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1/29/2018
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Continuing Education Webinar Series
All Content © 2015 Immucor, Inc.
February 7 Conquering the Prozone Effect
February 14 Detecting HLA Antibodies: We’re NOT the Chemistry Lab
February 28 Proficiency, Competency, and QC: A practical approach to CLIArequirements and AABB, CAP, and Joint Commission Expectations
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Link to register: https://immucor.webinato.com/register
All Content © 2015 Immucor, Inc.All Content © 2015 Immucor, Inc.All Content © 2015 Immucor, Inc.
Continuing Education
• ABHI, PACE, Florida and California DHS
• 1.0 Contact Hours
• Each attendee must register to receive CE at:https://www.surveymonkey.com/r/TxnRxnWebinar
• Registration deadline is February 16, 2018
• Certificates will be sent via email only to those who have registered by March 2, 2018
1/29/2018
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Transfusion Reactions: What? How? What now?Margo Rollins, MD
Assistant Professor of Pathology
Emory University SOM
Assistant Medical Director for Tissue, Transfusion & Apheresis
Children’s Healthcare of Atlanta
Immucor Webinar Series
January 26, 2018
Children’s Healthcare of Atlanta | Emory University
Disclosures
• None
Children’s Healthcare of Atlanta | Emory University
Objectives
• Define and categorize transfusion reactions
• Describe clinical manifestations of specific transfusion reactions
• Discuss patient evaluation and management when transfusion reaction is suspected
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Children’s Healthcare of Atlanta | Emory University
Background
• Blood transfusions are one of the most common procedures for hospitalized pts
• Transfusion reactions are the most frequent adverse event associated with the administration of blood products
• A transfusion reaction can lead to severe discomfort for the patient and extra cost burden to the health‐care system
• Although rare, reactions can be fatal‐ 1: 200,000–420,000 units associated with death
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
Background
https://patientsafety.aabb.org/NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Transfusion Reactions and Prevalence
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
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Children’s Healthcare of Atlanta | Emory University
Hillyer, Shaz, Zimring, Abshire. Transfusion Medicine and Hemostasis, 2009
Transfusion Risks Over Time
Children’s Healthcare of Atlanta | Emory University
Technical Definition of Transfusion Reactions
• Each CDC‐defined transfusion‐associated adverse reaction must be classified according to:– Reaction‐specific case definition
– Severity
– Imputability
• Surveillance definitions are distinctly different from clinical definitions – Designed to capture data consistently and reliably in order to identify trends and inform quality improvement practices
– Not intended as clinical diagnostic criteria or to provide treatment guidance
https://patientsafety.aabb.org/NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Technical Definition of Transfusion Reactions
https://patientsafety.aabb.org/content/public-docs/linkedcontent/AABB-Center-for-Patient-Safety-Double-sided-Flyer.pdf
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Children’s Healthcare of Atlanta | Emory University
General Management Rules
• Transfusion reactions are usually reported to the physician by the nurse administering the blood product and often cause a change in vital signs or a new symptom
• Depending on the severity, the main treatment strategy for all reaction types is:– STOP the transfusion and keep the intravenous line open with
normal isotonic saline– Start supportive care to address the patient’s cardiac,
respiratory, and renal functions as necessary– Provide symptomatic therapy
• The blood product labelling and patient identification should be rechecked to confirm that the patient received their intended product and the reaction should be reported to the blood transfusion laboratory for additional testing
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
Children’s Healthcare of Atlanta | Emory University
Allergic Transfusion Reaction (Mild)
• Occurs within 4hrs of cessation of transfusion
• Mild urticaria– Frequently associated with
platelet transfusions (302/100,000 platelet units).
