What are the markers and management of hemolysis?

From the Guidelines

Hemolysis is characterized by elevated lactate dehydrogenase (LDH), increased unconjugated bilirubin, decreased haptoglobin, elevated reticulocyte count, and the presence of schistocytes or spherocytes on peripheral blood smear, and its management depends on the underlying cause, with first-line treatment including corticosteroids like prednisone (1-2 mg/kg/day) for immune-mediated hemolysis, as recommended by the American Society of Hematology 2020 guidelines 1.

Key Markers of Hemolysis

• Elevated lactate dehydrogenase (LDH)
• Increased unconjugated bilirubin
• Decreased haptoglobin
• Elevated reticulocyte count
• Presence of schistocytes or spherocytes on peripheral blood smear

Management of Hemolysis

• Treating the primary condition
• Providing supportive care
• Preventing complications
• For immune-mediated hemolysis:
  • First-line therapy: corticosteroids like prednisone (1-2 mg/kg/day) 1
  • Second-line treatment: rituximab (375 mg/m² weekly for 4 weeks) 1
  • Severe cases: intravenous immunoglobulin (1 g/kg for 2 days) or plasma exchange 1
• For non-immune hemolysis: removing the triggering agent or managing the underlying condition
• Blood transfusions for symptomatic anemia, typically when hemoglobin falls below 7 g/dL
• Folic acid supplementation (1 mg daily) to support increased erythropoiesis

Specific Considerations for Hyperhemolysis

• Defined as a rapid hemoglobin decline to below the pretransfusion level and rapid decline of the posttransfusion HbA level 1
• Treatment includes immunosuppressive therapy, such as IVIg and high-dose steroids, with eculizumab as a second-line agent 1
• Avoidance of further transfusion unless patients are experiencing life-threatening anemia with ongoing hemolysis, and consideration of extended matched red cells if transfusion is warranted 1

From the Research

Hemolysis Markers

• Increased reticulocytes, an indicator of marrow compensatory response 2
• Elevated lactate dehydrogenase, a marker of intravascular hemolysis 2, 3
• Reduced haptoglobin 2, 3
• Unconjugated hyperbilirubinemia 2, 3
• Direct antiglobulin test, the cornerstone of autoimmune forms 2
• Blood smear examination, fundamental in the diagnosis of congenital membrane defects and thrombotic microangiopathies 2
• Erythrocyte adenylate kinase, a red cell specific enzyme released from damaged red cells 4

Management of Hemolysis

• Corticosteroid treatment, usually the first-line treatment for warm autoimmune hemolytic anemia (WAIHA) 5
• Intravenous immunoglobulins (IVIGs), rituximab, or splenectomy, may be applied in cases with poor response to corticosteroid treatment 5
• Therapeutic plasma exchanges (TPEs), may be considered as a therapeutic option in patients with severe WAIHA without response to corticosteroid and IVIG treatment 5
• Prednisone, may be used to treat autoimmune hemolytic anemia (AIHA) with normal serum lactate dehydrogenase level 6

Diagnostic Considerations

• A comprehensive clinical and laboratory evaluation is advisable for a correct diagnostic and therapeutic workup of the different hemolytic conditions 2
• Hemoglobin defines the clinical severity of hemolysis, and thrombocytopenia suggests a possible thrombotic microangiopathy or Evans' syndrome 2
• Reticulocytopenia occurs in 20-40% of autoimmune hemolytic anemia cases and is a poor prognostic factor 2