MLT 502 IMMUNOHEMATOLOGY II TRANSFUSION REACTION

2. According to Medscape, Online Medical Dictionary, transfusion reaction can be
define as reaction of the body to a transfusion of blood that is not compatible
with its own blood during or within 24 hours of a blood transfusion.
Transfusions are given:
a) To restore lost or depleted blood components
b) To improve clotting time
c) To improve the ability of the blood to deliver oxygen to the body’s tissues.

4. What is Acute Hemolytic Transfusion?
Types of transfusion reaction associated with
hemolysis.
It occur as soon as possible after blood is being
transfused.
AHTR also known as ‘Immediate Hemolytic
Transfusion Reaction’.
Types of AHTR
1)Immune Mediated
2)Non-immune Mediated

5. • IMMUNE MEDIATED cause by :
- Anti A, Anti B or both
- Rh
- Kell
-Duffy
• This result in severe intravascular hemolysis and
later cause extravascular.
• NON IMMUNE MEDIATED occurs when there are
damage of RBC before transfusion which result in
hemoglobinemia and hemoglobinuria. Patient shows
asymptomatic or milder symptoms.

6. Sign and Symptoms
Fever
Hemoglobinemia
hemoglobinuria
Red or dark urine
Chills
Hypotension
Renal failure
DIC (Disseminated intravascular
coagulation)
Back pain

7. Management
1)When reaction become more severe :
- stop transfusion and inform doctor for
immediate patient review.
-check vital sign and respiratory status.
- check patient ID and recheck again detail
on blood unit and compatibility label or tag.
2) Inform transfusion service immediately.
3)Administered low dose of dopamine for hypotension
patient (1-5ug/kg/min)
4) Monitor urine output commonly using
catheterisation.

8. Complication
 Acute kidney failure.
 Anemia
 Lung problems
 Shock
Treatment
 Mild symptom can be treated with :
- paint reliever and acetaminophen can
reduce fever and discomfort.
-intravenous

9. Prevention
 Prevent mislabeled
 Collect the correct sample.
 Must form bedside check before
administer blood product.
 Make sure correct bar coding of blood
component and patient ID.
 Transfusion practice should be done by
experience physician and nurse.

11. Definition : hypersensitivity reaction to a particular
allergen
2 types of allergic reaction:
• urticaria transfusion reaction
• anaphylactic transfusion reaction

12. • Simple allergic reaction
• Usually begin minutes after infusion
• The reaction is simple to diagnose and do not cause
significant problems to the patient.
• Patient are treated with an antihistamine such as
diphenhydramine (Benadryl).

13. Mechanism of urticaria transfusion reaction
• Urticaria transfusion reaction caused by soluble allergenic
substances in donor product
• The recipient IgE antibody will reacts against this allergenic
subtances, most commonly a donor plasma protein resulting in a
"type I hypersensitivity" reaction
• Histamine and other substances are released from mast cells and
basophils through interaction with IgE.
• The secretions result in the formation of pruritic (itchy) raised,
red-rimmed "wheals" on the skin of the recipient.

14. Sign & symptom of urticaria transfusion
reaction:
• No fever
•Erythema
• Cutaneous flushing
• Angioedema
• Nausea
• Vomiting
• Diarrhea
http://upload.wikimedia.org/wikipedia/commons/6/63/EM
minor2010.JPG

15. Treatment of urticaria transfusion reaction:
Temporarily stop the transfusion
Maintain intravenous access
Give diphenhydramine 20–50 mg IV
If the symptoms resolve, restart the transfusion slowly
If the symptoms do NOT resolve, stop the transfusion

16. •Rapidly developing and serious allergic reaction
• This reaction affects a number of different body systems at one time.
• Severe anaphylactic reactions can be fatal
• Associated with IgA deficiency deficiency
•Patient treated with epinephrine

17. Mechanism of anaphylactic transfusion reaction
• Usually caused by exposure of an antigen to a sensitized patient.
•Reaction commonly occur when recipient has no IgA antibody and
transfusion was elicits anti-IgA response of recipient
• The "classic" type of anaphylaxis involves IgE antibodies on the
surface of a mast cell targeted against an offending antigen. When
the patient is exposed to the antigen a second time, the IgE
stimulates the mast cells, leading to an outpouring of histamine.

