Allergic - 1 to 3 percent

- Epi: true prevalence is unknown because these are likely to be underreported

- GENERAL: major difference between allergic reactions and anaphylactic reactions is of degree;
allergic reactions are mild, whereas anaphylactic reactions are associated with massive release of
histamine and other mediators
- Urticarial reactions present with hives or urticaria, which can occur during, at the end, or shortly after a
transfusion
o This timing differs from anaphylactic reactions, which typically occur within minutes of starting a
transfusion
- No other allergic findings are present (ie, there is no wheezing, angioedema, or hypotension)
- MOA: a soluble substance in the plasma of the donated blood product (or the recipient) reacts with
pre-existing IgE antibodies in the recipient (or the product), respectively. Urticarial reactions are
thought to be due to mast cell or basophil release of histamine, although other mechanisms may be
involved.
- Type I hypersensitivity reaction against plasma proteins in transfused blood. IgA deficient individuals
must receive blood products without IgA.
- Antigen-antibody interaction that occurs between patient and the product; commonly implicated
antigens include a number of donor serum proteins
- Presentation: A commonly cited example of urticarial reactions is donor peanut allergy, with hives in
the recipient triggered by recent peanut ingestion by the recipient [34-36]. The converse (recipient
peanut allergy, with peanut antigen in the donated product) has also been described
- Management: If there is evidence of hypotension or respiratory distress, the possibility of anaphylaxis
should be evaluated urgently
- 0.3mL of 1:1000 solution IM
- Prevention: These manipulations (removal of plasma, washing) should only be used for patients who
experience severe or repeated urticarial reactions that cannot otherwise be prevented. It is appropriate
to try concentrating the implicated cells (RBCs or platelets) first (by removing plasma) and only
washing the cells if plasma removal does not prevent the urticarial reactions.

Anaphylactic reaction - 1:20,000 to 1:50,000

- Anaphylaxis results from sudden (typically massive) systemic release of mediators such as histamine
and tryptase by mast cells and basophils, typically in response to an IgE-mediated (or IgG-mediated)
immune reaction
- Anaphylactic reactions may occur in IgA-deficient individuals who produce anti-IgA antibodies that
react with IgA in the transfused product, or patients who have allergies to another constituent in the
transfused product.

Hemolytic Transfusions - 1:76,000

 MOA: Intravascular hemolysis (ABO blood group incompatibility) or extravascular hemolysis (host
antibody reaction against foreign antigen on donor RBCs
 AHTRs are typically associated with rapid intravascular hemolysis, which can lead to acute renal
failure, disseminated intravascular coagulation (DIC), and hemodynamic collapse
 recipient of a plasma-containing product (eg, Plasma Frozen Within 24 Hours After Phlebotomy
[PF24], Thawed Plasma, Fresh Frozen Plasma [FFP]; platelets) or of; intravenous immune
globulin (IVIG) or Rh(D) immune globulin may develop an AHTR due to antibodies in the plasma or
immunoglobulin product that react with the recipient's RBCs
 presence of hemoglobinemia (red or dark plasma), hemoglobinuria (red or dark urine), DIC, shock,
and acute renal failure due to acute tubular necrosis are indicative of intravascular hemolysis
 normal saline should be infused immediately to reduce the risks of hypotension and renal injury
 Findings suggestive of extravascular hemolysis include a positive DAT without pink or dark brown
serum or urine, as well as laboratory evidence of hemolysis. Later testing of the urine may show urine
hemosiderin.
 Delayed
- More than 24 hrs, days to weeks
- Extravascular hemolysis
- Gradual, less severe, clinically silent; low grade fever, jaundice
- Increased LDH, indirect bilirubin, decreased haptoglobin, positive direct/indirect Coombs test
- Mild anemia/failure of hemoglobin to increase as expected after transfusion
- OR estravascular hemolysis – spherocytes on peripheral blood smear
- DHTRs almost always result from an anamnestic response following re-exposure to a foreign RBC
antigen such as one from the Kidd or Rh system. Previous exposure may have occurred through
transfusion or pregnancy. DHTRs generally do not require any treatment except for future avoidance
of transfusions containing the implicated RBC antigen.
- DHTR is accompanied by hemolysis of the patient's own RBCs, a condition termed "hyperhemolysis"
or hyperhemolytic crisis. This phenomenon has been seen most often in multiply-transfused patients
with sickle cell disease, but it has also been reported in patients with thalassemia and in other settings
[41]. The mechanism by which such "bystander hemolysis" occurs is not known. This complication and
its management are discussed separately.
- No specific interventions are required for a DHTR in the absence of brisk hemolysis
- it is critical to avoid future transfusions containing the implicated RBC antigen. It is therefore important
to perform the evaluation, document the alloantibody, and inform the patient and caregivers of the
importance of avoiding the antigen in future transfusions

