Immune hemolytic anemia
Immune hemolytic anemia
Updated: 07/14/2024
© Jun Wang, MD, PhD
General features
- Autoimmune
o Warm antibody autoimmune hemolytic anemia
o Cold agglutinin disease
- Alloimmune
o Hemolytic disease of the newborn
o Transfusion reaction to ABO-incompatible blood
o Graft-vs-host reaction
- Diagnosis requires antibodies and/or complement on RBC
o Direct Coombs antiglobulin test (DAT): detects antibodies and/or complement bound to patient’s red cells
o Indirect Coombs antiglobulin test (IAT): detects antibodies against RBCs in patient’s serum
o Warm antibodies: reacts more strongly at 37°C
o Cold antibodies: reacts more strongly at 4°C
Warm antibody autoimmune hemolytic anemia
- More commonly IgG-mediated, less commonly IgA
- RBC antigens include Rh complex, glycophorin, etc
- Most cases are idiopathic
- Secondary causes include autoimmune disorders, drugs, lymphoid neoplasms such as CLL/SLL
- Commonly extravascular hemolysis
- Remitting and relapsing, with variable severity
- Commonly splenomegaly
- Positive direct Coombs antiglobulin test (DAT)
- Other laboratory features of hemolytic anemia
- Spherocytosis and increased reticulocytes
- Treatment: Immunosuppression, splenectomy
Cold agglutinin disease
- Caused by cold-reacting autoantibodies
- Predominantly mediated by IgM, rarely IgG, IgA, λ light chain
- Most against I or i antigens
- Primary: Chronic, >50 yo, Monoclonal cold-reacting Ig
- Secondary
o Monoclonal (adults, chronic) or polyclonal (children/young adults, transient)
o Associated with infection or lymphoproliferative disorders
- Clinical features
o Painful fingers and toes with purplish discoloration associated with cold exposure
o Associated with RBC agglutination in cold area capillaries
- Laboratory findings
o Complement on RBC surface, autoantibody detached from RBC at warm temperatures
o Serum with high titer of cold agglutinin Igs to RBCs
o Peripheral smear: RBC agglutination at room temperature
- Management
o Protect against cold temperature
o Transfusion, complement inhibitors if severe, acute
Hemolytic disease of the fetus and newborn
- Caused by maternal antibodies (IgG) against fetal RBCs
- Most anti-D (Rh), A, B
- Anti-D
o RhD-negative mother, RhD-positive child
o Usually not first pregnancy (IgM does not cross placenta)
o Caused by fetal RBCs entered maternal circulation
- Anti-A or B
o Group O mother, group A or B child
o May affect first pregnancy
o Usually mild
- Lead to fetal anemia, hydrops fetalis and death in utero
- Lead to neonatal anemia, hyperbilirubinemia and kernicterus
- Extramedullary hematopoiesis, hepatosplenomegaly
- Laboratory findings
o Positive direct antiglobulin test
o ABO mismatch: antibody screening might be negative
o Identification of maternal antibodies against child RBCs
o Anemia with reticulocytosis, spherocytes, polychromasia, and nucleated RBCs
o Hyperbilirubinemia: unconjugated bilirubin
- Prenatal treatments
o Intrauterine transfusion
o Therapeutic plasma exchange
o Intravenous immune globulin (IVIG)
- Postnatal treatments
o Phototherapy to convert serum unconjugated bilirubin to the water-soluble form
o Double volume exchange transfusion: replacing the baby's total blood volume twice, leaving the intravascular amount the same
Iatrogenic blood transfusion incompatibility
- Alloantibodies against any of RBC group antigens, may cause hemolysis
- Most clinically important: ABO and Rh groups
- Anti-A and anti-B
o Naturally occurring, usually IgM,
o In plasma of people lack corresponding antigen
- Anti-Rh
o Rarely occur naturally
o Usually IgG after prior exposure
- Hemolytic reactions
o Immediate: during or within 24 h of transfusion (ABO: preformed antibodies, clerical error)
o Delayed: after 24h (Kell, Duffy, Kidd, or MNS, previous exposure)
- Acute hemolytic transfusion reaction
o Hemolytic shock phase
§ Rapid onset
§ Urticaria, pain in low back, flushing, fever, chills, hypotension
§ Hemoglobinuria, jaundice, DIC, leukocytosis
o Oliguric phase: acute tubular necrosis and renal failure
o Diuretic phase: Fluid and electrolyte imbalance
- Delayed hemolytic reactions
o May occur 1-2 weeks after transfusion
o May be asymptomatic, or have features of hemolysis
o Extravascular hemolysis and associated lab findings
- Management
o Stop transfusion and begin investigation
o Maintain blood pressure with IV fluids, vasopressors if needed
o May need additional transfusions (after repeat crossmatch
o IV corticosteroids
o Antihistamines
o Manage renal failure, hemodialysis if needed
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