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1. Blood Transfusion ReactionsBlood Transfusion Reactions

2. ObjectivesObjectives
 Early identification of commonEarly identification of common
transfusion rxns.transfusion rxns.
 Differentiate life threatening reactionsDifferentiate life threatening reactions
from benign transfusion rxns.from benign transfusion rxns.
 Manage common immunologic tranxManage common immunologic tranx
rxns.rxns.

3. Types of ReactionsTypes of Reactions
Immune mediated transfusion reactionsImmune mediated transfusion reactions
 Febrile non hemolytic tranx rxnsFebrile non hemolytic tranx rxns
 Immune mediated hemolysisImmune mediated hemolysis
------Acute and delayed hemolytic reactionsAcute and delayed hemolytic reactions
 Anaphylactic transfusion rxnsAnaphylactic transfusion rxns
 Urticarial transfusion rxnsUrticarial transfusion rxns
 Post-transfusion purpuraPost-transfusion purpura
 GVHDGVHD
 TRALI (pulm leuko-agglutinin reactions)TRALI (pulm leuko-agglutinin reactions)

4. Non immune mediated reactionsNon immune mediated reactions
 Physical reactions: thermal i.e. heat or cold inducedPhysical reactions: thermal i.e. heat or cold induced
 Infectious; Hepatitis B/C, malaria, HIV, CMV,Infectious; Hepatitis B/C, malaria, HIV, CMV,
Chagas dx, CJ Virus, West Nile virusChagas dx, CJ Virus, West Nile virus
 Chemical; citrate toxicity, hypo/hyperkalemia, ironChemical; citrate toxicity, hypo/hyperkalemia, iron
overloadoverload
 Acute hypotensive reaction: mediated byAcute hypotensive reaction: mediated by
bradykinins and occurs in patients with faultybradykinins and occurs in patients with faulty
bradykinin metabolism on ACE Ibradykinin metabolism on ACE I
 Osmotic injuryOsmotic injury
 Congenital and acquired hemolytic anemiaCongenital and acquired hemolytic anemia

5. Immunologic rxnsImmunologic rxns
classic blood tranx rxns are usually immunologic and occurclassic blood tranx rxns are usually immunologic and occur
2/2 to interactions of inherited/ acquired Ab with foreign Ag2/2 to interactions of inherited/ acquired Ab with foreign Ag
from transfused bloodfrom transfused blood
Incidence of rxnsIncidence of rxns
SHOT trial (serious hazards of tranx)SHOT trial (serious hazards of tranx)
-most common cause is tranx of non-matched blood-most common cause is tranx of non-matched blood
mostly 2/2 to clerical errormostly 2/2 to clerical error
-2x more common in infants than adults-2x more common in infants than adults
-more common in pxts with hematological and-more common in pxts with hematological and
oncological conditionsoncological conditions

6. Case scenario 1Case scenario 1
 A 35-year-old woman was hospitalized for anemia 2/2 sickleA 35-year-old woman was hospitalized for anemia 2/2 sickle
cell disease, she is receiving 2 units of PRBC. After her 1cell disease, she is receiving 2 units of PRBC. After her 1stst
unit of blood she developed a temp of 38.3 °C (101.0°F). Sheunit of blood she developed a temp of 38.3 °C (101.0°F). She
has no other symptoms.has no other symptoms.
On exam she appears anxious but her vital signs are stableOn exam she appears anxious but her vital signs are stable
with Bp 120/70mmHg, HR 80bpm 18cpm Pox 98% 0n RAwith Bp 120/70mmHg, HR 80bpm 18cpm Pox 98% 0n RA
She has no skin rash and her urine color is amberShe has no skin rash and her urine color is amber
What are your differential diagnosis and how would you manageWhat are your differential diagnosis and how would you manage
this pxt?this pxt?

