Transfusion-related acute lung injury

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Transfusion-related acute lung injury

• Presented by Intern ???
• Intern ???

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Transfusion-related acute lung injury

• Case report
• Med Sci Monit, 2005 11(5) CS19-22
• Transfusion-related acute lung injury
• a literature review
• Anaesthesia, 2006, 61, pages 777785

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Case report (I)

• 56-year-old woman
• She had undergone a low anterior resection in
  2002 because of a Dukes stage D adenocarcinoma
  of the rectum.
• In June 2003 she was referred to our department,
  presenting symptoms and signs of ileus.

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Case report (II)

• Abdominal radiograph revealed multiple air-fluid
  levels, while a computed tomography scan showed
  disease dissemination.
• Colonoscopic control verified recurrent disease
  in the anastomotic area.
• At surgery, a palliative loop ostomy was
  generated.

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Case report (III)

• In the 4th postoperative day it was decided that
  one unit of pRBCs be transfused (Hb 7.6 g/dL).
• Within 35 minutes of the onset of transfusion,
  and having received 40 ml of RBCs, she
  experienced sudden onset of respiratory distress,
  dyspnea, severe hypoxemia (SpO2 lt70), a rise in
  body temperature from 37.2C to 38.4C,
  shivering, tachycardia (120/min), and
  hypertension (190/120 mmHg).

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Case report (IV)

• She underwent chest radiograph within the first 8
  h of the episode.

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Case report (V)

• After cardiac catheterization, the patients
  cardiac pressures were normal and a
  transesophageal echocardiogram showed normal
  function, with no evidence of left ventricular
  failure or volume overload.
• A clinical diagnosis of a non-cardiogenic
  pulmonary edema was made.

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Case report (VI)

• Hemodynamic stabilization and resuscitation
  required diuretics and a high concentration of
  inspired oxygen in combination with
  bronchodilators.
• Clinical improvement occurred 12 hours later.

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Case report (VII)

• Full recovery of the syndrome was observed in 6
  days, while chest X-ray returned to normal
  findings within 4 days.

4 days after transfusion
8 hrs after transfusion
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Transfusion-related acute lung injuryN. A.
Barrett and P. C. A. KamAnaesthesia, 2006, 61,
pages 777785
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Transfusion-related acute lung injury

• Introduction
• Definition
• Incidence
• Aetiology
• Pathology
• Clinical manifestations

• Diagnosis
• Management
• Prognosis
• Prevention
• Conclusion

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Introduction (I)

• Transfusion-related acute lung injury (TRALI) is
  a serious and potentially fatal complication of
  transfusion of blood and blood components.
• The United States Food and Drug Administration
  (FDA) currently estimates it to be the leading
  cause of transfusion-related mortality.

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Introduction (II)

• TRALI is under-diagnosed and under-reported
  because of a lack of awareness.
• Despite the fact that it is estimated to be the
  leading cause of transfusion-associated death,
  little research towards optimising management
  strategies has been undertaken because it is a
  relatively rare condition.

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Definition (I)

• Respiratory complications following blood
  transfusion that resemble the syndrome of TRALI
  have been reported since the 1950s.
• The term transfusion-related acute lung injury
  was proposed in 1983 by Popovsky to refer to
  pulmonary edema complicating blood transfusion.

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Definition (II)

• A definition emerged from the TRALI consensus
  conference in 2004 and from the US National
  Heart, Lung and Blood Institute.
• Acute lung injury (ALI) is defined by the the
  American-European Consensus Committee (AECC) as a
  syndrome based on clinical and radiological
  findings rather than a pathological or a
  pathophysiological diagnosis.

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Definition (III)

• The AECC definition of ALI is characterised by
• Acute onset
• Hypoxemia (PaO2 / FiO2 300 mmHg at sea level
  regardless of level of positive end-expiratory
  pressure or SpO2 lt 90 on room air)
• Bilateral pulmonary infiltrates on the frontal
  chest
• radiograph
• No clinical evidence of left atrial-hypertension
  or circulatory overload

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Definition (IV)

• Risk factors associated with the development of
  ALI include increased age, ethanol or tobacco
  abuse, severe illness, and the presence of the
  variant surfactant B Gene.

