From the Guidelines
Hemolysis can be caused by a variety of factors, including intrinsic causes such as hereditary conditions like sickle cell disease, thalassemias, hereditary spherocytosis, G6PD deficiency, and other membrane or enzyme defects, as well as extrinsic causes like immune-mediated hemolysis, mechanical trauma, infections, toxins, and certain medications. The causes of hemolysis can be broadly categorized as intrinsic (within the red blood cell) or extrinsic (outside factors). Intrinsic causes include hereditary conditions like sickle cell disease, thalassemias, hereditary spherocytosis, G6PD deficiency, and other membrane or enzyme defects. Extrinsic causes encompass immune-mediated hemolysis (autoimmune hemolytic anemia, drug-induced, or transfusion reactions), mechanical trauma (prosthetic heart valves, microangiopathic hemolytic anemia), infections (malaria, babesiosis, clostridial infections), toxins, and certain medications.
Some key points to consider in the diagnosis and management of hemolysis include:
- Diagnosis typically requires a complete blood count, peripheral blood smear, reticulocyte count, and specific tests like Coombs test, hemoglobin electrophoresis, or enzyme assays depending on the suspected cause.
- Treatment varies based on the underlying cause, ranging from addressing the primary condition to supportive care with transfusions, immunosuppression for immune-mediated cases, or splenectomy for certain hereditary conditions.
- Prompt identification of the cause is essential as some hemolytic conditions can lead to life-threatening complications if left untreated, as noted in studies such as 1.
- In cases of hyperhemolysis, such as those seen in sickle cell disease, treatment with immunosuppressive agents like IVIg, high-dose steroids, eculizumab, and/or rituximab may be necessary, as recommended in guidelines like those from the American Society of Hematology 1.
- For patients experiencing life-threatening anemia with ongoing hemolysis, transfusion with extended matched red cells should be considered, and supportive care should be initiated, including erythropoietin with or without IV iron, as suggested in studies like 1.
- In all cases, a thorough diagnostic workup is crucial to determine the underlying cause of hemolysis and guide appropriate treatment, as outlined in guidelines such as those from the American Society of Clinical Oncology 1.
From the Research
Causes of Hemolysis
- Hemolysis can be caused by various factors, including autoimmune hemolytic anemia (AIHA) 2, hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and extrinsic nonimmune causes 3.
- Autoimmune hemolytic anemia (AIHA) is a condition where the immune system produces antibodies that attack and destroy red blood cells, leading to hemolysis 2, 4.
- Extrinsic nonimmune causes of hemolysis include thrombotic microangiopathies, direct trauma, infections, systemic diseases, and oxidative insults 3.
- Medications can also cause hemolytic anemia through several mechanisms, including antibody-mediated destruction and direct cellular destruction 3.
Laboratory Diagnosis
- Laboratory tests that confirm hemolysis include reticulocytosis, increased lactate dehydrogenase, increased unconjugated bilirubin, and decreased haptoglobin levels 3, 5.
- The direct antiglobulin test (DAT) can establish the diagnosis and subclassify the majority of autoimmune hemolytic anemias 2, 4.
- A peripheral blood smear should be performed when hemolysis is present to identify abnormal red blood cell morphologies 3.
Factors Influencing Hemolysis
- Hemolysis rates are higher in Emergency Departments, for non-antecubital draws, for specimens drawn using an intravenous catheter, and for samples transported by pneumatic tube 6.
- Hemolysis rates are also higher when specimens are not collected by professional phlebotomists, larger volume specimen tubes are used, specimen tubes are filled less than halfway, and tourniquet time is greater than one minute 6.