Tests of haemolysis - bilirubin

Role

Serum bilirubin (predominantly unconjugated/indirect bilirubin) rises in haemolysis, reflecting increased haem breakdown from accelerated red cell destruction exceeding the liver's conjugation capacity
One of the standard "haemolysis screen" tests, used alongside LDH, haptoglobin, and reticulocyte count to confirm and characterise haemolytic anaemia

Red cell destruction releases haemoglobin, which is broken down to unconjugated bilirubin - when haemolysis is significant, the rate of unconjugated bilirubin production can exceed the liver's conjugation capacity, causing an unconjugated hyperbilirubinaemia pattern (raised total and indirect bilirubin, normal/near-normal direct/conjugated fraction)

An isolated unconjugated hyperbilirubinaemia (normal conjugated fraction, normal other LFTs) supports a pre-hepatic cause (haemolysis or, alternatively, Gilbert syndrome - a benign conjugation disorder, an important differential particularly when bilirubin elevation is mild and isolated with no other haemolysis markers abnormal)
Bilirubin alone is a relatively insensitive/nonspecific haemolysis marker compared with LDH and haptoglobin - used as part of the combined panel rather than in isolation

A raised unconjugated bilirubin in the context of anaemia should prompt the full haemolysis screen (LDH, haptoglobin, reticulocyte count, blood film) rather than being interpreted alone
Distinguishing haemolysis-driven from Gilbert syndrome-driven unconjugated hyperbilirubinaemia relies on the absence of anaemia/other haemolysis markers in Gilbert syndrome

Haemolytic anaemia (all causes), Gilbert syndrome (a key benign differential for isolated unconjugated hyperbilirubinaemia), neonatal jaundice

Bilirubin's rise in haemolysis is a downstream, relatively nonspecific consequence of increased haem turnover - LDH and haptoglobin are generally more sensitive and specific markers, and bilirubin should be interpreted as one component of a combined haemolysis panel rather than a standalone diagnostic test

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