From the Guidelines
Low haptoglobin levels are primarily caused by conditions involving hemolysis, where red blood cells break down prematurely, releasing hemoglobin that binds to haptoglobin and leads to rapid clearance from circulation. The etiology of low haptoglobin (hypohaptoglobinemia) can be attributed to various conditions, including:
- Hemolytic anemias, such as pyruvate kinase deficiency, as discussed in the study by 1, which highlights the features of chronic hemolysis, including increased reticulocyte count, increased lactate dehydrogenase (LDH), reduced haptoglobin, and elevated bilirubin.
- Autoimmune hemolytic anemia (AIHA), which can be diagnosed with reticulocyte count, haptoglobin, and DAT, as mentioned in the study by 1.
- Other hemolytic causes, such as sickle cell disease, thalassemias, G6PD deficiency, paroxysmal nocturnal hemoglobinuria, mechanical heart valves, and microangiopathic hemolytic anemias like DIC and TTP.
- Severe liver disease, which can reduce haptoglobin levels since the liver is responsible for its production.
- Genetic factors, such as congenital haptoglobin deficiency (anhaptoglobinemia), which occurs in approximately 1 in 1,000 individuals, particularly those of East Asian descent.
- Certain medications that cause drug-induced hemolysis, such as penicillins, cephalosporins, NSAIDs, and quinine, can indirectly lower haptoglobin.
- Massive blood transfusions may temporarily decrease haptoglobin levels due to the introduction of free hemoglobin. When investigating low haptoglobin, clinicians should consider these various etiologies and look for other markers of hemolysis, such as elevated LDH, increased reticulocyte count, and presence of schistocytes on peripheral blood smear, as supported by the study by 1.