What is the cause of hemolysis (breakdown of red blood cells)?

From the Guidelines

Hemolysis in patients with sickle cell disease should be managed with prompt initiation of immunosuppressive therapy, including first-line agents such as IVIg and high-dose steroids, to prevent life-threatening complications. Hemolysis is the destruction or breakdown of red blood cells, resulting in the release of hemoglobin into the surrounding fluid, and can occur within blood vessels (intravascular hemolysis) or outside them in organs like the spleen and liver (extravascular hemolysis) 1. Common causes of hemolysis include autoimmune disorders, genetic conditions like sickle cell disease and thalassemia, infections, medications, toxins, and mechanical trauma to red blood cells.

When hemolysis occurs, patients may experience anemia, fatigue, jaundice, dark urine, and in severe cases, organ damage. Diagnosis typically involves blood tests including complete blood count, peripheral blood smear, reticulocyte count, and specific tests for hemolytic disorders 1. Treatment depends on the underlying cause and may include corticosteroids for autoimmune hemolysis, discontinuation of offending medications, blood transfusions for severe anemia, or specific treatments for genetic disorders.

In patients with sickle cell disease, hyperhemolysis can occur with no identifiable antibody and a negative direct antiglobulin test, and recognition is critical to avoid additional transfusions that may worsen the condition and potentially induce multiorgan failure and death 1. Immunosuppressive therapy, such as IVIg and high-dose steroids, should be initiated promptly in patients with life-threatening hemolysis, and extended matched red cells should be considered if transfusion is warranted 1. Supportive care, including erythropoietin with or without IV iron, should also be initiated in all patients.

Some key points to consider in the management of hemolysis include:

• Prompt identification of the cause and appropriate management to prevent complications
• Use of immunosuppressive therapy, such as IVIg and high-dose steroids, in patients with life-threatening hemolysis
• Consideration of extended matched red cells if transfusion is warranted
• Supportive care, including erythropoietin with or without IV iron, in all patients
• Avoidance of further transfusion unless patients are experiencing life-threatening anemia with ongoing hemolysis 1.

From the Research

Definition and Mechanisms of Hemolysis

• Hemolysis is defined by the premature destruction of red blood cells, and 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 be induced by two general mechanisms: intravascularly due to complement fixation, trauma, or other extrinsic factors, or extravascularly in the mononuclear-phagocytic system due to intrinsic defects or bound immunoglobulins 3.

Diagnosis of Hemolysis

• Diagnosis of hemolysis is based on the presence of anemia with sustained reticulocytosis in the absence of blood loss 3.
• 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 further differentiates immune causes from nonimmune causes 2.
• A peripheral blood smear should be performed when hemolysis is present to identify abnormal red blood cell morphologies 2.

Treatment of Hemolysis

• Treatment of hemolysis is usually supportive, with effective therapy directed to treat the underlying cause of hemolysis 3.
• Corticosteroids are the first-line therapy for warm autoimmune hemolytic anemia (AIHA) 4.
• Rituximab is becoming the preferred second-line treatment for refractory/relapsed AIHA, and is now recommended as first-line treatment for cold agglutinin disease (CAD) 4.
• Intravenous immunoglobulin and steroids may correct severe anemia in hyperhemolytic transfusion reactions 5.

Classification of Hemolytic Diseases

• Hemolytic diseases are classified into hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and extrinsic nonimmune causes 2.
• Extrinsic nonimmune causes include the thrombotic microangiopathies, direct trauma, infections, systemic diseases, and oxidative insults 2.
• Medications can cause hemolytic anemia through several mechanisms 2.