9-3-19 10.20-10.50 Transfusion reactions - 2019.pdf

Transfusion reactions common Issues

1. Transfusion reactions
ChonladaLaoruangroj, M.D.
Division of Hematology, Department of Medicine
PhramongkutklaoHospital

2. Types of blood components
RBC Platelet FFP Cryoprecipitate
PRC
(WBC5x10
9
)
Platelet
concentration
Dose 10-15 ml/kgI (fibrinogen), VIII,
XIII,vWF
LPRC
(WBC 5x10
8
)
PooledLPPC Dose 10 kg/bag
LDPRC
(WBC 5x10
6
)
SDP
SDR

3. Pitfalls to avoid
•Do NOT store component in nursing unit or
unmonitored refrigerator
•Do NOT keep blood out of a monitored refrigerator
for more than 30 minutes before beginning
transfusion
•Do NOT warm blood in an un monitored water bath
or sink
•Do NOT administer any blood component without a
blood filter

4. Pitfalls to avoid
•Do NOT use the same blood filter for more than 4 hours
•Do NOT transfuse a unit of blood for over 4 hours
•Do NOT add medications, including those intended for
intravenous use, to blood or components or infused
through the same administration set as the blood
component
•Do NOT allow any solution other than 0.9% normal
saline to come in contact with the blood component or
the set

5. Transfusion reactions
Acute (immediate) (< 24 h) Delayed (> 24 h)
Immune
•Acute hemolytictransfusion
reaction (AHTR)
•Febrile non-hemolytic
transfusion reaction (FNHTR)
•Allergic reaction/anaphylaxis
•Transfusion related acute lung
injury (TRALI)
•Delayed hemolytictransfusion
reaction (DHTR)
•Alloimmunization
•Post-transfusion purpura (PTP)
•Transfusion associated graft
versus host disease (TA-GVHD)
Non-immune
•Transfusion associatedsepsis
(TAS)/bacterialcontamination
•Transfusion associated
circulatory overload (TACO)
•Depletion or dilution of
coagulation factors and platelets
•Iron overload
•Airembolism

6. Transfusion reactions
Adverseevent Approximate Risk Per-Unit
Transfusion of RBCs
Febrile reaction 1:60
TACO 1:100
Allergic reaction 1:250
TRALI 1:12,000
Hepatitis C virus infection 1:1,149,000
Hepatitis B virus infection 1:1,208,000 to 1:843,000
HIV infection 1:1,467,000
Fetal hemolysis 1:1,972,000
Approximate Risk Per-Unit Transfusion of Red Blood cells
Carson JL, et al. JAMA 2016;316(19):2025-2035.

7. Acute (immediate)
Transfusion Reaction

8. Acute hemolytic transfusion reaction (AHTR)
•Occur quickly upon transfusing a few millilitres,
with in minutesor up to 1–2 hours post-
transfusion
•Medical emergency as it results from rapid
destruction of the donor red blood cells by host
antibodies
•ABO blood group incompatibility -the most
severe of which often involves group A red cells
being given to a patient with group O type blood
Delaney M, et al. Lancet2016;388:2825-36.

9. Acute hemolytic transfusion reaction (AHTR)
•Immune-mediated:
-IgM anti-A, anti-B (ABO incompatibility)
severe, fatal complement-mediated intravascular
hemolysis
-IgG Rh, Kell, Duffy, or other non-ABO antibodies
extravascular sequestration, shortened survival of
transfused red cells, and relatively mild clinical
reactions
•Nonimmune-mediated:RBCs are damaged before
transfusion (heat, drugs, hypotonic solution)
hemoglobinemiaand hemoglobinuriawithout
significant clinical symptoms.
Delaney M, et al. Lancet2016;388:2825-36.

10. Acute hemolytic transfusion reaction (AHTR)
•Classic triad: fever, flank pain, and red or brown urine (rare)
•Fever and chills -most common (80%)
•Flank pain, back pain, chest pain, or abdominal pain
(free Hb+ NO NO vasospasm)
•Dyspnea, anxiety
•Hemoglobinuria, oliguria
•Pain on infusion site
•Acute renal failure due to acute tubular necrosis
•Hypotension, shock
•DIC, oozing blood from puncture site
•Systemic bleeding
Delaney M, et al. Lancet2016;388:2825-36.

