Question 1 · Hard
A 30-year-old man is admitted with pneumonia. On day 3 of treatment his hemoglobin falls from 14.2 to 10.1 g/dL [142 to 101 g/L] and his urine turns dark. Results: reticulocytes 6.5%, LD 690 U/L (reference 125-220), total bilirubin 3.6 mg/dL [62 µmol/L] with direct bilirubin 0.4 mg/dL [7 µmol/L], DAT negative. The smear shows bite and blister cells, and G6PD activity is later found to be low. CRP is 185 mg/L (below 10), and haptoglobin is 96 mg/dL [0.96 g/L] (reference 30-200). Why is the haptoglobin within the reference range?
- AInflammation has raised haptoglobin synthesis
- BLysed red cells have released haptoglobin
- COxidative hemolysis does not consume haptoglobin
- DHemopexin has bound the free hemoglobin first
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Answer: A · Inflammation has raised haptoglobin synthesis
Haptoglobin binds free hemoglobin, and the complex is quickly removed by macrophages, so the level usually falls in hemolysis. But haptoglobin is also a positive acute phase protein: IL-6 from the pneumonia drives the liver to make more, as the very high CRP shows. Increased synthesis can balance consumption and leave a normal level that hides active hemolysis. Here the falling hemoglobin, raised reticulocytes, high LD, raised indirect bilirubin and bite cells show the hemolysis anyway. A normal haptoglobin during inflammation therefore does not rule out hemolysis.
- B: Haptoglobin is made by the liver; red cells do not contain it.
- C: Hemoglobin from G6PD hemolysis binds haptoglobin like any other free hemoglobin.
- D: Hemopexin binds free heme only after haptoglobin is used up.