Term
| Cold agglutinin AIHA physiology |
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Definition
usually IgM antibodies against RBCs, binding at cold temp, targets I/i blood group antigen
after binding to RBCs, IgM activates complement cascade à C3b binds, phagocytosis by
hepatic macrophages (rather than splenic RES cells) |
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Term
| Chronic Cold AIHA vs. Acute |
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Definition
o Chronic Disorder – common, occurs in 5th decade or later, often concurrent with B-lymphocyte neoplasm
o Acute Disorder – rare, occurs younger, often complication of infectious dz (mycoplasma anti-I, mono anti-i) |
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Term
| Cold agglutinin AIHA labs |
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Definition
o Blood smear – will show RBC agglutination, spherocytes, polychromasia
o DAT – positive for C3 only (not IgG)
o Cold agglutinins – test positive, obviously
low Hgb, hemolysis signs (reticulocytes, spherocytes, bilirubin, polychromatophilia, LDH), blood smear, DAT, agglutinins |
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Term
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Definition
treat underlying cause first, and then varying levels of care:
o Avoidance of cold exposure – most basic conservative Tx, usually pretty effective
o Combination chemotherapy – for refractory, can be helpful
o Glucocorticoids – rarely helpful
o Splenectomy – rarely indicated |
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Term
| rare AIHA disorder, occurs in children following viral illness, tertiary/congenital syphillis |
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Definition
Paroxysmal Cold Hemoglobinuria (PCH)
(caused by IgG binding RBCs at cold temperatures, but falls off at 37oC) |
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Term
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Definition
incubate normal RBCs w/ patient’s serum vs. normal serum, measure lysis at 4oC, 37oC
o DAT – usually negative, since IgG’s elute off cells in normal temp
o P blood group antigen – Donath-Landsteiner antibody à Dx of PCH |
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Term
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Definition
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Term
| Mechanisms for Drug Induced Immune Hemolytic Anemia |
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Definition
| • Hapten Mechanism, • Immune Complex Mechanism , • Autoantibody Mechanism , • In Vivo Sensitization Mechanism |
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Term
drugs binds to RBC membrane, IgG against drug binds => RBC destroyed
oDAT – tests positive for IgG |
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Definition
| most commonly penicillins; also ampicillin, methicillin, cephalosporins |
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Term
drug binds to plasma protein/Ig, forms immune complex, binds RBC à
complement activation & hemolysis
o Prevalence – most common drug-induced immune hemolytic anemia, usually IgM antibody
o DAT – positive for complement (no IgG… IgM here) |
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Definition
| most commonly quinine, phenacetin, antihistamines, insulin, acetaminophen, sulfa |
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Term
offending drug induces autoantibody formation, usually for Rh antigen
o DAT – positive for IgG, C3 negative |
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Definition
| most commonly alpha-methyldopa, also ibuprofen |
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Term
| • In Vivo Sensitization Mechanism |
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Definition
drug binds RBC membrane antigen, forms immune complex, anti-drug Ig then binds to “neo-antigen” combination drug on RBC à hemolysis. WILL NOT BIND TO EITHER BY ITSELF!
o DAT – positive for IgG |
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Term
| Non-Immune Hemolytic Anemias - 3 types |
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Definition
| infection, hypersplenism, fragmentation hemolysis (microangiopathy) |
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Term
| peripheral blood smear shows fragmented RBCs |
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Definition
| result of mechanical shearing of RBCs from damaged microvasculature, cardiac abnormalities, AV shunts, turbulent flow, drugs (cyclosporine, cocaine) |
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Term
| Splenomegaly – not synonymous; splenomegaly caused by wide variety of factors |
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Definition
| functionally hyperactive spleen à too much sequestration of all blood cells |
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Term
| acquired clonal disorder of hematopoietic stem cells producing defective RBCs |
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Definition
| Paroxysmal Nocturnal Hemoglobinuria |
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Term
| PNH what happens? and due to what gene? |
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Definition
o Defective RBCs are produced! – have an unusual susceptibility to complement-mediated hemolysis
o Pig-a¬ gene – mutation affects glycosylphophatidylinositol (GPI) linkage in RBC membranes |
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Term
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Definition
o Leukocyte alkaline phosphatase (LAP) – test/score is low, (only occurs with leukemia or this)
o Sucrose & Ham’s acid hemolysis – RBCs more susceptible to lysis under these stress tests
o Flow cytometry – can analyze for PIG-linked antigens |
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Term
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Definition
| try to correct anemia, prevent thrombosis, stimulate hematopoiesis, give eculizumab against C5 so interferes w/ hemolysis and thrombosis |
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Term
| T/F Absence of anemia rules out hemolytic disorder |
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Definition
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Term
| Dx Sx and Haptoglobin levels of intravasc hemolysis |
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Definition
o Dx – verified by hemoglobinemia, hemoglobinuria, hemosiderinuria
o Sx – include constitutional symptoms, tachycardia, back ache, Sx related to renal failure
o Haptoglobin – decreased |
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Term
| Dx Sx and Haptoglobin levels of extravasc hemolysis |
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Definition
RBCs lysed outside of vessels (often spleen):
o Sx – jaundice, splenomegaly (RBCs lysed in spleen)
o Haptoglobin – typically normal, or slightly decreased |
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Term
| role of Plasma haptoglobin |
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Definition
| binds hemoglobin if it is free in plasma, decreased haptoglobin when bound |
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Term
| Direct Antiglobulin Test (DAT)/Coomb’s Test |
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Definition
detects presence of IgG or C3 bound to RBC
o Autoimmune hemolytic anemia – hallmark is the positive Coomb’s test
o Process – wash patient’s RBCs free of plasma, add antiglobulin reagent, centrifuge, look for agglutination |
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Term
| Indirect Antiglobulin Test/Indirect Coomb’s |
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Definition
detects autoimmune hemolytic anemia as well…
o Process – incubate patient’s serum with normal blood, look for reaction (x-fusion compatibility) |
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Term
| Autoimmune hemolytic anemia (AIHA) definition? |
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Definition
| antibody/complement binds to RBC membrane antigens => shortened RBC lifespan |
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Term
| Why do you get spherocytes in warm-Ab AIHA? |
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Definition
when IgG binds RBC membrane à thru spleen & engulfed by macrophages
o Spherocyte – results when part of cell membrane removed by macrophage in spleen
o Result – spherocytes eventually cleared by extravascular mechs in spleen |
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Term
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Definition
can be 1o idiopathic, or 2o to lymphoproliferative dz, CT dz (SLE), immune deficiency, Rx
o Immune deficiencies – including AIDS, and common variable immunodeficiency
o Drugs – classically alpha-methyldopa |
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Term
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Definition
No therapy for well-compensated hemolytic process.
Corticosteroids – mainstay of Tx!!! Interferes w/ the synth/fxn of Fc-receptor on macros that bind/destroy Ab-coated RBCs
o RBC transfusion – only for severe refractory life-threatening cases, risk of hemolytic reaction
o Splenectomy – also for refractory, when corticosteroids fail
o IVIg – may increase RBC survival by saturating Fc receptors on macrophages, can’t deal w/ RBC
o Immunosuppressive therapy – including danazol, vinca alkaloids, rituximab (against CD20 – kill B lymphocytes)
o Folic Acid – give for all patients, to ensure RBC production |
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