This document provides definitions and details regarding Transfusion Reaction Reporting Form (TRRF) and Investigative Surgical Blood Transfusion (ISBT) forms. It describes the structure and sections of each form including patient information, transfusion reaction details, transfusion product details, investigations, nature of adverse reactions, and imputability assessment. It also defines various blood components, their indications, storage requirements, and dosages. Signs and symptoms of transfusion reactions and their classifications are outlined. Key investigations for transfusion reactions are also mentioned.

1. TRRF And ISBT Proposed
Standard Definitions
Presented by:
Rayaz Ahmad Bhat
Jammu and Kashmir
Student:
M.Pharm Pharmacy Practice
National Institute Of Pharmaceutical Education And
Research,Guwahati, Assam
Email: reyazrab@gmail.com
Mentor Institute: National Institute Of Biologicals , Noida , Delhi
Mentor:
Dr. Akanksha Bisht
Officer Incharge – HvPI & Scientist Grade-III

2. Transfusion Reaction Reporting Form
(TRRF)
Structure of TRRF
A. Patient Information
B. Transfusion Reaction Details
C. Transfusion Product(s) Details
D. Investigations
E. Nature of Adverse Reaction(s)
F. Imputability Assessment
 Monthly Denominator Reporting Form

3. A. Patient Information
• Hospital Code No.
• Patient Initials
• Gender
• Hospital Admission no.
• Age/Date of Birth
• Primary Diagnosis
• Medical History

4. B. Transfusion Reaction Details
• Anaesthesia: General/Spinal/Local
• Pre-transfusion Vitals
• Vitals at the time of Reaction
Vital signs are measurement of body’s most basic
functions , include( as per TRRF):
 Temperature: Normal-36.5 oC to 37.2 oC
 Pulse: Normal 60-100 beats/minute
 Blood Pressure: Normal Bp – 120/80
 Respiratory Rate: Normal- 12-16 breaths/minute
 SpO2: Normal blood oxygen saturation 95-100%

5. Signs and Symptoms of Transfusion Reactions as
per TRRF
• Generalized
• Pain
• Respiratory
• Renal
• Circulatory
• Other

6. Generalized
• Fever with or without chills: Most common
feature in any transfusion reaction
• Rigors: episodes of shivering
• Nausea with or without vomiting
• Urticaria: Commonly known as hives –
characterized by itchy rash caused by tiny
amounts of fluid that leak from the blood vessels
just under the skin in response to an immune
reaction.
• Flushing: Characterised by redness of skin with
a sensation of warmth or burning of face, neck
and less frequently upper trunk and abdomen.

7. • Restlessness
• Anxiety: Feeling of uneasiness such as worry,
concern or fear, that can be mild or severe.
• Pruritus: itching
• Edema: Accumulation of fluid
• Jaundice: Characterised as yellowing of skin
and sclera due to abnormally high levels of
bile pigments.
• Other symtoms

8. Pain
• Chest Pain: Can be due to acute intravascular
haemolysis.
• Abdominal pain
• Back/Flank pain
• Pain at infusion site : due to local injury or in
more adverse conditions due to bacterial
contamination
• Pain at other sites

9. Respiratory Signs and Symptoms
• Dyspnoea: Shortness of breath
• Wheeze: Breathing with a whistling or rattling sound
in the chest
• Cough : Respiratory reflex
• Hypoxemia: Abnormally low levels of oxygen in blood
• Bilateral infiltrates on chest X-ray
• Other

10. Renal Signs and Symptoms
• Haematuria: Blood in urine
• Haemoglobinuria: excretion of free haemoglobin
in urine
• Oliguria: Low urine output
• Other

11. Circulatory
• Tachycardia: Increased heart rate
• Hypertension: Increased blood pressure above
normal values
• Hypotension: Decrease in blood pressure below
normal
• Raised JVP(Jugular Venous Pressure)
• Arrhythmias: Irregular heart beating
• Other

12. C. Transfusion Product Details
This section contains blood component details about:
• Type of Blood Component
• Indication
• Date and Time of issue of Blood Product
• Date and Time of Transfusion
• Unit Id (Transfused)
• Blood Group
• Volume Transfused(ml)
• Expiry Date of Blood Component
• Manufacturer of Blood Bag
• Batch/ Lot. No. of Blood Bag
• Transfusion record : Ist time or Repeat

13. Whole Blood
• Whole blood is the donor blood mixed with
anticoagulant preservative solution.
• Whole blood is now considered as a raw
material rather than a transfusion medium .
• Indications:
• The main indication of whole blood is to provide
both oxygen carrying capacity and increase in
blood volume in an actively bleeding patient
with blood loss greater than 25%.
• Exchange transfusion (Blood should be less
than 5 days old)

14. Storage and Shelf-life
• Storage:
• 1-6 o C
• 2-8 o C during transportation .
• Shelf-life:
• ACD/CPD/CP2D-21 days
• CPDA-1: 35 days
• A unit of whole blood ( approximately 350ml) will
increase haemoglobin by about 0.75g/dl while a unit
of 450 ml by 1g/dl in an adult patient of about 60-70
kg who is not actively bleeding.
• In pediatric patients the transfusion of 8ml/kg of red
cells will increase the haemoglobin by approx. 1g/dl

15. Blood Components
• Modern blood transfusion envisages the optimal
use of every blood donation by a way of blood
component therapy.
• The development of plastic blood collection bags
with integral tubing, high speed refrigerated
centrifuge, deep freezers, and cell separator
machines have made blood component
preparation easier and practical.
• With more advanced techniques such as Plasma
fractionation various plasma derivatives are now
available , treating multiples of health conditions.