11. AHTR-Management
•Stop transfusion, record V/S, and maintain airway, BP, and HR
•Keep IV line open with normal saline (avoid RLS, dextrose-
containing solutions), keep urine output > 1 mL/kg/hour.
•Force diuresis
•A clerical check of the information on the blood unit label and
the patient's identification should be performed to ensure that
the "right" blood unit was administered to the "right" patient.
•Return the residual contents of the blood component container
to the blood bank
•Afreshly collected blood sample from the patient, and a
transfusion reaction investigation should be initiated (positive
DAT)
Delaney M, et al. Lancet2016;388:2825-36.

12. AHTR-Prevention
•Hemovigilance
•Double check, clerical check
•Barcode system
•Patient identification-wrist band
Delaney M, et al. Lancet2016;388:2825-36.

13. Transfusion-associated sepsis (TAS)
Bacterial contamination and endotoxemiamay
result from
•Inadequate sterile preparation of the
phlebotomy site (Staphylococcus, Bacillus)
•Opening the blood container in a nonsterile
environment
•The presence of bacteria in the donor's
circulation at the time of blood collection
eg. salmonella
Funk MB, et al.TransfusMed Hemother2011; 38: 266–71.

14. Transfusion-associated sepsis (TAS)
•Commonly found after platelet transfusion
(collected at room temp., shelf life 5 days)
•Fever, chills, rigors, and SIRS
•Shock, DIC, renal failure
Funk MB, et al.TransfusMed Hemother2011; 38: 266–71.

15. TAS-management
•Stop transfusion
•Empirical ATB (gram positive, gram negative)
•Hemoculturefrom the patient & blood
component
•Supportive treatment
TinegateH, et al. Br J Haematol2012; 159: 143–53.

16. TAS-Prevention
•Donor screening and selection: postpone blood
donation
eg.-History of dental extraction within 3 days
(transient bacteremia)
-Diarrhea within 7 days
(salmonella, Yersinia)
•Sterile technique, skin preparation
•Diversion pouch
RobillardP, et al. Transfusion 2011; 51: 1405–11.
KatusMC, et al.VoxSang 2014;107: 103–13.

17. Febrile non-hemolytic transfusion
reaction (FNHTR)
•The most common transfusion reaction
•Characterised by an otherwise unexplained rise in
temperature of at least 1º C or 2º F
•Usually caused by cytokines (IL-1, IL-6, IL-8, and
TNFa) from leukocytes in transfused red cell or platelet
•Occur ~1% of PRC transfusion
30% of platelet transfusion
•S/S: non severe, fever, chills, or rigors within 1-6 hours
one to six hours after transfusion
•Adiagnosis of exclusion, because hemolyticand septic
reactions can present similarly

18. FNHTR-management
•Stop transfusion
•Antipyretic drugs and pethidine
•Exclude AHTR and TAS
Prevention:
•Pre-storage filtration (Pre-storage leucocyte
reduction)
1
•Platelet additive solutions
2
•Premedication: Paracetamol? (does not decrease
rate of reactions)
3
1. Heddle NM, et al.Transfusion 2002; 42: 556–66.
2. Cohn CS, et al.Transfusion 2014; 54:1927–34.
3. Sanders RP, et al. Br J Haematol2005;130: 781–87.

19. Allergic reaction
•Symptoms may either occur within seconds or
minutes after transfusion or may take several hours
to develop
•Hypersensitivity to allogeneic proteins in plasma, on
leukocytes or platelets or, uncommonly, soluble
allergens found in the transfused blood component
•IgEor IgG-mediated
•Associated with anti-IgA in recipients who are IgA
deficient (Europe), haptoglobindeficiency
Hirayama F, et al. Br J Haematol2013; 160: 434–44.

20. Allergic reaction
•Urticarial reaction: most common 1-3%
-Rash, urticaria, or pruritus
-Treatment: antihistamine, corticosteroid
•Anaphylactic reaction: severe form
-Incidence 1:20,000-1:50,000
-Commonly seen in IgA deficient recipients
-Urticaria, angioedema, bronchospasm, shock
-Treatment: adrenaline(1:1000) 0.5 ml IM
repeated q 5-15 min x 3 times
Hirayama F, et al. Br J Haematol2013; 160: 434–44.

