Sickle Cell Disease Overview

sudden, intense pain caused by blocked blood flow in sickle cells

Infection in the lungs, often triggered by a blood clot obstructing airflow

Severe neurological condition resulting from a blocked or ruptured blood vessel in the brain

Low oxygen levels in the blood

A temporary blockage of blood flow to the brain, often a warning sign of a future stroke

A condition where the blood is more likely to clot than usual.

The process of activating clotting factors in the blood leads to the formation of a blood clot.

In sickle cell disease, coagulation activation is a key factor that contributes to the disease's complications.

Protein S is a crucial protein involved in the breakdown of blood clots.

A study investigating the potential benefits of targeting protein S in treating sickle cell disease.

Protein S binds to approximately 6% of red blood cells (RBCs) in patients with Sickle Cell Disease (SCD).

The binding of protein S to RBCs in SCD can be removed by the addition of calcium.

Protein S binds to phosphatidylserine which is exposed on the surface of RBCs.

Protein S is involved in phagocytosis, a process where macrophages engulf and remove cells.

The SHBG domain of protein S binds to the TAM receptor on macrophages, facilitating the phagocytosis of phosphatidylserine-exposing cells.

PS003biv is a single-domain antibody designed to enhance the activity of protein S, a crucial protein in breaking down blood clots. It works by binding to protein S, improving its ability to cooperate with activated protein C, a natural anticoagulant, to regulate blood clotting.

Protein S deficiency is a condition where the body doesn't produce enough protein S, leading to a higher risk of blood clots. This deficiency has been observed in mice with sickle cell disease, suggesting a potential role in the disease's complications.

The PROSICK study aims to investigate the potential benefits of targeting protein S in treating sickle cell disease. It explores the role of protein S deficiency in the disease, investigates its contribution to the disease's pathogenesis, and seeks to develop pharmacological approaches that target protein S.

The FeCl3-induced murine thrombosis model is a laboratory method used to study blood clots in mice. Researchers inject a substance called FeCl3 into the mice to induce clot formation, then observe the effects of different treatments, including potential therapies targeting protein S.

The bleeding model is another laboratory method used to assess the safety of treatments targeting protein S. It involves inducing bleeding in mice and then evaluating the effects of the treatments on blood clotting and bleeding time.

Microparticles (MP) are tiny vesicles released from cells, particularly endothelial cells and monocytes. These particles carry various molecules, including those associated with coagulation activation. They are often observed in patients with sickle cell disease (SCD) and are linked to the increased risk of clotting.

A hypercoagulable state in SCD means that the blood is more likely to clot than in individuals who do not have SCD. This heightened risk of clotting leads to a significantly increased chance of developing thromboembolic events, such as pulmonary embolism (PE) and deep vein thrombosis (DVT).

In patients with SCD, up to 25% experience venous thromboembolism (VTE), a major complication involving blood clots in veins. This risk is substantial, and the reoccurrence rate is significant, further emphasizing the importance of managing this condition in individuals with SCD.

SCD patients have a significantly higher risk of bleeding compared to those without the disease. This duality of increased clotting risk and bleeding risk underscores the complexities of managing coagulation complications in SCD.

Tissue factor (TF) is a key molecule in the coagulation cascade. In SCD, TF levels are elevated, leading to increased clotting activity. Antibodies targeting TF, such as 1H1, have been shown to effectively inhibit this clotting process, highlighting a potential therapeutic approach to managing SCD complications.

The buildup of Hb-S (sickle hemoglobin) in the blood contributes to the hypercoagulation state in SCD. This accumulation further enhances the coagulation process, making it more likely for blood clots to form in individuals with SCD.

The coagulation cascade is a complex series of reactions involving various clotting factors. In SCD, this cascade is often overactive, leading to increased clotting. Understanding the intricate interplay of clotting factors, including factors VIIa, IXa, XIa, and others, is essential for managing SCD complications related to clotting.

Platelets play an essential role in blood clotting. They contribute to clot formation and contribute to the hypercoagulable state in SCD. Understanding their role is crucial for managing clotting issues in individuals with SCD.

A type of mouse model used for sickle cell disease research, carrying a gene for human beta-globin S. Their red blood cells behave similar to those in humans with sickle cell disease.

A method used to simulate a sickle cell crisis by directly introducing heme into the bloodstream of Townes sickle mice.

A drug called PS003biv, which is being investigated for its potential to improve the symptoms of sickle cell disease.

A technique where a thin sheet of light is used to illuminate a sample, allowing for 3D imaging.

A protein found on the surface of red blood cells that is used as a marker for imaging.

The state of the Townes sickle mice when they are not experiencing a vaso-occlusive crisis.

The state of the Townes sickle mice after they have been given a heme injection, inducing a vaso-occlusive crisis.

The state of the Townes sickle mice after they have been given a heme injection and PS003biv, representing the treatment group.