16. Advantages of Component Therapy
• It maximizes the use of one unit of blood.
• The shelf-life of the components is longer than the
whole blood.
• Better patient care without danger of overloading
or side effects due to other components.
• Cost-effective
• Reduced adverse drug reactions , reduced
alloimmunization.

17. • With blood component therapy , it is possible to
benefit four different types of patients with one unit
of blood:
• Red cell concentrate for Anemic patients
• Fresh Frozen Plasma(FFP) for bleeding due
coagulation factor deficiencies.
• Platelet concentrate(PC) for bleeding due to
thrombocytopenia .
• Cryoprecipitate(CP) for Haemophilia, Fibrinogen
deficiency.

18. Packed Red Blood Cells
• Red Blood Cells are prepared by removing
approximately 200 to 250 ml of plasma from
a unit of 450 ml of whole blood or 150 to 175
ml of plasma from a unit of 350 ml of whole
blood.

19. Indications
• Severe anemia to reduce circulatory
overload.
• Haemolytic anemia especially in aplastic
crisis
• Various hypoplastic anemias
• Various aplastic anemias
• Anemia accompanying chronic renal disease

20. Transfusion Guidelines for PRBCs as per
American College of Anaesthology
• Haemoglobin concentration less than 6 g/dl:-
– Transfusion indicated
• Hb concentration greater than 10 g/dl:-
– Transfusion unnecessary
• Hb concentration between 6-10 g/dl:-
– Individualize treatment based upon clinical condition

21. Storage, Shelf-life and Dose
Category Storage Shelf-life
PRBC 1-6o C ACD/CPD/CP2D- 21
days
CPDA-1: 35 days
RBC + Additive solution 1-6o C 42 days
RBC Washed 1-6o C 24 hours
Leucoreduced RBCs 1-6o C ACD/CPD/CP2D-21
days
CPDA-1: 35 days
RBCs Open System 1-6o C 24 hours
RBCs Frozen Liquid
Nitrogen < - 120o C
10 years
Dose: as of whole human blood

22. Leukoreduced RBCs
• The leukoreduced red cells imply the removal of
at least 70% of the leukocytes with the loss of
less than 20% of red cells.
• Leukocytes are responsible for many of the
adverse effects of transfusion including febrile
non-hemolytic transfusion reactions, HLA
alloimmunization, and transmission to
leukotropic viruses.
• The average content of leukocytes collected in
whole blood unit is roughly 2-3 × 109 leukocytes.
Contd…

23. • The usual levels of leukodepletion to prevent
FNHTR is 0.5 × 108 i.e. 1 log reduction called
Critical Antigenic Leukocytic Load(CAL) and can
be achieved by removing the buffy coat.
• For prevention of HLA immunization to HLA
antigens or preventing the transmission of
leukotropic virus like CMV , the level of residual
leukocytes should not be more than 5 × 106 , called
Critical Immunogenic Leukocyte Load( CIL).
• FDA has defined leukoreduced blood component as
the one with residual leikocyte count of < 5 × 106
per container.

24. Methods of Leukoreduction
• Centrifugation:
• Washing using saline
• Freezing and Deglycerolization
• Filtration using 3rd generation leukofilters
• Buffy coat removal using automated component
extractor
Now-a-days , mostly filtration and buffy coat removal
techniques are used for the preparation of
leukodepleted Red cells.

25. Platelets
• Random Donor Platelets:
Obtained from whole blood
Supplied as either:
Single donor unit or
Multiple donor pooled unit: Prepared from 4-6 single
donor units pooled into one pack .
One Single donor PC contains 5.5 × 1010 Platelets
in 50-60 ml plasma
Multiple donor pooled unit contains 3 × 1010 platelets
in 150-200 ml plasma.
Contd…

26. • Apheresis Platelets: Obtained by apheresis.
• One apheresis platelet concentrate is equivalent
to 6 random donor platelet concentrates and
hence the number of donor exposures is
reduced.
• Apheresis platelets contain 3 × 1011 platelets in
150-300 ml of plasma

27. Dose
• Random Donor Platelets:
• Adult: 1 unit/10 kg body weight ( minimum 6 units)
• 1 unit raises 5000-10,000 platelets/ul
• Child: 1 unit/10 kg body weight
1 unit raises 20,000 platelets/ul
• Neonate: 1 unit/2.5 kg body weight
• 1 unit raises 75,000-1,00,000 platelets/ul
• Apheresis platelets:
• Adult: 1 unit , raises 25000-30,000 platelets/ul

28. Indications
• Amegakaryocytic thrombocytopenia
– Leukemia
– Chemotherapy
– Bone marrow transplantation
– Drug or radiation induced hypoplasia
• Functional platelet abnormalties
• Vral diseases associated with
thrombocytopenia e.g. Dengue
• Disseminated intravascular coagulation

