trali power point 2
TRANSCRIPT
Objectives:
1. Obtain a basic understanding of the clinical presentation and treatment of transfusion-related acute lung injury (TRALI) in a transfused patient.
2. Obtain a basic understanding of which laboratory tests will aid the clinician in their diagnosis.
3. Obtain a brief introduction into the pathophysiology of TRALI and the current proposed mechanisms of TRALI.
4. Review the laboratory work-up of TRALI.
5. Obtain a brief overview of how to prevent TRALI.2
Patient History:
A 69 year old male recently diagnosed with refractory anemia with excess blasts (RAEB) is returning to his oncologist for a follow up visit. Current Treatment(s): Induction phase
with supportive care Chief Complaint(s): Weakness and
fatigue which has been increasing during the last week.
Physician Order(s): Complete blood count (CBC) Basic metabolic panel (BMP) 3
Laboratory Results:Test : CBC
Patient Results
Reference Range
WBC 2.6x103 /μL 4.5-11.0 x103/μL
RBC 2.46x106/μL
4.5-5.9 x106/μL
Hemoglobin
7.4 g/dL 13.5-17.5 g/dL
Hematocrit
21.8 % 41.0-53.0 %
Platelet 7.0x103/μL 150-450 x103/μL
Neutrophil 63% 40-75 %Lymphocyte
27% 20-45 %
Monocyte 8% 0-12 %Eosinophil 1% 0-5 %Basophil 1% 0-2%
Test: BMP
Patient Results
Reference Range
Glucose 128 mg/dl 65-99 mg/dl
Creatinine
1.0 mg/dl 0.7-1.20 mg/dl
Bun 15.0 mg/dl 8.0-23 mg/dl
Calcium 8.5 mg/dl 8.8-10.2 mg/dl
Sodium 138 mmol/L
136-145 mmol/L
Potassium
3.9 mmol/L 3.5-5.1 mmol/L
Chloride 100 mmol/L
98-107 mmol/L
Bicarbonate
25 mmol/L 22-29 mmol/L
Anion Gap
17 mmol/L 9-18 mmol/L
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Physician Order(s):
Patient to be admitted for short term observation.
Type and Cross match for 2 units of leukoreduced packed red blood cells (LPRBC’s) and one unit of aphaeresis platelets to be transfused the same day.
Pre-medicate with Acetaminophen 325 mg and Benadryl 5mg both to be taken orally.Test Patient Results
ABO/Rh O PositiveAntibody Screen NegativeLPRBC’s 2 units O Pos LRPBC’s
are cross-match compatible and available
Aphaeresis Platelets 1 unit O Pos platelets available
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RN Admission Work-up:
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While the blood bank is setting up the blood the patient goes to the medical floor to be admitted. After proper identification the nurse proceeds with her admission work-up.Assessment Patient results
Blood Pressure 130/85Pulse 74 beats/ minTemperature 38.0 °CPulse oximetry 99%Lung sounds ClearIntravenous line Left forearm
Time-line:
The blood is signed out in the blood bank and per protocol ,the patient is properly identified at the bedside by two nurses and the transfusion is started.
He is monitored for the first fifteen minutes. The patient is tolerating the transfusion well so the nurse continues her rounds.
Approximately two and a half hours later the first unit has finished and the nurse obtains the platelet unit from the blood bank and the transfusion is started again per protocol.
After the platelet transfusion is complete there is a delay for the second unit of LPRBC’s as the nurse is taking care of another admission.
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Time-line: Thirty minutes post platelet transfusion the
patient starts to complain of shortness of breath. Seeing the patient struggling for his breath the nurse administers supplemental oxygen by nasal prongs.
Re-checking the patients vital signs the nurse finds the following and the physician is notified.Vital Sign Patient Results
Blood Pressure 110/70Pulse 90 beats/minuteTemperature 39.0°C Pulse Oximetry 90 %Skin appearance No reddening, rash or
hives 8
Time-line: After the physician is notified the last unit of LPRBC’s is
placed on hold and a transfusion reaction is initiated. After another 10 minutes the patient is continuing to
deteriorate, vitals are now:
Physician orders the patient to be moved to the critical care unit for possible initiation of mechanical support.
Orders the following tests: EKG, portable chest x-ray, arterial blood gas (ABG), creatine kinase-muscle brain (CK-MB), troponin (cTnI), B-natriuretic peptide (BNP) and d-dimer.
