Transfusion Reactions:

Melissa R. George, D.O., F.C.A.P.

Medical Director, Transfusion Medicine & Apheresis

Penn State Milton S. Hershey Medical Center

Office: HG069, Phone: 717-531-4627

E-mail: mgeorge5@hmc.psu.edu

Disclosures

• Novartis Medical Advisory Board Member, May 2013- May 2014.

Overview

Serious

• Acute hemolytic

• Delayed hemolytic

• Anaphylactic

• Transfusion Associated Circulatory Overload (TACO)

• Transfusion Related Acute Lung Injury (TRALI)

• Bacterial contamination

Uncomfortable, not serious

• Allergic/anaphylactoid

• Febrile non-hemolytic

• Hypotensive

Scenario

• Your pager goes off at 2 AM. You see that the call is coming from the blood bank.

• You return the call and are presented with the following information:

– Mr. Smith had a transfusion reaction, 150 mL into a platelet transfusion he developed a fever of 38.5°C and chills, no other S & S

• What should you do?

The serious

• Acute hemolytic transfusion reactions (AHTR)

• Delayed hemolytic transfusion reactions (DHTR)

• Anaphylaxis

• Transfusion Associated Circulatory Overload (TACO)

• Transfusion Related Acute Lung Injury (TRALI)

• Bacterial Contamination

Acute Hemolytic Transfusion Reactions (AHTR)

Acute Hemolytic Transfusion Reactions (AHTR)

• Pathophysiology: Mostly ABO incompatibility: mislabeled blood sample or improper patient identification

– Intravascular hemolysis

– Naturally occurring IgM ABO antibodies

– RBC stroma activates cascades: bradykinin, inflammation, coagulation, etc.

• Incidence: ~1 in 100,000 transfusions

• Significance: Up to 60% fatal

AHTR recognition

• Timing: Happens within 10-15 minutes

• S & S: fever, chills, nausea/vomiting, flank & abdominal pain, headache, dyspnea, hypotension, tachycardia

• Labs: DAT positive, urine hemosiderin later

Delayed Hemolytic Transfusion Reaction (DHTR)

Image used with permission of Stephanie Griggs, Brand and Sales Coordinator, Mr Men Little Miss

LITTLE MISS LATE

Delayed Hemolytic Transfusion Reactions (DHTR)

• Pathophysiology: – Antigens other than ABO

– Extravascular hemolysis

– Alloantibody (IgG) stimulated by prior exposure • Undetectable or missed pre-transfusion

• Anamnestic response

• Incidence: 1 in 7,000 transfusions

• Significance: Fatality rare

Extravascular Hemolysis

Scanning electron micrograph - reaction

of phagocyte to antibody-coated red cell

1-Phase contrast photomicrograph - interaction

of antibody-coated red cell and phagocyte

3-Separation of internal and external portions of red

cell; the external portion of red cell circulates as spherocyte2-Further interaction of phagocyte and antibody-coated cell

resulting in internalization of portion of red cell

Images from Petz LD and Garratty G; Immune Hemolytic Anemias, second edition: 2004; 145

Scanning electron micrograph

Slide courtesy of Dr. Saleh Ayache

DHTR Recognition

• Timing: Hours to days after transfusion

• S & S: Typically patient feels fine

• Labs: Positive DAT, drops in H & H

Anaphylaxis

License agreement to use image through Condé Nast Cartoon Bank 3-6-14

Anaphylaxis

• Pathophysiology: Anaphylatoxins produce secondary mediators, complement activation

• Incidence: Uncommon, 1:20-50,000 transfusions

• Significance: May be fatal

Anaphylaxis Recognition

• Timing: Usually early onset, minutes

• S & S: Hypotension, edema, dyspnea, stridor, wheezing, cramping, diarrhea, shock, loss of consciousness

• No fever or chills

• Labs: Anti-IgA reported (uncommon), DAT negative

Anaphylaxis Reaction Prevention

• IgA deficiency with anti-IgA: frozen, washed RBCs or blood from IgA deficient donor (only option for plasma based products)

• Steroid premedication unproven

• Recurrence not predictable

No

TACO

¡No quiero TACO!