29. Corrected Count Increment(CCI)
• To assess the efficiency of platelet transfusion,
should be done at 1 hour and 24 hours post-
transfusion.
CCI =
Post transfusion - Pre-transfusion
Platelet count platelet count × Body surface area(m2 )
No. of Platelets transfused × ( 1011 )

30. Fresh Frozen Plasma
• Plasma separated from whole blood , frozen
within 6-8 hours of collection and stored at
-20o C and below.
• Fresh frozen plasma from a standard donation
of whole blood (450 ml) usually measures 175-
250 ml, containing 70-80 units/dl of factor VIII.
Factor IX, vWF and other clotting factors.
Fibrinogen 200-400 mg
• Shelf-life of 1 year at or below -20o C

31. Dosage
• The accepted dose of FFP for infusion is 12-
15 ml/kg, however the actual dose depends
on the underlying clinical condition.
• Post-transfusion assessment of patient’s
coagulation parameters like PT, PTT or
specific factor assay is important for
monitoring the efffectiveness of FFP.

32. Indications
• Active bleeding due to multiple clotting factor
deficiencies in:
– Liver diseases
– DIC
– Coagulopathies in massive transfusion
• Familial factor V deficiency
• Reversal of coumarin drug effect
• Open heart surgery
• Immunodeficiency syndromes
PT/PTT > 1.5 × Normal

33. Cryoprecipitate
• Precipitated proteins of plasma , rich in factor VIII
and fibrinogen, obtained from FFP , prepared by
thawing FFP at 4-6 o C and removal of supernant,
within 6-8 hours of collection
• Cryoprecipitate ( 1 Pack) Contents:
Constituents Amount
Volume 10-20 ml
Factor VIII 80 – 120 IU
Fibrinogen 150 – 250 mg
Von-Willebrand Factor 40 – 70 % 0f original FFP
Fibronectin 55 mg
Factor XIII 20 – 30 % 0f original

34. Storage, Shelf-life and Dosage
Storage: - 20o C
Shelf-life:
Frozen- 1 Year
Thawed- 6 hours
Dosage: Depend on severity of deficiency and
bleeding.
Each unit of Cryo raises Factor VIII by 2%,
therefore to achieve plasma factor VIII rise of
20%, 10units/kg have to be infused

35. Indications
• Haemophilia A
• Von-Willebrand disease
• Congenital or acquired fibrinogen deficiency
• Factor XIII deficiency
• Also used in local haemostatic agents as a
source of fibrin

36. Granulocyte concentrates
• Available as:
• Buffy coat granulocyte concentrates
• Content: 0.6 × 109 / L in 15-20ml plasma
• Apheresis granulocytes
• Contents: 1 × 1010 /L granulocytes in 200-400 ml
plasma

37. Storage , Shelf-life and Dosage
Storage:
20 – 24 o C for 24 hours
• Dosage:
• Adult: 1 apheresis unit or 18-20 buffy coats daily
• Neonates: 0.5-0.6 × 1010 /L granulocytes daily or
8-10 buffy coats or half unit of apheresis
granulocytes daily.

38. Indications
• Chronic Granulomatous
Disease(Congenital Neutrophil defects)
• Chemotherapy induced Neutropenia
• Treatment of infection
• Infection prophylaxis
• Aplastic Anaemia
• Neonatal Sepsis

39. Cryoprecipitate Poor Plasma
• Byproduct of Cryoprecipitate preparation
• Lacks factor V , VIII and Fibrinogen
• Indications:
• Coagulopathies due to deficiency of other
stable clotting factors, drugs etc.
• Dose: Same as FFP

40. D. Investigations as per TRRF
• Clerical Check:
Clerical Check must be performed to ensure that
right blood was administered to the right pateint
.
1. Check on the cross match label and on the blood
bag:
 Blood bag number and blood group
2. Check on the cross match label and the patient’s
file:
 Patient’s name and CR No.

41. • Repeat Blood Grouping:
To Re-Confirm Blood Type
• Repeat Crossmatch:
To Re-confirm Compatibility
• Repeat Antibody Screen:
To detect the presence of unexpected
antibodies
• Antibody identification
To detect type of antibody involved.

42. Direct Antiglobulin Test
• To detect invivo sensitization ( coating) of
red cells with immune antibody IgG or the
compliment component generally C3d.
• Principle:
Red cells coated with incomplete
antibody (IgG) or C3 component of the
complement , will be agglutinated by the
antihuman globulin (AHG) reagent.

43. Other Tests
• Haemoglobulin test
• Plasma Haemoglobulin test
• Urine haemoglobulin test
• Bilirubin(Total/Conjugated) test
• Platelet count
• Prothrombin time
• Blood culture of patient and blood bag
• Chest x-ray in case of suspected TRALI

44. General Definitions of Adverse Events
• Adverse event is an undesirable and
unintended occurrence before, during or after
transfusion of blood or blood component which
may be related to the administration of the blood
or component. It may be the result of an error or
an incident and it may or not result in a reaction
in a recipient.

