Why haptoglobulin is decreased in intravascular hemolysis and normal in extravascular hemolysis

Why haptoglobulin is decreased in intravascular hemolysis and normal in extravascular hemolysis

Haptoglobin binds to the hb in blood and that’s why decreased in intravascular hemolysis . It is almost zero in PIGA mutation

In extravascular hemolysis Hb goes inside splenic macrophages not letting it to attach with heptoglobin

In extravascular hemolysis, the RBCs are destroyed by the reticular endothelial system (macrophages of the spleen, liver and lymph nodes). Macrophages consume RBC and breakdown the hemoglobin. Globin breaks down to amino acids, heme breakdown to iron and protoporphyrin, protoporphyrin breaksdown to unconjugated bilirubin. As for the findings, we will see anemia with splenomegaly (due to spleen consuming RBCs). Jaundice due to increase of unconjugated bilirubin, bile gallstones and marrow hyplerplasia since BM is normal and begins to pump up reticulocytes (corrected reticulocyte > 3%)

In intravascular hemolysis, the hemoglobin leaks out from the RBC and binds to haptoglobin (the levels of free haptoglobin decrease because it binds to hemaglobin). The hemaglobin haptoglobin complex goes to the spleen to be reprocessed since the body wants to save hemoglobin. Since the haptoglobin is minimal in the serum, it doesnt do much to save hemoglobin except in small amounts. So the hemaglobin builds up in the blood creating hemoglobinemia. Hemoglobin from the blood will leak out to urine since its water soluble and create hemaglobinuria. As the hemaglobin goes through the tubule, the renal tubular cells take up the hemoglobin. The iron will pile up as hemosiderin. Eventually the cells will turn over and release the hemosiderin creating hemosiderinuria.