Can hemolysis cause elevated aspartate transaminase (AST)/alanine transaminase (ALT) levels?

From the Guidelines

Hemolysis can indeed cause elevated aspartate transaminase (AST) and alanine transaminase (ALT) levels due to the release of these enzymes from ruptured red blood cells. According to the most recent and highest quality study 1, hepatocellular injury causes the release of ALT and AST in serum, and while the study primarily focuses on hepatocellular causes of elevated liver enzymes, it also mentions that if the aminotransferase rise is predominantly AST, nonhepatic causes such as hemolysis should be considered. Key points to consider include:

• AST levels are increased in fatty liver disease and cirrhosis, but a predominantly AST rise should prompt consideration of nonhepatic causes like hemolysis, myopathy, thyroid disease, or exercise 1.
• Hemolysis can lead to misleading test results suggesting liver damage when none exists, as red blood cells contain AST and, to a lesser extent, ALT, which are released into the serum during hemolysis.
• Other laboratory markers like lactate dehydrogenase (LDH) and haptoglobin can help confirm whether hemolysis is present, as LDH will be elevated and haptoglobin decreased in hemolytic conditions.
• The study 1 provides guidelines for managing hemolysis in the context of sickle cell disease but does not directly address the impact of hemolysis on AST and ALT levels. However, the primary concern in clinical practice, based on the most recent evidence 1, is to recognize that hemolysis can cause elevated AST and ALT levels, which may not accurately reflect liver function.

From the Research

Hemolysis and Elevated AST/ALT Levels

• Hemolysis can affect the results of various laboratory tests, including AST and ALT levels 2, 3, 4.
• Studies have shown that hemolysis can cause an increase in AST levels, although the effect may be less pronounced compared to other analytes 2.
• In one study, hemolysis was found to affect AST levels almost at undetectable levels of hemolysis by visual inspection (plasma hemoglobin < 0.5 g/L) 3.
• Another study found that AST levels increased proportionally with the degree of hemolysis, along with other tests such as potassium, lactate dehydrogenase, and thymol turbidity test (TTT) 4.
• In contrast, ALT levels were found to be less affected by hemolysis, with one study showing that ALT levels were not interfered with up to severely hemolyzed levels (hemoglobin: 2.5-4.5 g/L) 3.
• However, another study found that ALT levels were affected by hemolysis, particularly when using dry chemistry methods, and that wet chemistry methods displayed superior anti-hemolytic ability compared to dry chemistry methods 2.

Mechanism of Hemolysis Interference

• Hemolysis can release intracellular enzymes and substances into the bloodstream, leading to interference with laboratory tests 5, 3.
• The release of these substances can cause an increase in AST and other enzyme levels, leading to inaccurate test results 2, 4.
• The degree of hemolysis can affect the extent of interference with laboratory tests, with more severe hemolysis leading to greater interference 3, 4.

Clinical Implications

• Hemolysis can lead to inaccurate laboratory test results, including elevated AST and ALT levels, which can affect clinical decision-making 2, 3, 4.
• It is essential to consider the potential effects of hemolysis on laboratory test results, particularly when interpreting AST and ALT levels 2, 3.
• The use of plasma or serum free hemoglobin concentrations can help detect hemolysis and prevent unnecessary sample rejections or reruns 3.