This document discusses non-infectious complications that can occur from blood transfusions. It describes various types of complications including acute hemolytic transfusion reactions caused by immune or non-immune mechanisms. Other complications discussed include febrile non-hemolytic transfusion reactions, transfusion-related acute lung injury, circulatory overload, and delayed hemolytic transfusion reactions. The mechanisms, signs and symptoms, diagnoses, and risk factors for each complication are explained in detail.

1. Transfusion Reaction
Mulugeta Melku(BSC, MSC)

2. Objectives
• At the end
Analyse the adverse complication of blood
transfusion
Identify the major noninfectious complication of
blood transfusion
Explain the mechanisms of complication of blood
transfusion
Recognize transfusion transmitted infection

3. Introduction
Transfusion
• can be autologous or Allogeneic
Autologous transfusion:
– is an alternative therapy for many patients
anticipating transfusion
Categories:
1. Preoperative collection
 blood is drawn and stored before anticipated need

4. Introduction cont’d
2. Perioperative collection and administration
A. Acute normovolemic Hemodilution
 blood is collected at the start of surgery and then
infused during or at the end of the procedure
B. Intraoperative collection
 shed blood is recovered from the surgical field or
circulatory device and then infused
C. Postoperative collection
 blood is collected from drainage devices and re-
infused to the patient

5. Introduction cont’d

6. Introduction cont’d
• Autologous Blood Donation
Disadvantages
 Does not eliminate risk of bacterial
contamination
 Does not eliminate risk of incompatibility error
 Increased incidence of adverse reactions to
autologous donation
 Subjects patients to perioperative anemia
and increased likelihood of transfusion

7. Introduction cont’d
• Allogeneic transfusion
Between similar species
Disadvantage
– the risks of transmissible disease and transfusion
reactions inherent in allogeneic transfusions.
– Alloimmunization
– GVHD
– Post transfusion purpura
– Circulatory over load

8. Introduction cont’d

9. Non-Infectious Complication
of Transfusion

10. Complication Cont’d
Four broad categories of transfusion reactions:
– Acute immunologic
– Acute nonimmunologic
– Delayed immunologic,
– Delayed non-immunologic complications
 pathophyiology, prevention and differential
criteria

11. Complication Cont’d
Manifestation:
• one should consider any adverse manifestation
occurring at the time of the transfusion
Fever with or without chills (rise of 1OC )
Shaking chills (rigors) with or without fever
Pain at the infusion site or in the chest, abdomen
Blood pressure changes
Respiratory distress, including dyspnea, tachypnea, wheezing,
or hypoxemia

12. Complication Cont’d
Skin changes, including urticaria, pruritis (itching),
flushing, or localized edema
Nausea with or without vomiting
Darkened urine or jaundice
Bleeding or other manifestations of a
consumptive coagulopathy

13. Complication Cont’d
Acute Transfusion Reactions(AHTR)
Definition:
 An AHTR features rapid destruction of RBCs immediately
after a transfusion
 But a hemolytic reaction occurring within 24 hours of the
inciting transfusion is generally considered to be an AHTR
Can be:
• Immune-mediated Hemolysis
• Non immune-mediated Hemolysis

14. Complication Cont’d
A. Immune-mediated Hemolysis
Pathophysiology and Manifestations
 The most severe hemolytic reactions
Occur when transfused red cells interact with
preformed antibodies in the recipient
 The interaction of transfused antibodies with
the recipient’s red cells rarely causes symptoms.
– there may be accelerated red cell destruction,
and plasma-containing products with high-titer ABO
antibodies can cause acute hemolysis

15. Complication Cont’d
Mechanisms
– The interaction of antibody with antigen on the red cell
membrane can initiate a sequence of complement
activation, cytokine
Classical pathway of C’ activation
– IgM bind on RBC  Fc binds to complement
– Membrane attack complex
 Severe symptoms can occur after the infusion of as little as
10 to 15 mL of ABO-incompatible red cells
 the initial manifestations of an acute HTR
– hemoglobinuria, hypotension, or diffuse bleeding at the surgical
site.