Vital Sign Patient ResultsBlood Pressure 90/50Pulse 110 (tachycardic) Pulse Oximetery 85 %Lung sounds Rales
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Test Results:Test Patient Results Reference RangeEKG Normal Sinus
tachycardia; no evidence of ischemic changes
Normal Sinus rhythm
X-ray extensive bilateral pulmonary infiltrates
seen
Heart and lungs look normal; no infiltrates
seenABG pH
7.312 7.35-7.45
paCO2 47.2 35-45 mmHg
paO2 62.0 80-100 mmHg
SpO2 86.1 95-100%
HCO3 22.3 22-26 mEq/L
B.E -3.9 -2.0-2.0 mEq/LCK-MB
26 0-23 IU/mlTroponin
0.252 0-0.2 ng/mlBNP
61.4 5-100 pg/mlD-Dimer
0.2 0-0.5 mcg/mlTransfusion Work-up
Negative Negative
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Treatment: Due to the rapid decline in the patients
respiratory status, the following was initiated. Mechanical support
Ventilator using positive end expiratory pressure (PEEP) of 10 mmHg.
Invasive hemodynamic monitoring Arterial blood pressure of 65/30 mmHg with normal
being 110/70 mmHg. Central venous pressure (CVP) of 15 mmHg with
normal range being 2-8 mmHg. Vasopressure support (agent that produces
vasoconstriction and a rise in blood pressure) Dopamine Dobutamine Non adrenaline 11
Patient Response to Treatment: After 48 hours from the onset of respiratory
distress his hemodynamics stabilized and he was removed from vasopressor support.
Within 72 hours the patient had responded to symptomatic measures.
It took another 2 days for the pulmonary infiltrates to clear and at this point he was weaned from the ventilator.
He was then transferred back to a medical room 24 hours after having been weaned from the ventilator to continue is recovery under medical supervision.
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Transfusion-Related Acute Lung Injury
2003 FDA lists it as the leading cause of transfusion related morbidity and mortality.
A working group was formed in 2003 by the National Heart Lung and Blood Institute to arrive at a consensus definition. “TRALI is an acute lung injury temporarily
related to transfusion and is not physiologically different from other forms of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).”
The plasma fraction of the blood or blood products appears to cause TRALI rather than the cellular components.
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Transfusion-Related Acute Lung Injury
Incidence 1/1333- 1/5000 transfusion Mortality rates of 5-35% with lower rates of 5-
10% being more common. Implicated blood products
Whole blood–derived platelet concentrates (WB-PLTs)Fresh frozen plasma (FFP)Packed red blood cells (PRBCs)Whole blood (WB)Apheresis platelet concentrates (A-PLTs)GranulocytesStem cell preparationsIntravenous gamma globulinCryoprecipitate
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Clinical Presentation: Occurs within 6 hours of the start of the
transfusion. Usually within 1-2 hours after the start of the
transfusion. Present with rapid onset of:
Tachypnea, cyanosis, dyspnea and fever (≥ 1°C) Hypotension is commonly reported but not
always consistently found. Diffuse crackles and decreased breath sounds.
Chest x-ray confirms bilateral fluffy infiltrate consistent with pulmonary edema.
Other Symptoms include: Acute hypoxia and decreased pulmonary
compliance even given near normal cardiac function.
IDENTICAL TO THAT OF ACUTE LUNG INJURY (ALI)
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Differential Diagnosis:
Transfusion associated circulatory overload (TACO). Occurs minutes to hours of the start of the
transfusion. Similar symptoms: tachypnea, tachycardia
and cyanosis with hypertension. Hypertension is rare in TRALI but has been reported.
Responds quickly to aggressive diuretic therapy and ventilator support.
Brain natriuretic peptide (BNP) and n-terminal pro-brain natriuretic peptide (NT-proBNP) are markers for congestive heart failure. 16
Differential Diagnosis:
Transfusion associated circulatory overload BNP
They measured the BNP of 80 respiratory failure patients who also underwent pulmonary catheter placement. BNP level was ≤200 pg/ml it was 91%
specific for acute lung injury. Values ≥1200 pg/ml were 92% specific for cardiogenic pulmonary edema.
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Differential Diagnosis:
Transfusion associated circulatory overload BNP
Zhou et. al. measured BNP levels in 21 patients with suspected transfusion related cardiac overload. They obtained pre and post transfusion levels. The BNP was considered significant if the post
transfusion to pre transfusion ration was ≥1.5 and the post transfusion BNP level was ≥200 pg/ml.
