and CORRECT Answers
Human Leukocyte Antigens - Present on most nucleated cells
- roles: recognition of self vs non-self and initiation of acquired immune
response
Class I - 3 loci A, B, and C - present on platelets and most nucleated cells in the body
- presence on WBCs and plts may be a concern
- Trace amount of antigen found on the RBCs of some individuals: Bennet-
Goodspeed (Bg) antigens
- antibodies to Bg antigens are not considered clinically significant but may
interfere in the ID of other significant antibodies
Class II - DR, DQ, and DP loci found on antigen presenting cells
Prevent refractoriness by transfusing leukoreduced cellular blood components to avoid formation of
HLA antibodies in the recipient
Once a patient has become refractory - transfuse plts with the same or similar HLA phenotype
- may use an HLA avoidance strategy in which the specificity of the HLA
antibodies is determined and antigen negative plts are transfused
- perform platelet crossmatch using patient serum tested against samples from
apheresis plts
Febrile nonhemolytic transfusion reactions a. Common transfusion reaction caused when HLA antibodies in the recipient
react to HLA antigens on donor WBCs. This triggers the activation of the C5a
portion of complement, which releases IL-1, a pyrogen, from monocytes and
macrophages.
b. Classic symptoms are fever and chills.
c. May be prevented by using leukoreduced cellular components, which
removes WBCs (and therefore HLA antigens) from the component.
Transfusion Associated-Graft vs Host Disease a. Reaction occurs when donor lymphocytes recognize the recipient's HLA
antigens as foreign and try to destroy cells possessing those antigens. The
recipient does not recognize the donor HLA antigens as foreign, either
because the donor and recipient have an HLA haplotype in common or
because the recipient is immunocompromised and cannot mount a counter
response.
b. Symptoms include fever, rash, diarrhea, and other nonspecific symptoms.
This reaction is fatal in >90% of cases.
c. Irradiation of components containing lymphocytes prevents TA-GVHD by
damaging the donor lymphocytes so they cannot respond to foreign antigens.
, Transfusion-Related Acute Lung Injury a . Caused by donor antibodies directed against WBC antigens in the recipient
1) Most frequently caused by anti-neutrophil antibodies (See HNA section that
follows)
2) May be caused by antibodies to HLA Class I or II antigens, with Class II be
implicated more often than Class I
b. Antibodies activate complement, leading to capillary leakage and
pulmonary edema.
c. Antibodies may bind to macrophages in the alveoli, resulting in the release of
cytokines and chemokines that attract more neutrophils to the lungs.
Bone marrow and Organ Transplant a. Number of loci typed and degree of match required will depend on the
organ or tissue being transplanted.
b. Generally, the better the HLA match, the better the long-term survival of the
graft.
c. HLA antigen matching is of primary importance in bone marrow/HPC
transplants.
d. HLA plays a secondary role in solid organ transplants (ABO is of primary
importance in these cases).
Human Neutrophil Antigens - Ten neutrophil antigen on 5 glycoproteins
- Antibody activates complement
- C3a and C5a cause release of histamines and serotonin from basophils and
plts
- Leads to: formation of neutrophil emboli that aggregate in the capillaries of
the lungs, release of chemicals that damage the pulmonary endothelium, and
capillaries in the lungs leak leading to pulmonary edema
- Common cause of transfusion related death
- Mitigate by collecting plasma from male donors only OR female donors who
have never been pregnant or female donors who have tested negative for
HNA antibodies
Human plt antigens (HPA) - 41 HPA found on 7 plts membrane glycoproteins
- Anti-HPA-1a is the most common HPA antibody detected, followed by anti-
HPA-5a and anti-HPA-5b
HPA and Fetal/Neonatal Alloimmune Mother has an IgG antibody to the fetus' platelets. The IgG antibody crosses
Thrombocytopenia the placenta and destroys the fetal platelets
(similar to HDFN), leaving the fetus thrombocytopenic.
- Anti-HPA-1a is most common
- testing includes screening maternal serum for anti-plts antibodies and testing
both parents for plts antigens
- risk of intracranial hemorrhage in infant, treat with: IVIgG, random donor plts
units to correct infant plts count, directed donor plts from mother that are
washed and irradiated, mother may recieve IVIG with steroids to mitigate harm
to fetus
Post transfusion purpura - plts count drops 5-10 days following transfusion
- usually have previously developed an HPA antibody due to a previous
transfusion, or in women, a previous pregnancy
- transient autoantibody develops that destroys the patients plts
- treated by administering intravenous gamma globulin or performing plasma
exchanges to remove plt antibodies
- future plts transfusions should be with antigen neg plts
Immune thrombocytopneic purpura - patient produces an autoantibody to plts; most frequently against GP IIb/IIIa,
Ia/IIa, or Ib/X
- two forms: acute and chronic