16. Complication Cont’d
Cause:
– severe acute HTRs today are usually caused by ABO
incompatibility
– occasionally may be caused by antibodies
with other specificities
• In contrast, hemolysis of an entire unit of blood can occur
in the virtual absence of symptoms and may be a
relatively slow process
– hemolysis is typically extravascular, without generation
of significant systemic levels of inflammatory mediators

17. Complication Cont’d
Complement Activation
 The binding of antibody to blood group antigens may
activate complement, depending on the characteristics of
both the antibody and the antigen
o C3 activation releases the anaphylatoxin C3a
o Red cells coated with C3b are removed by phagocytes
with complement receptors, more rapidly than if
antibody is present alone
• enzymatic cascade proceeds to completion and a
membrane attack complex is assembled, intravascular
hemolysis results production of C5a

18. Complication Cont’d
 This sequence is characteristic of ABO incompatibility and causes
the cardinal manifestations of hemoglobinemia 
hemoglobinuria.
hemoglobinuria
Anaphylatoxins
 Interact with a wide variety of cells [monocytes/macrophages,
granulocytes, platelets, vascular endothelial cells, and smooth
muscle cells ]hypotension and bronchospasm,
 cause the release or production of multiple local and systemic
mediators [granule enzymes, histamine
and other vasoactive amines, kinins, oxygen radicals,
leukotrienes, nitric oxide, and cytokine]
mimicking manifestation of allergy

19. Complication Cont’d
• These events cause hypotension,
Vasoconstriction and renal ischemia, and the
activation of the coagulation system
Cytokines
 They mediate some of the effects of alloimmune hemolysis
 stimulation of endothelial cells to increase expression of
adhesion molecules and procoagulant activity, and
recruitment and activation of neutrophils and platelets
 Vasodilatation: Hypotension And renal failure

20. Complication Cont’d
Coagulation Activation
Several mechanisms may be responsible for
abnormalities of coagulation in HTRs
AB-Ag interaction activates intrinsic clotting cascade
by Hageman factor(XII)
activated Hageman factor (Factor XIIa) acts on the
kinin system  bradykinin
 bradykinin: vasoactive
o Dilates arterioles, causing a decrease in systemic arterial
pressure

21. Complication Cont’d
 activated C’ cytokines, interleukin may increase the
expression of tissue factor by leukocytes and endothelial
cells
• Tissue factor activates the “extrinsic”coagulation pathway
DIC
– formation of thrombi within the microvasculature and ischemic
damage to tissues and organs
– consumption of fibrinogen, platelets, and other coagulation
factors
– activation of the fibrinolytic system and generation of fibrin
degradation products
Generalized oozing or uncontrolled bleeding.
bleeding

22. Complication Cont’d
How is could be Diagnosed ?
Hypotension
 secondary manifestation of ischemia
– Hypotension provokes a compensatory sympathetic
nervous system response that produces Vasoconstriction
in organs and tissues with a vascular bed rich in alpha-
adrenergic receptors, renal, splanchnic, pulmonary, and
cutaneous capillaries, aggravating ischemia in these sites
 Renal failure:
Free hemoglobin
AB-Ag deposition
Thrombi formation

23. Complication Cont’d
Differential Diagnosis
patients receiving transfusion therapy can develop a
hemolysis from many sources
– it is important to distinguish an AHTR from acute hemolysis of
other causes.
 Most common cause of hemolysis in transfused patients
 improper storage of RBCs
thermal injury, mechanical trauma, inappropriately
mixed with hypotonic solutions or drugs, or contaminated
by bacteria.
 Patients with congenital or acquired forms of hemolytic anemia
may be incorrectly assumed to have had an AHTR
• hereditary spherocytosis, sickle cell anemia, or RBC enzyme
deficiency
• coexistent microangiopathic hemolytic anemia
• a patient with thrombotic thrombocytopenic purpura
•

24. Complication Cont’d
• Confirmation of the Diagnosis
The initial suspicious of AHTR
Discontuation of transfusion and initiate lab
investigation
o Observation of post-transfusion plasma
o Perform DAT
o Inspect the blood bag
o Repeat Pretransfusion testing

25. Complication Cont’d

26. Complication Cont’d
Nonimmune-Mediated Hemolysis
Causes
Red cells may undergo in-vitro hemolysis
– unit is exposed to improper temperatures
– mishandled at the time of administration
– Malfunctioning blood warmers, use of microwave
ovens or hot water-baths,
– inadvertent freezing may cause temperature-related
damage
– pressure infusion pumps, pressure cuffs, or small-
bore needles

