ideal one is unclear.

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“…Recent studies have underscored the central role of sickle vasculopathy in the generation of sickle cell-related acute events and chronic organ complications. [2][3][4] The pathophysiology of these complications is based on intravascular sickling in capillaries and small vessels leading to vaso-occlusion, impaired blood flow, vascular inflammation, and thrombosis with ischemic cell damage. [2][3][4] Studies in various models of vasculopathy, including those with ischemia and inflammation, have shown protective effects of ω-3 polyunsaturated fatty acid (PUFA) supplementation.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] The pathophysiology of these complications is based on intravascular sickling in capillaries and small vessels leading to vaso-occlusion, impaired blood flow, vascular inflammation, and thrombosis with ischemic cell damage. [2][3][4] Studies in various models of vasculopathy, including those with ischemia and inflammation, have shown protective effects of ω-3 polyunsaturated fatty acid (PUFA) supplementation. 5 This is supported by several mechanisms: (i) favorable changes in cell membrane lipid composition; 6 (ii) modulation of soluble and cellular inflammatory responses; 7 (iii) modulation of the coagulation cascade, 8 and (iv) production of nitric oxide.…”

Section: Introductionmentioning

confidence: 99%

Dietary -3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease

et al. 2015

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The anemia of sickle cell disease is associated with a severe inflammatory vasculopathy and endothelial dysfunction, which leads to painful and life-threatening clinical complications. Growing evidence supports the anti-inflammatory properties of ω-3 fatty acids in clinical models of endothelial dysfunction. Promising but limited studies show potential therapeutic effects of ω-3 fatty acid supplementation in sickle cell disease. Here, we treated humanized healthy and sickle cell mice for 6 weeks with ω-3 fatty acid diet (fish-oil diet). We found that a ω-3 fatty acid diet: (i) normalizes red cell membrane ω-6/ ω-3 ratio; (ii) reduces neutrophil count; (iii) decreases endothelial activation by targeting endothelin-1 and (iv) improves left ventricular outflow tract dimensions. In a hypoxia-reoxygenation model of acute vaso-occlusive crisis, a ω-3 fatty acid diet reduced systemic and local inflammation and protected against sickle cell-related end-organ injury. Using isolated aortas from sickle cell mice exposed to hypoxia-reoxygenation, we demonstrated a direct impact of a ω-3 fatty acid diet on vascular activation, inflammation, and anti-oxidant systems. Our data provide the rationale for ω-3 dietary supplementation as a therapeutic intervention to reduce vascular dysfunction in sickle cell disease. ABSTRACTmice. 16,17 The animal protocol was approved by the Animal Care and Use Committee of the University of Verona (CIRSAL). Twomonth old animals were fed for 6 weeks with either the standard AIN-93M purified rodent diet (soy-diet with n6/n3 ratio of 8:1 -Dyets Inc., Bethlehem, PA, USA), containing 140 g/kg casein, 1.8 g/kg L-cystine, 100 g/kg sucrose, 465.9 g/kg cornstarch, 155 g/kg dextrose, 40 g/kg soybean oil, 0.8 mg/kg t-butylhydroquinone, 50 g/kg cellulose, 35 g/kg mineral mix, 10 g/kg vitamin mix, and 2.5 g/kg choline bitartrate 18 or the ω-3 FD, an AIN-93M-based purified rodent diet in which all of the calories provided by fat (10%) are replaced by 7.9% from HCO and 2.1% from ω-3 oil (Dyets Inc., Bethlehem, PA, USA). At the end of the 6 weeks of FD supplementation, animals were anesthetized with isofluorane, and whole blood was collected from each mouse via retro-orbital venipuncture by heparinized microcapillaries. Mice were euthanized and organs removed immediately. The organs were divided into two and either frozen immediately in liquid nitrogen or fixed in 10% formalin and embedded in paraffin for histology. Whenever indicated, 6-week old mice were exposed to hypoxia (8% oxygen for 10 h) followed by 3 h of reoxygenation (21% oxygen) (H/R stress) to mimic an acute VOC, as previously described.

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Interplay between coagulation and vascular inflammation in sickle cell disease

Cited by 140 publications

References 154 publications

Elevated hypercoagulability markers in hemoglobin SC disease

Elevated hypercoagulability markers in hemoglobin SC disease

Coronary Artery Ectasia in Atherosclerotic Coronary Artery Disease, Inflammatory Disorders, and Sickle Cell Disease

Dietary -3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease

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