From the Guidelines
Hemolysis is the rupture or destruction of red blood cells, causing the release of hemoglobin into the surrounding fluid, and can be caused by various factors including genetic disorders, autoimmune conditions, infections, and incompatible blood transfusions, as noted in the 2020 American Society of Hematology guidelines for sickle cell disease 1. This process can occur inside blood vessels (intravascular hemolysis) or outside them (extravascular hemolysis, typically in the spleen or liver). Hemolysis happens naturally as part of the normal life cycle of red blood cells, which typically live about 120 days before being removed from circulation. However, accelerated or excessive hemolysis can lead to various medical conditions, including anemia. Some key causes of hemolysis include:
- Genetic disorders (like sickle cell disease or G6PD deficiency)
- Autoimmune conditions
- Infections
- Certain medications
- Toxins
- Mechanical trauma to red blood cells
- Incompatible blood transfusions When hemolysis occurs, the released hemoglobin can cause symptoms including:
- Jaundice (yellowing of skin and eyes)
- Dark urine
- Fatigue
- Shortness of breath
- In severe cases, organ damage Laboratory tests can detect hemolysis through elevated levels of indirect bilirubin, lactate dehydrogenase (LDH), decreased haptoglobin, and the presence of reticulocytes in the blood, as discussed in the guidelines for transfusion support in patients with sickle cell disease 1. In cases of hyperhemolysis, which can occur with no identifiable antibody and a negative direct antiglobulin test, recognition is critical to avoid additional transfusions that may worsen the condition and potentially induce multiorgan failure and death 1. The management of hyperhemolysis may involve supportive care, erythropoietin, IVIg, steroids, rituximab, and eculizumab, with the optimal approach determined on a case-by-case basis through discussion between the hematologist and transfusion medicine specialist 1.
From the Research
Definition and Mechanisms of Hemolysis
- Hemolysis refers to the premature destruction of red blood cells, which can be chronic or life-threatening 2.
- Mechanisms of hemolysis include poor deformability leading to trapping and phagocytosis, antibody-mediated destruction through phagocytosis or direct complement activation, fragmentation due to microthrombi or direct mechanical trauma, oxidation, or direct cellular destruction 2.
- Hemolysis can occur intravascularly, extravascularly in the reticuloendothelial system, or both 2.
Types and Classification of Hemolytic Anemia
- Hemolytic anemia can be classified into hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and extrinsic nonimmune causes 2.
- Autoimmune hemolytic anemia (AIHA) is a type of hemolytic anemia characterized by the presence of an antibody that causes short red blood cell life 3.
- AIHA can be further classified into warm and cold forms, depending on the thermal characteristics of the autoantibody 4.
Clinical Features and Diagnosis
- Clinical features of hemolytic anemia include acute anemia, jaundice, hematuria, dyspnea, fatigue, tachycardia, and possibly hypotension 2.
- Laboratory test results that confirm hemolysis include reticulocytosis, as well as increased lactate dehydrogenase, increased unconjugated bilirubin, and decreased haptoglobin levels 2.
- The direct antiglobulin test can differentiate immune causes from nonimmune causes of hemolysis 2.
Complications and Immune Regulation
- Hemolysis can alter immunological functions and increase the risk of severe complications in hemolytic disorders 5.
- Complications of autoimmune hemolytic anemia include cutaneous, thrombotic, renal disorders, and infectious disorders 6.
- Hemolysis breakdown products can regulate immune cell differentiation and function, including the induction of neutrophil extracellular traps and the inhibition of dendritic cell maturation 5.