Characterizing blood microparticles: Technical aspects and challenges

Although long considered to be cellular debris, microparticles (MPs) are more recently considered reflective of cellular stimulation, activation, and degeneration/apoptosis. MPs that arise from the cellular components of blood and the endothelial lining of blood vessels are referred to as blood MPs and by general consensus are small (≤1.5 μm), expose the anionic phospholipid (PL) phosphatidylserine (PS) on the outer leaflet of their membrane, and bear surface membrane antigens reflecting their cellular origin. This brief review summarizes the different approaches used by several groups to study blood MPs. The aim of this article is to review the technical aspects of characterizing the morphological and functional properties of blood MPs with emphasis on the preanalytical and analytical variables involved in these studies

Community-Based Interventions : Implications for childhood anemia prevention and control in India

Background: Nutritional iron deficiency is the number one cause of anemia worldwide. Iron deficiency anemia has morbidity and mortality effects borne predominantly by premenopausal women and children living in South Asia and sub-Saharan Africa. Community-based interventions have successfully addressed several global health problems, although there is limited evidence of their effectiveness for childhood anemia. The overall aim of this thesis was to test the hypothesis that community-based education and counseling delivered to mothers of anemic children by health workers would improve anemia cure rates. Methods: The thesis included 4 studies, two of which (Study I and II) were cross sectional studies constituting the background for intervention design. The social cognitive theory framework guided the development of the intervention, which consisted of five monthly education sessions delivered by a health worker covering: i) maternal anemia awareness, ii) adherence to iron treatment, iii) dietary modification, and iv) hygiene and sanitation. The intervention was evaluated in a pragmatic mixed methods trial conducted among 12-59 month old children from 55 villages of the Chamarajnagar district, Karnataka. Villages (and health workers therein) were randomly assigned 1:1 to provide anemic children either the usual iron treatment alone or the same treatment complemented by education and counseling of their mothers/caregivers. The primary trial outcome was the difference in anemia cure rates (return of hemoglobin to ≥11g/dL) at the end of six months. Thematic analysis with the framework method was utilized to understand health workers acceptance of the intervention and their perceptions of obstacles and opportunities connected to its implementation (Study III). A cluster randomized trial contrasting intervention to usual treatment condition was used to study the effects of the intervention (Study IV). The statistical analysis was conducted taking into account the cluster design, using multilevel regression. Results: A high prevalence of childhood anemia was found in healthy rural toddlers (75%) mainly due to iron deficiency anemia (Study 1). Coverage of children with iron supplements from the national anemia control program was low (Study II). Health workers delivering the intervention found it acceptable and feasible to implement during routine work activities (Study III). After six months, anemic children in the intervention group had significantly higher anemia cure rates compared with anemic children in the usual treatment group (55.5% vs. 41.4%; relative risk ratio 1.33, confidence interval [CI], 1.04-1.69). The proportion of anemic children consuming >75% of prescribed iron was higher in the intervention group compared with the usual treatment group (61.7% vs. 48.4%; p=0.001). The results indicated that seven mothers needed to be counselled in order to cure one anemic child (Study IV). Conclusions: The studies included in this thesis indicate that mother/caregiver education achieved a perceivable improvement to the cure rate of nutritional iron deficiency anemia in children from rural India, probably through improved adherence to iron treatment. High intervention acceptance at the health worker level suggests that wider implementation is possible. Scientific evaluations of community-based interventions are feasible even in rural disadvantaged environments

The molecular basis for the prothrombotic state in sickle cell disease

The genetic and molecular basis of sickle cell disease (SCD) has long since been characterized but the pathophysiological basis is not entirely defined. How a red cell hemolytic disorder initiates inflammation, endothelial dysfunction, coagulation activation and eventually leads to vascular thrombosis, is yet to be elucidated. Recent evidence has demonstrated a high frequency of unprovoked/recurrent venous thromboembolism (VTE) in SCD, with an increased risk of mortality among patients with a history of VTE. Here, we thoroughly review the molecular basis for the prothrombotic state in SCD, specifically highlighting emerging evidence for activation of overlapping inflammation and coagulation pathways, that predispose to venous thromboembolism. We share perspectives in managing venous thrombosis in SCD, highlighting innovative therapies with the potential to influence the clinical course of disease and reduce thrombotic risk, while maintaining an acceptable safety profile

A community based field research project investigating anaemia amongst young children living in rural Karnataka, India: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Anaemia is an important problem amongst young children living in rural India. However, there has not previously been a detailed study of the biological aetiology of this anaemia, exploring the relative contributions of iron, vitamin B12, folate and Vitamin A deficiency, inflammation, genetic haemoglobinopathy, hookworm and malaria. Nor have studies related these aetiologic biological factors to household food security, standard of living and child feeding practices. Barriers to conducting such work have included perceived reluctance of village communities to permit their children to undergo venipuncture, and logistical issues. We have successfully completed a community based, cross sectional field study exploring in detail the causes of anaemia amongst young children in a rural setting.</p> <p>Methods and design</p> <p>A cross sectional, community based study. We engaged in extensive community consultation and tailored our study design to the outcomes of these discussions. We utilised local women as field workers, harnessing the capacity of local health workers to assist with the study. We adopted a programmatic approach with a census rather than random sampling strategy in the village, incorporating appropriate case management for children identified to have anaemia. We developed a questionnaire based on existing standard measurement tools for standard of living, food security and nutrition. Specimen processing was conducted at the Primary Health Centre laboratory prior to transport to an urban research laboratory.</p> <p>Discussion</p> <p>Adopting this study design, we have recruited 415 of 470 potentially eligible children who were living in the selected villages. We achieved support from the community and cooperation of local health workers. Our results will improve the understanding into anaemia amongst young children in rural India. However, many further studies are required to understand the health problems of the population of rural India, and our study design and technique provide a useful demonstration of a successful strategy.</p

