The Positive DAT and Immune-mediated Hemolysis (Ch. 17)

what conditions are associated with the acute and chronic forms of cold agglutinin syndrome?

*acute cold agglutinin syndrome* (polyclonal, showing normal light chain distribution) -lymphoproliferative disorders -Mycoplasma pneumoniae infection *chronic cold agglutinin syndrome* (monoclonal, showing light chain restriction) -old age -lymphoproliferative disorders -Waldenstrom's macroglobulinemia

usually, the specificity of the antibody is cold agglutinin syndrome is anti-___

I note: sometimes it is anti-i as well; these cases are often associated with infectious mononucleosis

pathophysiology of cold agglutinin syndrome

IgM antibodies attach to RBCs in the colder temperatures of the peripheral circulation and assemble complement on them as the RBCs circulate to areas with warmer temps, the IgM dissociates but the complement components remain note: may or may not cause hemolysis

what are some symptoms of cold agglutinin syndrome?

acrocyanisis hemoglobinuria note: you may also be able to see agglutination of RBCs in an EDTA tube at room temp

autologous adsorption

allows you to see if there is an alloantibody being masked by a warm autoantibody does not work if patient has recently been transfused (because the transfused cells in the patient's blood means that the adsorption using the patient RBCs isn't fully autologous) uses the patient's own RBCs to remove autoantibody, leaving the alloantibody behind to be tested in isolation

allogeneic adsorption ("alloadsorption")

allows you to see if there is an alloantibody being masked by a warm autoantibody works even if patient has been recently transfused uses reagent RBCs to remove autoantibodies -gets tricky if you don't know the patient's phenotype (because alloantibody specificity is uknown, red cells of different phenotypes will usually be used to adsorb several aliquots of the patient's serum)

what is meant by the term "biphasic hemolysin" in paroxysmal cold hemoglobinuria?

binding to RBCs occurs only at lower temps, but hemolysis does not occur until the RBCs are warmed to 37 C

autoantibodies causing hemolysis often have ____________ activity, and will destroy transfused cells as well as the patient's own cells

broad therefore, the decision to transfuse should be undertake carefully with the clinical situation in mind -transfuse the least amount possible to maintain adequate tissue oxygenation -don't aim for an arbitrary Hb level

in almost all cases of cold agglutinin syndrome, _______________ is the only protein found on RBCs (hint: result of DAT)

complement there will be no immunoglobulin on the cells, and the eluate will be nonreactive

the presence of a positive DAT is not _____________

diagnostic need to know info about: -recent drugs -pregnancy -transfusion history always need to be in close contact with the clinician

patients with warm autoantibodies may have no apparent _____________________ or may have life-threatening anemia

hemolysis

the DAT should be performed whenever the presence of ______________ has been established

hemolysis

what 4 situations warrant further investigation of a positive DAT?

history of recent transfusion administration of drugs previously associated with immune-mediated hemolysis history of hematopoietic progenitor cell or organ transplantation administration of IVIG or IV anti-D

in many cases of warm autoimmune hemolytic anemia, _______ antibody specificity is apparent

no the patient's serum reacts with all RBCs tested if testing is performed with cells of rare Rh phenotype like D-- or Rh-null, some autoantibodies react weaker with these cells, suggesting a broad specificity to the Rh system

what if a patient with a nonspecific warm autoantibody is revealed to have no masked alloantibody, and needs a transfusion?

no units will be crossmatch compatible, so choose random units with appropriate ABO/Rh type and transfuse there is no antibody with specific activity, so there is no way to select antigen-negative units

the risk of drug-induced immune hemolytic anemia is _____ in one million

one mechanism unknown and there be more than one mechanism (see image for proposed unifying theory of drug-induced antibody reactions) many drugs implicated

the DAT is first performed with _____________ antihuman globulin (AHG) then, if positive, it is performed with _______________ antihuman globulin

polyspecific (IgG and C3d) monospecific (test both separately) -monospecific IgG -monospecific C3d

if you transfuse a patient with XM-compatible blood and the patient has an immune response to it, how long will it take for a positive DAT to show up in: -primary immunization? -secondary response?

primary immunization: 7-10 days secondary response: 1-2 days -note: these antibodies may not show up on the antibody screen or crossmatch because the patient may have had primary immunization a long time ago and the current titer may be low -but the anamnestic response will kick in and can cause problems

paroxysmal cold hemoglobinuria

rare form of AIHA usually presents as an acute transient condition in children 2/2 viral infections caused by a cold-reactive IgG complement-binding antibody; it reacts with red cells in colder areas of the body (usually the extremities), causes C3 to bind irreversibly to red cells, and then the antibody dissociates from the red cells as the blood circulates to warmer parts of the body

how does ABO hemolytic disease of the fetus and newborn (HDFN) occur, given that IgM does not cross the placenta?

some of the naturally occuring anti-ABO antibodies are IgG (even though we were taught in med school they were all IgM)

what 3 further investigations can be done on a positive DAT?

test with monospecific reagents to find out what type of proteins(s) are coating the RBCs (C3d vs. IgG) test the serum/plasma to identify clinically significant antibodies against RBC antigens test an eluate made from the DAT-positive RBCs to define whether the coating protein has RBC antibody activity -when complement is the only coating protein, eluates are frequently nonreactive -Lui freeze-thaw method is most common

if the patient has a warm autoantibody and needs a transfusion, how can you tell if there is also an alloantibody?

the autoantibody is usually panreactive (including with the autocontrol), so you can't tell if it is masking an alloantibody without additional testing, unless there is an alloantibody present which reacts more strongly or at different phases than the autoantibody -this is referred to as "masking" ways to test for alloantibodies which may be masked by a warm autoantibody -autologous adsorption (only if the patient has not recently been transfused) -allogeneic adsorption (works even if the patient has been recently transfused)

the majority of AIHA cases are caused by _______- reactive autoantibodies,

warm

what is the fundamental question you should be asking yourself as a physician when dealing with a patient that has an antibody which makes finding compatible units very difficult?

which is the greater risk to the patient, transfusing incompatible blood now, or further delaying transfusion? in some situations, it is better to transfuse incompatible blood than to wait *use your clinical judgement*, work with the other members of the care team, and keep up with the situation in real time