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53 Cards in this Set
- Front
- Back
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what are the essentials of immune hemolytic anemias (IHA)?
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binding of IgG or IgM antibodies to RBC surface antigens with consecutive initiation of RBC destruction via the complement system and the reticuloendothelial system
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what are the principal types of immune hemolytic anemias?
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autoimmune
alloimmune = isoimmune drug-induced |
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what does the degree of hemolysis seen in IHA depend on?
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characteristic of the bound antibody
quantitiy specificity ability to fix complement/ tissue macrophages target antigen densitiy expression patient age |
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what are characteristics of IgG auto-antibodies in IHA?
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relatively poor activators of the classic complement pathway (ie antigen-antibody), but are readily recognized by Fc receptors of various phagocytic cells
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what are the principal sites of hemolysis?
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intravascular
extravascular |
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what type of hemolysis takes place in RBC bound by IgG?
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extravascular hemolysis
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which circumstance can potentiate hemolysis in IgG bound RBC?
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reticuloendothelial cells also have receptors for complement factors C3b and iC3b, which, if present, can potentiate the extravascular hemolysis seen in IgG bound RBC
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what are characteristics of IgM antibodies in IHA?
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readily activate the classic complement pathway, in contrast to IgG antibodies
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what type of hemolysis takes place in RBC bound by IgM?
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extra- and intravascular hemolysis, because of ready activation of the classic complement pathway by IgM
more commonly extravascular hemolysis due to presence of regulatory RBC proteins (CD55, CD59) which inhibit intravascular hemolysis |
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what is the principal site of IgG-associated extravascular hemolysis?
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spleen
mnemonic: Gee, he's got a spleen! |
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what is the principal site of IgM-associated extravascular hemolysis?
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liver (Kupffer cells)
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what are the subclassifications of AIHA?
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warm AIHA
cold AIHA mixed AIHA drug-induced AIHA |
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what disorders cause half of cases of both secondary warm and cold AIHA?
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lymphoproliferative disorders
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what is the second leading cause of secondary warm AIHA?
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autoimmune disorders
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what is the second leading cause of secondary cold AIHA?
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infections
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what are the epidemiologic characteristics of idiopathic AIHA?
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peak incidence in the fourth and fifth decades
more common in women |
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what criteria must be met for a diagnosis of AIHA?
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serologic evidence of an auto-antibody and clinical or laboratory evidence of hemolysis
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what does a positive direct Coomb's test (DAT) indicate
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in vivo RBC binding of either IgG or C3d
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in what other HA beside IHA can a direct Coomb's test (DAT) be found?
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hemoglobinopathies: sickle cell disease and beta-thalassemia
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what are other disorders beside HA in which a positive DAT can be found?
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renal disease
multiple myeloma autoimmune diseases AIDS other diseases with elevated immunoglobulines |
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how can auto-antibodies and allo-antibodies in AIHA be differentiated?
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auto-antibodies are generally panreactive, while allo-antibodies exhibity antigen specificity
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what are lymphoproliferative diseases commonly associated with warm AIHA?
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CLL, Hodgkins disease, non-Hodgkins lymphoma and Waldenström macroglobulinemia
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what are autoimmune disorders commonly associated with warm AIHA?
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SLE, RA, scleroderma, ulcerative colitis
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what IgG subclass-autoantibody is found in the vast majority of warm AIHA?
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IgG1
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what is the first-line treatment in warm AIHA?
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first-line treatment are glucocorticoids
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what Ig isotype of auto-antibody is most commonly found in warm AIHA?
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IgG
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what Ig type of auto-antibody is most commonly found in cold AIHA?
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IgM
mnemonic: M for minus temperatures |
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what are laboratory findings in AIHA?