7. Febrile non hemolytic tranx rxnsFebrile non hemolytic tranx rxns
 Most common, usually benign without sequelaeMost common, usually benign without sequelae
 Concerning because initial presentation is similar to moreConcerning because initial presentation is similar to more
adverse rxns. i.e. fever, chills +/- mild dyspnea.adverse rxns. i.e. fever, chills +/- mild dyspnea.
 15% will have a rxn in the future with subsequent tranx15% will have a rxn in the future with subsequent tranx
EtiologyEtiology
1.1. Class 1 HLA ab directed against contaminating wbc in redClass 1 HLA ab directed against contaminating wbc in red
cell conc. Although these are not always foundcell conc. Although these are not always found
2.2. 2/2 to cytokines IL-1, 6,8 and Tnf alpha generated in stored2/2 to cytokines IL-1, 6,8 and Tnf alpha generated in stored
blood/products.blood/products.
3.3. Determining factor is age of blood productsDetermining factor is age of blood products
ManagementManagement
Discontinue tranx, rule out hemolysis i.e. check labels, repeatDiscontinue tranx, rule out hemolysis i.e. check labels, repeat
type and cross, coombs testtype and cross, coombs test
Antipyretics +/- meperidine for chills and rigorsAntipyretics +/- meperidine for chills and rigors

8. Prevention
• Leukoreduction: evidence is scarce but few studies have shown a
decrease in number of reactions.
• Although tylenol and antihistamine premedication is widely used
there are no evidence to support that their use actually prevents
rxn.

9. Case scenario 2Case scenario 2
 A 35-year-old woman was hospitalized for anemia 2/2 sickle cellA 35-year-old woman was hospitalized for anemia 2/2 sickle cell
disease, she is receiving 2 units of PRBC. Her 1disease, she is receiving 2 units of PRBC. Her 1stst
unit of blood wasunit of blood was
transfused without events but 5minutes into her 2transfused without events but 5minutes into her 2ndnd
unit, Sheunit, She
complains of new flank pain and fever.complains of new flank pain and fever.
On exam she appears very anxious, diaphoretic and in acuteOn exam she appears very anxious, diaphoretic and in acute
distress, she is febrile to 38.8C with Bp 100/60mmHg, HR 101 bpm,distress, she is febrile to 38.8C with Bp 100/60mmHg, HR 101 bpm,
18cpm, Pox 98% 0n RA18cpm, Pox 98% 0n RA
She has no skin rash but is oozing out of IV sites and her urine colorShe has no skin rash but is oozing out of IV sites and her urine color
is now reddish brown.is now reddish brown.
Labs: elevated Bun/creat, increased PTT, PT and decreased HCT.Labs: elevated Bun/creat, increased PTT, PT and decreased HCT.
What is the diagnosis and how would you manage this patient?What is the diagnosis and how would you manage this patient?

10. Acute hemolytic rxnsAcute hemolytic rxns
 Medical emergencyMedical emergency
 Occurs due to rapid transfused RBC destruction byOccurs due to rapid transfused RBC destruction by
preformed recipients Abspreformed recipients Abs
 Mostly 2/2 to ABO incompatibility-typically type OMostly 2/2 to ABO incompatibility-typically type O
receiving non O blood. May occur with other bloodreceiving non O blood. May occur with other blood
typestypes
 IgM mediated complement fixation leading to rapidIgM mediated complement fixation leading to rapid
intra vascular hemolysisintra vascular hemolysis
 Most common causes are clerical or proceduralMost common causes are clerical or procedural
errorserrors
 Complications includes DIC, shock, ARF 2/2 to ATNComplications includes DIC, shock, ARF 2/2 to ATN

11. Clinical presentation
Classic presenting triad of Fever, flank pain and reddish brown urine from
hemoglobinuria are rarely seen
DIC may be presenting mode
Labs
Direct Coombs +, Pink plasma, Lactate, FDP in DIC
Management
1. Stop transfusion, alert blood bank to start search for clerical error since
another patient may be at risk
2. R/o tranx rxn i.e. check labels, repeat type and cross with unit, check
urine for hemoglobin
3. Supportive care; ABC +/-pressors
4. cardiac monitoring because of risk of hyperkalemia
5. Infuse NS to maintain BP and promote diuresis, avoid LR and dextrose
because calcium in LR will promote clotting in IV line and dextrose will
increase hemolysis. Maintain urine output >100-200ml/hour
6. With DIC early heparinization 10u/kg/hr may be beneficial

