Antithrombin-III mitigates thrombin-mediated endothelial cell contraction and sickle red blood cell adhesion in microscale flow.

Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III (ATIII), an endogenous serine protease inhibitor, inhibits several enzymes in the coagulation cascade, including thrombin. Here, we utilize a biomimetic microfluidic device to model the morphology and adhesive properties of endothelial cells (ECs) activated by thrombin and examine the efficacy of ATIII in mitigating the adhesion of SCD patient-derived red blood cells (RBCs) and EC retraction.

Prevalence of relative systemic hypertension in adults with sickle cell disease in Ghana.

Individuals with sickle cell disease particularly with the homozygous (SS) genotype historically have relatively low blood pressure. Nonetheless, they develop vasculopathy-associated organ dysfunction and the risk of organ dysfunction increases at blood pressures that are normal in the general population. This phenomenon is termed relative systemic hypertension (RSH) with a systolic blood pressure range of 120-139 mmHg, and diastolic blood pressure range of 70-89 mmHg.

Organ damage in sickle cell disease study (ORDISS): protocol for a longitudinal cohort study based in Ghana.

Introduction: Sickle cell disease is highly prevalent in Africa with a significant public health burden. Nonetheless, morbidity and mortality in sickle cell disease that result from the progression of organ damage is not well understood. The Organ Damage in Sickle Cell Disease Study (ORDISS) is designed as a longitudinal cohort study to provide critical insight into cellular and molecular pathogenesis of chronic organ damage for the development of future innovative treatment.

Nonhematopoietic Nrf2 dominantly impedes adult progression of sickle cell anemia in mice.

The prevention of organ damage and early death in young adults is a major clinical concern in sickle cell disease (SCD). However, mechanisms that control adult progression of SCD during the transition from adolescence are poorly defined with no cognate prophylaxis. Here, we demonstrate in a longitudinal cohort of homozygous SCD (SS) mice a link between intravascular hemolysis, vascular inflammation, lung injury, and early death.