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2376 Part XIII: Transfusion Medicine Chapter 138: Blood Procurement and Red Cell Transfusion 2377

mediators within the transfused component, which activate pulmonary infused blood product, and/or an underlying cardiac, renal, and/or pul-
neutrophils, which, in turn, damage the endothelium. The mediators monary pathology. The fluid volume transfused may be less important
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are often antibodies specific for either class II HLA or for human neu- than the infusion flow rate and the patient’s ability to process the fluid.
trophil antigens (HNAs). There are also cases in which no antibody was The incidence of TACO is difficult to ascertain, as there are incon-
detected, which are thought to be a result of proinflammatory medi- sistent case definitions, passive reporting systems and poor clinical
ators, bioactive lipids, and CD40 ligand that accumulate in the blood recognition. Approximately 1 percent of orthopedic patients developed
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product during storage. Despite reports of a direct correlation between TACO postoperatively, compared to 6 percent of patients in an ICU set-
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storage time of cellular blood components and TRALI, this mechanism ting. Reports of TACO have surged as awareness has increased. Active
remains controversial. surveillance also increases the number of cases. In one institution the
Specific patient factors (first hits) that are associated with a greater historical prevalence rate from 6 years of passive reporting was one in
risk of TRALI include patients on mechanical ventilation, sepsis, chronic 1566 from plasma transfusions. After 1 month of active surveillance the
alcohol abuse, severe liver disease, hematologic malignancy, and others. prevalence rate jumped to one in 68. 71
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It is not known whether the risk is determined by the patient’s condi- TACO is seen more in younger and advanced age patients. Addi-
tion, or by a greater transfusion requirement. The two-hit hypothesis tional risk factors include female sex, a history of congestive heart fail-
accounts for critically ill patients who develop TRALI; however, there ure, hemodialysis, mechanical ventilation, recent vasopressors, and
are reports of TRALI in reasonably healthy patients. This observation positive fluid balance. 73
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led to the threshold model of TRALI. In this paradigm, a threshold, Clinical Presentation Symptoms of TACO may include dyspnea,
or tipping point, must be surpassed to induce TRALI. A healthy patient orthopnea, cough, headache, and hypoxemia, which are not specific.
may develop TRALI when transfused with a high titer of antibody. Con- However, signs such as rales, hypertension, and jugular vein distention
versely, a critically ill patient with primed neutrophils can be tipped into may differentiate TACO from TRALI. These signs and symptoms usu-
TRALI with a lower titer of antibody. ally present within 2 hours of the onset of transfusion, but may be up to
Clinical Presentation and Differential Diagnosis It is often 6 hours or even 24 hours after the onset of transfusion.
impossible to fully distinguish TRALI from other causes of respiratory Laboratory Evaluation Oxygen saturation may decrease along
distress. The typical presentation of TRALI is the sudden development with the partial pressure of oxygen in the arterial blood. New bilateral
of dyspnea, severe hypoxemia (O saturation <90 percent in room air) infiltrates on chest x-ray is characteristic for TACO; however, it is also
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hypotension, and fever that develop within 6 hours of transfusion and seen in TRALI. Elevated levels of B-type natriuretic peptide (BNP) and
usually resolves with supportive care within 48 to 96 hours. Although N-terminal pro-BNP (NT-proBNP) are both useful markers for TACO,
hypotension is considered one of the important signs in diagnosing but NT-proBNP may be more useful as it has a longer in vivo and in
TRALI, hypertension can occur in some cases. vitro half-life. Unfortunately neither peptide was found to be useful in
In addition to new or worsening oxygen desaturation, TRALI is distinguishing TACO from TRALI in critically ill patients. 74
characterized by chest x-ray findings of bilateral diffuse patchy pulmo- Management Once TACO is suspected, intravenous fluids
nary densities without cardiac enlargement. TRALI can be ruled out as should be restricted, followed by the administration of supplemental
the sole cause of pulmonary failure by the presence of rales and jugular oxygen and a diuretic, if not contraindicated. Placing the patient in a
venous distention on physical exam and/or dilated pulmonary arteries sitting position can also be helpful. In severe cases, mechanical ventila-
on chest x-ray, which are evidence of congestive heart failure with or tion may be required.
without transfusion-associated circulatory overload (TACO). Transient If a patient is at risk for TACO and blood transfusion is impera-
leukopenia, which follows the reaction within few hours, can also dis- tive, blood should be administered slowly at a rate of 1 to 4 mL/kg/h.
tinguish TRALI from TACO. Most blood banks can also reduce the transfusion volume by splitting
Management Supportive care is the mainstay of therapy in the blood product into smaller volumes if the transfusion is going to
TRALI, including oxygen supplementation and aggressive respira- last longer than 4 hours. Close monitoring of the patient’s vital signs
tory support plus intravenous fluid and vasopressors for hypotension, throughout the transfusion may also help in decreasing the develop-
if indicated. It has been suggested that diuretics, which are indicated ment of TACO.
in TACO management, are not efficacious and should be avoided in
TRALI. Glucocorticoids may provide benefit. Transfusion-Related Sepsis
Prevention HLA alloimmunization has been directly correlated Transfusion-related sepsis when it occurs is usually from platelet units
with the number of times a woman is pregnant and plasma from mul- that are stored at room temperature. Red cells, stored at refrigerator
tiparous women has been implicated as a risk factor in TRALI. To reduce temperatures, are very rarely contaminated by unusual cold-growing
this risk, blood banks attempt to collect plasma from males, nulliparous organisms (e.g., Yersinia, Serratia, Pseudomonas). The rate of fatal
females, and/or females tested and found to be negative for HLA anti- transfusion- transmitted bacteremia from red cells has been estimated
bodies. After blood collection centers implemented TRALI mitigation to be 0.13 per million units transfused in the United States. 75
strategies, the incidence of TRALI dropped from an estimate of one in Clinical Presentation The infusion of large numbers of Gram-
4000 transfusions, to approximately one in 12,000. Nonetheless, TRALI negative microorganisms may lead to fever (>38.5°C), rigors, marked
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continues to be the leading cause of transfusion-related fatalities. hypotension, abdominal pain, vomiting, diarrhea, and the development
Pooled plasma may also be used for TRALI mitigation because of profound shock. Gram-positive contaminants may cause fever and
antibody titers drop due to dilution. No cases of TRALI resulting rigors, but are not associated with the severe symptoms produced by
from transfusion of pooled solvent detergent treated plasma have been Gram-negative toxins.
reported. 68,69 Laboratory Evaluation Rapid diagnosis usually may be made via
Gram stain of the residual donor blood; however, a culture of the trans-
Transfusion-Associated Circulatory Overload fused component is necessary.
TACO occurs when patients are unable to effectively process the expan- Management Septic shock from transfusion of contaminated
sion in intravascular volume from a blood transfusion. Circulatory blood should be managed as for septic shock from other causes and is
overload may be the consequence of the infusions rates, the volume of not discussed further here.

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