12. Delayed hemolytic transfusion rxns
Generally occurs within 2-10 days of tranx
Usually due to senescent Ab response on re-exposure to a foreign red cell
Ag
History of previous pregnancy, transfusion or transplant
Usually extra vascular and is less severe than acute
Other Abs often Rh and Kidd
Clinical presentation
Falling HCT, low grade fever, slight increase in indirect bili, spherocytes on
blood smear
Diagnosis
New +DAT and new Ab test when new blood is ordered
Txt
None in the absence of rapid hemolysis
Avoid offending Ag in future tranx

13. Anaphylactic reactions
-life threatening emergency
-Occurs within a few seconds to minutes following tranx
-Characterized by rapid onset of anaphylaxis
-Can occur with all blood products but generally unseen with serum albumin,
plasma protein fractions or coagulation factors
Incidence
1 in 20-50 thousand
Mechanism
Presence of class specific IgG and anti IgA abs in pxts who are IgA def
-Selective IgA def is fairly common, occurring in 1/300-500 people but majority
of them do not develop Abs
-Ahaptoglobinemia with antihaptoglobin Abs is similar and occur primarily in
East Asian
Treatment
As in all cases of anaphylaxis: stop tranx, epi 0.3ml of 1.1000 soln IM
Consider IV epinephrine drip
ABC +/- pressor support

14. Prevention
Establish diagnosis: usually after the fact
Use IgA def products for all further tranx (extra washed red cells or platelets)
Urticarial reactions
-Allergenic products in blood products activates IgE in recipient leading to
histamine release from mast cells and basophils
-Only rxn in which tranx can be resumed
-Give benadryl 25-50mg IV/PO if urticaria is extensive

15. Case scenario 3Case scenario 3
 30 year old kidney30 year old kidney transplanttransplant recipientrecipient onon chronicchronic
ImmunosupressiveImmunosupressive therapy admitted for anemia and receivedtherapy admitted for anemia and received
2 units of2 units of non irradiated PRBCnon irradiated PRBC from hisfrom his sistersister 3 days ago3 days ago
develops skin bullae, diarrhea and abdominal crampsdevelops skin bullae, diarrhea and abdominal cramps
VS: notable for low grade fever of 37.9C otherwise normalVS: notable for low grade fever of 37.9C otherwise normal
PE: Jaundice, swollen skin with multiple bullaPE: Jaundice, swollen skin with multiple bulla
Labs; new thrombocytopenia, elevated LFT, increasedLabs; new thrombocytopenia, elevated LFT, increased
bilirubin.bilirubin.
What is your diagnosis?What is your diagnosis?

16.  Very rareVery rare (0.1-1%) complication seen in Immuno-compromised individuals(0.1-1%) complication seen in Immuno-compromised individuals
esp in solid tumor cancer pxts on chemo, but can occur with acute/chronicesp in solid tumor cancer pxts on chemo, but can occur with acute/chronic
leukemia, lymphomas, new borne with erythroblastosis fetalis and transplantleukemia, lymphomas, new borne with erythroblastosis fetalis and transplant
pxtspxts
 Different from transplant GVHD by it’s effect on bone marrow (BM aplasia)Different from transplant GVHD by it’s effect on bone marrow (BM aplasia)
 It occurs in immuno-compromised recipients of blood products from donorsIt occurs in immuno-compromised recipients of blood products from donors
with identical HLA haplotypes. They are heterozygous for a HLA haplotypewith identical HLA haplotypes. They are heterozygous for a HLA haplotype
for which the donor is homozygous .e.g. genetically identical relativesfor which the donor is homozygous .e.g. genetically identical relatives
HLA ag are shared by donor and recipient, thus donor lymphocyte areHLA ag are shared by donor and recipient, thus donor lymphocyte are
engrafted by recipient because they are the only Ag seen by the host.engrafted by recipient because they are the only Ag seen by the host.
On the flip side the donor lymphocytes view the recipient’s tissues as foreignOn the flip side the donor lymphocytes view the recipient’s tissues as foreign
leading to immunologic activationleading to immunologic activation and GVHD.and GVHD.
 Bone marrow aplasia is the primary cause of deathBone marrow aplasia is the primary cause of death
Transfusion associatedTransfusion associated
GVHDGVHD