45. • Incident is a case where the patient is
transfused with a blood component which did
not meet all the requirements for a suitable
transfusion for that patient, or that was
intended for another patient. It thus
comprises transfusion errors and deviations
from standard operating procedures or
hospital policies that have lead to
mistransfusions. It may or may not lead to an
adverse reaction.

46. • Near miss is an error or deviation from
standard procedures or policies that is
discovered before the start of the transfusion
and that could have led to a wrongful transfusion
or a reaction in a recipient.
• Adverse reaction is an undesirable response
or effect in a patient temporally associated with
the administration of blood or blood component.
It may, but need not, be the result of an incident.

47. Adverse Event
Adverse Reaction
Near Miss
Incident

48. Transfusion Reactions
• Any unfavourable transfusion related
event(Adverse Event) occurring in a patient
during or after transfusion of blood or blood
components.
• Depending upon the time of occurrence,
transfusion reactions are divided into:
– Acute/immediate: within < 24 hrs
– Delyaed : >24 hrs

49. Based upon Onset of Reaction

50. Based upon severity:
• Grade 1 (Non-Severe):
- the recipient may have required medical
intervention (e.g. Symptomatic treatment) but
lack of such would not result in permanent
damage or impairment of a body function.

51. • Grade 2 (Severe):
• the recipient required in-patient hospitalization
or prolongation of hospitalization directly
attributable to the event; and/or
• the adverse event resulted in persistent or
significant disability or incapacity; or
• the adverse event necessitated medical or
surgical intervention to preclude permanent
damage or impairment of a body function.

52. • Grade 3 (Life-threatening):
The recipient required major intervention following
the transfusion (vasopressors, intubation, transfer to
intensive care) to prevent death.
• Grade 4 (Death):
The recipient died following an adverse transfusion
reaction.
Grade 4 should be used only if death is
possibly, probably or definitely related to
transfusion. If the patient died of another
cause, the severity of the reaction should be
graded as 1, 2 or 3.

53. Based upon Etiopathogenesis
A. Immune Mediated TRs
I. Immediate TR II. Delayed TR
1. Acute hemolytic TR(AHTR)
2. Febrile Non-Hemolytic TR (FNHTR)
3. Allergic TR
4. Anaphylactic TR
5. Transfusion Related Acute Lung
Injury(TRALI)
1. Delayed hemolytic TR (DHTR)
2. Alloimmunization
3. Post-transfusion Purpura
4. Transfusion related Graft versus
host disease(GvHD)
5. Immunomodulation
B. Non-immune mediated TRs
I. Immediate TR II. Delayed TR
1. Hemolytic –Physical/chemical damage to
RBCs
2. Bacterial contamination
3. Circulatory overload
4. Coagulopathy: Depletion/dilution of
coagulation factors or platelets
5. Air embolism
6. Metabolic citrate toxity, hyperkalemia,
hypokalemia
1. Transfusion associated
infections
2. Iron overload

54. E. Based Upon Nature of Transfusion Reaction
• Hemolytic Transfusion Reactions
– Most severe type of transfusion reactions
A hemolytic transfusion reaction is one in which
symptoms and clinical or laboratory signs of
increased red cell destruction are produced by
transfusion. Hemolysis can occur intravascularly or
extravascularly and can be immediate (acute) or
delayed.

55. HTRs
• Acute HTRs
• Delayed HTRs
• Intravascular TR
• Extravascular TR

56. Acute Hemolytic Transfusion Reaction(AHTR)
An AHTR has its onset within 24 hours of transfusion.
Common signs of AHTR
are:
• · Fever
• · Chills/rigors
• · Facial flushing
• · Hypotension
• · Pallor
• · Jaundice
• · Oligoanuria
• · Diffuse bleeding
• Chest pain
• Abdominal pain
• Back/flank pain
• Nausea/vomiting
• Diarrhea
• Dark urine

57. • Common laboratory features are:
– · Hemoglobinemia
– · Hemoglobinuria
– · Decreased serum haptoglobin
– · Unconjugated hyperbilirubinemia
– · Increased LDH an AST levels
– · Decreased hemoglobin levels
Not all clinical or laboratory features are
present in cases of AHTR.

58. • Blood group serology usually shows
abnormal results but absence of
immunological findings does not exclude
AHTR. AHTR may also be due to
erythrocyte auto-antibodies in the recipient
or to non immunological factors like
mechanical factors inducing hemolysis
(malfunction of a pump of a blood warmer,
use of hypotonic solutions, etc.).

59. • Delayed hemolytic transfusion reaction
(DHTR)
A DHTR usually manifests between 24 hours
and 28 days after a transfusion and clinical or
laboratory features of hemolysis are present.
Signs and symptoms are similar to AHTR but are
usually less severe. DHTR may sometimes
manifests as an inadequate rise of post -
transfusion hemoglobin level or unexplained fall
in hemoglobin after a transfusion. Blood group
serology usually shows abnormal results.

