Transfusion reactions are those reaction which is caused by the transfusion of blood or blood products at the time of transfusion or after completion of transfusion. each reaction should be consider serious.

1. Hazards of Transfusion
Muhammad Asif Zeb
Lecturer-Hematology
Khyber medical university
Peshawar

7.  Hazards to the Donor
 Hazards to Recipient / Patient

8. Transfusion risks and adverse reactions
 Many of the signs and symptoms of transfusion reactions are
Similar
 All reactions should be taken seriously
 The most commonly encountered reactions are
– Allergic – not life-threatening
– Febrile – respond to treatment
 Reactions that cause the most concern are
– Transfusion related acute lung injury (TRALI),
– ABO mismatch,
– TA-GvHD
– Sepsis
Introduction

9. Introduction
 ABO incompatible blood can lead to serious consequences.
 Precautions should be taken during:
– Collection of specimen of blood
– Cross matching procedures
– At the time of issue
– At the time infusion of the crossmatched unit of blood
ensure that no error in patient identification is made.

10. Haemolytic reactions
 When transfused red cells are destroyed in the recipient, this is
classified as a haemolytic transfusion reaction.
 These reactions are either acute or delayed,
& cell destruction is either intra- or extravascular.
Acute reactions
 Reactions that occur shortly after the start of the transfusion ar
termed acute.
 Although there are many reasons why a recipient could react
immediately – it may be an indication of ABO incompatibility

11. Haemolytic reactions
Delayed reactions
 Occur due to red cell incompatibility - becomes apparent > 24
hours after transfusion.
 Recipient red cell antibodies – too weak for detection during
crossmatching or antibody screening
 Immune response occurs in the recipient – transfused cells ar
removed from the circulation.
 No reaction occurs immediately after transfusion – reaction is
suspected when the Hb fails to increase after transfusion.
 Kidd antibodies are sometimes implicated in delayed reactions

12. Extravascular haemolytic reactions
 Extravascular reactions – antibodies - that do not activate compleme
– Rh, Duffy or Kell etc.
 Incompatible - sensitized red cells – removed from by RE systems
liver or spleen.
 Hyperbilirubinaemia is seen
 The severity of a haemolytic reaction depends
– Immunoglobulin class of antibody
– Specificity of antibody
– Thermal range of antibody
– Activation of complement
– Titre and strength or potency of antibody responsible and
– Volume of red cells (with the corresponding antigen)
transfused.

13. Major incompatibility
 Serious haemolytic transfusion reactions may occur when
a patient receives blood of the incorrect ABO group,
usually as a result of misidentification.
 patient Such errors mostly occur
– In emergency situations when personnel are under
extreme pressure
– During quiet times when there is lack of concentration
on the job at hand.
 The reactions usually involve antibodies in the recipient
that react with antigens on the incoming red cells.

14. Minor incompatibilities
 An adverse reaction seen
– Plasma high titre or haemolysing ABO antibodies – transfu
into a compatible but ABO non-identical group
– Example : donor group O plasma with high titre or haemoly
anti- A – transfused to group A recipient.
– Donor plasma contains strong, irregular antibodies of
other specificities – in recipient with corresponding
antigen
 These adverse reactions are termed minor
incompatibilities – occur rarely

15. Haemolytic transfusion reaction
Signs and symptoms
– Urticaria/rash
– Pruritus (itching)
– Headache
– Restlessness
– Unexplained bleeding
– Lower back and joint pain
– Tachycardia and chest pain
– Sudden change in blood pressure

16. CLASSIFICATION
Transfusion reaction
acute delayed
Immunologic Nonimmunologic Immunologic Nonimmunologic

17. Haemolytic transfusion reaction
Indication when recipient is anaesthetize
 Haemoglobinuria
 Oliguria and / or anuria
 Shock.

18. ABO hemolytic transfusion reaction
 ABO mismatch blood administration
 Activation of complement system lead to lysis of RBC,s
 C3a, C5a are anaphylotoxin and cause activation and
attraction of Monocytes and neutrophils, endothelial cells,
macrophages, platelets.
 Activation leads to release of interleukin and cytokines, e.g
IL 6,8,1, TNFα,
 Interleukin 8 (IL-8), which activates neutrophils, and
tumor necrosis factor alpha (TNFα), which activates the
coagulation cascade.