TRALI - <0.01 percent

- acute lung injury that occurs when recipient neutrophils are activated by the transfused product in an
appropriately primed pulmonary vasculature
- largely supportive and may include intubation and mechanical ventilation
- identifying an implicated donor so that individual does not continue to donate and potentially cause
TRALI in other patients.
- patient can receive blood products from other donors without restrictions, but should not receive any
remaining untransfused portion of the implicated product or any other products from the implicated
donor.
- more likely in patients who have respiratory distress out of proportion to the volume of fluid received or
early on during the transfusion.
- Individuals with underlying acute lung injury or an alternative risk factor for acute lung injury are
referred to as having "possible TRALI.
- fluid in the alveoli is an exudate (ie, the ratio of protein in the edema fluid to protein in the plasma is
>0.75)

A "two-hit" hypothesis for the pathogenesis of TRALI holds that recipient neutrophils are primed for activation
by virtue of the patient's underlying clinical condition. The second hit involves activation of these neutrophils
by pre-formed anti-leukocyte antibodies or biological response modifiers contained in the transfused product.
In rare cases, the transfused product may provide both hits

The first hit involves neutrophil sequestration and priming in the lung microvasculature, due to recipient
factors such as endothelial injury.
The second hit is activation of recipient neutrophils by a factor in the blood product.
Activation is associated with the release from neutrophils of cytokines, reactive oxygen species, oxidases, and
proteases that damage the pulmonary capillary endothelium. This damage causes inflammatory (non-
hydrostatic) pulmonary edema. Transfused factors responsible for host neutrophil activation can include
antibodies in the blood component directed against recipient antigens, or soluble factors such as bioactive
lipids that can activate neutrophils. Donor anti-leukocyte antibodies can bind to antigens on recipient
neutrophils or possibly to other cells such as monocytes or pulmonary endothelial cells
PTP can be thought of as a delayed transfusion reaction involving platelets, in which an anamnestic response
to a previously encountered foreign platelet antigen leads to an increase in production of anti-platelet
antibodies by the recipient. The antigen most commonly implicated is the platelet antigen PlA1, now known as
human platelet antigen 1a, (HPA-1a) [44]. Unlike a delayed hemolytic reaction, however, these antibodies
cause destruction of both the PlA1-positive transfused platelets as well as bystander destruction of the
patient's own PlA1-negative platelets, leading to thrombocytopenia. The mechanism by which the antibodies
destroy the recipient's own platelets lacking the antigen is not well understood. Possibilities include adsorption
of immune complexes onto the patient's own platelets, which are then destroyed, passive acquisition of the
antigen from donor plasma, or elaboration of a new autoantibody to another platelet antigen.

An alternative and even rarer syndrome leading to post-transfusion thrombocytopenia has been reported, in
which the recipient of a plasma-containing blood product such as Fresh Frozen Plasma (FFP) develops
severe thrombocytopenia, which may be accompanied by bleeding and an acute transfusion reaction, caused
by the passive transfer of anti-platelet antibodies (eg, anti-HPA-1a/PlA1)from a previously immunized donor
[46]. The time-course is much more rapid than PTP; thrombocytopenia due to passive antibody transfer
occurs in hours rather than days, and recovery typically occurs within five days. Implicated donors are
females with a history of pregnancy; these donors should be deferred from subsequent donations.

Treatment and prevention of PTP — The preferred therapy for PTP is intravenous immune globulin (IVIG) in
high doses (400 to 500 mg/kg per day), usually for five days; alternatively, 1 g/kg per day for two days can be
given for severe thrombocytopenia [48-50]. It usually takes about four days for the platelet count to
exceed 100,000/microL [48,49].

High-dose glucocorticoids have been useful in some patients with PTP, as has exchange transfusion;
however, both of these treatments take two or more weeks to act and have side effects (eg, alterations in
blood glucose, infectious risk); therefore, these are not our preferred therapies.