18. Sign and symptoms of anaphylactic transfusion reaction:
• Hypotension
• Tachycardia
• Chest pain
• Loss of consciousness
• Arrhythmia
• Wheezing
• No fever
• Patient can have upper
and lower airway obstruction such as
hoarseness and dypsnea
http://www.cambrianfirstaid.co.uk/mediaf
iles/anaphylaxis%20baby%20gif.gif

19. Treatment of anaphylactic transfusion reaction:
Stop the transfusion
Maintain IV access with normal saline
Administer oxygen
Intubation may be needed
Epinephrine is most effective medication for treatment of anaphylaxis
Steroid and H1-receptor antagonists have been used
Observe the patient closely
Report the reaction to the transfusion medicine service

21. • TRALI=Transfusion Related Acute Lung Injury
• TRALI is a complication of allogenic blood transfusion
that typically manifested by shortness of breath due
to noncardiogenic pulmonary edema,fever and
hypotension.
• It can cause transfusion-associated mortality.

22. • There are two types of mechanisms that
involve with the TRALI which are:
▫ A) Immunologic Mechanism
▫ B) Nonimmunologic Mechanism
• Mechanism of TRALI pathogenesis is differ
among patients.

23. A)Immunologic mechanism
Principle
Types of
Alloatibodies
involve
• Involve antibody-mediated
event.
• Alloantibodies are responsible
for TRALI.
• Anti-human leukocyte
antigen(anti-HLA) class I or class II
antibody
• Also associated with
antilymphocyte,antimonocyte
• Specific neutrophil
alloantigen:HNA-1a,HNA-1b,HNA3a and HNA-2a

24. Donor
alloantibody
interact with
recipient
leukocyte
antigen
Increased vascular
permeability lead to
capillary leak and
pulmonary tissue
damage
Activation of
complement
cascade,cytokines
Initiate antigenantibody interacion
Activation of
complement
components and
neutrophils
Produce
inflammatory
mediators.

25. B) Nonimmunologic Mechanism
• It involve soluble mediator-mediated not antibody mediated event.
• In this mechanism, antigranulocyte or anti-HLA antibodies are not
detected in either recipient or donor
• It is suggested that the granulocyte activation is mediated by a
soluble lipid substance that will accumulate during the storage of the
products
• It also postulated that, biologically active lipids or interleukins is
generated and present in increased concentration in stored blood
products.
• All this event cause pathogenesis of TRALI due to nonantibody mediated.

26. Biologically active
lipids that
accumulate during
the storage
Alveolar damage
Pulmonary edema
Increase in
permeability of
pulmonary
circulation

27. Sign and Symptoms
•
Acute hypoxemia and
noncardiogenic pulmonary edema
(NPE).
•
Acute onset of respiratory
compromise.
•
Severe hypoxemia within 6 hours
of beginning transfusion caused
by a decrease in pH and pO2 and
an increase in pCO2 levels in
arterial blood gas analysis.
•
Progressive dyspnea
•
Cyanosis
•
Fever (increase of 1-2˚C)
•
Tachycardia
•
Hypotension (may not respond to
IV fluid resuscitation)
•
Frothy sputum (yellow or pink in
color)

28. BILATERAL LUNG INFILTRATES ON THE CHEST RADIOGRAPH
www.ssm.gov.mo/cts/Download/6thEdE.pdf

29. TREATMENT AND PREVENTION
• Mild TRALI needs supplemental oxygen therapy.
• Severe TRALI may require mechanical ventilation and
ICU support.
• Upgrade blood transfusion guidelines which will be
minimize the unnecessary transfusions are occurred.
• Advocate temporary disqualification of donors
implicated in TRALI reactions until leukocyte antibody
testing can be completed.
• Rejected all multiparous females from plasma
donation.
• No administration of diuretics

31. What is GVHD??
• Graft-versus-host disease or GVHD is a term used to
describe a battle between the transplanted stem cells and
the patient’s body. This is a complication that occurs when
the new stem cells (the graft) reject or assume body (the
host) as foreign.
• GVHD is rare in autologous transplants (stem cells come
from own blood or bone marrow), it occurs in
approximately 50% of patients who have an allogeneic
(donor) transplant.
• GVHD is less likely to occur if the donor and recipient are
matched – have identical tissue or “HLA (human leukocyte
antigen)” types.