60. Hemolysis
• Immunological
ABO Incompatibility, Alloimmunization
• Non-immune-mediated hemolytic transfusion
reactions
• These are generally related to improper storage and handling
of blood leading to hemolysis in vitro prior or during transfusion:
• Thermal injury: During re-warming of the blood if temperatures
reach more than 42°C
• Cold injury: Inappropriate storage with exposure to ice or
temperatures less than 6°C
• Mechanical injury: Lysis during transfusion through small-bore
catheters.
• Infection
• Concomitant drug-induced hemolysis
Concomitant administration of hypotonic solutions (D5%W,
hypotonic saline) leading to osmotic injury.

61. Intravascular Transfusion Reaction
• In Intravascular Transfusion Reaction, the
hemolysis of red blood cells takes place within the
circulatory system. This type of hemolysis is mainly
due to IgM antibodies, mediated by rapid activation
of complement and is usually associated with ABO
incompatibility. The clinical effects of an
intravascular transfusion reaction are immediate,
usually within minutes after starting the transfusion
, thus also called Acute Hemolytic Transfusion
Reaction(AHTR). This is the most severe and life
threatening reaction.

62. • Extravascular transfusion reactions are rarely
severe and occur mainly due to IgG antibodies eg.
Rh, Kell, Duffy system. These antibodies bring
about the destruction of red cells by the
macrophages in the spleen or liver.
• Clinical evidence of reaction is somewhat slower
and in some cases may be delayed up to two
weeks or more after transfusion, thus also called
Delayed Haemolytic Transfusion Reaction which
could be due to
Primary alloimmunization
Anamnestic or secondary response
Extravascular Transfusion Reaction

63. • In primary alloimmunization , the patient develops
an antibody after couple of weeks after transfusion
and is mostly due to incompatibility of Rh or Kell
system.
• Anamnestic or secondary response occurs in
patients, previously sensitized to red cell antigens,
but the level of circulating antibody to transfused
RBC is so low that they cant be detected in the
cross-match procedure, but since the patient is
immunized , there is increase in antibody
production(anamnestic response) resulting in red
cell destruction.This type of reaction is usually mild
to moderate and the signs and symptoms include
fever, anema, jaundice, and rarely haemoglobinuria.

64. Causes of Haemolytic Transfusion Reactions
• Clerical Errors
Majority of haemolytic transfusion reactions
are due to clerical errors and are mainly due
to:
 Inadequate or incorrect labelling of blood i.e.
Recipient’s pre-transfusion sample, blood
bag or pilot tube.
 Improper identification of patient either at the
time of sample collection or trabsfusion of
blood.

65. • Technical Errors
• Error in blood grouping of recipient or donor
• Incompatibility not detected in cross matching
procedure due to improper technique.
• Destruction of recipients RBCs by donor
antibodies, due to indiscriminate use of group
‘O’ blood.
• Failure to detect weak antibodies.

66. ABO Incompatibility
• The A and B antigens are the most immunogenic;
hence transfusion of an ABO incompatible unit causes
the recipient antibodies to interact with the donor RBC
surface antigens, triggering complement activation and
resulting in the acute intravascular hemolysis of the
transfused donor RBCs.
•
Complement activation causes various pro-
inflammatory effects via release of active C3a and C5a
subcomponents. These are anaphylatoxins which
cause histamine and serotonin release from mast cells,
increase vascular permeability causing a capillary leak
syndrome and stimulate smooth muscle contraction.
These translate clinically into the classical symptoms of
flushing, hypotension and bronchospasm, respectively.

67. • Experimental evidence supports a central role for
cytokines in the pathophysiology of hemolytic
transfusion reactions. Tumor necrosis factor (TNF)
appears to be the most commonly identified mediator
of intravascular coagulation and end-organ injury
although other cytokines have been implicated
including interleukin (IL)-8, monocyte chemoattractant
protein, and IL-1 receptor antagonist.
•
Ultimately, the complement cascade terminates with
activation of the membrane attack complex (MAC)
leading to cytolysis. The released hemoglobin
tetramers complex with haptoglobin and are removed
by the liver, causing haptoglobin depletion. Residual
free hemoglobin circulates in the plasma or gets
converted to oxidized methemoglobin in the blood,
imparting a reddish or brownish color, respectively.

68. • Small, unbound hemoglobin dimers are also filtered by
the glomerulus which causes hemoglobinuria. This
heme pigment causes acute kidney injury directly or
via tubular obstruction or vasoconstriction. In practice,
this heme-induced acute tubular necrosis requires a
secondary factor like dehydration, nephrotoxin use or
sepsis to translate into significant renal insufficiency.
•
The hemoglobin is taken up by the renal tubular cells,
degraded and the iron is stored as hemosiderin. When
these renal tubular cells are sloughed in the urine 3-10
days later, hemosiderinuria becomes detectable.

69. • Delayed serologic reaction (DSTR)
There is a DSTR when, after a transfusion, there
is demonstration of clinically significant
antibodies against red blood cells which were
previously absent (as far as is known) and when
there are no clinical or laboratory features of
hemolysis. This term is synonymous with
alloimmunization.

