It is defined by hemolytic anemia (with spur cells and acanthocytes), hyperlipoproteinemia (excessive blood lipoprotein), jaundice (elevation of unconjugated bilirubin), and abdominal pain.

[citation needed] Diagnosis of Zieve's syndrome should be considered in patients with prolonged alcohol use (especially after an episode of binge drinking) with an elevation of unconjugated bilirubin and without obvious signs of gastrointestinal bleeding.

[2] The proposed mechanism of the characteristic haemolytic anemia in Zieve's syndrome is due to alteration of the red cell metabolism, namely pyruvate kinase instability leaving them susceptible to circulating hemolysin such as lysolecithin.

[3] Changes in membrane lipid compositions such as increased cholesterol and polyunsaturated fatty acid (PUFA) have been reported during the hemolytic phase.

Individuals with markedly elevated triglycerides, particularly with a history of pancreatitis or intracerebral hemorrhage, may require plasmapharesis to avoid complications associated with hypertriglyceridemia.