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. Results demonstrated 1) similar adhesion of sickle RBCs and healthy RBCs to trophoblast but 2) a greater adhesion of sickle RBCs to the extracellular matrix of trophoblasts as compared with healthy RBCs. This greater adhesion could partly involve the Lu/BCAM glycoproteins and could participate to the complications reported in SCD pregnant women.
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http://dx.doi.org/10.3233/CH-2011-1525 | DOI Listing |
Front Immunol
January 2025
Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, United States.
Sickle cell disease (SCD) is a devastating hemolytic disease, marked by recurring bouts of painful vaso-occlusion, leading to tissue damage from ischemia/reperfusion pathophysiology. Central to this process are oxidative stress, endothelial cell activation, inflammation, and vascular dysfunction. The endothelium exhibits a pro-inflammatory, pro-coagulant, and enhanced permeability phenotype.
View Article and Find Full Text PDFCardiovasc Hematol Agents Med Chem
December 2024
Department of Pharmacology, Rungta College of Pharmaceutical Science and Research, Bhilai, Chhattisgarh, 490023, India.
Red blood cells with sickle cell anemia (SCA) have an irregular shape, and it is a genetic blood condition that can cause several problems and shorten life expectancy. Traditional treatments have focused on symptom management, but recent advancements in drug delivery systems offer promising pathways for targeted therapies. This abstract explores novel approaches to combat SCA through innovative drug delivery systems, gene therapy, and new pharmaceutical interventions.
View Article and Find Full Text PDFHaematologica
November 2024
Hematology Center, University of Campinas - UNICAMP, Campinas - São Paulo.
Continuous vaso-occlusive and inflammatory processes cause extensive end-organ damage in adults with sickle cell disease (SCD), and there is little evidence that longterm hydroxyurea therapy prevents this. In initial trials, P-selectin blockade with crizanlizumab reduced SCD vaso-occlusive crisis frequency, and interleukin (IL)-1β inhibition in SCD patients, using canakinumab, lowered inflammatory markers. We used murine SCD models to examine the effects of acute and chronic blockade of Pselectin and of IL-1β on vaso-occlusive events, their inflammatory profile and organ health.
View Article and Find Full Text PDFJ Clin Med
October 2024
Servicio de Hematología y Hemoterapia, Hospital Universitario de Guadalajara, 19002 Guadalajara, Spain.
Despite advancements in treatment of sickle cell disease (SCD), hydroxyurea, a ribonucleotide reductase inhibitor, remains the cornerstone of therapy. While its primary effect is the elevation of fetal hemoglobin (HbF), hydroxyurea's mechanisms of action are multifaceted. Hydroxyurea (HU) reduces leukocyte and platelet counts, decreases the expression of endothelial adhesion molecules CD36 and CD49d, and increases nitric oxide and cyclic nucleotide levels, which may facilitate vascular dilation and further HbF induction.
View Article and Find Full Text PDFTher Adv Hematol
November 2024
Division of Hematology-Oncology, East Carolina University, Greenville, NC, USA.
Background: Crizanlizumab is a novel inhibitor of P-selectin, a key player in multicellular adhesion and inflammatory signaling, that leads to vaso-occlusion in sickle cell disease (SCD).
Objectives: The SOLACE-adults study evaluated the pharmacokinetics, pharmacodynamics (P-selectin inhibition), safety, and efficacy of crizanlizumab, with or without hydroxyurea/hydroxycarbamide, in patients with SCD.
Design: Phase II, single-arm, multicenter study.
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