Absence of jugular venous distension and S3 gallop.
Central venous pressure (CVP) and pulmonary wedge pressure are normal. 18
Differential Diagnosis:
Anaphylactic transfusion reaction Respiratory distress related to
bronchospasms manifested by tachypnea, wheezing, cyanosis and severe hypotension.
Facial and truncal reddening of the skin with a rash or hives is present which are not seen in TRALI.
Related to laryngeal and bronchial edema rather than the pulmonary edema seen in TRALI.
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Differential Diagnosis:
Bacterial contamination of blood components Transfusion-related bacterial sepsis.
Fever, hypotension, vascular collapse which may include respiratory distress.
Culturing of implicated blood component will give negative results and rule this out.
Hemolytic transfusion reactions Some signs and symptoms can mimic TRALI
Hemolysis noted in the plasma and urine will rule this out.
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Treatments:
Identical to Acute lung injury Aggressive respiratory support.
Use of supplemental oxygen and mechanical ventilation
Corticosteroids and diuretics do not play a role in the treatment of TRALI. Diuretics may harm the patient by
decreasing their vascular volume.
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Pathophysiology
Not well understood but they have proposed two basic mechanisms.
Most reported cases involve an immune (antibody) mediated mechanism
In rare cases where no antibody has been found, a non-immune mechanism has been proposed.
A newer third mechanism involving neutropenic patients is now emerging.
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Pathophysiology:
(A) Single clinical event, infusion of donor antibodies directed against host leukocytes.
(B) Two clinical events, the first is health condition of the host which causes endothelial activation and adherence in the lung. Second the transfusion of biologic response modifiers.
(C) Neutropenic patients, agents that cause endothelial fenestration.
http://bloodjournal.hematologylibrary.org/cgi/reprint/105/6/2266.pdf
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Pathophysiology: Immune (antibody)-mediated TRALI
In 1970, Ward proposed infusion of donor antibodies to explain TRALI. Popovsky and Moore confirmed this in 1985. 89% of cases had donor antibodies to granulocytes
and 72% were antibodies to Human leukocyte antigens (HLA). Most granulocyte antibodies did not exhibit specificity,
but 59% of HLA class I antibodies did. 10% of cases involved binding of recipient
antibodies to cognate antigens on transfused donor granulocytes.
Infusion of specific HLA antibodies has been confirmed in 50-60% of documented cases of TRALI.
This mechanism requires that antibodies bind to the cognate antigen in the host. Causes pulmonary sequestration and activation of
PMNs resulting in the release of cytotoxic agents, endothelial damage, capillary leak and ALI.
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Pathophysiology: Immune (antibody)-mediated TRALI
Dykes et al demonstrated a case in which a women underwent a lung transplant. Post transplant she was given two units of
packed red blood cells (PRBC’s). Became dyspneic, had marked hypoxia and
chest x-ray revealed a unilateral “white-out” of the transplanted lung. HLA-B44 antibodies were present in the donor
of the second unit of PRBC’s and the cognate antigen was present in the transplanted lung, but not in the uninvolved lung.
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Pathophysiology: Immune (antibody)-mediated TRALI
Animal models Ex vivo rabbit model
Infused a mixture of human PMN’s (HNA-3a (5b) positive), human HNA-3a antibodies and rabbit plasma for complement source . Pulmonary edema occurred within 3-6 hours post
infusion. However, if on of the 3 components were missing,
the lung pulmonary edema would not occur. Also they found if immunoglobulins with
indeterminate antigen specificity were infused with complement and human PMN’s, acute lung injury was not reported.
This study has been recently updated by Brux et al and demonstrates that using antigranulocyte antibodies and PMN’s that have cognate antigen does cause pulmonary edema without the addition of complement.
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Pathophysiology: Immune (antibody)-mediated TRALI
Constraints with HLA class I and granulocyte antibodies. 59% of immunoglobulin's identified
demonstrated antigen specificity. 50% of the implicated antibodies demonstrated
specificity for recipient antigens. Precise mechanism for immune (antibody)-
mediated TRALI is not know. Antibodies have been transfused into patients
with cognate antigen on their leukocytes and many did not acquire TRALI.
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Pathophysiology:
Immune (antibody)-mediated TRALI HLA class II antibodies have also been
implicated. Kopko et al and several other groups have
postulated that TRALI can also be caused by infusion of HLA class II antibodies that have specificity for HLA class II antigens in the recipient.
