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1 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:

2 Disclosures Novartis Medical Advisory Board Member, May May 2014.

3 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

4 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?

5 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

6 Acute Hemolytic Transfusion Reactions (AHTR)

7 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

8 AHTR recognition Timing: Happens within minutes S & S: fever, chills, nausea/vomiting, flank & abdominal pain, headache, dyspnea, hypotension, tachycardia Labs: DAT positive, urine hemosiderin later

9 Delayed Hemolytic Transfusion Reaction (DHTR) LITTLE MISS LATE Image used with permission of Stephanie Griggs, Brand and Sales Coordinator, Mr Men Little Miss

10 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

11 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 Scanning electron micrograph 2-Further interaction of phagocyte and antibody-coated cell resulting in internalization of portion of red cell 3-Separation of internal and external portions of red cell; the external portion of red cell circulates as spherocyte Slide courtesy of Dr. Saleh Ayache Images from Petz LD and Garratty G; Immune Hemolytic Anemias, second edition: 2004; 145

12 DHTR Recognition Timing: Hours to days after transfusion S & S: Typically patient feels fine Labs: Positive DAT, drops in H & H

13 Anaphylaxis License agreement to use image through Condé Nast Cartoon Bank

14 Anaphylaxis Pathophysiology: Anaphylatoxins produce secondary mediators, complement activation Incidence: Uncommon, 1:20-50,000 transfusions Significance: May be fatal

15 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

16 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

17 No No quiero TACO! TACO Microsoft clip art

18 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

19 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

20 Transfusion Related Acute Lung Injury (TRALI)

21 TRALI Donor factors: Anti-HLA antibodies in plasma Chemokines released during product storage Recruitment of neutrophils in small vessels of lung infiltrates Recipient s underlying disease state Chest x-ray image from Peter Maslak, ASH Image Bank 2011;

22 TRALI Incidence:??? 1 in 1,300 to 190,000 Significance: Usually resolves, but can be fatal

23 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

24 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

25 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 ECHO B/L infiltrates/pulmonary edema Cardiomegaly with increased vascular pedical width Systolic or diastolic dysfunction (EF<45%) B/L infiltrates/pulmonary edema 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

26 Bacterial Contamination Wikimedia Commons- General Permission to Use Image

27 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

28 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

29 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

30 Uncomfortable but not serious Febrile Non-Hemolytic Transfusion Reactions Allergic Reactions Acute Hypotensive Reactions

31 Febrile Nonhemolytic Transfusion Reactions (FNHTR)

32 Febrile Nonhemolytic Transfusion Reactions (FNHTR) Pathophysiology: Donor derived cytokines, nonrecurrent (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

33 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

34 Allergic Reactions Permission to use this cartoon granted via by Aaron Schaff, Inkjot Comics

35 Allergic Reactions Pathophysiology: Allergens mainly in plasma Incidence: Most common, 1-3 % of transfusions, serious recurrences uncommon Significance: Annoying but not usually serious

36 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

37 Acute Hypotensive Reactions

38 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

39 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

40 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

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