Erythrocytic Enzyme Defects and Acquired Hemolytic Anemia

Definition: Acquired hemolytic anemia is characterized by the premature destruction of red blood cells (RBCs) due to various external factors rather than intrinsic defects.

Bacteria
- Bartonella bacilliformis
- Borrelia recurrentis
- Clostridium perfringens
- Escherichia coli O157
- Haemophilus influenzae
- Mycobacterium tuberculosis
- Mycoplasma pneumoniae
- Neisseria meningitidis
- Salmonella typhi
- Streptococcus species
- Vibrio cholerae
Parasites
- Babesia microti
- Babesia divergens
- Leishmania species
- Plasmodium falciparum
- Trypanosoma brucei gambiense
- T. brucei rhodesiense
Viruses
- Cytomegalovirus
- Epstein-Barr virus

Autoimmune Hemolytic Anemias
- Associated with warm-type antibodies
- Associated with cold-type antibodies
- Associated with both warm- and cold-type antibodies
Isoimmune Hemolytic Anemias
- Hemolytic disease of the fetus and newborn (HDFN)
  - Rh incompatibility
  - ABO incompatibility
Drug-Induced Hemolytic Anemia
- Adsorption of immune complexes to red blood cell membranes
- Adsorption of drug to red blood cell membranes
- Induction of autoantibody formation to drugs
- Nonimmunological adsorption of immunoglobulin to red blood cell membranes

Warm AIHA
- Optimal temperature of reactivity: 37°C
- Immunoglobulin class: IgG
- Complement activation: +
- Site of hemolysis: Extravascular
Cold AIHA
- Optimal temperature of reactivity: 4°C
- Immunoglobulin class: IgM
- Complement activation: ±
- Site of hemolysis: Intravascular

Cold-type autoimmune hemolytic anemia: In AIHA, the condition is associated with cold-type autoantibody, such as in cold hemagglutinin disease. Erythrocytes are typically coated with IgM.
Warm- and cold-type AIHA: These anemias are mediated by IgG warm antibodies and complement, as well as IgM cold hemagglutinins.

PNH is identified as a rare, acquired, clonal blood disorder originating from nonmalignant clonal expansion of one or more stem cell lines.
Key Mutation: Occurrence of mutations in a gene named phosphatidylinositol glycan-A (PIGA), which results in the absence of various protective G protein-coupled receptors on the hematopoietic cell surface that shield the cells from complement binding.
Example of Protective Markers: Include CD55 and CD59, along with at least 14 other markers noted in the literature.

Evolution of Conditions: 25% of PNH cases evolve into or arise from aplastic anemia.
Cancer Association: Approximately 5% to 10% of PNH patients may eventually develop terminal acute myelogenous leukemia.
Demographics: The median age at diagnosis is 42 years, with a range from 16 to 75 years.
Survival Rate: The median survival after diagnosis is estimated to be 10 years. Spontaneous long-term remission may occur in some patients.

Typically begins insidiously in patients aged between 30 and 60 years.
A notable manifestation is the irregular episodes of hemoglobinuria that are often associated with sleep.

Most patients exhibit severe anemia with hemoglobin concentrations less than 6 g/dL.
Peripheral blood smears can show hypochromic, microcytic red cells if iron deficiency develops due to cell lysis.
Autohemolysis: Increased after 48 hours; hemolysis may further increase upon adding glucose to the test.
Diagnostic Tests: The sucrose hemolysis (sugar-water) test and Ham's test (acid-serum lysis) are recognized diagnostic procedures for PNH.
Hemosiderinuria: The excretion of hemosiderin, which is an iron-containing pigment, is a classic indicator of chronic intravascular hemolysis.
Flow Cytometry: Increasingly used to detect the absence of necessary CD markers, aiding in immunophenotyping erythrocytes for diagnosis of PNH.