[Pathophysiology of sickle cell disease].

Area of Science:

• Hematology
• Molecular Biology
• Pathophysiology

Context:

• Sickle cell disease (SCD) was first reported 100 years ago, with hemoglobin S (HbS) identified in 1949.
• The molecular pathophysiology involving deoxyhemoglobin S polymerization and red blood cell (RBC) sickling has been understood since the 1960s-70s.
• Current understanding explains hemolytic anemia and vasoocclusive crises (VOC) but not the triggers for VOC.

Purpose:

• To review recent findings on factors contributing to sickle cell disease pathophysiology.
• To explore novel mechanisms underlying vasoocclusive crises (VOC).

Summary:

• Deoxyhemoglobin S polymerization distorts RBCs, causing sickling and shortened lifespan, leading to hemolytic anemia.
• This process underlies vasoocclusive crises (VOC) but doesn't fully explain their initiation.
• Recent data highlight RBC dehydration, altered RBC adhesion, inflammation, cellular activation, vascular tone, and carbon monoxide metabolism as key factors.

Impact:

• Provides new insights into the complex pathophysiology of sickle cell disease.
• Advances understanding of the triggers for vasoocclusive crises (VOC).
• Contributes to the study of the first identified molecular disease.