17. Clinical presentationClinical presentation
SkinSkin: Swollen, erythroderma and bullae formation- most: Swollen, erythroderma and bullae formation- most
commoncommon
GIGI: Diarrhea and abdominal cramps: Diarrhea and abdominal cramps
Liver:Liver: Elevated LFT and HyperbilirubinemiaElevated LFT and Hyperbilirubinemia
HemeHeme: Bone marrow aplasia, persistent thrombocytopenia: Bone marrow aplasia, persistent thrombocytopenia
Skin manifestation of GVHD
Generalized swelling, erythroderma and bullous
formation

18.  Non Irradiated whole bloodNon Irradiated whole blood
 PRBCPRBC
 PlateletsPlatelets
 GranulocytesGranulocytes
 Fresh non frozen plasmaFresh non frozen plasma
It has not been seen with frozen deglycerolized RBC, FFP orIt has not been seen with frozen deglycerolized RBC, FFP or
CryoprecipitateCryoprecipitate
TreatmentTreatment
Poor response to standard immunosuppressive therapies,Poor response to standard immunosuppressive therapies,
Thalidomide has been tried with variable success.Thalidomide has been tried with variable success.
PreventionPrevention
Key since response to treatment is poorKey since response to treatment is poor
Gamma irradiation and leuko-reduction of productsGamma irradiation and leuko-reduction of products
Avoid blood products from genetically identical donorsAvoid blood products from genetically identical donors
Implicated productsImplicated products

19. Case scenario 4Case scenario 4
 A 35-year-old woman was hospitalized for thrombotic thrombocytopenicA 35-year-old woman was hospitalized for thrombotic thrombocytopenic
purpura for which she underwent therapeutic plasma exchange with freshpurpura for which she underwent therapeutic plasma exchange with fresh
frozen plasma. After 7 days of treatment, she had improved sufficiently tofrozen plasma. After 7 days of treatment, she had improved sufficiently to
allow for weaning from daily transfusions; however, at the conclusion ofallow for weaning from daily transfusions; however, at the conclusion of
plasma exchange, she developed a cough and a temperature of 38.3 °Cplasma exchange, she developed a cough and a temperature of 38.3 °C
(101.0 °F), with progression of respiratory symptoms to severe dyspnea,(101.0 °F), with progression of respiratory symptoms to severe dyspnea,
with some wheezing.with some wheezing.
On physical examination, the blood pressure is 120/80 mm Hg. There isOn physical examination, the blood pressure is 120/80 mm Hg. There is
no rash or hives. She is tachycardic and cyanotic on cardiopulmonaryno rash or hives. She is tachycardic and cyanotic on cardiopulmonary
examination. Oxygen saturation is 80% on room air, and a blood gas studyexamination. Oxygen saturation is 80% on room air, and a blood gas study
shows an arterial PO2 of 55 mm Hg. A chest radiograph reveals diffuseshows an arterial PO2 of 55 mm Hg. A chest radiograph reveals diffuse
opacifications of both lungs and a normal-sized heart and no pleuralopacifications of both lungs and a normal-sized heart and no pleural
effusion.effusion.
Which of the following is the most likely cause for this patient's reaction?Which of the following is the most likely cause for this patient's reaction?
1.1. Pulmonary embolismPulmonary embolism
2.2. Antileukocyte antibodiesAntileukocyte antibodies
3.3. Allergy to donor plasma proteinsAllergy to donor plasma proteins
4.4. Circulatory overloadCirculatory overload

20. Transfusion related acuteTransfusion related acute
lung injurylung injury
 New acute lung injury occurring during or within 6New acute lung injury occurring during or within 6
hour of blood product tranxhour of blood product tranx
 All blood products have been implicatedAll blood products have been implicated
 May progress to ARDsMay progress to ARDs
 Immune mediated non cardiogenic pulm edemaImmune mediated non cardiogenic pulm edema
Risk factorsRisk factors
No definite risk factors but prolonged storage ofNo definite risk factors but prolonged storage of
blood products, massive tranx, cytokine txt,blood products, massive tranx, cytokine txt,
multiparity, thrombocytopenia and active infectionsmultiparity, thrombocytopenia and active infections
have been implicated in a number of studies.have been implicated in a number of studies.