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Definition (V)

• For a diagnosis of TRALI to be made there must be
  no pre-existing ALI before transfusion, the onset
  of signs and symptoms must occur during or within
  6 h of transfusion and there must be no temporal
  relationship to an alternative risk factor for
  ALI.

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Definition (VI)

• If both transfusion and another cause for ALI are
  temporally related, the consensus conference
  recommended that the term possible TRALI be
  used in these cases.

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Incidence (I)

• Estimates of the incidence of TRALI include
• 1 in 5000 blood and blood components transfused
• 1 in 2000 plasma-containing components
• 1 in 7900 units of fresh frozen plasma
• 1 in 432 units of whole blood-derived platelet
  concentrates
• 1 in 1323 blood components transfused

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Incidence (II)

• The FDA estimated that TRALI is the leading cause
  of transfusion-related death in the US.
• TRALI was a leading cause of transfusion-related
  morbidity and mortality in the UK.
• The French haemovigilance network reported that
  15 of transfusion related fatalities were caused
  by TRALI.
• In Germany, 101 out of 765 cases associated with
  complications of blood transfusion that were not
  related to infections were caused by TRALI.

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Aetiology

• The antibody-mediated model
• The two-event (biologically active mediator)
  model
• Combined model

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The antibody-mediated model (I)

• The antibody-mediated model postulates that the
  reaction is secondary to antibodies in donor
  plasma against antigens present on the
  recipients leucocytes.
• These may be antibodies to the human leucocyte
  antigen (HLA) or to other leucocyte antigens.

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The antibody-mediated model (II)

• HLA antibodies may be directed against either HLA
  class I antigens that are present in all
  leucocytes or HLA class II antigens found on B
  lymphocytes and monocytes or infusion of donor
  leucocytes into a recipient whose antibodies are
  directed against these donor leucocytes.

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The antibody-mediated model (III)

• The antibodyantigen interaction causes
  complement activation, resulting in the pulmonary
  sequestration and activation of neutrophils,
  endothelial cell damage and a capillary leak
  syndrome in the lungs leading to TRALI.

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The antibody-mediated model (IV)

• Rabbit and rat models for antibody-mediated TRALI
  have been developed.
• This study demonstrated granulocyte sequestration
  within the pulmonary capillaries, extravasation
  of granulocytes into the alveoli and pulmonary
  edema with proteinaceous material in the alveoli.

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The antibody-mediated model (V)

• Clinical studies of patients who experienced
  TRALI have demonstrated the presence of either
  anti-HLA or anti-granulocyte antibodies in donor
  plasma.
• Several look-back studies followed up
  recipients of blood components from a donor
  implicated in a TRALI reaction to determine the
  risk associated with subsequent transfusions from
  such donors.

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The antibody-mediated model (VI)

• These look-back studies demonstrated that
  single donors could cause TRALI reactions in more
  than one patient, lending support for the
  antibody-mediated hypothesis.
• However, blood containing anti-leucocyte
  antibodies may be transfused without causing
  TRALI, indicating that the antibody alone is
  insufficient to cause the syndrome.

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The antibody-mediated model (VII)

• There is also evidence that TRALI is commoner in
  recipients of blood products from multiparous
  donors who are more likely to possess anti-HLA
  and anti-HNA antibodies.

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The two-event model (I)

• The first event is the clinical condition of the
  patient, resulting in pulmonary endothelial
  activation and neutrophil sequestration.
• The second event is the transfusion of
  biologically active mediators (lipids,
  anti-granulocyte antibodies) that activate
  adherent neutrophils leading to endothelial
  damage, capillary leak and TRALI.

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The two-event model (II)

• The first event can be caused by a variety of
  insults to the pulmonary vascular endothelium
  such as sepsis, cardiopulmonary bypass,
  haematological malignancy, thermal injury and
  trauma.

