Rate of sickling in sickle cell anemia is directly proportional to all the following EXCEPT:
Ans. c (Raised HbF). (Ref. Robbin, Pathologic Basis of Diseases, 5th/592; 6th/611)A number of factors affect the rate and degree of sickling:# HbS (directly proportional)# HbF (inversely proportional as it inhibits polymerization of HbS)# HbC and HbD (directly proportional) HbSC have more severe disease than those with HbSA.# MCHC (directly proportional). Dehydration facilitates sickling by upper MCHC.# Fall in pH (directly proportional) by upper amount of deoxygenated Hb.Educational points:SICKLE CELL DISEASEPathogenesis# HbS (a2b6 Glu -Val) polymerizes reversibly when deoxygenated to form a gelatinous network of fibrous polymers that stiffen the RBC membrane, increase viscosity, and cause dehydration due to potassium leakage and calcium influx. These changes also produce the sickle shape.# Sickled cells lose the pliability needed to traverse small capillaries.# Hemolysis occurs because the spleen destroys the abnormal RBC.C/f:SyndromeC/fSickle cell traitUsually asymptomatic.Anemia and painful crises are exceedingly rare.An uncommon but highly distinctive symptom is painless hematuria often in adolescent males, probably due to papillary necrosis.Isosthenuria is more common.Sickle cell anemiaVasoocclusive crises with infarction of spleen, brain, marrow, kidney, lung;A septic necrosis of bone;Gallstones;Priapism;Ankle ulcers.Rx:# The most significant advance in the therapy of sickle cell anemia has been the introduction of hydroxyurea as a mainstay of therapy for patients with severe symptoms.# Hydroxyurea (10-30 mg/kg per day) increases fetal hemoglobin and may also exert beneficial affects on RBC hydration, vascular wall adherence, and suppression of the granulocyte and reticulocyte counts; dosage is titrated to maintain a white cell count between 5000 and 8000 per mL.# The 5-deoxyazacytidine (decitabine) can elevate HbF with acceptable toxicity.# Bone marrow transplantation can provide definitive cures but is effective and safe only in children.
Raised HbS
Raised HbC
Raised HbF
Hb deoxygenation
Blood