Sickle cell trait patient do not have manifestations as that of Sickle cell disease, because: (AIIMS Nov 2009)
|A||50% HbS is required for occurrence of sickling|
|B||HbA prevents sickling|
|C||HbS is less than 50% & HbA has low affinity for HbS|
|D||HbA prevents polymerization of HBS|
HbS is less than 50% & HbA has low affinity for HbS
Factors influencing sickling
1. Amount of HbS directly proportional to sickling
a. Homozygous – 100%
b. Heterozygous – 40%
2. Presence of other type of hemoglobin
a. Hb C, D - Increase sickling
b. Hb F - Prevent sickling
3. Acidosis – Increase sickling
a. Intracellular dehydration – sickling ↑
b. Viscosity ↑ - Sickling ↑
5. O2 tension: ↓ O2 tension - ↑ sickling
6. Length of time RBC exposed to ↓ O2 tension : i. It flow is sluggish (time ↑) – sickling ↑
7. Presence of α - thalassemia - ↓ sickling
8. 2, 3. DPG - ↑ sickling
1. The most important factor affecting the rate and degree of sickling is the amount of HBs and its interaction with other hemoglobin chains in the cell.
2. Patients with sickle cell trait (Heterozygotes) have 40% of haemoglobin in the form of HbS, the rest being HbA, which interacts only with HbS when deoxygenated.
3. Both the low concentration of HbS and the presence of interfering HbA act to prevent effective HBs aggregation and polymerization and thus red cells in sickle cell trait (heterozygotes) do not sickle.
1. In the deoxygenated state the HbS molecules polymerize and causes sickling of RBCs.
2. Sickle cells are rigid, and haemolyse, and block small vessels to cause infarction.
3. Deoxygenated Hb align in parallel forming tactoid that distort the RBC into the classic sickle and oak leaf shaped cells.
Fig: Pathophysiology of sickle cell crisis (Ref. Hari- 18th ed., Pg. 855, fig 104.3)