Acquired Hemolytic Anemia

Etiologies of Acquired hemolytic anemia

Infection
Malaria
Enterotoxic E coli
(HUS)
Clostridium

Mechanical destruction
March Hemoglobinuria
Prosthetic valves

Direct Injury
Toxin mediated
Ag-Ab mediated (Non-RBC Ag)

Toxins
Oxidative process
Hyperbaric oxygen
Nitrate / Chlorate
Dapsone / Cisplatin
Non-oxidative process
Lead poisoning

Ag-Ab mediated (RBC Ag)

Autoimmune

Post-blood transfusion
Paroxysmal Cold hemoglobinuria
Cold agglutinin Disease
Warm antibody type
Paroxysmal Nocturnal hemoglobinuris

Autoimmune hemolytic anemia (AIHA)

Ab

RBC
Coated Ag

Fc Receptor

Macrophage
Phagocytosis
Fragmentation
Cytotoxicity
Complement
Extra-vascular Hemolysis
Intra-vascular Hemolysis

Warm Ab Immunohemolytic Anemia

The most common form (48% to 70%) of
immune hemolytic anemia
50% of cases are idiopathic (primary)
Most causative antibodies are of the
immunoglobulin G (IgG) class
Antibodies often against Rh blood group
antigens
Antigens- penicillin and cephalosporins &
Quinidine, -methyldopa

 Hemolysis is mainly extravascular

Takes place by splenic macrophages
Partial phagocytosis results in loss of
membrane and formation of spherocytes
which are later removed by spleen

Warm AIHA

Warm AIHA

Warm AIHA

Cold agglutinin Disease (CAD)

Antibody mediated RBC lysis at cold temperature
Antibody to I antigen (Usually IgM which
effectively binds complement)
Hemolysis both extravascular and intravascular
Ag-Ab reaction leads to B-cell proliferation in high
concentrations
Associated with Waldenstrom macroglobinemia

Cold AIHA

Anti-Globulin (Coombs) Testing

Direct antiglobulin testing

+
Patients RBCs

Anti-C3d
Anti-IgG

Indirect antiglobulin testing

+
Patients serum RBCs

+
Anti-IgG

Paroxysmal cold hemoglobinuria (PCH)

Post viral infection

Donath-Landsteiner antibody
Antibody binds to RBC at low temperature
Antibody is specific to P antigen
RBC lysis mediated by complement at normal
temperatures

AIHA : Clinical features

Anemia (Abrupt, acute or chronic)

Jaundice
Hemoglobinuria (Intravascular hemolysis)
Splenomegaly
May be isolated AIHA
May be part of generalized autoimmune
phenomenon

AIHA : Situations
Abrupt onset
Mismatched blood transfusion

Acute onset
Paroxysmal cold hemoglobinuria (PCH)

Chronic
Paroxysmal nocturnal hemoglobinuria (PNH)
Cold agglutinin disease (Raynauds phenomenon)

Paroxysmal nocturnal hemoglobinuria

Only hemolytic anemia caused by an acquired
intrinsic defect in the cell membrane
results from acquired (somatic) mutations in
phosphatidylinositol complementation glycan A
(PIGA) - essential for the synthesis of the GPI
anchor (X linked)
complement mediated lysis of Red cells, white
cells, and platelets

Paroxysmal nocturnal hemoglobinuria

Three GPI-linked proteins mutated /
deficient in PNH
decay-accelerating factor (DAF) or CD55;
membrane inhibitor of reactive lysis, or
CD59; (is the most important in PNH)
C8 binding protein

Paroxysmal Nocturnal hemoglobinuria

Paroxysmal passage of red urine (Hb-uria)
Recurrent abdominal pain (venous thrombosis)
May lead to hepatic venous occlusion
(Hepatomegaly, ascitis Budd Chiari Syndrome)
Secondary thrombocytopenia, BM aplasia, and
hemorrhage,leukemia
Diagnosis:sucrose lysis test,acidified hams
test,flow cytometry

PNH Pathogenesis
RBCs normally inhibit MAC and C3 convertase
(mediated by CD59 / CD 55 Ag)
Complement activation
CD 59

+
C3 convertase
CD 55

C3

C3b

C3b

C5

C3 convertase
C3b Complex
C5b

Membrane Attack Complex

In PNH CD59/CD55 deficient cells undergo

intravascular hemolysis
Complement activation

C3 convertase
C3

Excess C3b formation

MAC mediated RBC lysis

C3b

C3b

C5

Intravascular hemolysis

C3 convertase
C3b Complex
C5b

Membrane Attack Complex

PNH - Pathogenesis
Mechanism of thrombosis unknown. Probable
activation of CD59 deficient platelets
Associated T-cell activation damages
hematopoietic B cells.
CD59 deficient stem cells escape T-cell
mediated damage
Targeted therapy with Eculizumab
(monoclonal Ab against C5) prevents
hemolysis

Eculizumab prevents Hemolysis by preventing

MAC generation
Complement activation

C3 convertase
C3

C3b

C3b

Eculizumab
C5

C3 convertase
C3b Complex
C5b