Clinical Manifestations of Hemolytic Anemia:

• The clinical manifestations of hemolytic anemia depend on the severity and rate of RBC destruction.
  • The common signs and symptoms of hemolytic anemia are pallor, fatigue, weakness, dyspnea, tachycardia, angina, jaundice, splenomegaly, hepatomegaly, dark urine, gallstones, leg ulcers, and bone deformities.
  • The specific signs and symptoms of inherited hemolytic anemia are related to the type of genetic defect. For example:
    • Hereditary spherocytosis causes spherocytes (small and round RBCs) that are prone to rupture in the spleen. It may present with aplastic crisis (severe anemia due to viral infection), hemolytic crisis (acute exacerbation of anemia due to stress), or megaloblastic crisis (anemia due to folate deficiency).
    • G6PD deficiency causes episodic hemolysis triggered by oxidative stress from drugs (such as sulfonamides), infections, or fava beans. It may present with acute hemolytic anemia, chronic nonspherocytic hemolytic anemia, or neonatal jaundice.
    • Sickle cell anemia causes sickle-shaped RBCs that are rigid and sticky. It may present with vaso-occlusive crisis (painful episodes due to ischemia and infarction of tissues), hemolytic crisis (acute exacerbation of anemia due to infection or dehydration), aplastic crisis (severe anemia due to parvovirus B19 infection), sequestration crisis (acute pooling of blood in the spleen or liver), or acute chest syndrome (pulmonary complications due to sickling).
    • Thalassemia causes reduced or absent synthesis of alpha or beta globin chains, resulting in hypochromic and microcytic RBCs. It may present with thalassemia minor (mild or asymptomatic anemia), thalassemia intermedia (moderate to severe anemia with splenomegaly and skeletal abnormalities), or thalassemia major (severe anemia with transfusion dependence, growth retardation, and organ damage).
  • The specific signs and symptoms of acquired hemolytic anemia are related to the type of extrinsic factor. For example:
    • Immune-mediated hemolytic anemia causes antibody-mediated destruction of RBCs. It may present with warm antibody hemolytic anemia (IgG antibodies that react at body temperature and cause extravascular hemolysis) or cold antibody hemolytic anemia (IgM antibodies that react at low temperature and cause intravascular hemolysis).
    • Infectious hemolytic anemia causes parasitic invasion or bacterial toxin release that damage the RBCs. It may present with malaria (Plasmodium infection that causes fever, chills, headache, and splenomegaly) or clostridial sepsis (Clostridium perfringens infection that causes gas gangrene, shock, and disseminated intravascular coagulation).
    • Mechanical hemolytic anemia causes physical trauma or shear stress that fragment the RBCs. It may present with cardiac hemolytic anemia (prosthetic heart valves that cause schistocytes or helmet cells) or microangiopathic hemolytic anemia (disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, or hemolytic uremic syndrome that cause schistocytes or burr cells).
    • Physiochemical hemolytic anemia causes thermal injury or chemical exposure that alter the RBC membrane. It may present with burns (heat damage that causes echinocytes or blister cells) or drug-induced hemolytic anemia (drug metabolites that bind to the RBC membrane and cause immune reaction or oxidative stress)