A patient with a haemoglobin variant (Hb Kansas) has threonine instead of asparagine at beta-102, at the alpha1-beta2 interface. This substitution destabilises the T-state. The clinical consequence is:
- A High oxygen affinity hemoglobin causing polycythemia due to impaired oxygen delivery to tissues
- B Unstable hemoglobin that precipitates as Heinz bodies causing hemolytic anemia
- C Low oxygen affinity hemoglobin causing cyanosis; tissue oxygen delivery is maintained but hemoglobin does not fully saturate in the lungs ✓
- D Methemoglobin formation due to oxidation of the heme iron at beta-102
Explanation
The alpha1-beta2 interface undergoes a 15-degree rotation between T-state (deoxy, low affinity) and R-state (oxy, high affinity). Hb Kansas (beta102 Asn→Thr) destabilizes the T-state contacts, shifting equilibrium toward the R-state to release oxygen more easily than normal — it has LOW oxygen affinity (shifts the oxygen dissociation curve right). Despite the right-shifted curve, hemoglobin doesn't fully load in the lungs, causing cyanosis from reduced arterial saturation, but tissue oxygen delivery is actually maintained. High O2 affinity hemoglobins (e.g., Hb Chesapeake) cause polycythemia. This is distinct from unstable hemoglobins that cause Heinz body hemolysis.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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Written and medically reviewed by the StethoPrep medical team.