Sickle Cell Disease Overview

GTG

3

autosomal recessive

<p>polymerising</p> Signup and view all the answers

<p>valine</p> Signup and view all the answers

<p>distort</p> Signup and view all the answers

<p>problem</p> Signup and view all the answers

<p>biomarkers</p> Signup and view all the answers

<p>phosphatidylserine</p> Signup and view all the answers

<p>11</p> Signup and view all the answers

<p>tissue factor</p> Signup and view all the answers

<p>biomarkers</p> Signup and view all the answers

<p>protein S</p> Signup and view all the answers

<p>stroke</p> Signup and view all the answers

<p>crises</p> Signup and view all the answers

<p>chest pain</p> Signup and view all the answers

<p>anemia</p> Signup and view all the answers

<p>extremities</p> Signup and view all the answers

<p>crises</p> Signup and view all the answers

<p>acute chest syndrome</p> Signup and view all the answers

<p>infarctions</p> Signup and view all the answers

<p>16</p> Signup and view all the answers

<p>vaso-occlusive</p> Signup and view all the answers

<p>PS003biv</p> Signup and view all the answers

<p>PS003biv</p> Signup and view all the answers

<p>lungs</p> Signup and view all the answers

<p>staining</p> Signup and view all the answers

<p>hemolysis</p> Signup and view all the answers

<p>steady</p> Signup and view all the answers

<p>neutrophils</p> Signup and view all the answers

<p>survival</p> Signup and view all the answers

<p>inflammatory</p> Signup and view all the answers

<p>leucocytosis</p> Signup and view all the answers

<p>WBCs</p> Signup and view all the answers

<p>pulmonary</p> Signup and view all the answers

<p>FII ASO</p> Signup and view all the answers

<p>Voxelotor</p> Signup and view all the answers

<p>coagulation</p> Signup and view all the answers

<p>anti-sense oligonucleotide</p> Signup and view all the answers

<p>TF</p> Signup and view all the answers

<p>hemolysis</p> Signup and view all the answers

<p>endothelial</p> Signup and view all the answers

<p>neutrophils</p> Signup and view all the answers

<p>MPO</p> Signup and view all the answers

<p>infiltration</p> Signup and view all the answers

<p>coagulation</p> Signup and view all the answers

<p>anti-TF</p> Signup and view all the answers

<p>endothelial</p> Signup and view all the answers

<p>control</p> Signup and view all the answers

An increased tendency for blood to clot, due to alterations in the normal coagulation cascade. This state underlies many complications in sickle cell disease.

The coagulation cascade is a multi-step process that leads to the formation of a blood clot (thrombus). In SCD, this cascade is chronically activated, leading to an increased risk of thrombosis.

Protein S is a crucial component of the coagulation cascade. It acts as a cofactor for activated protein C (APC), which inhibits clotting. In SCD, protein S levels can be reduced.

Targeting protein S in SCD could be a therapeutic strategy. This would be aimed at restoring the balance of coagulation and reducing the risk of thrombosis.

The PROSICK study investigated the use of recombinant protein S (rPS) in patients with SCD and a history of thrombosis. The goal was to assess its efficacy and safety in preventing future thrombosis.

A common genetic disorder affecting millions globally, characterized by a single base change in the beta chain of the hemoglobin gene.

Caused by a mutation in the gene responsible for producing hemoglobin, leading to the production of Hemoglobin S.

Hemoglobin S polymerizes when oxygen is released, forming rigid fibers that distort red blood cells into a sickle shape.

Individuals with sickle cell disease inherit two copies of the mutated gene, one from each parent.

An inherited disease with a mutation in the gene that makes the beta chain of hemoglobin.

The sickle-shaped red blood cells are less flexible and prone to block blood vessels, leading to pain and organ damage.

Sickle cell disease is a disorder affecting the red blood cells, responsible for carrying oxygen throughout the body.

A condition where the blood is more likely to clot, increasing the risk of blood clots.

The process by which reactive oxygen species (ROS) are produced within cells, leading to oxidative stress and damaging effects.

A vicious cycle where sickle cell disease leads to complications that further worsen the disease, creating a continuous loop.

A sudden, sharp pain caused by the blockage of blood vessels by sickled red blood cells.

A serious lung complication characterized by inflammation and fluid buildup, often triggered by infection.

A blockage or rupture of a blood vessel in the brain, leading to brain damage.