21. Allergic reaction-Prevention
•Washed PRC or platelet
•Allogeneic proteins negative blood donor
Hirayama F, et al. Br J Haematol2013; 160: 434–44.

22. Transfusion-related acute lung injury (TRALI)
•Most common cause of death
from blood transfusion in US
and UK 1:1000-1:5000
•Mortality 50%
•Two-event hypothesis
•Lead to pulmonary edemain
the absence of circulatory
overload.
Silliman C, et al. Blood2005;105:2266-2273.

23. TRALI-Antibody hypothesis
•Human leukocyte antigen (HLA class I, HLA class II) or
human neutrophil antigen (HNA) antibody in the transfused
component reacts with neutrophil antigens in the recipient
(ie, when antileukocyteantibodies are transfused passively
in a plasma-containing blood component)
•Antibodies commonly found in multiparous woman
•The recipient's neutrophils lodge in the pulmonary
capillaries and release mediators that cause pulmonary
capillary leakage
•Transient leukopenia
•Typically associated with plasma products such as FFP,
platelet
Silliman C, et al. Blood2005;105:2266-2273.

24. TRALI-clinical presentation
•Impossible to distinguish TRALI from adult
respiratory distress syndrome (ARDS)
•Sudden dyspnea, tachypnea, hypoxemia (Pao2/FiO2
< 300 mmHg), O2 saturation < 90% in room air,
hypotension, and fever
•Onset: 1-2 hours or within 6 hours after transfusion
and usually resolve with supportive care within 48 to
96 hours.
•CXR: bilateral alveolar infltration(non-cardiogenic
pulmonary edema
Silliman C, et al. Blood2005;105:2266-2273.

25. TRALI-Diagnosis
•Clinical diagnosis
•Presence of leukocyte antibodies in transfused
plasmathat reacts with neutrophil antigens in the
recipient (80%) by reference laboratory
Silliman C, et al. Blood2005;105:2266-2273.

26. TRALI-management
•Oxygen therapy &supportive care is the
mainstay of therapy
Prevention:
•Male-only plasma
•SD plasma
Silliman C, et al. Blood2005;105:2266-2273.

27. Transfusion-associated
circulatory overload (TACO)
•Occurs when the volume of the transfused blood
components and that of any coincidental
infusions cause acute hypervolemia
•Typically, this causes acute pulmonary edema
•Risk factors: older age, renal failure (especially if
on dialysis), pre-existing fluidoverload, cardiac
dysfunction, administration of large volumes of
blood products, and rapid administration rate
AndrzejewskiC Jr,et al. Transfusion2013; 53: 3037–47.

28. TACO: clinical presentation
•Dyspnea, orthopnea, engorged JVP, S3 gallop
•High blood pressure & wide pulse pressure
•CXR: pulmonary edema, increased CT ratio
•Abnormal ECG, troponin & BNP
NHSN definition: new onset, or acute exacerbation of ≥ 3 of
the following, within 6 h of transfusion
-Respiratory distress -Raised BNP or NT-pro-BNP
-Increased CVP -Left heart failure
-Positive fluidbalance -Pulmonary edema
AndrzejewskiC Jr,et al. Transfusion2013; 53: 3037–47.

29. TACO: management
•Diuretics
•Supportive treatment e.g. supplemental oxygen
•Slow infusion over 3-4 h with the smallest
quantity of blood products
•The benefitof diuretics before or during the
transfusion has not been studied, but might be
logical in the haemodynamicallystable patient.
AndrzejewskiC Jr,et al. Transfusion2013; 53: 3037–47.

30. Hypotensive transfusion reaction
•Uncommon
•An abrupt drop in SBP or DBP> 30 mm Hg within 15
min of the start of transfusion and resolving quickly
(within10 min) once transfusion is stopped
•Activation of the intrinsic contact activation pathway of
the coagulation cascade and generation of bradykinin 
kininvasodilators
•Hypotension, flushing, GI symptoms
•Patients who are taking ACEI and are being transfused
blood products through a negatively charged bedside
leucocyte reduction filter
•Management: -Stop transfusion
-Exclude anaphylactic reaction, TAS
-Avoid ACEI, bedside filter
Delaney M, et al. Lancet2016;388:2825-36.

