Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies

Manwani, Deepa; Frenette, Paul S.

doi:10.1182/blood-2013-05-498311

Cited by 293 publications

(186 citation statements)

References 52 publications

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“…This finding is consistent with other previous studies which linked white cell and platelet counts with disease severity in sickle cell disease [40,41]. Current patho-physiologic mechanism of vaso-occlusion in sickle cell disease has been found to involve the white cells and platelets as well as the expression of their intercellular adhesion molecules [42,43]. A high platelet count was observed to positively correlate with a tendency to develop avascular necrosis (AVN).…”

Section: Discussionsupporting

confidence: 92%

Correlation between Body Mass Index and Hematological Indices in Young Adult Nigerians with Different Hemoglobin Genotypes

Ajayi¹,

Akinbo²,

Okafor³

2017

Am. J. Biomed. Sci.

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In view of the association of various haemoglobin electrophoretic patterns with different pathological conditions and obesity with its attendant risk factors for cardiac and pulmonary disorders, the present study evaluated the relationship between body mass index and haematological indices by randomly selecting young adult Nigerians with different haemoglobin electrophoretic patterns within the age group of 17-45 years and mean age of ±31 years old. 215 participants were enlisted for this study with their BMI and other anthropometric indices measured and grouped into different BMI categories as recommended by the World Health Organization. Haematological indices such as packed cell volume, total and differential white blood cell count, and platelets as well as haemoglobin (Hb) electrophoresis were assessed in relation to their anthropometric measurements using standard methods. We observed a significantly increased neutrophil and platelet counts in the subjects with BMI > 25 kg/m 2 . BMI was also observed to be positively correlated with the neutrophil, monocyte counts and MCV of haemoglobin AS and SS genotype groups in this study. This study showed a higher percentage of overweight and obesity among females, and haematological dyscrasias in mostly the HbSS subjects. Knowledge of the relationship between BMI and hematological indices of apparently healthy individuals within any population is therefore essential in healthcare planning, as a justification for early prognosis and genetic counselling policy strategically reducing the incidence of obesity, its attendant conditions and haemoglobinopathies in Nigeria.

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Section: Discussionsupporting

confidence: 92%

Correlation between Body Mass Index and Hematological Indices in Young Adult Nigerians with Different Hemoglobin Genotypes

Ajayi¹,

Akinbo²,

Okafor³

2017

Am. J. Biomed. Sci.

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“…We observed adhesion of different RBC subpopulations to FN and LN, reminiscent of RBC subpopulations defined in the literature for vaso-occlusion. 100 Furthermore, although deformable sickle RBCs adhere in higher numbers (especially to LN), nondeformable RBCs display greater adhesion strength, suggesting a critical contribution by both populations to vaso-occlusion.…”

Section: Discussionmentioning

confidence: 97%

Sickle cell disease biochip: a functional red blood cell adhesion assay for monitoring sickle cell disease

Alapan

Kim

Adhikari

et al. 2016

Translational Research

105

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Sickle cell disease (SCD) afflicts millions of people worldwide and is associated with considerable morbidity and mortality. Chronic and acute vaso-occlusion are the clinical hallmarks of SCD and can result in pain crisis, widespread organ damage, and early movtality. Even though the molecular underpinnings of SCD were identified more than 60 years ago, there are no molecular or biophysical markers of disease severity that are feasibly measured in the clinic. Abnormal cellular adhesion to vascular endothelium is at the root of vaso-occlusion. However, cellular adhesion is not currently evaluated clinically. Here, we present a clinically applicable microfluidic device (SCD biochip) that allows serial quantitative evaluation of red blood cell (RBC) adhesion to endothelium-associated protein-immobilized microchannels, in a closed and preprocessing-free system. With the SCD biochip, we have analyzed blood samples from more than 100 subjects and have shown associations between the measured RBC adhesion to endothelium-associated proteins (fibronectin and laminin) and individual RBC characteristics, including hemoglobin content, fetal hemoglobin concentration, plasma lactate dehydrogenase level, and reticulocyte count. The SCD biochip is a functional adhesion assay, reflecting quantitative evaluation of RBC adhesion, which could be used at baseline, during crises, relative to various long-term complications, and before and after therapeutic interventions.

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“…2 Sickle cell patients homozygous for Hb S (SS disease) or heterozygous for Hb S and either Hb C (SC disease) or β-thalassemia (S–β thalassemia), are all at increased risk for vascular occlusions. 3,4 …”

mentioning

confidence: 99%

Expression Pattern of HIF-1α and VEGF Supports Circumferential Application of Scatter Laser for Proliferative Sickle Retinopathy

Rodrigues

Kashiwabuchi

Deshpande

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeRetinal vascular occlusions in sickle cell anemia patients cause tissue ischemia and the release of angiogenic mediators that promote the development of retinal neovascularization, initiating proliferative sickle retinopathy (PSR). Laser photocoagulation (LPC) has emerged as the most common treatment for PSR. Nonetheless, only two randomized controlled clinical trials have evaluated the use of LPC for PSR, and both failed to definitively demonstrate efficacy of this approach. This may be due to a lack of knowledge regarding the appropriate location for placement of laser coagulations in PSR eyes. To help address this question, we examined the expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in PSR eyes.MethodsThe expression pattern of HIF-1α and VEGF in PSR (n = 5) and control (n = 3) eyes was examined by immunohistochemistry in different retinal regions defined by the presence or absence of retinal vessels.ResultsHypoxia-inducible factor 1α and VEGF were expressed in the inner retina of 5/5 untreated PSR eyes adjacent to retinal neovascularization; expression of HIF-1α was not detected (and VEGF only lightly detected) in normal retinal and choroidal vasculature of 3/3 control eyes. Hypoxia-inducible factor 1α and VEGF were strongly expressed in retinal cells within avascular (nonperfused) retina, anterior to the boundary between perfused and nonperfused retina, as well as in posterior ischemic retina in the presence or absence of neovascular sea fans.ConclusionsIf the goal of LPC in PSR is to quench the expression of HIF-1–driven angiogenic mediators, our results support broad application of peripheral laser for its treatment.

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Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies

Cited by 293 publications

References 52 publications

Correlation between Body Mass Index and Hematological Indices in Young Adult Nigerians with Different Hemoglobin Genotypes

Correlation between Body Mass Index and Hematological Indices in Young Adult Nigerians with Different Hemoglobin Genotypes

Sickle cell disease biochip: a functional red blood cell adhesion assay for monitoring sickle cell disease

Expression Pattern of HIF-1α and VEGF Supports Circumferential Application of Scatter Laser for Proliferative Sickle Retinopathy

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