Hemolytic jaundice

Did You Know?

• Intensive phototherapy at saturation dose decreases unconjugated bilirubin by adding oxygen, allowing the liver to convert it into excretable products.
• In immune hemolytic jaundice, intravenous immunoglobulin therapy blocks monocyte Fc-receptors to prevent further hemolysis.
• Serum bilirubin concentration in hemolytic jaundice rarely exceeds 4 mg/dL unless concurrent liver disease is present.

Causes

Hemolytic jaundice arises from disorders that cause hemolysis. Common causes include thrombotic thrombocytopenic purpura (TTP), in which reduced ADAMTS13 activity leads to microangiopathic hemolytic anemia; laboratory findings show very high serum lactate dehydrogenase and negative Coombs test, and dark urine from hemoglobinuria may be observed. Autoimmune hemolytic anemia (AIHA) involves autoantibodies destroying red blood cells, with increased lactate dehydrogenase, decreased haptoglobin, and positive Coombs test; jaundice or dark urine occurs in about one-third of cases. Less common causes include hemolysis secondary to drug toxicity, thalassemia minor, and congenital dyserythropoietic anemia. Rare causes such as Bartonella infection, transfusion reactions, and microangiopathic hemolytic anemia should be considered when specific symptoms appear.

Pathophysiology

Bilirubin overproduction in hemolytic jaundice occurs through two main sites of hemolysis. In intravascular hemolysis, red blood cells break down within the vasculature; hemoglobin forms haptoglobin-hemoglobin complexes that are degraded by hepatocytes and spleen. Excess unbound hemoglobin converts to methemoglobin, whose heme binds to hemopexin or albumin; both complexes are internalized by hepatocytes and degraded to bilirubin. In extravascular hemolysis, macrophages in the reticuloendothelial system phagocytose red blood cells; hemoglobin is degraded to heme, which microsomal heme oxygenase converts to iron, carbon monoxide, and biliverdin. Biliverdin reductase immediately reduces biliverdin to unconjugated bilirubin, which is released into plasma. Only low levels of conjugated bilirubin accumulate in serum (normally under 4% of total) because conjugated bilirubin is efficiently excreted in bile. Increased conjugated bilirubin occurs only with coexisting hepatobiliary abnormalities. Unconjugated bilirubin binds to albumin and accumulates in elastic tissues of skin and sclera, causing yellow discolouration.

Diagnosis

Visual assessment identifies jaundice through yellowing of skin and sclera. In newborns, a clinical jaundice scale adapted from Kramer's scale quantifies severity by cephalocaudal progression from zone 1 (head) to zone 5 (palms and soles); progression to zones 4 and 5 correlates with serum bilirubin of at least 11.0 mg per 100 ml, indicating need for treatment. Conjunctival icterus can be quantified by the Jaundice Eye Colour Index (JECI) using digital photography, where 0 is white and 0.1 is intense yellow. Urine testing checks urobilinogen levels; increased urobilinogen indicates excess bilirubin in the intestine, ruling out bile flow blockage and pointing to pre-hepatic or hepatic causes. Normal urine colour indicates absence of unconjugated bilirubin. A complete blood count (CBC) and serum testing for total and fractionated bilirubin confirm findings; increased reticulocytes and schistocytes on blood smear indicate hemolysis. In hemolytic jaundice, conjugated bilirubin accounts for less than 15% of total serum bilirubin. Liver biopsy analysis showing normal alkaline phosphatase, aspartate transaminase, and alanine transaminase indicates no significant hepatocellular damage.

Complications

Poorly treated jaundice may lead to neurodevelopmental complications including hearing loss, visual impairment, and in severe cases, mortality. Hyperbilirubinemia occurs when excessive hemolysis produces more bilirubin than can be excreted, leading to bilirubin buildup in blood and tissues. Untreated hyperbilirubinemia can progress to kernicterus (chronic bilirubin encephalopathy), a brain-damaging condition in preterm and full-term infants where unconjugated bilirubin becomes neurotoxic. Kernicterus primarily affects the basal ganglia and may spread to the hippocampus, geniculate nuclei, and cranial nerve nuclei, causing athetoid cerebral palsy and potentially death. Most cases develop after early hospital discharge from phototherapy.