21. PathogenesisPathogenesis
-Abs against HLA-Abs against HLA
-2 hit hypothesis:-2 hit hypothesis:
11stst
hit is an underlying pulm pathology that leads to localizationhit is an underlying pulm pathology that leads to localization
of neutrophils in the pulm vasculature 2of neutrophils in the pulm vasculature 2ndnd
hit is the transfusionhit is the transfusion
of blood products containing sensitized neutrophils Ab leadingof blood products containing sensitized neutrophils Ab leading
to release of vasoactive Cytokine and pulm edemato release of vasoactive Cytokine and pulm edema
 Leading cause of transfusion related fatalities in the USA
 1 case for every 1000-2400 units transfused
 6-9% mortality rate
Epidemiology

22. Clinical presentationClinical presentation
 Acute onset of respiratory distress (hypoxemia) during or shortly afterAcute onset of respiratory distress (hypoxemia) during or shortly after
blood tranx. On the average within 1-2 hours post tranxblood tranx. On the average within 1-2 hours post tranx
 Fever, tachycardia, tachypnea, +/-hypotensionFever, tachycardia, tachypnea, +/-hypotension
 In intubated pxts; elevated peak airway pressures, pink frothy airwayIn intubated pxts; elevated peak airway pressures, pink frothy airway
secretionsecretion
 CXR bilateral patchy alveolar infiltrates, normal cardiac pictureCXR bilateral patchy alveolar infiltrates, normal cardiac picture
 Labs; eosinophilia and transient drop in neutrophils, Leuko-agglutininLabs; eosinophilia and transient drop in neutrophils, Leuko-agglutinin
testingtesting
DiagnosisDiagnosis
Clinical presentation and CXR findingsClinical presentation and CXR findings
-Labs; granulocyte/ leuko-agglutinating abs, decline in C3 or C5 levels-Labs; granulocyte/ leuko-agglutinating abs, decline in C3 or C5 levels
12-36 hours after onset of symptoms followed by rise 4-7 days later12-36 hours after onset of symptoms followed by rise 4-7 days later

23. (a) Bilateral patchy alveolar infiltrate in TRAL (b) Complete resolution
a b
Criteria for the diagnosis of TRALI
• No acute lung injury immediately before transfusion
• New acute lung injury:
1. acute onset lung injury,
2. no circulatory overload or PA pressures <18mmHg,
3. bilateral pulm infiltrate on Cxr,
4. Hypoxemia:Pa02/FiO2 <300, or sat <90% on RA.
• Onset within 6 hours after transfusion
• No temporal relation to an alternate risk factor for acute lung injury
Popovsky TP et al TRALI; definition and review. Crit care Med 2005

24. Ddx includesDdx includes
 Acute fluid overload:Acute fluid overload: ↑↑ JVP,JVP, ↑SBP and widened pulse↑SBP and widened pulse
pressure during dyspneic episode, ↑ pulm vascular markingspressure during dyspneic episode, ↑ pulm vascular markings
on CXRon CXR
 Hemolytic transfusion rxnsHemolytic transfusion rxns
 IgA mediated anaphylaxis in IgA def patientsIgA mediated anaphylaxis in IgA def patients
Management
-Mostly supportive with abrupt resolution in symptoms within a few days
-A majority of patients may require mechanical ventilation
-Diuretics play no role in management since it is microvascular damage
and not due to volume. It has been shown to actually worsen TRALI
Prognosis
Increased risk of recurrence if they receive products from the implicated
donor but no risk from other donors

25. ConclusionConclusion
 Transfusion reactions are mostly due toTransfusion reactions are mostly due to
clerical errors and can range from benignclerical errors and can range from benign
reactions to life threatening emergenciesreactions to life threatening emergencies
 Early detection, discontinuation ofEarly detection, discontinuation of
transfusion and instituting supportive caretransfusion and instituting supportive care
are key to management.are key to management.
 Reporting of all reactions helps to improveReporting of all reactions helps to improve
standard practices and reduce futurestandard practices and reduce future
occurrences.occurrences.