What is the mechanism of sickle cell disease?

It is caused by an A to T point mutation in the beta globin gene that produces hemoglobin S, which polymerizes in the deoxygenated state, resulting in physical deformation or sickling of erythrocytes. Sickle erythrocytes promote vaso-occlusion and hemolysis, which are two major hallmarks of the disease.

What is the function of hydroxyurea?

Hydroxyurea is used to prevent painful episodes and reduce the need for blood transfusions in patients with sickle cell anemia. It works by making the red blood cells more flexible. This medicine is available only with your doctor’s prescription.

How does hydroxyurea inhibit DNA synthesis?

Hydroxyurea is commonly thought to inhibit ongoing DNA replication indirectly by targeting the class Ia ribonucleotide reductase (nrdAB gene products) of E. coli and depleting the dNTP pools required for DNA synthesis to occur (5, 6, 10).

When is hydroxyurea used in sickle cell anemia?

We consider hydroxyurea for children with sickle cell disease who have had: Many painful events, • Several cases of acute chest syndrome (pneumonia), • Severe anemia, or • Other special problems with their internal organs.

What mechanisms contribute to anemia in patients with SCD?

Abnormal versions of beta-globin can distort red blood cells into a sickle shape. The sickle-shaped red blood cells die prematurely, which can lead to anemia. Sometimes the inflexible, sickle-shaped cells get stuck in small blood vessels and can cause serious medical complications.

What causes vaso occlusion in sickle cell disease?

A vaso-occlusive crisis, or VOC, occurs when sickled red blood cells block blood flow to the point that tissues become deprived of oxygen. This in turn sets in motion an inflammatory response as the body tries to rectify the problem.

How does hydroxyurea affect the cell cycle?

Hydroxyurea (HU) has been used for the treatment of multiple diseases, such as cancer. The therapeutic effect is generally believed to be due to the suppression of ribonucleotide reductase (RNR), which slows DNA polymerase movement at replication forks and induces an S phase cell cycle arrest in proliferating cells.

How does hydroxyurea increase fetal hemoglobin?

Hydroxyurea induces fetal hemoglobin by the nitric oxide–dependent activation of soluble guanylyl cyclase.

Does hydroxyurea decrease hemoglobin S?

Hemoglobin, the protein that carries oxygen in red blood cells. Hydroxyurea works by making your hemoglobin level go up.