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IMMUNE HEMOLYTIC ANEMIA

IMMUNE HEMOLYTIC ANEMIA. IMMUNE HEMOLYTIC ANEMIA General Principles. All require antigen-antibody reactions Types of reactions dependent on: Availability of complement Environmental Temperature Functional status of reticuloendothelial system Manifestations Intravascular hemolysis

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IMMUNE HEMOLYTIC ANEMIA

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  1. IMMUNE HEMOLYTIC ANEMIA

  2. IMMUNE HEMOLYTIC ANEMIAGeneral Principles • All require antigen-antibody reactions • Types of reactions dependent on: • Availability of complement • Environmental Temperature • Functional status of reticuloendothelial system • Manifestations • Intravascular hemolysis • Extravascular hemolysis

  3. IMMUNE HEMOLYTIC ANEMIAGeneral Principles - 2 • Antibodies combine with RBC, & either • Activate complement cascade, &/or • Opsonize RBC for immune system • If 1, if all of complement cascade is fixed to red cell, intravascular cell lysis occurs • If 2, &/or if complement is only partially fixed, macrophages recognize Fc receptor of Ig &/or C3b of complement & phagocytize RBC, causing extravascular RBC destruction

  4. IMMUNE HEMOLYTIC ANEMIACoombs Test - Direct • Looks for immunoglobulin &/or complement of surface of red blood cell (normally neither found on RBC surface) • Coombs reagent - combination of anti-human immunoglobulin & anti-human complement • Mixed with patient’s red cells; if immunoglobulin or complement are on surface, Coombs reagent will link cells together and cause agglutination of RBCs

  5. IMMUNE HEMOLYTIC ANEMIACoombs Test - Indirect • Looks for anti-red blood cell antibodies in the patient’s serum, using a panel of red cells with known surface antigens • Combine patient’s serum with cells from a panel of RBC’s with known antigens • Add Coombs’ reagent to this mixture • If anti-RBC antigens are in serum, agglutination occurs

  6. HEMOLYTIC ANEMIA - IMMUNE • Autoimmune Hemolysis • Warm autoimmune hemolysis • Cold autoimmune hemolysis • Alloimmune Hemolysis • Hemolytic Transfusion Reaction • Hemolytic Disease of the Newborn • Drug-Related Hemolysis

  7. Autoimmune hemolytic anemia (AHA) • Autoimmune hemolytic anemia (AHA) is characterized by shortened red blood cell (RBC) survival and the presence of autoantibodies directed against autologous RBCs.

  8. AUTOIMMUNE HEMOLYSIS • Due to formation of autoantibodies that attack patient’s own RBC’s • Type characterized by ability of autoantibodies to fix complement & site of RBC destruction • Often associated with either lymphoproliferative disease or collagen vascular disease

  9. Autoimmune Hemolytic Anemia • Classified by thermal reactivity • Warm react near 37 o C, Cold at 0-4 o C • Serologic evidence is positive DAT (direct Coomb’s test) with IgG or C3d present • Indirect Coomb’s test and specificity (serum / eluate) • Diagnostic Criteria- • serologic evidence and laboratory or clinical hemolysis

  10. AIHA Classification • Warm autoimmune hemolytic anemia • Idiopathic, Secondary • (Lymphoproliferative disorders, autoimmune diseases) • Cold autoimmune hemolytic anemia • Cold agglutinin syndrome • (Idiopathic, Secondary- mycoplasma, infectious mono, LPD) • Paroxysmal cold hemoglobinuria • (Idiopathic, Secondary- measles, mumps, syphilis) • Drug-induced IHA • (Autoimmune, Drug adsorption, Neoantigen)

  11. AUTOIMMUNE HEMOLYSISWarm Type • Usually IgG antibodies • Fix complement only to level of C3,if at all • Immunoglobulin binding occurs at all temps • Fc receptors/C3b recognized by macrophages;  • Hemolysis primarily extravascular • 70% associated with other illnesses • Responsive to steroids/splenectomy

  12. Diagnosis • 2 Anaemia. • 2 Spherocytes on peripheral blood film. • 2 Reticulocytes are increased. • 2 Neutrophilia common. • 2 RBC coated with IgG, complement or both (detect using DAT). • 2 Autoantibody —often pan-reacting but specificity in 10–15% (Rh, • mainly anti-e, anti-D or anti-c).

  13. Diagnosis • LDH increased. • 2 Serum haptoglobindecreased. • 2 Exclude underlying lymphoma (BM, blood and marrow cell markers). • 2 Autoimmune profile—to exclude SLE or other connective tissue disorder.