70. Non-Haemolytic Transfusion Reactions
• Febrile non hemolytic transfusion reaction
(FNHTR)
• Allergic reaction
• Anaphylaxis
• Transfusion associated graft-versus-host disease
(TA-GVHD)
• Post transfusion purpura (PTP)
• Transfusion-related acute lung injury (TRALI)
• Transfusion associated dyspnea (TAD)
• Transfusion associated circulatory overload
(TACO)
• Hypotensive transfusion reaction
• Transfusion transmitted infections

71. Febrile non-hemolytic transfusion reaction
(FNHTR)
• There is a FNHTR in the presence of one or more of:
Fever (≥38oC oral or equivalent and a change of ≥1oC
from pretransfusion value), chills/rigors
• This may be accompanied by headache and nausea.
• Occurring during or within four hours following transfusion
without any other cause such as hemolytic transfusion
reaction, bacterial contamination or underlying condition.
• FNHTR could be present in absence of fever (if chills or
rigors without fever).
• FOR THE PURPOSE OF INTERNATIONAL
COMPARISONS ONLY THE MOST SERIOUS CASES
OF FNHTR SHOULD BE ACCOUNTED FOR:
• Fever (≥39oC oral or equivalent and a change of ≥2oC
from pretransfusion value) and chills/rigors

72. Contd..
• FNHTRs result from the patient’s reaction to
donor white blood cells or to biological response
modifiers in the component.4
• Pre-storage leukoreduction reduces the rate of
FNHTRs.5
• Patients may present with either mild, moderate or
severe reactions.6

73. • Allergic reaction
• An allergic reaction may present only with
mucocutaneous signs and symptoms:
– · Morbilliform rash with pruritus
– · Urticaria (hives)
– · Localized angioedema
– · Edema of lips, tongue and uvula
– · Periorbital pruritus, erythema and edema
– · Conjunctival edema
• occurring during or within 4 hours of transfusion. In this
form it usually presents no immediate risk to life of
patient and responds quickly to symptomatic treatment
like antihistamine or steroid medications. This type of
allergic reaction is called ‘minor allergic reaction’ in
many hemovigilance systems.
• For the purpose of classification this type of allergic reaction
would be graded as 1, i.e. non-severe.

74. • Anaphylaxis
• An allergic reaction can also involve respiratory and/or
cardiovascular systems and present like an anaphylactic
reaction. There is anaphylaxis when, in addition to
mucocutaneous systems there is airway compromise or
severe hypotension requiring vasopressor treatment (or
associated symptoms like hypotonia, syncope). The
respiratory signs and symptoms may be laryngeal (tightness
in the throat, dysphagia, dysphonia, hoarseness, stridor) or
pulmonary (dyspnea, cough, wheezing/bronchospasm,
hypoxemia). Such a reaction usually occurs occurring during
or very shortly after transfusion.
• For the purpose of classification this type of allergic reaction
would be graded as 2 (severe), 3 (life-threatening) or 4 (death)
depending on the course and outcome of the reaction.

75. • An allergic reaction classically results from
the interaction of an allergen and preformed
antibodies. A rise of mast cell tryptase can
support the diagnosis of an allergic
reaction. IgA deficiency and/or anti-IgA in
the recipient has been associated with
severe allergic reactions but is only one
infrequent cause out of many others.

76. Transfusion associated graft-versus-host
disease (TA-GVHD)
• TA-GVHD is a clinical syndrome characterised by
symptoms of fever, rash, liver dysfunction,
diarrhea, pancytopenia and findings of
characteristic histological appearances on biopsy
occurring 1-6 weeks following transfusion with no
other apparent cause.
• The diagnosis of TA-GVHD is further supported by
the presence of chimerism.

77. Graft versus Host Disease
• Graft versus host disease is a rare complication following
transfusion but has been reported in a variety of
conditions in which the immune system is depressed. It
is caused by the donor’s lymphocytes engrafting in the
recipient and reacting against host antigen. Patients with
congenital immunodeficiency syndrome , lymphomas
(especially Hodgkin's disease) and post chemotherapy
patients are at risk.
• GVHD occurs in three phases:
– The presentation of host protein by host’s antigen
presenting cells to donor T cells.
– Activation , proliferation , and migration of donor-T
cells.
– Damage of host target tissue.

78. Post Transfusion Purpura (PTP)
• PTP is characterized by thrombocytopenia arising 5-12
days following transfusion of cellular blood components
with findings of antibodies in the patient directed against
the Human Platelet Antigen (HPA) system.
• PTP is caused by platelet-specific antibodies in a patient
who has been previously exposed to platelet antigens
through pregnancy or transfusion. The most frequently
identified antibody is Anti-PLA1, which reacts with platelet
antigen HPA-1a. The platelet antibody binds to the platelet
surface, which allows for extravascular removal through the
liver or the spleen. The patient's own platelets are
destroyed as well, thus aggravating the thrombocytopenia.4
• Treatment with intravenous immunoglobulin,corticosteroids,
exchange transfusion, and plasmapheresis has been
reported with variable success.5

79. Transfusion-related acute lung injury
(TRALI)
• TRALI is defined as noncardiogenic pulmonary oedema
following blood transfusion. Although all blood components
have been implicated in TRALI, frozen plasma is the most
common.2
• In patients with no evidence of acute lung injury (ALI) prior
to transfusion, TRALI is diagnosed if a new ALI is present.
• Features:
– Acute onset
– Hypoxemia
– Pa02 / Fi02 < 300 mm Hg or
– Oxygen saturation is < 90% on room air or
– Other clinical evidence
– Bilateral infiltrates on frontal chest radiograph
– No evidence of left atrial hypertension (i.e. circulatory
overload)
– No temporal relationship to an alternative risk factor for
ALI during or within 6 hours of completion of transfusion

80.  Alternate risk factors for ALI are:
• Direct Lung Injury
– Aspiration
– Pneumonia
– Toxic inhalation
– Lung contusion
– Near drowning
• Indirect Lung Injury
– Severe sepsis
– Shock
– Multiple trauma
– Burn injury
– Acute pancreatitis
– Cardiopulmonary bypass
– Drug overdose
Contd...

