From the Guidelines
Decreased haptoglobin levels are primarily caused by hemolysis, which is the destruction of red blood cells, as supported by the 2019 study on pyruvate kinase deficiency 1. When red blood cells break down, they release hemoglobin that binds to haptoglobin, causing the complex to be rapidly cleared from circulation by the liver, thus reducing haptoglobin levels. Common causes of hemolysis include:
- Autoimmune hemolytic anemia
- Mechanical heart valves
- Microangiopathic hemolytic anemia (such as DIC or TTP)
- Sickle cell disease
- Thalassemias
- G6PD deficiency
- Certain medications like sulfonamides, nitrofurantoin, and quinine Other non-hemolytic causes of decreased haptoglobin include:
- Liver disease (since haptoglobin is produced in the liver)
- Malnutrition
- Congenital ahaptoglobinemia, a rare genetic condition where individuals are born without the ability to produce haptoglobin
- Transiently decreased during acute inflammatory responses, as noted in the context of re-evaluating other causes of hemolysis by specific tests or NGS platform 1 When evaluating a patient with low haptoglobin, it's essential to check other markers of hemolysis, such as elevated LDH, increased reticulocyte count, and presence of schistocytes on peripheral blood smear, to determine if hemolysis is the underlying cause, considering the diagnostic gaps in pyruvate kinase deficiency 1. Additionally, decreased haptoglobin is useful only after 6 months of age 1, and other indices of hemolysis like carboxyhaemoglobin evaluation should be considered, especially in cases where shipment at 4°C is impossible, and the assay must be performed by 3–5 days 1.
From the Research
Causes of Decreased Haptoglobin
- Hemolysis: Decreased haptoglobin levels are a marker of hemolysis, as haptoglobin binds to free hemoglobin released from lysed red blood cells, preventing its toxic effects 2, 3, 4.
- Liver Cirrhosis: Diminished haptoglobin values have been observed in patients with liver cirrhosis, which can be attributed to decreased haptoglobin production 2.
- Malnutrition: Low levels of haptoglobin have been associated with malnutrition 5.
- Hepatic Disease: Decreased haptoglobin levels have been linked to hepatic disease, as the liver is the primary site of haptoglobin production 5, 4.
- Allergic Reactions: Decreased haptoglobin levels have been observed in patients with allergic reactions 5.
- Seizure Disorders: Low levels of haptoglobin have been associated with seizure disorders 5.
- Hyper-hemolytic Conditions: During hyper-hemolytic conditions or with chronic hemolysis, haptoglobin is depleted, leading to decreased levels 4.