From the Guidelines
Hemolysis can indeed cause elevated folate levels due to the release of intracellular folate from ruptured red blood cells. When considering the impact of hemolysis on folate levels, it's crucial to understand that red blood cells contain significantly higher concentrations of folate than serum. Although the provided evidence, such as the espen micronutrient guideline 1, focuses on folic acid supplementation in cases of deficiency or chronic hemodialysis, it does not directly address the effect of hemolysis on folate levels. However, based on the general principles of biochemistry and the effects of hemolysis on serum components, it is reasonable to infer that hemolysis would lead to an increase in measured folate levels due to the release of folate from lysed red blood cells. Key points to consider include:
- The concentration of folate in red blood cells is approximately 30 times higher than in serum.
- Even minor hemolysis can significantly elevate serum folate levels.
- Hemolysis can occur during blood collection, sample processing, or storage, and it is essential to recognize its potential to falsely elevate folate measurements.
- If hemolysis is suspected in a sample with unexpectedly high folate levels, repeating the test with a carefully collected non-hemolyzed sample is advisable to accurately assess the patient's folate status.
From the Research
Hemolysis and Folate Levels
- Hemolysis can affect folate analysis in plasma, leading to biased results 2
- The relationship between folate concentration and degree of hemolysis has been explored, with a linear relationship found between the increments in folate concentration and hemolysis index 2
- However, the evidence does not suggest that hemolysis directly causes elevated folate levels, but rather that it can lead to inaccurate measurements of folate concentration 2
Folate Deficiency and Hemolysis
- Folate deficiency can lead to megaloblastic anemia, which is characterized by ineffective red blood cell production and intramedullary hemolysis 3
- Hemolysis can also occur in cases of megaloblastic anemia due to vitamin B12 and folate deficiency, with hyperhomocysteinemia potentially playing a role in the pathogenesis of hemolysis 4
- Folate deficiency can have various manifestations beyond megaloblastic anemia, including increased predisposition to occlusive vascular disease and thrombosis, and disturbances of mood 5
Folate Metabolism and Hemolysis
- Dihydrofolate reductase (DHFR) deficiency due to a homozygous DHFR mutation can cause megaloblastic anemia and cerebral folate deficiency, leading to severe neurologic disease 6
- The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency 6