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The two-event model (III)

• Isolated rat lung model
• Non-cardiogenic pulmonary edema developed
  after the pulmonary vasculature was primed by
  lipo-polysaccharide with subsequent infusion of
  supernatant from 42-day-old red cell concentrates
  and from 5-day-old platelet concentrates.

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Combined model

• They suggested that TRALI occurred in patients
  when the pulmonary vascular bed was primed by
  sepsis, trauma or transfusion followed by the
  activation of primed neutrophils by either
  biologically active mediators or by
  anti-granulocyte antibodies leading to pulmonary
  vascular endothelial damage.

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Pathology

• Dilation of pulmonary capillaries
• - Sequestration of granulocytes within the
  capillaries
• - Extravasation of granulocytes into the
  alveoli
• - Interstitial and intra-alveolar edema
• - Presence of proteinaceous material

Blood, Vol. 105, Issue 6, 2266-2273
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Clinical manifestations and diagnosis

• Common symptoms and signs
• - progressive dyspnea
• - tachypnea
• - frothy sputum
• - hypoxemia
• - hypotension or (rarely) hypertension
• CXR
• - Bilateral pulmonary infiltrates
• - Without cardiogenic pulmonary edema

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Clinical manifestations and diagnosis

• Criteria for the diagnosis of TRALI AECC
• 1. ALI as evidenced by
• - acute onset of S/S
• - hypoxemia
• - bilateral infiltrates on CXR w/o
  cardiomegaly
• - no clinical evidence of left atrial
  hypertension
• 2. no preexisting ALI before transfusion
• 3. within 6 h of transfusion
• 4. no temporal relationship with an
• alternative risk factor for ALI

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Clinical manifestations and diagnosis

• Laboratory
• - no specific markers
• Neutropenia, antileucocyte AbAg pairs
• ? support the diagnosis
• high protein in pulmonary edema fluid
• ? D/D

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Management

• Supportive
• Ceasing transfusion immediately
• Respiratory support -- varying
• Hemodynamic support required
• Diuretics and Corticosteroids -- unproven

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Prognosis

• Most patients recover within 4896 h
• Hypoxemia and CXR change can persist for 7 days
• Mortality 510

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Prevention

• To limit the transfusion of blood products using

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• A multicenter, randomised, controlled clinical
  trial of transfusion requirements in critical
  care (NEJM 1999 340 40917.)

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Prevention

• For pre-operative strategies
• - Dietary supplements or erythropoietin
• - Prevention of hypothermia
• - Antifibrinolytic drugs

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Prevention

• British Committee for Standard in Hematology
• Red cell transfusion
• British Journal of Hematology 2001 113 2431
• FFP transfusion
• British Journal of Haematology 2003 122 1023
• Platelet transfusion
• British Journal of Haematology 2004 126 1128

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Prevention

• To donors
• - permanently disqualified?
• Multiparous donors
• - More likely to possess antileucocyte
  antibodies
• - Higher incidence of TRALI

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Prevention

• Shorter periods of blood product storage
• No evidence support

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Conclusion

• TRALI presenting as a spectrum
• largely unrecognized

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Complications of Blood Transfusion

• IMMUNE COMPLICATIONS
• Hemolytic reactions
• Acute vs. delayed
• Nonhemolytic reactions
• Febrile reactions
• Urticarial reactions
• Anaphylactic reactions
• TRALI (noncardiogenic pulmonary edema)
• Graft-versus-host disease
• Posttransfusion purpura
• Immune supression
• INFECTIOUS COMPLICATIONS
• MASSIVE BLOOD TRANSFUSION

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A Woman Who Developed Acute Pulmonary Edema
During Operation -- A Case Report

• By R2 ???
• August 2002

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(No Transcript)
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Differential Diagnosis

• Transfusion-associated circulatory overload
• Anaphylactic transfusion reactions
• Transfusion-related bacterial sepsis
• Immediate hemolytic transfusion reaction

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Final Thought
The disgnosis of TRALI should be considered in
all cases of respiratory distress with
significant hypoxemia temporally related to a
transfusion and should satisfy the criteria for
diagnosis of ALI.
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Thanks for Your Attention