– Hives, angioedema, pruritis, erythema, flushing
– NOT ASSOCIATED WITH VITAL SIGN CHANGES
– IgE response to soluble proteins in donor plasma, release histamine, leukotrienes, prostaglandins
• Cutaneous symptoms only)‐H₁ antihistamine
• Transfusion can be re‐started with the same unit at a slower rate if symptoms resolve
• Discontinue transfusion if :– Symptoms recur– Additional symptoms appear
beyond local cutaneous manifestations
Definition Management
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Anaphylactic Transfusion Reaction (Severe)
• Occurs within 4hrs of cessation of transfusion– Incidence 8/100,000 units
– Usually occurs during / shortly after cessation of transfusion
• Mucocutaneous symptoms in addition to respiratory and/or cardiovascular systems:– Hypotension, hypotonia, syncope
– Laryngeal (tightness in the throat, dysphagia, dysphonia, hoarseness, stridor) or pulmonary (dyspnea, cough, wheezing, bronchospasm, hypoxemia) symptoms
• PROMPT IM administration of epinephrine
• Supportive measures as clinically indicated
• Second‐line drugs:– H₁ antihistamine – Bronchodilators (β₂ adrenergic
agonist)– Glucocorticoids (IV)– H₂ antihistamine
• R/o serum protein deficiency (immunoglobulin A and haptoglobin)
Definition Management
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
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Children’s Healthcare of Atlanta | Emory University
Allergic Transfusion Reaction:Pre-medications• Previous mild allergic transfusion reaction:
– No evidence to support routine prophylaxis with antihistamines or glucocorticoids
• Previous moderate to severe allergic transfusion reaction:– Counselled about their diagnosis and needs for future
transfusion– Premedication with antihistamines – Plasma reduction:
• Centrifugation • Washing
– Platelets stored in additive solutions• Reduces incidence or decreases severity of future reactions
– Use of corticosteroids as premedication has not been studied but is used widely clinically
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Acute Hemolytic Transfusion Reaction (AHTR)
• During or within 24 hours of cessation of transfusion with new onset of the following:– Back/flank pain, renal failure
– Chills/rigors, fever
– DIC, oozing at IV site
– Hematuria (gross)
– Hypotension
– ↓ fibrinogen OR haptoglobin
– ↑ bilirubin OR LDH
– Hemoglobin‐emia/uria
– Spherocytes on blood film
– +DAT (anti‐IgG or anti‐C3)
– +Elution (Allo‐Abs present on the transfused RBCs)
• STOP THE TRANSFUSION IMMEDIATELY
• Post transfusion labs (CBCD, CMP, DAT, Urinalysis, Coags)
• Management is supportive
• No evidence exists for the use of any specific intervention after an ABO‐incompatible RBCtransfusion (case reports suggest use of RBCx or PLEX, IVIG, and complement‐inhibiting drugs)
Definition Management
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Acute Hemolytic Transfusion Reaction (AHTR)
• Two forms of AHTR:
– Immune‐mediated• Clinical findings and demonstration of serological incompatibility
• Result from infusion of RBCs that are incompatible with the pt’s anti‐A, anti‐B, or other RBC antibodies (Abs)
• Usually caused by failure of Pt identification at specimen collection or transfusion, and less commonly by infusion of incompatible plasma, usually from an apheresis platelet transfusion
– Non‐Immune‐mediated • Occur when RBCs are hemolyzed by factors other than Abs:
– Co‐administration of RBCs with incompatible crystalloid solution
– Incorrect storage of blood
– Use of malfunctioning or non‐validated administration systems
• Commonly responsible Abs: Rh, Kell, Duffy, Kidd, MNS, Diego Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
1/29/2018
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Children’s Healthcare of Atlanta | Emory University
Delayed Hemolytic Transfusion Reaction (DHTR)
• +DAT for Abs 24hrs‐ 28 days after cessation of transfusion
• + Elution with alloantibody present on the transfused RBC
• Newly‐identified RBC allo‐Abs in recipient serum
• Inadequate rise of post‐transfusion Hgb or rapid fall in Hgb back to pre‐transfusion levels
• Dark urine
• Jaundice (45–50%)
• Fever, chills
• Pain (chest, abdominal or back)
• Dyspnea
• Post transfusion labs (CBCD, CMP, DAT, Urinalysis, Coags)
• Management is supportive
• Most patients do not require treatment
• Additional transfusions to maintain desired hemoglobin
• RBCx to remove incompatible red cells
• Anti‐CD20 + steroids have been proposed for management in severe cases
Definition Management
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Delayed Hemolytic Transfusion Reaction (DHTR)
• Anamnestic immune response
– Commonly responsible Abs: Rh, Kell, Duffy, Kidd, MNS, Diego
– The recipient is unknowingly EXPOSED to RBCs that express foreign antigens
– Foreign antigen causes a rise in RBC Ab titers 24 h to 28 days after transfusion accompanied by clinical manifestations
• Incidence:– 1/2500 transfusions
– Rises to 11% in pts with sickle‐cell disease (SCD)
• Pts at risk:
– history of RBC Abs (pregnancy or transfusion exposure) ‐ Ab titer subsequently ↓ to levels undetectable by rou ne Ab detec on tes ng
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Special Note:Hyper-hemolysis in SCD
• RAREMainly caused by destruction of both donor AND recipient RBCs
– Exact mechanism is still not well understood
– Autologous RBC destruction is “bystander hemolysis”= sickled RBCs are destroyed by Abs without expressing the specific antigen against which this Ab is directed
– RBC destruction is associated with activation of Mφperipheral destruction
• Characterized by:– Severe anemia (Hgb lower than pre‐transfusion levels)
– Pain, Fever
– Signs of hemolysis (jaundice, ↑LDH, iBili, and hemoglobinuria)
– Reticulocytopenia Reticulocytosis
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
1/29/2018
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Children’s Healthcare of Atlanta | Emory University