Microsoft clip art

Transfusion Associated Circulatory Overload (TACO)

• Pathophysiology: Rapid intravascular volume expansion, depends on rate/volume of transfusion

• Common in infants and elderly

• Incidence: 1 in 350-5,000 reported

• Significance: Same as CHF, can be fatal

TACO Recognition

• Timing: Variable, depending on other fluids given

• S & S: Dyspnea, orthopnea, cyanosis, cough, JVD, CHF, tachycardia, hypertension, headache, responds to diuresis

• Labs: Elevated BNP

• Treat like CHF, space transfusions over time

Transfusion Related Acute Lung Injury (TRALI)

TRALI

Donor factors: Anti-HLA antibodies in plasma

Chemokines released during product storage

Recipient’s underlying disease state

Chest x-ray image from Peter Maslak, ASH Image Bank 2011; 2011-3672

Recruitment of neutrophils in small vessels of lung infiltrates

TRALI

• Incidence: ??? 1 in 1,300 to 190,000

• Significance: Usually resolves, but can be fatal

TRALI Recognition

• Timing: Later in transfusion, usually high plasma content products rather than pRBC

• S & S: Dyspnea, pulmonary edema/ new infiltrates, cyanosis, tachycardia, chills, hypotension, does not respond to diuresis

• Labs: DAT negative, antibody testing of donor and antigen testing of recipient

• Diuretics worsen condition, supportive care

TRALI Prevention

• Use of male-only plasma for transfusion

• Deferral of donors with anti-HLA/HNA antibodies

• New AABB guidance will close loopholes for AB plasma and impact inventory

TACO TRALI

Clinical history Underlying cardiac dysfunction, + fluid balance

No underlying cardiac condition

Physical exam Sudden elevation of BP, JVP, wheezing

Hypotension

Chest x-ray B/L infiltrates/pulmonary edema Cardiomegaly with increased vascular pedical width

B/L infiltrates/pulmonary edema

ECHO Systolic or diastolic dysfunction (EF<45%)

Could be normal

Labs Increased BNP Pulmonary edema albumin / plasma albumin >0.55 Short-lived, sudden drop in neutrophil count

Response to diuretics

Rapid improvement No response

Bacterial Contamination

Wikimedia Commons- General Permission to Use Image

Bacterial Contamination

• Pathophysiology: Sepsis

– Platelet: skin flora, Salmonellae sp.

– RBC: psychrophilic, esp. Y. enterocolytica

• Incidence: Had been common in past with platelets (1 in 3,000 platelet transfusions)

• Significance:

– With platelet transfusion, 25% fatal

– Rare in RBC units, ~75% fatal

Bacterial Contamination

• Older platelets ( >5 days) had log phase growth

• Asymptomatic donor bacteremia and skin plugs retrograde into product

• All platelets now screened/cultured

– Also, first blood in draw diverted

Bacterial Contamination

• Timing: Late onset, may occur hours after transfusion

• S & S: Hypotension, fever, chills, headache, back/flank pain, dyspnea, abdominal pain, oliguria, coagulopathy, endotoxic shock

• Labs: Culture patient, Quarantine unit for possible culture

Uncomfortable but not serious

• Febrile Non-Hemolytic Transfusion Reactions

• Allergic Reactions

• Acute Hypotensive Reactions

Febrile Nonhemolytic Transfusion Reactions (FNHTR)

Febrile Nonhemolytic Transfusion Reactions (FNHTR)

• Pathophysiology: Donor derived cytokines, non-recurrent (product dependent) OR patient WBC antibodies, recurrent (patient dependent)

• Incidence: Had been most common

– 1% of RBC transfusions

– 30% of platelet transfusions

– Decreasing with leukoreduction

• Significance: Uncomfortable but not fatal

FNHTR Recognition

• Timing: Usually toward the end of transfusion or within short time of completion

• S & S: Rise in temperature > 1 °C*, other sx overlap with AHTR namely chills, rigors, headache, nausea, vomiting, hypertension, tachycardia, dyspnea

• Labs: DAT negative

* Can be masked by premedication

Allergic Reactions

Permission to use this cartoon granted via e-mail by Aaron Schaff, Inkjot Comics

Allergic Reactions

• Pathophysiology: Allergens mainly in plasma

• Incidence: Most common, 1-3 % of transfusions, serious recurrences uncommon

• Significance: Annoying but not usually serious

Allergic Reaction Recognition

• Timing: Usually early in transfusion

• S & S: Pruritus, erythema, urticaria localized to IV site, may become systemic, bronchospasm

• Labs: DAT negative

* Can restart transfusion if symptoms are mild and resolve

Acute Hypotensive Reactions

Acute Hypotensive Reactions

• Pathophysiology: ACE inhibitors often associated

– Multiple factors create risk

• Genetic variability in BK metabolism

• Negatively charged filters

• Contact system activation in product

• BK receptor induction

• Incidence: ???

• Significance: Recovery generally rapid

Acute Hypotensive Reactions

• Timing: Rapid onset (minutes)

• S & S: Hypotension, lightheadedness, anxiety

– Rarely nausea, dyspnea, flushing, hives

– No fever, chills, wheezing, edema

– Rapid recovery once transfusion stopped

• Labs: DAT negative

Summary

• Signs and symptoms of TRs can overlap, so even simple, allergic reactions should be reported

• Most “transfusion reactions” are actually due to underlying disease