Handouts Transfusion Reaction - Immucor, Inc. Program Handouts/TxnRxn...reported to the blood transfusion laboratory for additional testing Delaney, M., et al. (2016). "Transfusion

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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

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.

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


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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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


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Hillyer, Shaz, Zimring, Abshire. Transfusion Medicine and Hemostasis, 2009

Transfusion Risks Over Time


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


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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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



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


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)



NHSN Biovigilance Component Hemovigilance Module Surveillance Protocol v2.4 www.cdc.gov/nhsn

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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



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)





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.


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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





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



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


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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



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




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


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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





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.



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




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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



Septic Transfusion Reactions: Transfusion Transmitted Pathogens

Updated from AuBuchon, Birkmeyer, Busch. Ann Intern Med 1997;127:904-9.


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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Clinically Significant Pathogens in Transfusion



Honorable Mention

• Transfusion Associated Circulatory Overload (TACO)

• Post‐Transfusion Purpura (PTP)

• Transfusion Associated Graft vs Host Disease (TA‐GvHD)


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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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


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!

Documents

Handouts Transfusion Reaction - Immucor, Inc. Program Handouts/TxnRxn...reported to the blood transfusion laboratory for additional testing Delaney, M., et al. (2016). "Transfusion