They have also found that these HLA class II antibodies could activate circulating monocytes that express these antigens which will cause the synthesis of Tumor necrosis Factor – α (TNF-α), Interlukin -1β and tissue factor.
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Pathophysiology: Immune (antibody)-mediated TRALI
HLA class II antigens can be expressed on endothelial cells, especially after inflammatory stimuli. Researchers question if the infused HLA
class II antibodies into a recipient with cognate antigen expressed on their pulmonary endothelium will actually manifest in TRALI.
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Pathophysiology: Immune (antibody)-mediated TRALI
Constraints with HLA class II antibodies. Time delay for the production of the cytokines
by circulating monocytes (4 hours). Must have recognition of antibody to specific
antigen. Resting PMN’s do express HLA class II antigens at
a very low level, or not at all. Cytokine-activated PMN’s do express high levels
of HLA class II antigens.
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Pathophysiology: Non Immune (Two-event) model of TRALI
There are cases documented in which antibodies have not been detected, either in the recipient or the donor.
If infusion of specific anti-leukocyte antibodies is sufficient to cause TRALI, than blood from donors with specific antibodies against common leukocyte antigens should cause TRALI in recipients who express the cognate antigen.
“Look-back” study of donors who have high titer “TRALI-implicated” antibodies. HLA class I alone, HNA-3a, HLA class I and HLA
class II or HLA class II alone. 31
Pathophysiology: Non-Immune (two-event) model of TRALI
Two-event model was postulated First event: Condition of the patient. Second event: Is inherent in the blood
product. Biologic response modifiers
During storage you have accumulation of lipids. Lysophophatdylcholines accumulate in the
plasma portion. Reach maximal concentration on the day of the
components outdate.
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Pathophysiology: Non-Immune (two-event) model of TRALI
Two-event model Initially verified in an isolated perfused lung
model and then reconfirmed in an in vivo rat model. Infused with saline or endotoxin (LPS) as the
first event Infusion of plasma from stored PRBC’s or
antibodies (OX18 and OX27) against HLA class I antigens as second event.
Both the plasma and the antibodies directed against HLA class I antigens caused ALI.
In the saline injected rats neither the plasma from stored PRBC’s nor the antibodies caused ALI. Even if a high titer of monoclonal antibody was
used.
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Pathophysiology: Non-Immune (two-event) model of TRALI
Clinical studies supporting the two-event model. The first study identified 4 separate first
events. Active infection, recent surgery, cytokine therapy
and massive transfusion. These have been documented by others in both
antibody-mediated TRALI and TRALI caused by BMR’s.
Nested case control study also documented involved two patient groups that were at particular risk for TRALI. Those were cardiac surgery patients and those with
hematological malignancies in the induction phase of therapy.
The second event for the nested case control study was the infusion of bioactive lipids from the stored products.
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Pathophysiology: Non-Immune (two-event) model of TRALI
Two-event constraints PMNs need to be sequestered in the
pulmonary vasculature. “Healthy” patients who experience TRALI would
seem to disprove the two-event mechanism. Study of the PMNs from 5 “healthy” donors , by
history demonstrated that their PMNs were grossly primed.
Determined by the appearance and activity of these PMNs.
All these donors acquired infections (viral or bacterial) over the next 24 hours.
So the question remains, is someone who is receiving a transfusion considered healthy?
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Pathophysiology:
Autologous TRALI case No leukocyte antibodies were detected, but
there were measureable amounts of biologic response modifiers (BRMs) present.
Neutropenic patients Etiology is thought to involve the
transfusion of permeability agents. Vascular endothelial growth factor (VEGF) .
Effective permeability factor. Infusion of antibodies against HLA antigens.
Reside on the pulmonary endothelium. Endothelial shape change, and fenestration.
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Laboratory Work-up: Granulocyte immunofluorescence test (GIFT)
and granulocyte agglutination test (GAT) in combination is an effective approach for detecting PMN reactive antibodies in serum or plasma. Detect both HNA and HLA class I , but further
work is necessary for detection of HLA class II. If HNA antibodies are suspected than it is
necessary to include GAT. The combination of GIFT and GAT applied to a
panel of phenotyped PMNs allows identification of HNA antibody specificity.
These techniques are limited to reference laboratories in the Granulocyte Working Party (GWP) of the ISBT (www.isbt-web.org).
