Fetal hemoglobin enables malaria parasite growth in sickle cells but augments production of transmission stage parasites.

Sickle cell trait is the quintessential example of the human evolutionary response to malaria, providing protection against severe disease, but leading to sickle cell disease (SCD) in the homozygous state. Fetal Hemoglobin (HbF) reduces the pathology of SCD and several mutations lead to the prolonged production of HbF into childhood and adult life. HbF has been suggested to contribute to protection against malaria.

Comparative histological analysis of spleens in pediatric patients with hemolytic anemias: Insights into the pathophysiological mechanisms of spleen destruction in sickle cell anemia.

While sickle cell anemia (SCA) and hereditary spherocytosis (HS) share common features of increased spleen erythrophagocytosis due to increased red blood cell (RBC) turnover, SCA is specifically characterized by susceptibility to infections. In this study, histological lesions in the spleens of pediatric patients with SCA were analyzed, in close correlation with past clinical history and comparatively to HS, healthy and transfused β-thalassemia patients (TDT). An evaluation of red pulp elementary lesions (red pulp fibrosis, iron deposition, number of Gandy-Gamna, and RBC trapping) combined into a severity score was established, as well as B-cell follicles analysis.

Oxidative Stress in Healthy and Pathological Red Blood Cells.

Red cell diseases encompass a group of inherited or acquired erythrocyte disorders that affect the structure, function, or production of red blood cells (RBCs). These disorders can lead to various clinical manifestations, including anemia, hemolysis, inflammation, and impaired oxygen-carrying capacity. Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense mechanisms, plays a significant role in the pathophysiology of red cell diseases.

Red Blood Cells: A Newly Described Partner in Central Retinal Vein Occlusion Pathophysiology?

Central retinal vein occlusion (CRVO) is a frequent retinal disorder inducing blindness due to the occlusion of the central vein of the retina. The primary cause of the occlusion remains to be identified leading to the lack of treatment. To date, current treatments mainly target the complications of the disease and do not target the primary dysfunctions.

Fetal hemoglobin rescues ineffective erythropoiesis in sickle cell disease.

While ineffective erythropoiesis has long been recognized as a key contributor to anemia in thalassemia, its role in anemia of sickle cell disease (SCD) has not been critically explored. Using in vitro and in vivo derived human erythroblasts we assessed the extent of ineffective erythropoiesis in SCD. Modeling the bone marrow hypoxic environment, we found that hypoxia induces death of sickle erythroblasts starting at the polychromatic stage, positively selecting cells with high levels of fetal hemoglobin (HbF).

Gas6 Promotes Inflammatory (CCR2CX3CR1) Monocyte Recruitment in Venous Thrombosis.

Objective: Coagulation and inflammation are inter-related. Gas6 (growth arrest-specific 6) promotes venous thrombosis and participates to inflammation through endothelial-innate immune cell interactions. Innate immune cells can provide the initiating stimulus for venous thrombus development.

Hydroxycarbamide decreases sickle reticulocyte adhesion to resting endothelium by inhibiting endothelial lutheran/basal cell adhesion molecule (Lu/BCAM) through phosphodiesterase 4A activation.

Vaso-occlusive crises are the main acute complication in sickle cell disease. They are initiated by abnormal adhesion of circulating blood cells to vascular endothelium of the microcirculation. Several interactions involving an intricate network of adhesion molecules have been described between sickle red blood cells and the endothelial vascular wall.

Vascular Gas6 contributes to thrombogenesis and promotes tissue factor up-regulation after vessel injury in mice.

Gas6 (growth-arrest specific gene 6) plays a role in thrombus stabilization. Gas6 null (-/-) mice are protected from lethal venous and arterial thromboembolism through platelet signaling defects induced only by 5 μM ADP and 10 μM of the thromboxane analog, U46619. This subtle platelet defect, despite a dramatic clinical phenotype, raises the possibility that Gas6 from a source other than platelets contributes to thrombus formation.

Growth arrest-specific gene 6 (gas6) and vascular hemostasis.

Gas6 (growth arrest-specific 6) belongs structurally to the family of plasma vitamin K-dependent proteins. Gas6 has a high structural homology with the natural anticoagulant protein S, sharing the same modular composition. Interestingly, despite the presence of a γ-carboxyglutamic acid domain in its structure, no role in the coagulation cascade has been identified for gas6.

Abnormal flow adhesion of sickle red blood cells to human placental trophoblast extracellular matrix.

Pregnancy in sickle cell disease (SCD) has been associated with increased complications such as vaso-occlusive crises, severe anemia and foetal loss. It has been proposed that the sickling of red blood cells (RBCs) inside the placenta circulation could participate to these complications. The present study investigated the adhesion of sickle RBCs on human trophoblast-derived cell and its extracellular matrix.

Differential modulation of adhesion molecule expression by hydroxycarbamide in human endothelial cells from the micro- and macrocirculation: potential implications in sickle cell disease vasoocclusive events.

Background: All the cellular partners of the vascular system and especially endothelial cells are involved in the pathophysiology of the vasoocclusive crises associated with sickle cell disease. In sickle cell disease, circulating cells adhere abnormally to endothelial cells in a chronic pro-inflammatory context. Hydroxycarbamide is the only drug with demonstrated efficacy to reduce the frequency of vasoocclusive crises.

Hydroxycarbamide stimulates the production of proinflammatory cytokines by endothelial cells: relevance to sickle cell disease.

Background And Objective: The clinical hallmarks of sickle cell disease (SCD) are vaso-occlusive crises (VOC) triggered by red blood cells (RBC) stiffening and abnormal adhesion to vascular endothelial cells (VEC) in the context of chronic inflammation, cell activation, and vascular tone abnormalities. Hydroxycarbamide (HC) is the only drug with a proven efficacy in decreasing VOC frequency. HC decreases RBC stiffening, modulates adhesion protein expression by RBC and VEC, and reduces endothelin-1 production by VEC.