31. Massive blood transfusion
•Transfusion of ≥ 10 units of red cells in 24 h
•>1 blood volume in 24 hours, or; >50% of
blood volume in 4 hours
•>4 units of PRBCs in 1 h when on-going
need is foreseeable
(adult blood volume ~ 70 mL/kg)
SihlerKC, et al. Chest 2010; 137: 209–20.

32. Massive blood transfusion (MBT)
Complications
•Citrate toxicity from citrate anticoagulant
-ionized calcium hypocalcemicsymptoms
-metabolic alkalosis
-risk factor: liver disease or hepatic dysfunction
•Hyperkalemia/hypokalemia
•Hemostatic abnormality: dilutionaleffects
-dilutionalcoagulopathy: thrombocytopenia,
prolonged aPTT/PT
•Hypothermia (cold toxicity)
SihlerKC, et al. Chest 2010; 137: 209–20.

33. MBT-management
•Monitor aPTT, PT and platelet count after the
administration of every 5-7 units of red cells
•Monitor acid-based balance, ionized calcium,
potassium
Replacement:
•Supplemental calcium (calcium gluconate or calcium
citrate)
•Platelet and FFP as indicated
SihlerKC, et al. Chest 2010; 137: 209–20.

34. Delayed transfusion
reaction

35. Delayed hemolytic transfusion reaction
(DHTR)
•Incidence 1:2500 (~11% in patients with sickle-cell
disease)
•Alloimmunehemolysis
•Occurs about 4-8 days after blood transfusion, but may
develop up to 1month later
•Many delayed hemolyticreactions will go undetected
because the red cell destruction occurs slowly
•Anemia or unexplained fall of Hb
•Fever with hemolysis (anemia, jaundice)
extravascular > intravascular hemolysis
•Leukocytosis
•Diagnosis: Coombs test (DAT) +, identify Ab
Delaney M, et al. Lancet2016;388:2825-36.

36. DHTR-Pathophysiology
•Occur in patients who have developed Ab from
previous transfusion or pregnancy but, at the time of
pretransfusiontesting, the antibody in question is too
weak to be detected by standard procedures
•Subsequent transfusion with red cells having the
corresponding antigen results in an anamnestic
antibody response and hemolysisof transfused red
cells
•Typical for Rh, Kell, Duffy, Kidd antibodies
Delaney M, et al. Lancet2016;388:2825-36.

37. DHTR-management
•Symptomatic treatment
•Record & notify blood blank
•Care must be taken that subsequently
transfused red cells lack the antigen
corresponding to the patient's antibody
Prevention:
•Identify Ab
•Antigen-negative RBC
Delaney M, et al. Lancet2016;388:2825-36.

38. Transfusion-associated graft versus host
disease (TA-GVHD)
Pathophysiology
•Viable T-lymphocytes in blood components are
transfused, engraft and react against the
recipient's tissues and the recipient is unable to
reject the donor lymphocytes
Anderson KC, et al. N EnglJ Med 1990; 323: 315–21.

39. TA-GVHD
•Occurs 4-30 days after transfusion (median 8-10 days)
•Fever, MP rash, N/V, diarrhea, transaminitis, jaundice
•Pantycopenia* from full marrow aplasia (differ from post-
transplant GVHD)
•Very poor prognosis (mortality rate > 90%)
•***Prevention***most important
Irridiateblood products to inactivate passenger T-
lymphocytes
(Gamma irradiation 25-30 Gyfor PRC & platelet conc.)
•Irradiation of thawed plasma and cryoprecipitate are not
necessary
•Fresh liquid plasma (never frozen) may have a small amount of
viable lymphocytes and should be irradiated if the patient has
indications for irradiated cellular blood products
Anderson KC, et al. N EnglJ Med 1990; 323: 315–21.