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Laboratory Work-up: HLA class I and class II antibody screening
methods are highly sensitive techniques . Will detect any antibodies in donor or recipient
sera that could be clinically important leading to graft rejection and/or graft versus host disease.
Because HLA antibody screening is widely available it is often the first step in many TRALI investigations. Reports have reveal that only a small number of
HLA class I antibodies actually induce TRALI. One questions the clinical relevance of all of the HLA
antibodies detected in TRALI. Current flow-based assays are so sensitive that a high
percentage of non-transfused males have demonstrated antibodies
Also flow-based assays used to detect HLA class II antigens are designed to detect very small amounts of antibodies and may overestimate the role of antibodies to HLA class II antigens in TRALI.
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Laboratory Work-up: Investigation of the cognate antigen.
It is important to do this, but there is great variability in how TRALI cross-matches are performed. Lymphocytotoxicity test (LCT), GIFT alone or GIFT
and GAT combination. LCT is based on stable and storable lymphocytes
which make them investigator friendly. Are not the primary target cell in TRALI and do not
express PMN-specific antigens (HNA1-2) so will not detect incompatibilities with these antigens.
Must interpret the results of this test, if done alone, with these limitations in mind.
Confirmation of cognate antigen implies the donor antibody has a target or substrate to react with, but does NOT confirm the antibody contributed etiologically to the TRALI reaction. 39
Laboratory Work-up: Investigation of cognate antigen
Testing of associated donor serum/plasma with the recipient’s effector cells (PMNs). Should employ the incubation using both the GIFT
and GAT techniques. If the case involves the antibody being in the
recipient than the cross match should also test recipient serum/plasma with the donor’s PMNs. Especially for granulocyte transfusions.
PMN cross-match is very valuable. Positive cross-match or incompatibilities provide in
vitro evidence of a reaction between recipient PMNs and associated donor serum/plasma antibodies.
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Laboratory Work-up:
Important points to consider In determining if an donor antibody did cause
TRALI a few points need to be considered and should continued to be researched. Method of detection Antibody titer Epitope specificity Antibody isotype Ability to prime PMN’s that express cognate
antigen. This detailed antibody information may shed
more light on the role of allo-antibodies in the TRALI mechanism.
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Laboratory Work-up:
Investigation of BRMs Very few laboratories world wide.
Research Department at Bonfils Blood Center, Denver, CO and Australian Red Cross Blood Service, Brisbane, Australia. Have their inherent quirks and require
trained personnel, but are not difficult assays to perform.
Usually you test samples as part of their research endeavors. If priming activity is found, further
identification is required including lipid identification or measurement of chemokines by commercial ELISA. 42
TRALI Prevention Blood product manipulation
Washing of cellular blood products does remove all of the implicated mediators in TRALI. Located in the plasma portion.
Expensive, time consuming and time constraints for critically ill patients may not allow for the time to remove the plasma from stored cellular components.
For scheduled surgical procedures this may be an option.
In some cases decreases in plasma in the cellular blood products has been tried but in a number of TRALI cases only small amounts of plasma are required.
Pre-storage leukoreduction. Does decrease a number of leukocyte and platelet
derived mediators it was NOT effective in inhibiting BRM-mediated TRALI in vivo.
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TRALI Prevention: Blood product manipulation
Solvent-detergent plasma (SDP) Manufactured from enormous pools of plasma in
which leukocyte antibodies are thought to be diluted and neutralized during processing, and cellular fragments are removed during the filtration. No cases of TRALI have been reported in Norway since
the use of SDP. The use of fresher products
Used for high risk patients who are not neutropenic. PRBCs for less than 14 days and platelet
concentrates for less than 2 days may avert the BRMs.
Donor selection Male predominant plasma.
Great Britain has had a significant decrease in the total cases of TRALI, particularly in the cases of fatal TRALI.
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TRALI Prevention: Donor Selection
Male predominant plasma. Disqualification of multiparous females.
Plasma from females has not been disproportionately implicated .
Most data does not support the disqualification of multiparous females. May be disastrous to blood centers where 20-30% of
the donor pool comes from these females. Disqualification of donors implicated in
TRALI. American Association of Blood Banks (AABB)
advocates this until antibody testing can be completed. If have antibodies to high frequency leukocyte
antigens HNA-3a, HLA-A2, HLA-B12. Disqualify from plasma
and platelet donation.