81. • It has been suggested by the Toronto TRALI
Consensus Panel to add a category of possible
TRALI that would have the same definition as
TRALI except for the presence of a temporal
relationship to an alternative risk factor for ALI (as
described above). In such a circumstance TRALI
should be indicated with a possible imputability to
transfusion.
• TRALI is therefore a clinical syndrome and
neither presence of anti-HLA or anti-HNA
antibodies in donor(s) nor confirmation of cognate
antigens in recipient are required for diagnosis.

82. Mechanism
• ALI results from capillary endothelial leak that
causes fluid to pass from the pulmonary vessels
first into the interstitial space and then into the
alveolar space causing pulmonary edema.
• It has now been established that neutrophills play a
central role in the occurrence of lung damage
through the release of granular enzymes, proteins,
and reactive oxygen species after being activated.
• Neutrophills may either be directly activated by one
strong stimulus, or are more commonly first primed
and then activated.
• It is the activation of neutrophills and their
interaction with the endothelium that leads to
endothelial damage and capilarry leakage
Contd.....

83. Various stimuli causing priming and activation of
neutrophills and endothelium
• Antibodies: these antibodies are present in transfused
blood products and TRALI is most commonly associated
with transfusion of plasma products. Antibodies may be:
• Leukocyte antibodies ; When transfused with plasma
products from multi transfused individual or multiparous
women. HLA-II antibodies are more commonly
implicated than HLA-I antibodies.
• Anti-neutrophill antibpdies (HNA): particularly notorious are
antibodies of specificity HNA-2a, HNA-3a,HNA-4a which are
capable of directly activating neutrophills and causing TRALI

84. Clinical Features of TRALI
• Sudden deterioration in lung function
• Tightness in the chest
• Shortness of breath
• Dry cough
• Nausea and dizziness
• Fever and rigors
• Hypoxia, hypotension, tachycardia, and tachypnoea
• Chest auscultation: widespread crepitations.
• Hallmark finding: Copious frothy tracheal exudates
in intubated patients.
• Chest X-ray : bat’s wing pattern of pulmonary
edema
• BNP< 250 pg/ml

85. Transfusion associated dyspnea (TAD)
• TAD is characterized by respiratory distress within
24 hours of transfusion that does not meet the
criteria of TRALI, TACO, or allergic reaction.
Respiratory distress should be the most prominent
clinical feature and should not be explained by the
patient’s underlying condition or any other known
cause.

86. Transfusion associated circulatory overload
(TACO)
• TACO is characterized by any 4 of the
following:
– Acute respiratory distress
– Tachycardia
– Increased blood pressure
– Acute or worsening pulmonary edema on
frontal chest radiograph
– Evidence of positive fluid balance
– Occurring within 6 hours of completion of
transfusion.
– An elevated BNP is supportive of TACO.

87. TACO is a condition characterised by left ventricular
failure and pulmonary oedema due to fluid overload.
This occurs either during transfusion or within the
following six hours, in transfusions with a rapid
infusion rate or a high volume of transfused products.
Risk factors include extremes of age (patients >60
years or <3 years), pre-existing cardiac and/or renal
dysfunction, transfusions after an acute myocardial
infarction, plasma transfusions, pre-existing positive
fluid balances in the 24 hours prior to the transfusion
and large-volume transfusions.2
Contd...

88. Patients present with acute respiratory distress,
dyspnoea, cyanosis, orthopnea, hypoxia, increase in
systolic blood pressure (>20 mmHg above the baseline)
and signs of cardiac overload (jugular venous pressure
elevation and bilateral crepitation).1 Patients tend to
respond to diuretics and worsen with fluid boluses. A
CXR will show pulmonary oedema and cardiomegaly
and an echocardiogram will be abnormal. There is
some evidence suggesting that B-type natriuretic
peptide (BNP) is a sensitive and specific marker of
TACO. Until further evidence is available, BNP levels
should be used as an adjunct marker to other features
of volume overload in confirming the diagnosis of
TACO.2

89. Hypotensive transfusion reaction
• This reaction is characterized by hypotension defined as
a drop in systolic blood pressure of ≥30 mm Hg
occurring during or within one hour of completing
transfusion and a systolic blood pressure ≤ 80 mm Hg.
• Most reactions do occur very rapidly after the start of the
transfusion (within minutes).
• This reaction responds rapidly to cessation of transfusion
and supportive treatment. This type of reaction appears
to occur more frequently in patients on ACE inhibitors.
• Hypotension is usually the sole manifestation but facial
flushing and gastrointestinal symptoms may occur.
• All other categories of adverse reactions presenting with
hypotension, especially allergic reactions, must have
been excluded. The underlying condition of the patient
must also have been excluded as a possible explanation
for the hypotension.