32. How GVHD develops?
• GVDH occur when the transplant affects recipient immune system. T cells
from donor’s bone marrow or stem cells will contain some T cells. T cells
are a type of white blood cells that function to attack and destroy cells
that recognize as foreign and can be harmful to the host.
• T cells don’t attack body own cells, because they recognize proteins on the
cells called HLA (human leukocyte antigens). HLA is inherited protein.
Apart from identical twins HLA is unique to each person.
• Tissue typing is a blood test to check how closely recipient and donor HLA
matches. . If recipient and donor have very similar HLA, the chances of
GVDH are lower. The more differences there are between recipient HLA
and donor, the more likely recipient are to get GVHD.
• After a transplant recipient bone marrow starts making new blood cells
from the donor stem cells. These new blood cells have the donor's HLA
pattern. They recognize the HLA pattern on recipient body cells as
different (foreign) and may begin to attack some of them. The GVHD may
affect different areas of body. Most commonly it affects the skin, digestive
system (including the bowel and stomach) and liver.

33. Types of GVHD
Two types of GVHD:
 Acute GvHD: occur early when the bone marrow starts to engraft around
two to four weeks after the transplant
▫ It often causes an itchy red skin rash. If the bowel, stomach or
liver are affected, nausea and vomiting, diarrhea and a jaundice
may be develop.
▫ Acute GvHD is more likely to affect recipient if:
 Recipient have a transplant at an older age
 the donor is unrelated or not such a close match to recipient
 Chronic GvHD: occurs after day 100 after transplant. It may develop as a
continuation of acute GVHD or occur without any prior history of acute
GVHD. Chronic GVHD is usually less serious.

34. Signs and Symptoms of GVHD
Acute GVHD
Involve three main body systems:
1. Skin
• a rash on the skin surface but it is mostly seen on the hands, feet,
abdomen and face.
• itching, redness on areas of the skin that initially looks sun-burnt.
2. Liver
• Jaundice (yellow coloring of the skin or eyes)
3. Gastrointestinal Tract
• Abdominal pain or cramps, nausea, vomiting, and diarrhea

35. Chronic GVHD
•
•
•
•
•
•
•
•
•
soreness or dryness of the mouth or eyes
lung and liver complications
changes in skin pigmentation
hair loss
weight loss
vaginal dryness
Cough
shortness of breath
joint problems

36. Possible benefits of GVHD
• Although GVDH may have a serious even life threatening
problem, it may give a benefit too. In case of transplant
for leukaemia, having mild GVHD may be a good thing.
• As well as attacking recipient body cells, the donor T cells
will also attack any remaining leukaemia or cancer cells.
Doctors call this the graft versus disease effect, or graft
versus leukaemia effect (GVL).
• The graft means "the donor T cells". There may also be
graft versus disease effect after a transplant for
lymphoma or myeloma.

37. Risk factors for GVHD
• Unrelated donor transplants
Risk of developing GVDH is greater if donor and recipient is not related
• Mismatched donors
If you have a mismatched transplant your donor will be as close an HLA match as possible.
But sometimes the best available bone marrow donor is still a slight mismatch. This
increases the risk of GVHD.
• High numbers of T cells in the donated stem cells or bone marrow
Donated stem cells or bone marrow that contain high numbers of T cells are more likely to
cause GVHD. This is called a T cell replete stem cell transplant. Whilst this type of
transplant may cause more GVHD, it may also lower the chance of relapse.
• Age
The older recipient and donor are, the greater recipient risk of developing GVHD.
• Having a donor of a different sex to you
If donor is a different sex to recipient, the risk of GVHD is slightly increased. This is
particularly true if a male has a female donor who has had children or been pregnant in the
past.