Factors Influencing Receipt of Iron Supplementation by Young Children and their Mothers in Rural India: Local and National Cross-Sectional Studies

<p>Abstract</p> <p>Background</p> <p>In India, 55% of women and 69.5% of preschool children are anaemic despite national policies recommending routine iron supplementation. Understanding factors associated with receipt of iron in the field could help optimise implementation of anaemia control policies. Thus, we undertook 1) a cross-sectional study to evaluate iron supplementation to children (and mothers) in rural Karnataka, India, and 2) an analysis of all-India rural data from the National Family Health Study 2005-6 (NFHS-3).</p> <p>Methods</p> <p>All children aged 12-23 months and their mothers served by 6 of 8 randomly selected sub-centres managed by 2 rural Primary Health Centres of rural Karnataka were eligible for the Karnataka Study, conducted between August and October 2008. Socioeconomic and demographic data, access to health services and iron receipt were recorded. Secondly, NFHS-3 rural data were analysed. For both studies, logistic regression was used to evaluate factors associated with receipt of iron.</p> <p>Results</p> <p>The Karnataka Study recruited 405 children and 377 of their mothers. 41.5% of children had received iron, and 11.5% received iron through the public system. By multiple logistic regression, factors associated with children's receipt of iron included: wealth (Odds Ratio (OR) 2.63 [95% CI 1.11, 6.24] for top vs bottom wealth quintile), male sex (OR 2.45 [1.47, 4.10]), mother receiving postnatal iron (OR 2.31 [1.25, 4.28]), mother having undergone antenatal blood test (OR 2.10 [1.09, 4.03]); Muslim religion (OR 0.02 [0.00, 0.27]), attendance at Anganwadi centre (OR 0.23 [0.11, 0.49]), fully vaccinated (OR 0.33 [0.15, 0.75]), or children of mothers with more antenatal health visits (8-9 visits OR 0.25 [0.11, 0.55]) were less likely to receive iron. Nationally, 3.7% of rural children were receiving iron; this was associated with wealth (OR 1.12 [1.02, 1.23] per quintile), maternal education (compared with no education: completed secondary education OR 2.15 [1.17, 3.97], maternal antenatal iron (2.24 [1.56, 3.22]), and child attending an Anganwadi (OR 1.47 [1.20, 1.80]).</p> <p>Conclusion</p> <p>In rural India, public distribution of iron to children is inadequate and disparities exist. Measures to optimize receipt of government supplied iron to all children regardless of wealth and ethnic background could help alleviate anaemia in this population.</p

Sickle Cell Disease: A Paradigm for Venous Thrombosis Pathophysiology

Venous thromboembolism (VTE) is an important cause of vascular morbidity and mortality. Many risk factors have been identified for venous thrombosis that lead to alterations in blood flow, activate the vascular endothelium, and increase the propensity for blood coagulation. However, the precise molecular and cellular mechanisms that cause blood clots in the venous vasculature have not been fully elucidated. Patients with sickle cell disease (SCD) demonstrate all the risk factors for venous stasis, activated endothelium, and blood hypercoagulability, making them particularly vulnerable to VTE. In this review, we will discuss how mouse models have elucidated the complex vascular pathobiology of SCD. We review the dysregulated pathways of inflammation and coagulation in SCD and how the resultant hypercoagulable state can potentiate thrombosis through down-regulation of vascular anticoagulants. Studies of VTE pathogenesis using SCD mouse models may provide insight into the intersection between the cellular and molecular processes involving inflammation and coagulation and help to identify novel mechanistic pathways

COVID-19 and venous thromboembolism risk in patients with sickle cell disease.

Venous thromboembolism (VTE) is a life-threatening complication observed among patients with sickle cell disease (SCD) and also among those with severe COVID-19 infection. Although prior studies show that patients with SCD are at risk of severe COVID-19 illness, it remains unclear if COVID-19 infection further increases VTE risk for this population. We hypothesized that patients with SCD hospitalized for COVID-19 would have higher VTE rates than those hospitalized for other causes. Using electronic health record data from a multisite research network, TriNetX, we identified 2 groups of patients with SCD hospitalized during 2020: (1) with COVID-19 and (2) without COVID-19. We compared VTE rates using risk ratios estimated based on adjusted Poisson regression model with log link and robust error variances. Of the 281 SCD patients hospitalized with COVID-19 and 4873 SCD patients hospitalized without COVID-19 , 35 (12.46%) and 418 (8.58%) had incident VTE within 6 months of the index hospitalization respectively. After adjusting for differences in baseline characteristics, no significant differences in VTE rates within 6 months were found between the 2 groups (adjusted relative risk, 1.06 [95% confidence interval, 0.79-1.41]). These data suggest that hospitalization with COVID-19 does not further increase VTE risk in patients with SCD