90. Transfusion transmitted Bacterial infections
Bacterial contamination of a blood component can
occur either at the time of donation (due to subclinical
donor bacteremia or non-adherence to aseptic
techniques during the phlebotomy) or during blood
component preparation, storage or handling. This can
cause a septic ATR when the component is tranfused to
a recipient. Both Gram-negative and -positive bacteria
have been implicated. Although these reactions
can occur with any blood component, platelets are
the most commonly implicated since they are stored
at room temperature which allows faster bacterial
growth. When the implicated unit is transfused, the
patient rapidly develops acute manifestations.
Contd...

91. • Bacterial contamination should be considered if
the patient presents with a moderate or severe
fever defined as a temperature ≥39 °C or a
temperature rise of ≥2 °C from baseline.
• Bacterial contamination should also be suspected
if any fever is accompanied with systemic
symptoms such as chills, rigors, severe
hypotension, shock, dyspnoea, myalgia, nausea or
vomiting.
• Symptoms may develop rapidly or within four
hours of the transfusion.
• The severity of the reaction is influenced by the
type of bacteria involved, bacterial load and the
recipient’s clinical status.

92. • Shock and disseminated intravascular coagulation
(DIC) can occur if a Gram-negative bacterially
infected unit with high levels of endotoxin was
transfused.
• There should be increased caution in patients
receiving blood transfusions while under
anaesthesia (where manifestations may be
masked) in patients with underlying fevers and in
those who have been pre-medicated with
antipyretics, as they may not develop a high-grade
temperature as a warning sign.

93. Transfusion Transmitted Parasitic Infections6
• Although the incidence of blood transfusion-transmitted
parasitic infections (TTPI) is lower in comparison to that of
bacterial and viral infections, these organisms pose a
considerable risk of illness, especially in
immunocompromised individuals.
• As we know, bacterial contamination can occur at numerous
points during the collection and the transfusion process but
the TTPI are always donor derived. The most common
parasitic organisms implicated in transfusion-transmitted
infections are Plasmodium spp., Trypanosoma cruzi,
Babesia microti, Toxoplasma gondii, Leishmania spp. etc.
• Of the major transfusion-transmitted diseases, malaria is a
major cause of TTIP in tropical countries whereas
babesiosis and Chagas’ disease pose the greatest threat to
donors in the USA In both cases, this is due to the
increased number of potentially infected donors.

94. Other transfusion reactions
a) Haemosiderosis
Transfusion-associated haemosiderosis is being
defined as a blood ferritin level of 1000
micrograms/l, with or without organ dysfunction in the
setting of repeated RBC transfusions.
b) Hyperkalemia
Any abnormally high potassium level (> 5 mml/l, or 1.5
mml/l net increase) within an hour of transfusion can
be classified as a transfusion- associated
hyperkaliemia.
c) Unclassifiable Complication of Transfusion (UCT)
Occurrence of an adverse effect or reaction temporally
related to transfusion, which cannot be classified
according to an already defined ATR and with no risk
factor other than transfusion and no other explaining
cause.

95. F. Imputability Assessment
This is, once the investigation of the adverse transfusion event is completed,
the assessment of the strength of relation to the transfusion of the ATE.
• Definite (certain):
when there is conclusive evidence beyond reasonable doubt that the adverse
event can be attributed to the transfusion
• Probable (likely):
when the evidence is clearly in favor of attributing the adverse event to the
transfusion
• Possible:
when the evidence is indeterminate for attributing the adverse event to the
transfusion or an alternate cause
• Unlikely (doubtful):
when the evidence is clearly in favor of attributing the adverse eventto causes
other than the transfusion
• Excluded:
when there is conclusive evidence beyond reasonable doubt that the adverse
event can be attributed to causes other than the transfusion

96. References
 1.Proposed standard definitions for surveillance of non infectious adverse
transfusion reactions by International society of blood transfusion(ISBT), july
2011
 2.Recognition, Investigation and Management of Acute Transfusion Reactions
by *Arwa Z. Al-Riyami,1 Sabria Al-Hashmi,2 Zainab Al-Arimi,3 Louis D.
Wadsworth,4 Abdulhakim Al-Rawas,5 Murtadha Al-Khabori,1 Shahina Daar6
 3.Hemolytic transfusion reactions (ABO incompatibility) by Kristen Kipps : The
journal of family practice
 4.Pathophysiology, Treatment, and Prevention of Post-Transfusion Purpura
(PTP): LabCE Online laboratory continuing education for clinical laboratories
and med techs
 5.Post-transfusion purpura: case report. Kumar R, Ghali A, Ekaldious AW,
Mahmoud OI Al-Lumai AS
 6. Transfusion-transmitted parasitic infections Gagandeep Singh and Rakesh
Sehgal: Department of Parasitology, PGIMER, Chandigarh-160012, India:
Asian Journal Of Transfusion Science
 Principles & Practice of Transfusion Medicine by Dr. (Prof) R. N. Makroo, Ist
edition ,2014