Page 2030 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 119 Transfusion Reactions to Blood and Cell Therapy Products 1801

hemolysis of recipient RBCs (minor incompatibility), or (3) anti-
bodies present in both the recipient and the donor interact with Other Infusion Complications Related to
incompatible RBCs (bidirectional, or two-way, incompatibility). It Hematopoietic Stem Cell Products
has been shown that both major and bidirectional ABO incompat-
ibility can delay stem cell engraftment. In such cases, anti-A and/ In addition to the problems related to DMSO and ABO mismatches,
or B antibodies suppress RBC precursors expressing these antigens, other adverse reactions sometimes occur with the use of HSC prod-
leading to reticulocytopenia and prolonged anemia. In the most ucts. Nausea and vomiting are frequently reported with infusion of
severe form of this process, HSC recipients can develop pure RBC freshly collected HSC products such as fresh marrow. Fever and chills
aplasia, a condition wherein bone marrow shows a virtual absence of are commonly seen with cryopreserved HSC; these have been specu-
immature erythroid elements more than 3 months posttransplanta- lated to be caused by the cellular debris and cytokines contained in
tion. In cases of either delayed engraftment or pure RBC aplasia, HSC products. Antipyretics and steroid premedication may be used
patients are dependent on RBC transfusions for prolonged periods for prevention. Severe adverse reactions to HSC infusion (such as
of time. cardiac arrest and neurologic symptoms, including loss of conscious-
Another risk factor associated with HSC infusion is the possibility ness and seizure) have been linked to high granulocyte counts in HSC
for RBC hemolysis. Both ABO and non-ABO antibodies are capable products.
of mediating RBC lysis. In such conditions, preformed antibodies in Respiratory problems are increasingly being recognized as an
either the recipient or HSC plasma can cause accelerated clearance important cause of morbidity and mortality in the setting of HSC
of incompatible RBCs by either intra- or extravascular mechanisms. infusion. Although many of these are late-onset problems (e.g., infec-
Presentation of hemolytic transfusion reactions immediately after tious complications associated with immunosuppression occurring
HSC infusion is no different from that of typical transfusion reaction. days or weeks after transplantation), some pulmonary issues will arise
Policies and protocols should be in place to prevent postinfusion acutely during HSC infusion. The National Marrow Donor Program
HSC-related hemolysis—for example, plasma depletion of HSC (NMDP) issued a report in 2010 regarding seven patients who expe-
products (in cases of minor mismatch and bidirectional ABO incom- rienced hypertension, chest pain, and decreased oxygen saturation after
patibility), limiting the infusion of incompatible RBCs (in cases of infusion of cord blood. Even though no clear-cut cause-effect relation-
major mismatch and bidirectional ABO), hydration of patients, and ship was established, some recommendations were made, including
prospective monitoring for hemolysis. minimizing thaw to infusion time, filtering HSC products with stan-
Although delayed hemolysis is rarely clinically significant in major dard 150–250-µm blood filters, avoiding very high infusion rate, and
ABO-mismatched HSC transplant, clinically significant delayed others. In addition, the classic pulmonary complications encountered
hemolysis is commonly reported in minor and bidirectional ABO- during HSC infusion may resemble TRALI in that they are associated
incompatible HSC transplants. As a result of donor lymphocyte with dyspnea, hypoxemia, a low-grade fever, and bilateral pulmonary
engraftment, typically occurring 1–2 weeks after HSC infusion, infiltrates, all occurring within a short time after initiation or comple-
donor ABO antibodies can cause hemolysis of residual recipient tion of infusion. Some authors have attributed these problems to a
RBCs. This delayed hemolysis is typically clinically evident with noncardiogenic capillary leak syndrome that appears to be independent
decreased hemoglobin, increased indirect bilirubin, increased LDH, of cardiac function, similar to the proposed pathophysiology of TRALI.
and decreased haptoglobin, and patients often require RBC transfu- Patients demonstrating signs or symptoms of respiratory distress
sion. Sometimes the hemolysis can be acute and massive and result during HSC infusion must be treated aggressively. The first response
in multiorgan failure and death. Thus it is important to monitor should be to stop the HSC infusion and provide immediate respira-
patients closely for anemia and hemolysis after minor and bidirec- tory support. The provision of corticosteroids or other immunosup-
tional ABO-incompatible HSC infusion, especially in the first two pressive agents is not likely to be of benefit for such reactions. It may
weeks post-HSC infusion. Timely support and treatments such as also be prudent to investigate whether the patient’s symptoms are
RBC exchange with donor type blood can be provided for massive related to circulatory overload rather than arising from noncardio-
hemolysis. genic pulmonary edema. This distinction may be assisted by measur-
ing plasma levels of brain-natriuretic peptide (BNP). If BNP is
elevated, then the patient’s symptoms may be attributable, in part, to
Infectious Complications volume overload.

As a result of an underlying bacteremia during collection, or con-
tamination through collection, processing, storage, thawing, and National Healthcare Safety Network
sampling, some HSC products may harbor microbial organisms
capable of mediating septic reactions during or immediately after The National Healthcare Safety Network (NHSN) is a national
HSC infusion. Such reactions may manifest with fever, tachycardia, program of combined governmental and private sector agencies
hypotension, nausea, or vomiting. Patients experiencing such symp- designed to evaluate and track transfusion reactions and other adverse
toms should be treated with broad-spectrum antibiotics to cover effects associated with infusion of blood products and derivatives.
both gram-positive and gram-negative organisms. Bone marrow Similar programs exist in other countries, including the United
collections have a higher contamination rate than apheresis HSC Kingdom (Serious Hazards of Transfusion, SHOT), the Netherlands
collections, although typically with coagulase negative Staphylococcus (Transfusion and Transplantation Related Incidents in Patients,
aureus and Propionibacterium acnes that grow only with extended TRIP), and Canada (Transfusion Transmitted Injuries Surveillance
culture. System, TTISS). Hemovigilance systems in other countries have
Fortunately, bacterial contamination of an HSC unit is often established efficacy of safety interventions, for example, reduction in
known well in advance of an actual HSC infusion because HSC TRALI using male-only plasma donors, and they can identify emerg-
products are typically cultured at the time of collection and process- ing threats to transfusion safety, especially when events are uncom-
ing. As such, clinical teams can be prepared for such reactions. In mon and are detectable only when large numbers of outcomes are
such circumstances, preventative measures include provision of pre- evaluated in aggregate.
infusion antibiotics to cover the documented organism(s) and close The Hemovigilance Module, the first protocol release of the
patient surveillance during and after infusion. One additional option Biovigilance Component of NHSN, was developed through a public-
would be to avoid infusion of a contaminated unit altogether. This private partnership between the Centers for Disease Control and
is possible if a patient has multiple, separate HSC products available Prevention (CDC) and subject-matter experts convened by AABB.
for infusion. Clinical and transplant teams can preferentially infuse The Hemovigilance Module is designed for transfusion services staff
noncontaminated HSC units first, saving the contaminated unit as a in health care facilities to monitor recipient adverse reactions and
“last resort” should the graft fail. quality-control incidents related to blood transfusion.