A long-term consequence of sickle cell disease, characterized by reduced production of red blood cells.

Damage to the spleen caused by repeated episodes of blockage by sickled red blood cells.

A broad term encompassing various complications arising from sickle cell disease, including damage to organs such as the kidneys, liver, and heart.

In sickle cell mice, the activation of coagulation is triggered by Tissue Factor (TF).

Blocking Tissue Factor (TF) does not affect the breakdown or maturation of red blood cells in sickle cell mice.

Inhibition of Tissue Factor (TF) leads to decreased levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and interleukin-6 (IL-6) in sickle cell mice.

In sickle cell mice, inhibition of Tissue Factor (TF) reduces inflammation and endothelial cell activation.

Berkeley sickle mice show increased neutrophil infiltration in their lungs and livers compared to wild-type (WT) mice.

Berkeley sickle mice exhibit elevated levels of myeloperoxidase (MPO) in their lungs and livers, indicating increased neutrophil activity.

Blocking Tissue Factor (TF) in Berkeley sickle mice (BERKBM) attenuates neutrophil infiltration into the lungs.

In sickle cell mice, Tissue Factor (TF) plays a significant role in both the activation of coagulation (blood clotting) and inflammation.

Neutrophils are an essential component of the immune response, but their excessive activation and infiltration can contribute to inflammation and tissue damage.

The research suggests that targeting Tissue Factor (TF) could be a therapeutic strategy for mitigating inflammation and coagulation issues in sickle cell disease.

A mouse model that mimics the sickle cell disease (SCD) phenotype by expressing human alpha-globin and beta-globin S genes. This model allows researchers to study SCD and test potential therapies in a living organism.

A model used to study vaso-occlusive crisis (VOC) in sickle cell disease (SCD). Mice are injected with heme, a compound that triggers VOC-like symptoms in SCD patients.

The group of mice in the heme injection vaso-occlusive crisis model that received PS003biv, a potential treatment for SCD.

The group of mice in the heme injection vaso-occlusive crisis model that received the vehicle solution (control) without any treatment.

A technique that uses a laser beam to illuminate a thin slice of tissue, creating a 3D image. This is helpful for visualizing blood vessels and other structures in the liver and lungs of the mice.

A marker or label that identifies red blood cells in light sheet microscopy images. TER 119 helps researchers visualize red blood cells in the tissue.

The state of the mice with SCD before any heme injection (baseline). This refers to the regular, non-crisis state of the mice.

The process of red blood cells breaking down prematurely, leading to anemia and other complications in SCD. It's one of the key features of SCD.

A condition where there is an imbalance in the clotting process, leading to increased coagulation and a higher risk of blood clots. This is a significant aspect of sickle cell disease (SCD) pathophysiology, contributing to complications like stroke and organ damage.

A key factor in the coagulation cascade, responsible for initiating clotting by activating other coagulation factors. Its inhibition has been shown to reduce inflammation in SCD.

A targeted approach to reducing the levels of thrombin, a key enzyme in clotting. This strategy has been proven to significantly improve survival rates in sickle cell mice models.

A type of treatment specific to sickle cell disease that focuses on decreasing the overproduction of thrombin, a key factor in coagulation and inflammation. A reduction in thrombin levels has been linked to improved survival and decreased inflammation in SCD.

An anti-sense oligonucleotide that reduces the production of thrombin by specifically binding to and hindering its synthesis. This therapeutic approach has shown promise in mitigating SCD complications.

A serious issue associated with Sickle Cell Disease (SCD) that is characterized by an overabundance of white blood cells (specifically neutrophils and monocytes), an abnormally high platelet count, and a heightened inflammatory response. These factors contribute to the complications and tissue damage characteristic of SCD.

A class of drugs that aim to prevent blood clots, but their use in SCD isn't without controversy. Further research is needed to determine their safety and effectiveness in this context.

A type of white blood cell that is particularly important for fighting bacterial infections. Elevated numbers of neutrophils, along with other indicators, are a defining characteristic of the thrombo-inflammatory state found in individuals with sickle cell disease.

An indicator of inflammation and vascular damage found in sickle cell disease (SCD). Elevated levels of this protein suggest that the body is fighting inflammation and possibly experiencing tissue damage.

A condition characterized by excessive clotting and inflammation, which is a key feature associated with sickle cell disease (SCD). This thrombo-inflammatory state is responsible for many complications, including strokes and organ damage.