Special Note:Hyper-hemolysis in SCD
• Classified into acute or delayed
– Acute: • Symptoms appear within seven days of receiving RBCs
• DAT generally negative
– Delayed:
• Usually appears seven days after a transfusion
• DAT results are usually positive
• New allo‐Abs can be detected in the pt's serum
• DO NOT TRANSFUSE unless life threatening exacerbation of hyper‐hemolysis
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
Children’s Healthcare of Atlanta | Emory University
Febrile Non Hemolytic Transfusion Reaction (FNHTR)
• Occurs during or within 4 hours of cessation of transfusion
• Fever > 38°C/100.4°F oral and a change of at least 1°C/1.8°F) from pre‐transfusion value
• Chills/rigors
• Transient HTN
• Antipyretics
• Lab testing:– DAT
– Visual check for grossly hemolyzed plasma
– Blood cultures from the patient and RBC unit if available
• Supportive management
Definition Management
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Febrile Non Hemolytic Transfusion Reaction (FNHTR)
• “Diagnosis of exclusion”
• Common‐ occurring 1% of transfusion episodes (1–3% per unit transfused)
• Caused by pro‐inflammatory cytokines or recipient Abs encountering donor antigen in the blood product
• Pre‐storage leukocyte reduction can prevent
• Premedication with antipyretics does not decrease rate of reactions in most pts and should be discouraged
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
1/29/2018
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Children’s Healthcare of Atlanta | Emory University
Hypotensive Transfusion Reaction
• HypoTN during or within 1 hrafter cessation of transfusion
– Adults (≥18 yo):
• ↓SBP ≥ 30 mmHg AND SBP ≤ 80 mmHg
– Children, adolescents (1 yo < 18yo):
• > 25% ↓ in SBP from baseline
– Neonates and small infants (< 1 yo OR any age and <12 kg):
• ≥ 25% ↓ in baseline measurement being recorded (MAP, BP)
• STOP transfusion immediately
• Supportive therapy
• No specific treatment is indicated HypoTN typically resolves once transfusion is discontinued
• The same unit should not be restarted
• No routine preventative measures have been identified other than not using bedside leucocyte reduction filters
Definition Management
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Hypotensive Transfusion Reaction
• Uncommon
• Thought to occur with activation of the intrinsic contact activation pathway of the coagulation cascade and generation of bradykinin and its active metabolite
• More likely to occur in patients who:
– Have hypertension
– Are taking angiotensin‐converting enzyme (ACE) inhibitors
– Are being transfused through a negatively charged bedside leukocyte reduction filter
– Undergoing apheresis
– Receiving plateletsDelaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Septic Transfusion Reaction
• During or within 4 hrs of cessation of transfusion
• Laboratory evidence of a pathogen in the transfusion recipient found in the transfused product
• STOP transfusion immediately
• Cultures on the pt and gram stain and culture of all units transfused (if possible)
• Supportive therapy
• Therapy directed antibiotics, anti‐parasitics or antiviral agents
• Inform the supplier IMMEDIATELY
Definition Management
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.
NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
1/29/2018
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Children’s Healthcare of Atlanta | Emory University
Septic Transfusion Reaction
• 58,000–75,000 transfusions/yr
• Bacterial contamination platelets > RBCs
– Platelet – 1/ 3000–5000 units
• Can be presumed in a culture‐negative patient with clinical sepsis if bacteria are isolated from the transfused unit
Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825-2836.NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Septic Transfusion Reactions: Transfusion Transmitted Pathogens
Updated from AuBuchon, Birkmeyer, Busch. Ann Intern Med 1997;127:904-9.
Children’s Healthcare of Atlanta | Emory University
Current Estimated Residual Risk of Some Transfusion-Transmittable Agents
HIV I/II 1:2,135,000 (ID-NAT)
HCV 1:1,930,000 (ID-NAT)
HBV 1:277,000 (ID-NAT)
HTLV-II 1:2,993,000
WNV 1:350,000
Malaria < 1:1,000,000-5,000,000
Bihl, Florian et al. “Transfusion-Transmitted Infections.” Journal of Translational Medicine 5 (2007): 25. PMC.
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Children’s Healthcare of Atlanta | Emory University
Clinically Significant Pathogens in Transfusion
NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
Children’s Healthcare of Atlanta | Emory University
Honorable Mention
• Transfusion Associated Circulatory Overload (TACO)
• Post‐Transfusion Purpura (PTP)
• Transfusion Associated Graft vs Host Disease (TA‐GvHD)
Children’s Healthcare of Atlanta | Emory University
Resources
• Delaney, M., et al. (2016). "Transfusion reactions: prevention, diagnosis, and treatment." The Lancet 388(10061): 2825‐2836.
• NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn
• http://www.aabb.org/research/hemovigilance
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Children’s Healthcare of Atlanta | Emory University
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Continuing Education
• ABHI, PACE, Florida and California DHS
• 1.0 Contact Hours
• Each attendee must register to receive CE at:https://www.surveymonkey.com/r/TxnRxnWebinar
• Registration deadline is February 16, 2018
• Certificates will be sent via email only to those who have registered by March 2, 2018
1/29/2018
13
All Content © 2015 Immucor, Inc.
February 7 Conquering the Prozone Effect
February 14 Detecting HLA Antibodies: We’re NOT the Chemistry Lab
February 28 Proficiency, Competency, and QC: A practical approach to CLIArequirements and AABB, CAP, and Joint Commission Expectations
Future Webinars
Link to register: https://immucor.webinato.com/register
All Content © 2015 Immucor, Inc.All Content © 2015 Immucor, Inc.All Content © 2015 Immucor, Inc.
Thank you!