From the Guidelines
Microangiopathic hemolytic anemia (MAHA) can indeed occur with normal bilirubin levels, particularly in early or mild cases, as the liver may initially compensate by efficiently clearing bilirubin from circulation. While hemolysis typically leads to increased bilirubin production as red blood cells are destroyed, several factors can result in normal bilirubin levels despite ongoing MAHA. According to the guidelines on the management of abnormal liver blood tests 1, bilirubin is predominantly the by-product of the breakdown of the haem component of haemoglobin by the reticuloendothelial system.
Some key points to consider in the context of MAHA and bilirubin levels include:
- The liver's capacity to process and clear bilirubin can initially compensate for increased bilirubin production due to hemolysis, potentially maintaining normal bilirubin levels 1.
- In cases where hemolysis develops gradually or is mild, the rate of red cell destruction may not exceed the liver's processing capacity, leading to normal bilirubin levels.
- Concurrent conditions affecting bilirubin metabolism or excretion can influence levels, potentially masking the effects of hemolysis on bilirubin production.
- Clinicians should not rule out MAHA based solely on normal bilirubin, as other laboratory findings like schistocytes on peripheral blood smear, decreased haptoglobin, elevated LDH, and negative direct Coombs test may confirm the diagnosis 1.
It is essential to consider these factors and not rely solely on bilirubin levels to diagnose or rule out MAHA. Serial monitoring of bilirubin and other hemolysis markers is crucial, as levels may rise as the condition progresses or with increased hemolytic activity.
From the Research
Microangiopathic Hemolytic Anemia with Normal Bilirubin
- Microangiopathic hemolytic anemia (MAHA) is a condition characterized by the fragmentation of red blood cells, leading to hemolytic anemia 2.
- The differential diagnoses of MAHA include thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), disseminated intravascular coagulation (DIC), idiopathic thrombocytopenic purpura (ITP), infections, malignancies, and solid organ transplantation 2.
- MAHA can occur in patients with cancer, including those with metastatic disease or those undergoing chemotherapy 3, 4.
- The condition is often associated with thrombocytopenia and can be caused by microvascular thrombosis, including TTP, Shiga toxin-mediated hemolytic uremic syndrome, and complement-mediated TMA 4.
- In some cases, MAHA may be the initial presentation of an underlying condition, such as metastatic signet-ring cell carcinoma of the colon 2.
- While bilirubin levels are often elevated in hemolytic anemia, MAHA can occur with normal bilirubin levels, as the condition is characterized by intravascular hemolysis, which may not always lead to significant bilirubin elevation 2.
Diagnosis and Treatment
- The diagnosis of MAHA is based on the presence of schistocytes on a peripheral blood smear, as well as other laboratory findings such as thrombocytopenia and elevated lactate dehydrogenase (LDH) levels 5, 6.
- Treatment of MAHA depends on the underlying cause and may include plasma exchange, eculizumab, or other therapies aimed at managing the underlying condition 5, 6.
- In patients with cancer, treatment of the underlying malignancy is essential, and MAHA may resolve with successful treatment of the cancer 3, 4.