38. LABORATORY DIAGNOSIS
• Several lab and imaging tests that can be done to diagnose
and monitor problems caused by GVHD :
▫ Liver function tests
 Elevation of the alkaline phosphatase concentration an early sign
of liver involvement by GVHD
 Hypoalbuminemia is usually due to GVHD-associated intestinal
protein leak and a negative nitrogen balance
▫ Serum electrolytes and chemistries
 Potassium, magnesium, bicarbonate levels can be altered
 Massive diarrhoea and diminished oral intake can lead to serious
electrolyte abnormalities
• A biopsy of the skin, mucus membranes in the mouth, or
other parts of the body can help to confirm the diagnosis.

39. Prevention and treatment
• Way to prevent GVDH
▫ Tissue typing.
 Tissue typing is a process to match the transplanted donor cells as
closely as possible to the host or patient cells.
 Of all the proteins in the body, it is crucial to try to match up the
proteins called HLA antigens that are found on the surface of all the
cells. The mixture of HLA proteins belonging to each of us is
inherited equally from our parents. The closer the HLA match
between the donor and host tissues, the less likely the outcome of
GVHD for the host (patient).
▫ Intake of drug before transplant (esp. Stem cell transfusion)
 Drug given such as cyclosporine and methotrexate, tacrolimus
(Prograf®) and methotrexate, tacrolimus and mycophenolate mofetil
(CellCept®) and Prograf and sirolimus (Rapamune®).
• Treatment
▫ Intravenously administered glucocorticoids, such as
prednisone.
 But this medicines have side effects, including kidney and liver
damage so close monitoring is needed.

41. DEFINITION
Bacterial contamination of blood component is the
second most common caused of death in
transfusion reaction
Platelet contamination is the most common blood
component that easily contaminated due to the
storage temperature (room temperature) may
facilitate bacterial growth
Infusion of contaminated component may be
asymptomatic or cause fever with evidence of
sepsis or septic shock and death
Bacterial psychrophilic gram negative bacteria
(pseudomonas, coliforms and achromobacters) are
common contaminants

42. TYPES OF BACTERIA
BLOOD COMPONENTS
ORGANISMS
PACKED RBC
Yersinia enterolotica
Pseudomonas fluorescnes
Serratia liquefaciens
PLATELETS
Stahplycoccus epedermidis
Staphylococcus aureus
Bacilus cereus
Propionibacterium spp.
Micrococcus spp.
Group C Streptococcus

43. Sources of bacterial contamination
External
▫ Venipuncture site
▫ Contaminated needle
▫ Collecting set
Internal
▫ Blood collected from donor suffers mild bacterimia or
infection

44. ETIOLOGY
ETIOLOGY FOR PLATELET CONTAMINATION
 Platelets is contaminated with bacteria because the storage for platelets is
at room temperature with gently agitation which facilitate the bacterial
growth
 The most common organism contaminating platelets are rapidly growing
aerobic organisms
 Organism may contaminate the platelet from the skin of donor
venipuncture site or from equipments that is used during collection and
processing
ETIOLOGY FOR PACKED RBC CONTAMINATION
 Being stored at 4 oC, most common organism that associated with packed
RBC contamination are psychrophilic bacteria which can withstand cold
temperature such as Yersinia enterolotica
 Donor infected with Yersinia enterolotica may have bacteremia during
donation of blood because infection may be asymptomatic
 Transfusion of packed RBC with Yersinia spp. Contaminated unit may caused
rapid development of life-threatening gram negative sepsis in recipient

45. Develop within minutes to up to 2 hours from start of transfusion
 Hypertension
 Nausea
 Vomiting
 Diarrhea fever
 Oliguria
 Shock
 Dyspnoea, wheezing and/or cough
 Respiratory distress
 Bleeding: endotoxin induce DIC
SIGN AND SYMTOMPS