  14. AUTOIMMUNE HEMOLYSISCold Type • Most commonly IgM mediated • Antibodies bind best at 30º or lower • Fix entire complement cascade • Leads to formation of membrane attack complex, which leads to RBC lysis in vasculature • 90% associated with other illnesses • Poorly responsive to steroids, splenectomy; responsive to plasmapheresis

  15. Diagnosis • 2 Anaemia. • 2 Reticulocytes are increased. • 2 Neutrophilia common. • 2 Positive DAT—C3 only. • 2 ± Autoantibodies —IgG or IgM • – Monoclonal in NHL. • – Polyclonal in infection-related CHAD. • 2 IgM antibodies react best at 4°C (thermal amplitude 4–32°C). • 2 Specificity

  16. Diagnosis • – Anti-I (Mycoplasma). • – Anti-i (infectious mononucleosis)—causes little haemolysis in adults • since RBCs have little anti-i (cf. newborn i >> I). • 2 LDH increased. • 2 Serum haptoglobindecreased. • 2 Exclude underlying lymphoma (BM, blood and marrow cell markers). • 2 Autoimmune profile to exclude SLE or other connective tissue disorder.

  17. IMMUNE HEMOLYSISDrug-Related • Immune Complex Mechanism • Quinidine, Quinine, Isoniazid • “Haptenic” Immune Mechanism • Penicillins, Cephalosporins • True Autoimmune Mechanism • Methyldopa, L-DOPA, Procaineamide, Ibuprofen

  18. DRUG-INDUCED HEMOLYSISImmune Complex Mechanism • Drug & antibody bind in the plasma • Immune complexes either • Sit on red blood cell • Antigen-antibody complex recognized by RE system • Red cells lysed as “innocent bystander” of destruction of immune complex • REQUIRES DRUG IN SYSTEM

  19. DRUG-INDUCED HEMOLYSISHaptenic Mechanism • Drug binds to & reacts with red cell surface proteins • Antibodies recognize altered protein, ± drug, as foreign • Antibodies bind to altered protein & initiate process leading to hemolysis

  20. DRUG-INDUCED HEMOLYSISTrue Autoantibody Formation • Certain drugs appear to cause antibodies that react with antigens normally found on RBC surface, and do so even in the absence of the drug

  21. Drug-Induced Autoimmune Hemolytic Anemia

  22. Drug-Induced Positive Antiglobulin Tests

  23. Treatment AIHA

  24. ALLOIMUNE HEMOLYSISHemolytic Transfusion Reaction • Caused by recognition of foreign antigens on transfused blood cells • Several types • Immediate Intravascular Hemolysis (Minutes) - Due to preformed antibodies; life-threatening • Slow extravascular hemolysis (Days) - Usually due to repeat exposure to a foreign antigen to which there was a previous exposure; usually only mild symptoms • Delayed sensitization - (Weeks) - Usually due to 1st exposure to foreign antigen; asymptomatic

  25. ALLOIMMUNE HEMOLYSISTesting Pre-transfusion • ABO & Rh Type of both donor & recipient • Antibody Screen of Donor & Recipient, including indirect Coombs • Major cross-match by same procedure (recipient serum & donor red cells)

  26. Manifestations of Delayed Hemolytic Transfusion Reactions • Clinical • Fevers • Chills • Symptoms of anemia • Jaundice • Oliguria or anuria (uncommon) • Generalized Bleeding (Rare) • Laboratory • Unexplained anemia (or decrease in hemoglobin) • Positive direct antiglobulin test • Hemoglobinemia • Hemoglobinuria (Uncommon) • Hemosiderinuria • Decreased haptoglobin • Responsible antibody in post-transfusion RBC eluate

  27. ALLOIMMUNE HEMOLYSISHemolytic Disease of the Newborn • Due to incompatibility between mother negative for an antigen & fetus/father positive for that antigen. Rh incompatibility, ABO incompatibility most common causes • Usually occurs with 2nd or later pregnancies • Requires maternal IgG antibodies vs. RBC antigens in fetus

  28. HYDROPS FETALIS

  29. ALLOIMMUNE HEMOLYSISHemolytic Disease of the Newborn - #2 • Can cause severe anemia in fetus, with erythroblastosis and heart failure • Hyperbilirubinemia can lead to severe brain damage (kernicterus) if not promptly treated • HDN due to Rh incompatibility can be almost totally prevented by administration of anti-Rh D to Rh negative mothers after each pregnancy

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