40. TA-GVHD-Prevention
Absolute indications for irradiation of cellular blood products
•Patients receiving products from first-degree relatives or HLA-
matched donors regardless of patient’s immune status
•Immunocompromised patients such as
-Infants (particularly premature)
-Intrauterine transfusion and/or neonatal exchange transfusion
recipients
-Congenital immunodeficiency disorders of cellular immunity
(i.e., SCID, DiGeorge)
-Hematopoietic progenitor cell transplant recipients
-Hodgkin’s disease, Leukemia, or Lymphoma patients
-Patients treated with purine analogs(i.e., fludarabine) or ATG
TreleavenJ, et al.Br J Haematol2011; 152: 35–51.

41. Post-transfusion purpura (PTP)
•Rare 1: 330,000
•Occurs primarily in women sensitized by
pregnancyor prior transfusion
•Ab to human platelet antigen 1a (HPA-1a)
•Severe degrees of thrombocytopenia (< 10 x10
9
/L,
often lasting days to weeks, develop about 5-12
days following transfusion(PRC, whole blood)
•Severe bleeding 30%, mortality rate 10%
•Diagnosis: anti-HPA in recipient plasma
Delaney M, et al. Lancet2016;388:2825-36.

42. PTP-management
•Self recovery within 2 weeks (1-28 days)
•If severe bleeding: IVIgplatelet in 3-5 days
•Washed blood products
•HPA-matched blood (autologous transfusion,
directed donation from relatives)
Win N, et al. VoxSang 1995;69: 138–39.

43. Non-bacterial transfusion
transmitted disease
Window period (days) by nucleic acid test (NAT)
•HIV 9
•HBV 38
•HCV 7.4
Others: hepatitis E, malaria, dengue, chikungunya, filarial,
parvovirus
***High index of suspicion
•Screening HIV, HBV, HCV, syphilis in blood donor (Thai)
GalelSA. Infectious disease screening. AABB Technical Manual 17
th
edition 2011: 239-70.

44. Transfusion reactions
Type Pathophysiology Symptoms/signs Management
AHTR RBCmismatch between
donor and recipient (ABO
incompatibility; IgM 
Type II hypersensitivity 
complement fixation
Fever, chills/rigors,back
pain/flank pain, dark
urine (hemoglobinuria),
pain along IV line, DIC,
bleeding, AKI,
hypotension, death
Stop transfusion,NSS
IV, maintain urine
output > 1 ml/kg/h,
promote diuresis
oxygen support
FNHTR Cytokinesform WBC in
blood unit
Fever, chills, rigors,
discomfort
Antipyretics(not
aspirin) ±meperidine
Leukofilteredblood
components
Allergic/
anaphylaxis
Allergicto specific protein
in plasma Type I
hypersensitivity (IgE-
mediated)
IgA deficiency severe
Urticaria, dyspnea,
wheezing, hypotension
Stop transfusion,
antihistamine, steroid
or adrenaline, oxygen
support
Washed blood
components
MazzeiCA,Technical Manual, 16
th
Ed. American Association of Blood Banks; 2008:715-749.

45. Transfusion reactions
Type Pathophysiology Symptoms/signs Management
TRALI Donor Ab against
recipientWBC
aggregated in lugs
Hypoxemia, non-cardiogenic
pulmonary edema, respiratory
failure, hypotension, fever
Stop transfusion,
oxygen &ventilator
support
TAS Blood products (esp.
platelet) contaminated
with bacteria
Fever, chills,hypotension,
shock
Stop transfusion, ATB
and management of
shock, bacterial culture
Donor selection,
sterile technique
DHTR Anamnestic immune
response to red cell
antigens
(alloAbagainst minor
blood group)
Fever, decreasedHct, mild
jaundice(extravascular
hemolysis)
Supportive Rx.
crossmatch
compatible unit after
identifying red cell
antibody
TACO Volume overload in
susceptible patients
Signs of heart failure,
shortness of breath, wheezing,
hypertension
Diuretics, oxygen
MazzeiCA,Technical Manual, 16
th
Ed. American Association of Blood Banks; 2008:715-749.

46. Transfusion reactions:
Algorithm to guide assessment and actions
Delaney M, et al. Lancet2016;388:2825-36.

47. Transfusion reactions:
Algorithm to guide assessment and actions
Delaney M, et al. Lancet2016;388:2825-36.

48. Transfusion reactions:
Algorithm to guide assessment and actions
Delaney M, et al. Lancet2016;388:2825-36.

49. Avoid Unnecessary
Use of Transfusion