Clinical implications of the sickle mutation

Genotype	Clinical findings	Interventions
Heterozygous sickle mutation (sickle cell trait)	Normal life expectancy Most individuals are asymptomatic Small but significant increased risk for certain complications: Exertion- heat- or dehydration-related sudden death or acute rhabdomyolysis Complications of high altitudes, or increased atmospheric pressure Increased risk of hematuria, UTI, CKD, hyposthenuria, renal medullary cancer Complications of traumatic hyphema* Slightly increased risk of VTE Underestimation of HbA1c	Counseling about risks of rare complications Conditioning and adequate hydration with exercise Immediate ophthalmology consultation for traumatic hyphema Gradual transition to extreme high altitudes Possible alternative methods of assessing glucose if HbA1c is borderline Preconception counseling and testing if appropriate
Homozygous sickle mutation or compound heterozygosity with another beta globin variant^¶ (sickle cell disease)	Acute and chronic pain Infection risk from functional asplenia Anemia or splenic or hepatic sequestration Stroke (ischemic and hemorrhagic) CKD Bone infarcts or avascular necrosis Priapism and erectile dysfunction Delayed puberty and reduced growth Skin ulcers Retinal artery occlusion or proliferative retinopathy VTE Multiorgan failure after exposure to G-CSF Reduced life expectancy	Comprehensive care Childhood vaccinations and penicillin Monitoring for disease complications Hydroxyurea in most cases Consideration of curative therapies Rapid intervention for complications Adequate pain control Avoidance of G-CSF Preconception counseling and testing if appropriate

This is a general summary, not a complete list. Findings differ even among individuals with the same genotype.

UTI: urinary tract infection; CKD: chronic kidney disease; VTE: venous thromboembolism; HbA1C: glycosylated hemoglobin; G-CSF: granulocyte colony-stimulating factor.

* Bleeding in the anterior chamber of the eye.

¶ Includes structural variants such as hemoglobin C and quantitative variants such as beta thalassemia. Disease severity depends on the nature of the other beta globin mutation as well as other mediators. As an example, sickle-beta⁰-thalassemia is generally more severe than sickle-beta⁺-thalassemia or hemoglobin sickle cell disease. However, all individuals with sickle cell disease require comprehensive care by a multidisciplinary team. Refer to UpToDate for more information.

Graphic 122837 Version 4.0

خرید پکیج

Clinical implications of the sickle mutation