46. PATHOGENESIS AND CLINICAL
MANIFESTATION
PATHOGENESIS OF BACTERIAL CONTAMINATION:
 The psychrophilic organisms multiples at 4oC
 These organism pseudomonas, coliform and achromobacter are all gram negative bacilli produces
endotoxin that present in the cell wall of these organisms
 These organisms metabolises citrate and produces endotoxins consisting of lipid polysaccharide
and amino acids
 Endotoxins are pyrogenic and causes granulocytosis and thrombocytopenia, gram negative
septicimia, endotoximic shock
 Fall in cardiac output leads to endotoximic shock that triggers disseminated intravascular
coagulation (DIC) which is responsible for the fatal outcome rather than bacterimia
CLINICAL MANIFESTATION OF BACTERIAL CONTAMINATION:
 Clinical manifestation may be observed after introduction of contaminated blood in the form of
circulatory collapse
 At the beginning, there may be fall in body temperature subsequently it rises
 It then effects the brain, the respiratory system and gastrointestinal tract resulting in
conciousness or semiconciousness, dyspnea, vomitting and loose motion
 Treatment consists of immediate discontinuation of blood transfusion, vigrous management of
endotoximic shock to avoid occurrence of DIC through suitable antibiotics

47. PREVENTION
GENERAL
 Written procedure for all aspects of procuring, issuing, and administering transfusion must be
prepared.
 Improve the technique for proper use of equipment, intravenous solutions, and drugs used
during the administration of blood and blood component.
 Equipment must be properly maintained and records kept of how and when items are used.
 Medications that can be given intravenously must never be injected into blood bags which only
use intravenous access devices.
BACTERIAL CONTAMINATION FOR PLATELETS




The storage time of platelets must be shorten as logically possible
Order platelet concentrated for transfusion only when the patient is ready to receive them
After platelet concentrates are pooled, it must be use within 4 hours
Once platelets have been delivered to the appropriate location, hang the bag and start
transfusion immediately
 No platelet concentrates can be leaved unattended in an uncontrolled, unmonitored
environment
 If platelet concentrates are ordered for a patient but then not transfused, it must be return as
soon as possible to the transfusion service for the appropriate storage.

48. MANAGEMENT
 Blood culture from the recipient
must be done
 Save and collect all blood
component units transfused
within 90 minutes of the
reaction diagnosis
 Obtain recipient`s post
transfusion blood sample for
transfusion reaction
investigation
Management for
Post-transfusion
sample and blood
component
 Send all the blood sample to
the microbiology laboratory
for gram stain as soon as
possible
 Reactions are potentially fatal
and they must be detected
and treated immediately if
suspected with bacterial
contamination
 Start with aggressive broadspectrum antibiotic therapy
and give supportive care such
as corcticosteroids.
 The patient`s intravascular
volume should be maintained
with crystalloid solution and
possible vasopressor drugs
such as dopamine

49. IRON OVERLOAD/ HEMOSIDEROSIS

50. • Each unit of blood contains 250mg of iron as iron can
be found in Hb molecule.
• Iron is released when RBCs is destroyed.
• Human lack major mechanisms for iron excretion,
thus iron is accumulated in liver, spleen, heart and
endocrine organ as hemosiderin.
• Frequent blood transfusion has high risk of iron
overload.

51. • The diseases that require frequent transfusion
include:
• Thalassemia
• Sickle cell disease
• Aplastic anemia
• Signs and symptoms of hemosiderosis:
•
•
•
•
•
•
Muscle weakness
Fatigue
Weight loss
Mild jaundice
Anemia
Cardiac arrhythmias

52. • Complications that may occur:
• Tissue damage
• Heart failure
• Liver failure
• Diabetes
• Hypothyroidism
• Treatment: chelating agent
 desferrioxamine, deferiprone, desferasirox
 binds to iron and helps remove it through the
urine or feces.

53. Picture of kidney under the microscope.
The brown area contains hemosiderin.
Retrieved from:
http://www.medialabinc.net/spg404281/iron_overload.aspx

54. References
• Borton, D. C. (2011, April 20). Patient.Co.UK. Retrieved from
Blood Transfusion Reactions:
http://www.patient.co.uk/doctor/blood- transfusion-reaction
• http://www.pathologyoutlines.com/topic/transfusionmedalle
rgic.html
• http://www.transfusionmedicine.ca/articles/transfusionrelated-acute-lung-injury-trali
• http://health.nytimes.com/health/guides/disease/graftversus-host-disease
• http://www.patient.co.uk/doctor/iron-overload