19.  C3a and C5a also activates mast cells and basophiles
releasing histamine and serotinin leading to
vasodilatation, smooth muscles constriction espicialy
bronchial and GIT
 Hypotension may be due to vasodilation of blood
vessels.
 DIC
 may lead to bleeding from different site
 Intrinsic pathway of coagulation activation due to Ag
Ab comlex

20.  Extrinsic due to Activated complement, as
well as TNFα and IL-1 which cause
increase expression of Tissue factor.
 Shock may be a component of DIC
 Renal failure
 Due to free hb
 Thrombus formation
 Ag Ab complexes
 vasoconstraction

23. Nonimmune-Mediated Hemolysis
 Transfusion-associated hemolysis can also occur from several
nonimmune-mediated causes.
 Before issue, improper shipping or storage temperatures as
well as incomplete deglycerolization of frozen red cells can
lead to hemolysis.
 At the time of transfusion, using a needle with an
inappropriately small bore size or employing a rapid pressure
infuser can cause mechanical hemolysis, which may be seen
with the use of roller pumps as well.
 Improper use of blood warmers or the use of microwave ovens
and hot water baths can cause temperature-related hemolysis.

24. Febrile Nonhemolytic
Transfusion Reactions
 Studies found that as few as 0.25 × 109 leukocytes could produce a
temperature elevation in the recipient.
 FNHTRs may also be the result of accumulated cytokines in a cellular
blood component.
 This mechanism may be particularly relevant in reactions seen after the
transfusion of platelets.
 Some FNHTRs are attributable to recipient antibodies, particularly HLA
anti- bodies, that react with antigens on transfused lymphocytes,
granulocytes, or platelets.
 Cytokine release in the recipient in response to these antigen-antibody
reactions may con- tribute to the severity of the reaction

25. Pathogenesis
 Fibrile non hemolytic transfusion reaction
• ?? Previous Transfusion &/Or Preganancies
• Temprature↑ α No: of Leucocytes Transfused
• ?Reacting - Antibodies to HLA reacting with donor leucocytes
Recipient Abs bind to Donor leucocyte Ags
↓
Fix Complements
↓
Activate recipients Monocytes, Lymphocytes & Endothelial cells
↓
secrete Pyrogens Mainly IL-1

26.  Platelet Transfusion
 ?? Without prior sensitization
• Due to presence of Pyrogenic Cytokines
IL-1β, IL-6 & TNF-α released from leucocytes during the 5
day platelets storage
Theory supported by
a. Very high levels of Cytokines during storage
b. Reaction associated with the plasma portion
c. Not prevented by bedside filteration
d. No ↑ of Cytokines if pre-storage leucocyte filtered

27. Signs and symptoms
 Chills or rigors and fever are noted after
transfusion.

28. Allergic Reactions
 Most allergic transfusion reactions are
mild, but the spectrum can range from a
simple allergic reaction (urticaria) to
anaphylaxis.
 Symptoms generally occur within
seconds or minutes of the start of the
transfusion.

30. Pathophysiology
 Allergic reactions are hypersensitivity reactions to allergens in
the component and are less commonly caused by antibodies
from an allergic donor.
 Preformed IgE antibody in the patient or recipient interacts wi
the allergen, usually a plasma protein in the component.
 Mast cells are activated by the binding of allergen to the IgE
bound to the mast cells (type I hypersensitivity).
 Activation results in degranulation, with the release of
preformed histamine, chemotactic factors, proteases, and
proteoglycans.
 Secondary mediators, including cytokines and lipid mediators
such as arachadonic acid metabolites, leukotrienes, and
prostaglandin D2, as well as platelet-activating factor, are
generated and released in response to mast cell activation

31. Signs and symptoms
 Simple allergic reactions – cause a diffuse rash (urticaria) &
itchy, swollen red areas on the skin
 Immune complexes of antigen–antibody in recipient or the
donor - stimulate tissue mast cells to release histamine
it results in
– Vasodilatation
– Raised red marks on the skin
occur during the transfusion or within an hour
 Oedema (swelling) of the face, lips or mouth - occasionally
 Difficulty in breathing occur sometimes

32. Transfusion associated acute lung injury
 TRALI is caused by anti-HLA or anti-granulocyte antibodies in donor
plasma.
 Antibodies formed - sensitization of donors
– With a history of pregnancy - multiparous female
– Previous blood transfusion.
 Plasma containing these antibodies may activate complement in vivo
 WhenTransfused,cause lung injury in the recipient.
 When large volumes of components containing plasma are transfused
-TRALI is more likely
 Small volumes of plasma may also cause a reaction.

