Hemolytic Anemia


Primary Thrombotic Microangiopathy (see Thrombotic Microangiopathy)


Red Blood Cell Membrane Defect

  • Cytoskeletal Membrane Defect
  • Lipid Membrane Disorders
  • Membrane Disorders Associated with Abnormalities of Erythrocyte Antigens
    • McLeod Syndrome
    • Rh Deficiency Syndromes
  • Membrane Disorders Associated with Abnormal Transport
    • Hereditary Xerocytosis

Red Blood Cell Enzyme Defects

  • Glycolytic
    • Aldolase Deficiency
    • Diphosphoglycerate Mutase (DPGM) Deficiency
    • Glucose-6-Phosphate Isomerase (G6PI) Deficiency
    • Glyceraldehyde-3-Phosphate Dehydrogenase (GAPD) Deficiency
    • Hexokinase Deficiency
    • Phosphofructokinase (PFK) Deficiency
    • Phosphoglycerate Kinase (PGK) Deficiency
    • Pyruvate Kinase (PK) Deficiency
    • Triose Phosphate Isomerase (TPI) Deficiency
  • Redox
  • Nucleotide Metabolism
    • Adenylate Kinase Deficiency
    • Pyrimidine 5′-Nucleotidase Deficiency


  • Congenital Erythropoietic and Hepatoerythropoietic Porphyrias
  • Congenital Erythropoietic Protoporphyria


Autoimmune Hemolytic Anemia (AIHA)

Warm Autoimmune Hemolytic Anemia (48-70% of AIHA cases)

Cold Autoimmune Hemolytic Anemia

Mixed-Type Autoimmune Hemolytic Anemia

Drug-Induced Autoimmune Hemolytic Anemia

Other Antibody-Mediated Hemolytic Anemia

Chemical Injury to Red Blood Cell

Hypersplenism (see Splenomegaly)

Mechanical Red Blood Cell Destruction

Macroangiopathic Hemolytic Anemia

Microangiopathic Hemolytic Anemia (MAHA) + Thrombocytopenia

Primary Thrombotic Microangiopathy Syndrome (see Thrombotic Microangiopathy)
Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation])
Giant Hemangioma (Kasabach-Merritt Syndrome) (see Kasabach-Merritt Syndrome)
Malignant Hypertension (see Hypertension)
Metastatic Carcinoma: due to activation of multifocal clotting -> hemolysis and thrombocytopenia
Pregnancy-Related Disorders
Rheumatologic Disease
Transplant-Related Disease



Paroxysmal Nocturnal Hemoglobinuria (see Paroxysmal Nocturnal Hemoglobinuria)

Physical Injury to Red Blood Cell

Red Blood Cell Membrane Defects


Background-Iron Physiology

Background-Red Blood Cell Physiology

Predominant Site of Hemolysis

Intravascular Hemolysis (RBC Destruction Within the Vascular Space)

Extravascular Hemolysis (Red Blood Cell Destruction in the Spleen, Other Reticuloendothelial Tissues, or Extravasated Blood/Hematoma)


Complete Blood Count (CBC) (see Complete Blood Count)

Serum Lactate Dehydrogenase (LDH) (see Serum Lactate Dehydrogenase)

Serum Haptoglobin (see Serum Haptoglobin)

Indirect Hyperbilirubinemia (see Hyperbilirubinemia)

Urinalysis (see Urinalysis)

Urine Hemoglobin (Hemoglobinuria) + Urine Hemosiderin (Hemosiderinuria) (see Hemoglobinuria and Hemosiderinuria)

Reticulocyte Count (see Reticulocyte Count)

Direct Coombs Test (Direct Anti-Globulin Test) (see Direct Coombs Test)

Iron Studies


Serum Vitamin B12 Level (see Serum Vitamin B12)

Serum Folate Level (see Serum Folate)

Peripheral Blood Smear (see Peripheral Blood Smear)


Leukoerythroblastic Smear

Schistocytes/Helmet Cells

Spur Cells (Acanthocytes)

Target Cells (Bell-Shaped Codocytes, Mexican Hat Cells)


Clinical Differentiation of Hemolytic Syndromes

Clinical Differentiation of Intravascular Hemolysis Syndromes


Clinical Manifestations

Hematologic Manifestations

Gastrointestinal/Hepatic Manifestations

Rheumatologic/Orthopedic Manifestations

Pulmonary Manifestations