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TRALI Prevention: Donor selection
Disqualification of donors implicated in TRALI. AABB recommendations
If antibody testing comes back negative Reinstate donor.
Questions that remain What is the expense of testing donor s
implicated in TRALI? Who will pay? What will the effect of deferring all donors in a whole blood platelet pool and the cost of testing all of them be? Multi-institutional prospective studies will
help to answer these and many other questions that exist.
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TRALI Prevention:
Donor selection Rapid methods of screening for donor
HLA and HNA antibodies appears pertinent, especially for apheresis donors. Cost and time required is not insignificant
and many of the assays employed have a level of sensitivity related to organ transplantation and have not been validated for Transfusion Medicine. Also, HNA antibody testing is a major hurdle
since there are currently no mass screening technology available. 47
TRALI Prevention:
Decreasing blood usage This will likely diminish the cases o f
TRALI. There are a number of unpleasant clinical
outcomes related to transfusion and these must be considered to maximize patient outcome especially for the critically ill patients that require transfusions.
Apply consistent transfusion guidelines. Decreases unnecessary transfusions and
the morbidity associated with needless exposure to blood products. 48
Conclusion Transfusion-related acute lung injury
Causes Passive infusion of antibodies against recipient
leukocytes. Infusion of biological response modifiers (BRMs). Infusion of permeability factors.
Single event antibody mediated mechanism Reasonable but questions still remain.
Occurs without the infusion of specific antibodies against recipient leukocytes.
Does not occur when we have an antibody infused in a patient known to have the cognate antigen.
Two-event mechanism Activation of pulmonary endothelium.
Sequestration of PMN. Activation of those primed sequestered PMN’s.
Endothelial damage, capillary leak and ALI.49
Conclusion:
Transfusion-related acute lung injury Variety of testing options to determine
TRALI after the initial reaction. Necessary to confirm the presence of an
antibody and cognate antigen. Blood product manipulation and donor
selections. Many options are available, you need to
chose what will work best in your institution.
Obviously having a consistent transfusion guideline will help decrease the amount of needless transfusions and exposure to many adverse transfusion reactions.
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References1. Haji AG, Sharma S, Vijaykumar DK, Paul J. Transfusion-
related acute lung injury presenting with acute dyspnea: A case report. J. med Case Reports 2008; 2:336-341.
2. Erol DD, Ahinel L. Transfusion-related acute lung injury (TRALI) in a multipara patient. The Internet Journal of Anesthesiology 2005; 9(2). Available from: http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ija/vol9n2/trali.xml
3. Peacock WF. The evolving role of BNP in the diagnosis and treatment of CHF: A summary of the BNP consensus panel report. A summary for emergency physicians. Emergency Medicine Cardiac Research and Education Group 2005; January; 1. Available from: http://www.emcreg.org/pdf/monographs/BNP05n.pdf
4. Seeger W, Schneider U, Kreusler B, von Witzleben E, Walmrath D, Grimminger F, et al. Reproduction of transfusion-related acute lung injury in an ex vivo lung model. Blood 1990;76(7):1438-44.
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References Continued
5. Paxton A. Catching, tracking and tackling TRALI. CAP Today, 2007. Oct. Available from: http://www.cap.org
6. Silliman CC, McLaughlin NJD. Transfusion-related acute lung injury. Blood Reviews 2006; 20: 139-159
7. Dennison CA. Transfusion-related acute lung injury. A clinical challenge. Dimens Crit Care Nurs . 2008 Jan/Feb; 27 (1):1-7.
8. Triulzi D. Transfusion-related acute lung injury: an update. Hematology Am Soc Hematol Educ Program.2006:497-501
9. Silliman CC, Ambruso DR, Boshkov LK. Transfusion-related acute lung injury. Blood 2005; 105(6): 2266-2272.
10. Seeger W, Schneider U, Kruesler B, von Witzleben E, Walmrath D, Grimminger F, et al. Reproduction of transfusion-related acute lung injury in an ex vivo lung model. Blood 1990; 76(7):1438-44.
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References Continued
11. Achar SA, Kundu S, Norcross WA. Diagnosis of acute coronary syndrome. Am Fam Physician. 2005 Jul 1; 72 (1):119-26.
12. Skeate RC, Eastlund T. Distinguishing between transfusion related acute lung injury and transfusion associated circulatory overload. Curr Opin Hematol. 2007 Nov;14(6):682-7.
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