Sickle cell disease in sub-Saharan Africa: transferable strategies for prevention and care.

Sickle cell disease can be life-threatening or chronically debilitating for both children and adults. Worldwide, more than 300 000 children are born with sickle cell disease every year, over 75% of whom in sub-Saharan Africa. Increased awareness and early interventions, such as neonate screening and comprehensive care, have led to considerable reductions in mortality in children younger than 5 years in high-income countries. However, sickle cell disease prevention and care have largely been neglected in Africa. Without intervention, 50-90% of affected children in many sub-Saharan African countries die before their fifth birthday. Fortunately, increasing initiatives in sub-Saharan Africa are piloting interventions such as neonate screening and comprehensive care, and as mortality declines, quality of life and increased life expectancy become major targets for interventions. Hydroxyurea (hydroxycarbamide) and haematopoietic stem-cell transplantation have already been shown to be effective therapies in high-income countries, but are either not widely accessible or too expensive for most African populations. These challenges are being alleviated by numerous networks evolving through international collaborations that are positively changing the outlook of sickle cell disease management in sub-Saharan Africa. In this Series paper, we describe the epidemiology, pathophysiology, clinicobiological profile, and psychosocial effects of sickle cell disease in sub-Saharan Africa. We highlight transferable strategies already used for the successful management of the condition and key strategies and recommendations for affordable and comprehensive care on the continent. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Blood flow, capillary transit times, and tissue oxygenation: the centennial of capillary recruitment.

The transport of oxygen between blood and tissue is limited by blood's capillary transit time, understood as the time available for diffusion exchange before blood returns to the heart. If all capillaries contribute equally to tissue oxygenation at all times, this physical limitation would render vasodilation and increased blood flow insufficient means to meet increased metabolic demands in the heart, muscle, and other organs. In 1920, Danish physiologist August Krogh was awarded the Nobel Prize in Physiology or Medicine for his mathematical and quantitative, experimental demonstration of a solution to this conceptual problem: capillary recruitment, the active opening of previously closed capillaries to meet metabolic demands. Today, capillary recruitment is still mentioned in textbooks. When we suspect symptoms might represent hypoxia of a vascular origin, however, we search for relevant, flow-limiting conditions in our patients and rarely ascribe hypoxia or hypoxemia to short capillary transit times. This review describes how natural changes in capillary transit-time heterogeneity (CTH) and capillary hematocrit (HCT) across open capillaries during blood flow increases can account for a match of oxygen availability to metabolic demands in normal tissue. CTH and HCT depend on a number of factors: on blood properties, including plasma viscosity, the number, size, and deformability of blood cells, and blood cell interactions with capillary endothelium; on anatomical factors including glycocalyx, endothelial cells, basement membrane, and pericytes that affect the capillary diameter; and on any external compression. The review describes how risk factor- and disease-related changes in CTH and HCT interfere with flow-metabolism coupling and tissue oxygenation and discusses whether such capillary dysfunction contributes to vascular disease pathology.

Stroke and presence of patent foramen ovale in sickle cell disease.

Sickle cell disease (SCD) is an inherited monogenic hemoglobinopathy characterized by formation of sickle erythrocytes under conditions of deoxygenation. Sickle erythrocytes can lead to thrombus formation and vaso-occlusive episodes that may result in hemolytic anemia, pain crisis and multiple organ damage. Moreover, SCD is characterized by endothelial damage, increased inflammatory response, platelet activation and aggravation, and activation of both the intrinsic and the extrinsic coagulation pathways. Cerebrovascular events constitute an important clinical complication of SCD. Children with SCD have a 300-fold higher risk of acute stroke and by the age of 45 about 25% of patients have suffered an overt stoke. Management and prevention of stroke in patients with SCD is not well defined. Moreover, the presence of patent foramen ovale (PFO) increases the risk of the occurrence of an embolic cerebrovascular event. The role of PFO closure and antiplatelet or anticoagulation therapy has not been well investigated. Moreover, during COVID-19 pandemic and taking into account the increased rates of thrombotic events and the difficulties in blood transfusion, management of SCD patients is even more challenging and difficult, since data are scarce regarding stroke occurrence and management in this specific population in the COVID-19 era. This review focuses on pathophysiology of stroke in patients with SCD and possible treatment strategies in the presence of PFO.

Anxiety level and clinical course of patients with sickle cell disease during the COVID-19 outbreak.

OBJECTIVES: Besides infectious pneumonia and death risks, the COVID-19 pandemic has prompted negative psychological impacts on communities, especially on people with chronic diseases. We aimed to evaluate COVID-19 and sickle cell disease (SCD)-related experiences, and the clinical course during the outbreak, to measure anxiety levels of adolescent and young adult patients with homozygous SCD, to analyze the correlations between their COVID-19 experiences and anxiety levels and painful episodes. METHODS: In this cross-sectional study, 47 patients aged between 14 and 24 years responded to a descriptive instrument and the State-Trait Anxiety Inventory. Clinical features requiring hospitalization for the same period (between March 10 and May 10) of two sequential years were compared. RESULTS: Sixty-six percent of the patients had at least one negative COVID-19 experience of dizziness, sleep disturbance, tonic immobility, appetite loss or nausea/abdominal distress. The number of negative COVID-19 experiences was correlated with the state anxiety score, the trait anxiety score, and the number of painful episodes (ρ=0.552, P<0.001; ρ=0.529, P<0.001; ρ=0.448, P=0.002, respectively). Both median state anxiety and trait anxiety scores were below the cut-off scores indicating significant clinical symptoms. The number of hospitalizations requiring vaso-occlusive crisis management and blood/exchange transfusion were similar for the same period of two sequential years, 2019 and 2020. CONCLUSION: These descriptive and correlation findings are the first reported on COVID-19-related anxiety in SCD patients. To develop screening and support strategies for mental health needs in pandemic times, further SCD studies should be conducted.