DAT Flashcards
Immune Hemolytic Anemia Definition
Shortened RBC survival
Lower than normal Hgb and Hct
Immune Hemolytic Anemia Classification
1) Alloimmune
2) Autoimmune
3) Drug-induced
Alloimmune
RBC hemolysis is the result of antibodies formed in response to foreign antigens
Autoimmune
RBC hemolysis is the result of antibodies formed in response to an individual’s own antigens
Drug-Induced
RBC hemolysis/damage is the result of antibodies produced in response to a drug or drug complex
Characteristics of Autoantibodies Definition
Antibodies directed against an individual’s own RBCs
Characteristics of Autoantibodies
1) Produced due to a failure of the immune response, possibly due to loss of suppressor T cell function
2) May cause destruction of RBCs in vivo
3) May interfere with testing procedures that involve RBCs
4) Most react with high incidence antigens and will agglutinate, sensitize, or lyse RBCs of most random donors as well as the individual that produces antibody
Characteristics of Autoimmune Hemolytic Anemia Definition
Can be demonstrated, usually by detection of positive auto control
Characteristics of Autoimmune Hemolytic Anemia
1) Immune RBC destruction extensive enough to cause anemia
2) Testing Results
- Decreased Hgb, Hct
- Increased retic count
- Increased bilirubin
- Increased LDH
- Decreased haptoglobin
- Hemoglobinemia
- Hemoglobinuria
- Positive Direct Antiglobulin Test (DAT)
Cold Reactive Autoantibodies
Most Common of the autoantibodies
Cold Reactive Autoantibodies Generic Info
IgM
Most reactive at 4 C
Bind complement
React well with enzyme treated cells
Benign
Low in titer
Cold Reactive Autoantibodies IgM
Most have I specificity - will react with almost all adult cells
Some have H and/or IH
Some have i (rarely an adult will be i positive and I negative)
Some have Pr, Gd, Sd, M
Cold Reactive Autoantibodies Interference
Usually at RT or lower
ABO Grouping - may cause false positive reactions
Rh typing - false positive reactions usually when using protein-based reagents
Positive DAT - in vitro activation of complement
IAT - May mask significant alloantibodies
Cold Reactive Autoantibodies Resolution
1) ABO - washing the cells with warm saline, warming the sample, and autoadsorbing serume
2) Rh Typing - washing cells with warm saline, using anti D reagents that are saline-based, using IgG AHG and using EDTA samples
3) Positive DAT - using EDTA samples and/or IgG AHG
4) IAT - using prewarmed techniques, adsorption techniques and IgG AHG
Pathologic Cold Autoantibodies Generic Info
Anti I and Cold Hemagglutinin Disease
Cause - idiopathic (associated with Mycoplasma pneumoniae infection)
Usually transient
Occurs in older adults
Rarely severe (seasonal)
IgM antibody that reacts best at 4 C and 21 to 31 C
Pathologic Cold Autoantibodies Presentation
Hemolysis
Cyanosis
Hemoglobinuria
Raynaud’s phenomenon (blue color in extremeties and intolerance to cold)
Increase Retic count
Positive DAT
Pathologic Cold Autoantibodies Treatment
Usually not necessary
Keep warm (especially extremeties)
Supportive care
Plasmapheresis
Blood may be transfused via warmer
Anti i
Usually a high-titered IgM Antibody that may cause hemolytic anemia
May be associated with infectious mononucleosis
Supportive Care
Paroxysmal Cold Hemoglobinuria (PCH)
Least common
Associated with viral illness in children
Bi-phasic IgG antibody (Donath-Landsteiner antibody)
Usually anti-P
PCH Test Results
Hemoglobinemia
Hemoglobinuria
Increased bilirubin
Severe anemia
Polychromasia
nRBCs
Warm Reactive Autoantibodies Generic Info
Occur less frequently than cold autoantibodies
True autoimmune hemolytic anemias due to warm reactive
IgG antibodies (usually IgG1 and IgG3) that fix complement
Antibodies react with high incidence antigens, usually Rh specific
Warm Reactive Autoantibodies Clinical Characteristics
1) Insidious or sudden onset of hemolysis, preceeded by infection, trauma, stress, or may be idiopathic
2) Hemolysis primarily extravascular
3) Patient presents with usual symptoms of anemia
4) Peripheral blood smear (Polychromasia, nRBCs, spherocytes, fragments)
5) Hemoglobinuria, hemoglobinemia, increased bilirubin, decreased haptglobin, increased LDH
Warm Reactive Autoantibodies Testing
1) ABO typing - usually not affected
2) Rh typing - may see positive Rh control due to DAT
3) Positive DAT
4) IAT and antibody identification
Warm Reactive Autoantibodies IAT Resolution
1) Separate autoantibodies from alloantibodies (patient history may provide important info - panel on patient serum and eluate from patient cells)
2) Detection of alloantibodies - use panel cells that are negative for that antigen to detect alloantibody
3) Remove autoantibody by atuoadsorption (not option if transfused)
4) Transfused - phenotype patient for common RBC antigens and adsorb the autoantibody with specific donor cells
5) Chloroquine-treated cells to do antigen typing
Warm Reactive Autoantibodies Treatment
1) Treat underlying disorder
2) Transfusion should be avoided if possible - compatibility with alloantibodies is primary concern, may have to transfuse least incompatible units
3) Steroids - decrease antibody synthesis, alter antibody activity, decrease clearance of antibody-coated cells
4) Splenectomy - decrease clearance of antibody-coated rbcs
5) Immunosuppressive drugs
Drug-Induced Hapten
Drug binds to RBC proteins and an antibody is formed
- Most are IgM
- Few are IgG
Common Drugs in Hapten
Penicillin (usually in massive doses)
Cephalosporins
Drug-Induced Hapten Testing
Positive DAT
IAT is usually negative
Crossmatches are usually compatible
Drug-Induced Hapten Confirmation
Test serum and eluate against RBCs that are coated with offending drug
Reactions will occur only when drug is present
Drug-Induced Hapten Treatment
Discontinue drug
Hemolysis is rarely severe
Drug-Induced Membrane Modification
Drug modifies RBC membrane so that plasma proteins (IgG, IgM, and complement) non-specifically bind to the RBCs
Non-immunologic process
Membrane Modification Drug List
Most common is Cephalosporins
Membrane Modification Laboratory testing
Positive DAT
Present in 3% of patients who are being treated with Keflin
Drug-Induced Membrane Modification Treatment
Usually not necessary
Autoantibody Formation Generic Info
Reason that is not clear
Autoantibody directed against RBC antigens forms and may cause hemolysis
Autoantibody Formation Drug List
Aldomet
Alpha-methyldopa
Autoantibody Formation Laboratory Testing
Positive DAT
Indistinguishable from WAIHA
Autoantibody Formation Treatment
Discontinue drug
Few patients experience significant hemolysis or require transfusion
