Page 2024 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 119 Transfusion Reactions to Blood and Cell Therapy Products 1795

the corresponding cellular antigens in the recipient’s blood. Leukocyte- Septic Transfusion Reaction
derived cytokines IL-8, IL-1β, and IL-6 accumulate in platelet
products in particular and induce fever. IL-1, through prostaglandin A 29-year-old women in week 38 of pregnancy received a unit of apher-
PGE 2 synthesis, is thought to stimulate the thermoregulatory center esis platelets prophylactically in clinic for a chronic bone marrow failure
of the hypothalamus to produce fever. Other mediators such as syndrome of unclear etiology. During the infusion, she developed flank
macrophage inflammatory proteins (e.g., MIP-1) may also participate pain and coughing. The transfusion was stopped and the patient was
in the febrile response, but this reaction is not mediated through admitted. She became febrile to 39.3°C 90 minutes after transfusion.
prostaglandin synthesis. CD154 (CD40 ligand) derived from plate- Blood cultures from the patient and bag grew Staphylococcus aureus
lets is also involved in febrile reactions by inducing cyclooxygenase-2 within 12 hours.
and PGE 2. Leukoreduction is less effective at preventing FNHTRs Blood transfusion is common in people with bone marrow failure,
to platelets than to red cell components because of platelet-derived either primary or secondary to myeloablative chemotherapy. These
patients are also often neutropenic, have central venous catheters, and/
biologic response modifiers. Nevertheless, studies show that genera- or are taking immunosuppressive medications. Despite these underlying
tion of cytokines during storage is directly proportional to the leu- risk factors, transfusion should always be considered a potential source
kocyte count of the unit and the duration of storage. of bacteremia. It is critical to always consider blood components as a
The frequency of febrile reactions for a nonleukoreduced unit has source of infection. There are usually other components manufactured
been estimated to be 6.8 per 100 units RBCs transfused and 2.2 per from the same collection, and the blood bank must quarantine them
100 units platelet transfused. With the advent of prestorage leukore- before release to another patient. It is only when the blood bank is
duction, these risks have been decreased to about 0.09–1.1 per 100 notified of a suspected septic reaction that this is possible. Yomtovian
units RBCs transfused and 0.04–1.56 per 100 units platelet trans- and colleagues prospectively cultured all platelets issued from a large
fused. Reactions are most commonly seen in recipients who have been hospital blood bank and found contaminated units similar to other
reported rates (~1 : 2000). When they relied on passive reporting of
exposed to multiple white cell or platelet antigens. Patients with bone septic reactions from clinicians, the incidence fell to zero, only to
marrow failure (primary or chemotherapy-induced) are at risk as a increase back to baseline once active culturing of platelets resumed.
result of frequent transfusions, as are multiparous women who may
have received multiple exposures during pregnancy and childbirth.
These groups of patients can form multiple HLA-, granulocyte-, or
platelet-specific antibodies that will react with white cells or platelets Prevention of febrile reactions also relies on the use of leukocyte-
upon subsequent exposure. depleted blood components. Several leukocyte depletion techniques
The workup of a febrile reaction must be undertaken promptly, are available. Prestorage leukocyte depletion filters are the most
because fever may also be the first sign of other, more severe reactions, common method used for preventing febrile reactions. They remove
including acute hemolysis or sepsis. A hemolytic transfusion reaction up to 4 logs (99.99%) of leukocytes, often lowering the level of white
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may be ruled out by reconfirming the ABO and Rh type of the cells in a unit of blood from 10 to 10 . They also are useful for
patient and the donor unit, repeating crossmatching to confirm preventing or delaying the onset of HLA alloimmunization and
patient-donor compatibility, evaluating the results of the pretransfu- preventing cytomegalovirus transmission. For these reasons, leukore-
sion and posttransfusion DATs, evaluating the serum for hemolysis, duction is universal in many centers. Cell washing or use of frozen
and rechecking the accuracy of paperwork. The posttransfusion DAT deglycerolized RBCs can remove up to 95% of contaminating white
should yield negative findings, because FNHTRs do not involve RBC cells. Individuals with a history of recurrent, severe febrile reactions
alloantibodies. should have notations made in their blood bank record to ensure
As laboratory testing is being completed, the workup should future use of leukocyte-reduced components.
include bedside patient evaluation. Fever and chills may be attribut-
able to drugs or underlying diseases, or they may be associated with
infection or inflammation. Neutropenic fever often complicates the ALLERGIC TRANSFUSION REACTIONS
clinical picture in patients undergoing myeloablative chemotherapy,
a population of patients likely to undergo repeated RBC or platelet Allergic transfusion reactions complicate up to 3% of all transfusions.
transfusions. Blood cultures of the patient and the blood product The allergic manifestations occur on a spectrum of severity. They can
should be considered, especially if the patient has high fever or shows include flushing, urticaria, pruritus, angioedema, hypotension,
signs of sepsis (see later text and box for a more in-depth discussion bronchospasm, stridor, abdominal pain, and emesis. Anaphylaxis is a
of septic transfusion reactions). The difficulty lies in knowing when systemic immediate hypersensitivity reaction, which can be defined
to order blood cultures, because there is a false-positive incidence as as allergic signs and symptoms in skin/mucosa and at least one other
a result of contamination during culturing. It is not routine to organ system (cardiovascular, respiratory, gastrointestinal). Shock is
identify the specificities of HLA, platelet, or granulocyte antibodies the most ominous manifestation of anaphylaxis, but bronchospasm
that could cause FNHTRs. Accordingly the diagnosis of an FNHTR and upper airway angioedema are more common manifestations (see
is usually made as a diagnosis of exclusion without isolating an box titled “Management and Prevention of Allergic Transfusion
identifiable antibody. Reaction).
Fever from an FNHTR usually responds to antipyretics, including Allergic transfusion reactions manifest as other IgE-mediated,
aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), and acet- immediate hypersensitivity reactions. The incidence is associated with
aminophen. Aspirin and NSAIDs should be avoided in thrombocy- the plasma content of the product, so it is thought that a plasma
topenic patients because of their inhibitory effects on platelet protein is responsible for many reactions. Examples of IgG or IgE
cyclooxygenase, including inhibition of transfused platelets. with specificity to IgA, haptoglobin, and C4 have been described.
Diphenhydramine is not indicated for treatment or prevention of There are several reports of allergic transfusion reactions to autologous
febrile reactions. transfusion, suggesting that a storage lesion may be responsible for
For patients with no history of febrile reactions, routine premedi- some reactions. Passive transfer of IgE with allergen exposure in the
cation is unnecessary. Most patients do not experience subsequent recipient is a mechanism that has been described for food and
FNHTRs. Those with a history of clinically significant FNHTRs may antibiotic-mediated allergic transfusion reactions, but these are
be premedicated with acetaminophen or an NSAID. Those patients uncommon.
with severe reactions despite premedication may require more inten- Mast cells are the primary allergic effector cells for immediate
sive pharmacotherapy, including corticosteroids 1–2 hours before hypersensitivity reactions; basophils may play a secondary role. Mast
transfusion. Patients with severe rigors can be treated with meperi- cells and basophils can be activated by cross-linking cell surface
dine. Febrile reactions after granulocyte transfusions and, less fre- high-affinity IgE receptors or via IgE-independent mechanisms, such
quently, after platelet transfusions can be so severe that hypotension as complement receptor binding by C5a. Upon activation, histamine
may occur. is released immediately, as it is stored preformed in granules. Platelet