Page 2029 - Hematology_ Basic Principles and Practice ( PDFDrive )

1800 Part XI Transfusion Medicine

TABLE Common Hematopoietic Stem Cell Infusion Reactions
119.4
Types Presentations Treatment and Prevention
DMSO toxicity Halitosis, nausea, vomiting, flushing, coughing, chest Antihistamine
tightness, dyspnea, abdominal pain, hypotension, Antiemetics
hypertension, cardiac toxicity (such as bradycardia and Limiting DMSO infusion volume
other arrhythmias), and rarely neurologic toxicity, such
as syncope and transient encephalopathy
Minor ABO mismatch Delayed hemolysis (1–2 weeks post HSC infusion) Plasma depletion of HSC product
RBC transfusion support compatible with donor and recipient
Monitor for hemolysis
RBC exchange with donor- and recipient-compatible blood if
massive hemolysis
Major ABO mismatch Hemolysis at the time of infusion Limiting the infusion of incompatible RBC
Delayed RBC engraftment Hydration
Monitor for RBC engraftment
Modify immunosuppression
Plasmapheresis to remove isohemagglutinins if significant
RBC engraftment delay
DMSO, Dimethyl sulfoxide; HSC, hematopoietic stem cell; RBC, red blood cell.

likely to respond to traditional transfusion therapy and may only be cord blood. As with blood transfusions, the infusion of HSCs carries
resolved with restoration of circulatory capacity and inhibition of the risk of the same types of transfusion reactions. However, addi-
fibrinolysis. tional risks are associated with HSC infusion, such as those related
Despite enhancements in understanding of early coagulopathy, to cryopreservatives. In general, infusions of cryopreserved cells are
platelet/coagulation factor dilution and consumption still remain more likely to cause reactions, as they contain higher concentrations
outstanding problems in the setting of massive transfusion. Patients of lysed RBCs and granulocytes than other blood products. For most
undergoing large-scale transfusion must be regularly monitored for reactions, it is difficult to identify the causative agent. Moreover,
hematocrit, platelet count, prothrombin time, activated partial because of the irreplaceable nature of HSC products, higher risks may
thromboplastin time, and fibrinogen. Reasonable goals to promote be tolerated. Only those reactions that are unique or more problem-
hemostasis in the setting of massive transfusion are to maintain (1) atic for HSC infusions are discussed in this section. A summary of
hematocrit >25%, (2) platelets >50,000/µL, (3) international nor- the reactions in given in Table 119.4.
malized ratio (INR) <1.7, and (4) fibrinogen ≥100–150 mg/dL.
Therefore it is imperative that clinicians provide more than just RBCs
to massively bleeding patients. To ensure a more appropriate provi- Dimethyl Sulfoxide Toxicity
sion of plasma and platelet products, many facilities have developed
protocols consisting of preset numbers of RBC, fresh frozen plasma The most common reactions to HSC have been attributed to dimethyl
(FFP), and platelet units that are immediately issued upon requests sulfoxide (DMSO), the most widely used cryopreservative. A variety
for massive transfusion. Such protocols, developed in conjunction of symptoms are associated with DMSO infusion and are generally
with surgical and trauma services, can drastically improve the effi- dose-dependent. A garlic odor commonly accompanies DMSO infu-
ciency of blood product provision in the setting of massive transfu- sion, and nausea and vomiting are often reported. Additional
sion. Although massive transfusion protocols are useful tools to DMSO-related symptoms include flushing, coughing, chest tight-
combat coagulopathy, controversy remains regarding the numbers of ness, dyspnea, abdominal pain, hypotension, hypertension, cardiac
plasma and platelet products that should be provided to patients toxicity (such as bradycardia and other arrhythmias), and rarely,
transfused with large volumes of RBCs. Trials and reports from mili- neurologic toxicity (such as syncope and transient encephalopathy).
tary trauma centers have promoted use of protocols based around a Some cases of DMSO toxicity are thought to arise from the release
1 : 1 : 1 ratio of RBC/plasma/platelets units. Data from combat the- of histamine. Agents such as diphenhydramine have been used for
aters suggest that such ratios are successful in avoiding the coagulopa- the treatment and prevention of DMSO-related toxicity. Antiemetic
thy of massive transfusion and ultimately lead to improved survival. agents such as prochlorperazine have been useful for ameliorating
Despite these data, it is unclear whether such approaches are relevant nausea and vomiting. Most clinical services have protocols in place
to noncombat, civilian hospitals, which frequently issue massive to limit the volume of DMSO that can be infused, such as setting
transfusions for wide-ranging indications such as surgical complica- an upper infusion limit of 1 g/kg/day, dividing HSC infusion doses,
tions, large gastrointestinal or retroperitoneal hemorrhages, or blunt or washing HSC products to remove DMSO (this, however, may
trauma. A 2015 randomized controlled trial (PROPPR Trial) com- result in cellular loss).
pared 1 : 1 : 1 and 2 : 1 : 1 RBC/plasma/platelet transfusion protocols
in civilian trauma patients. Results showed an absolute difference of
4% lower 24-hour and 30-day mortality in the 1 : 1 : 1 group, but the Red Blood Cell Engraftment and Hemolysis
difference was not statistically significant.
Although mismatched ABO and non-ABO blood groups do not
Complications Associated With Hematopoietic prevent successful HSCT, these antigens (and their corresponding
antibodies) can create problems during the transplant period. When
Stem Cell Infusion considering incompatibilities within the ABO system, three scenarios
are possible: (1) antibodies present in the recipient interact with
Hematopoietic stem cells (HSCs), the most widely used cell therapy incompatible cells present in the graft (major incompatibility),
products, may be derived from bone marrow, peripheral blood, and (2) antibodies present in the plasma portion of the graft mediate