Hb/ hematocrit reticulocytes WBC count peripheral blood smear haptoglobin |
Hb/hematocrit varies widely
reticulocyte count varies WBC typically mild leukocytosis, mostly due to neutrocytosis peripheral blood smear with polychromasia and macrocytosis from reticulocytosis as well as nucleated RBC bone marrow typically with erythroid hyperplasia haptoglobin normal or even increased because it is an acute phase reactant, provided hemolysis is mild and hepatic function adequate |
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what are characteristics of warm autoantibodies?
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react more strongly at 37° than at lower temperatures
are generally polyclonal generally IgG, thus poor activators of the classical complement pathway |
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what is the second-line treatment in warm AIHA?
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splenectomy, as it removes the primary site of extravascular hemolysis and less importantly is a site of antibody production
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what is the third-line treatment in warm AIHA?
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cytostatic drugs, most commonly cyclophosphamide or azathioprine
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what are pathologic cold autoantibodies characterized by?
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large thermal amplitude or a high titer, with thermal amplitude as the better predictor of hemolysis
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what are the distinct entities of cold AIHA?
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cold agglutinin syndrome (CAS)
paroxysmal cold hemoglobinuria (PCH) |
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what are typical infectious causes of CAS?
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mycoplasmal pneumonia or infectious mononucleosis
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what are other infectious causes of CAS?
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adenovirus, CMV, VZV, HIV
E. coli, Listeria monocytogenes, Treponema pallidum |
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what are laboratory findings found with increasing severity of hemolysis?
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indirect bilirubinemia, LDH elevation
decreased haptoglobin hemoglobinemia hemoglobinuria, urine hemosiderin |
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what is the clinical presentation in warm AIHA?
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highly variable, typically insidious onset of anemic symptoms
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what are the characteristics of the Ig found in primary and secondary CAS?
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idiopathic CAS and those secondary to lymphoproliferative typically monoclonal IgM kappa
CAS secondary to infection with polyclonal IgM kappa or lambda |
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what is the significance of the detection of a cold agglutinin?
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cold agglutinins can be detected in most healthy individuals
the majority of cold antibodies are thus clearly benign |
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what part of the blood group system are cold agglutinins commonly specific to?
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commonly show specificity against the Ii blood group system, with 90% directed against the I antigen
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what are the therapy principles in CAS?
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avoidance of cold exposure
steroids rarely helpful, splenectomy only in the rare cases with IgG cold autoantibodies |
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what is the etiology and course in paroxysmal cold hemoglobinuria(PCH)?
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acute transient pathology secondary to infection, most involving an antecedent upper respiratory infection
causative agent often is not identified |
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what is the clinical presentation of PCH?
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acute attack of high fever, chills, back and/or leg pain and abdominal cramping
hemoglobinuria typically occurs, with dark red to black urine |
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what is the cause in PCH?
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biphasic IgG autoantibody (Donath-Landsteiner antibody), which fixes complement at low temperatures but ultimately dissociates at higher temperatures
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what is the result of the DAT in PCH?
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positive only with anti-C3
generally negative with anti-IgG unless performed at lower temperatures |
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what is the diagnostic test in PCH?
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Donath-Landsteiner test
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what is an important cause for chronic PCH?
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syphilis
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what are drugs commonly associated with drug-induced IHA?
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alpha-methyldopa and high-dose penicillin, as well as second and third generation cephalosporins, especially ceftriaxon and cefotetan
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what are the three major mechanisms in drug-induced IHA?
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neoantigen formation
induction of autoantibodies drug adsorption onto RBC |
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what are the principal manifestations of allo-immune HA?
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hemolytic transfusion reactions and hemolytic disease of the newborn (HDN)
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what are the three principal types of hemolytic disease of the newborn (HDN)?
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AB0 hemolytic disease of the newborn
Rhesus hemolytic disease of the newborn anti-Kell hemolytic disease |
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what are the three most common forms of severe hemolytic disease of the newborn (HDN)?
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Rhesus D HDN
anti-Kell1-antibody HDN Rhesus c HDN |
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what is the diagnostic test in HDN in the mother?
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indirect Coombs test (IAT)
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