33. Transfusion associated acute lung injury
Signs and symptoms
 Dyspnoea
 Hypotension
 Fever and rigors soon after the onset of reaction
 Pulmonary oedema
 Hypovolaemia
 Hypotension
 This is quickly followed by severe hypoxia – with
frothy fluid in the trachea

34. Sepsis – bacterial contamination of
products transfused
 Blood is an ideal medium for growth of harmful bacteria.
 It is important to:
– Clean the venepuncture site thoroughly prior to donation
– Maintain the cold chain for storage & transportation of
blood components
 Platelet concentrate is at the greatest risk of bacterial
contamination – stored at the higher temperature of
22°C ± 2°C.

35. Reasons of Bacterial Contamination of blood
donation
• Introduction of micro-organisms – time of donation
– Inadequately cleaned venepuncture site
– Contamination of needle
• Introduction of micro-organisms – component preparation and storage
– Faulty equipment or blood bags
– Introduction of air into the container of blood
• Storage and transportation of blood – at high temperatures
• Bacteraemia in an apparently healthy donor
– Endotoxin-producing Gram-negative bacilli – Yersinia
enterocolitica - present as subclinical infection in donor
– Endotoxins may lead to extremely severe reactions & death of
recipient.

36.  Bacterial contamination of a unit of stored blood may
be obvious, with a dark brown or purple appearance.
 Heavily infected blood may look normal.
 Cloudiness may be a sign of contamination in a unit of
platelet concentrate.
 Some transfusion services have the facility to screen
all platelet concentrates and discard contaminated PC

37. Signs and symptoms
 When infected blood is transfused, symptoms usually appear
within 30 minutes.
 These are
– Chills
– Headache
– Vomiting
– Muscular pain
– Diarrhoea
– High fever
– Hypotension (low blood pressure)
– Shock.
 There is marked erythema (redness) of the skin – in contrast to
the pale, cold skin of haematogenic shock (through blood
loss).

38. Delayed Hemolytic Transfusion
Reaction (DHTR)
 Mechanism
– Antibodies that exist in low titers prior to the transfusion
– Typically to the Kidd, Duffy or Kell system
– Upon re-exposure, titer increases from memory B-cells
– Resulting Extra vascular red cell distruction
– Usually occur 5-10 days after Tx
Delayed HTRs are defined as fever and other symptoms / signs
of haemolysis more than 24 hours after transfusion; confirmed
by one or more of: a fall in Hb or failure of increment, rise in
bilirubin, positive DAT and positive cross-match not detectable
pre-transfusion.

39. Pathophysiology
 A patient may make an antibody to a red cell antigen he or
she lacks after transfusion, transplantation, or, as seen in
hemolytic dis- ease of the fetus and newborn, after
pregnancy.
 Red cell antibodies may cause a delayed transfusion
reaction if the patient subsequently receives a unit of blood
that expresses the corresponding red cell antigen.
 Primary alloimmunization may occur any- where from
days to months after transfusion of antigen-positive red
cells depending on the immunogenicity and dose of the
antigen.

40.  D-negative blood is usually transfused to D-negative patients, so
although anti-D is capable of causing DHTRs, the frequency
attributable to anti-D is relatively low.
 Newly formed alloantibodies are routinely detected during
pretransfusion screening.
 Recently transfused or pregnant patients must have samples
drawn for compatibility testing within 3 days of the scheduled
transfusion to ensure identification of any potential new
alloantibodies

41. Transfusion-Associated Graft-vs-Host
Disease
Presentation
The clinical manifestations of transfusion- associated GVHD
(TA-GVHD) typically begin 8 to 10 days after transfusion.
Symptoms can occur as early as 3 days and as late as 30 days
after transfusion.
Signs and symptoms include a maculopapular rash, fever,
enterocolitis with watery diarrhea, elevated liver function tests,
and pancytopenia.
The rash begins on the trunk and progresses to involve the
extremities. In severe cases, bullae may develop

42. Pathophysiology
 Commonly in severely immunocompromised
patient
 Donor lymphocytes engrafted in recipient &
multiply
 Engrafted lymphocytes react with host tissues
 AIDS patients – HIV infects even donor
lymphocytes
 Fresh blood – lymphocytes are more active and
hence chance of engraftment is more

43. Implicated blood products
Reported after transfusion of non irradiated
• whole blood
• packed red cells
• platelets
• granulocytes
• fresh, non‐frozen plasma
No report of TAGvHD after
• frozen, deglycerolized red cells,
• fresh frozen plasma,
• cryoprecipitate.