27. Complication Cont’d
Causes cont’d
– Osmotic hemolysis in the blood bag or infusion set
– Inadequate deglycerolization of frozen red cells may
cause the cells to hemolyze after infusion
– Bacterial growth in blood units
– intrinsic red cell defect of patient or donor has an,
such as G-6-DH deficiency

28. Complication Cont’d
Febrile Nonhemolytic transfusion
Reactions(FNHTR)
Pathophysiology and Manifestations
is often defined as:
– a temperature increase of >1o C associated with
transfusion and without any other explanation.
– Such reactions are often associated with chills or
rigors
Cause
• Non-leukocyte reduced red cell transfusions
• Previous opportunities for alloimmunization
• After platelet transfusion (1-38%

29. Complication Cont’d
• Many febrile reactions are thought to result from
an interaction between
antibodies in the recipient’s plasma and antigens
present on transfused lymphocytes, granulocytes, or
platelets, most frequently HLA antigens

30. Complication Cont’d
Transfusion-Related Acute Lung Injury (TRALI)
Pathophysiology and Manifestations
Transfusion recipient
 Experiences acute respiratory insufficiency and/or X-ray
findings are consistent with bilateral pulmonary edema but
has no other evidence of cardiac failure or a cause for
respiratory failure
• Defined acute lung injury (ALI) as a syndrome of:
– acute onset;
– hypoxemia
– bilateral lung infiltrates on a chest x-ray; and
– no evidence of circulatory overload.
• New ALI occurring during transfusion or within 6 hours of
completion

31. Complication Cont’d
• Mechanisms
– Donor antibodies directed against recipient HLA class
I or II antigens, or neutrophil antigens of the recipient
Sequence of events that increase the permeability
of the pulmonary microcirculation
high-protein fluid enters the interstitium and
alveolar air spaces
– Infrequently, antibodies in the recipient’s circulation
against HLA or granulocyte antigens initiate the same
events

32. Complication Cont’d
→suggest that pulmonary edema in TRALI is caused by
neutrophil-mediated endothelial damage, initiated by
damage
antibodies activating neutrophils directly or via activation of
monocytes, pulmonary macrophages, and/or endothelial cells
→ Complement activation after granulocyte transfusion
→Anaphylatoxins C3a and C5a, aggregation of granulocytes into
leukoemboli that lodge in the pulmonary microvasculature
→Transfusion of cytokines that have accumulated in stored
blood components
→Reactive lipid products from donor blood cell membranes

33. Complication Cont’d
Circulatory Overload
Pathophysiology and Manifestations
 Transfusion therapy may cause acute pulmonary
edema due to volume overload, and this can have
severe consequences, including death
• Rapid increases in blood volume are especially poorly
tolerated by patients with compromised cardiac or
pulmonary status and/or chronic anemia with expanded
plasma volume

34. Complication Cont’d
 The infusion of 25% albumin, which shifts large
volumes of extravascular fluid into the vascular
space, may also cause circulatory overload.
 Hypervolaemia must be considered if dyspnea,
cyanosis, severe headache, hypertension, or
congestive heart failure occur during or soon
after transfusion.

35. Complication Cont’d
Coagulopathy in Massive Transfusion
Pathophysiology
• Of greater concern is the occurrence of coagulopathy
during massive transfusion
• Classically, this coagulopathy is ascribed
– to dilution of platelets and clotting factors, which
occurs as patients lose hemostatically active blood
• The lost blood is initially replaced with red cells and fluids
• progressive increase in the incidence of “microvascular
bleeding” as a result of multiple transfusion of stored
whole blood

36. Complication Cont’d
Delayed Consequences of Transfusion

37. Complication Cont’d
DELAYED HEMOLYTIC TRANSFUSION REACTIONS
Pathophysiology
 Primary alloimmunization, evidenced by the appearance of
newly formed antibodies to red cell antigens, becomes
apparent weeks or months after transfusion
• DHTRs commonly occur in patients who have been
immunized to foreign blood group antigens during previous
transfusions and/or pregnancies
– but the antibody decreases over time and is not detected in
subsequent pretransfusion testing
Transfusion of seemingly compatible blood stimulate Ab
intr/extravascular hemolysis

38. Complication Cont’d
Definition and incidence
 accelerated destruction of transfused red cells that begins
only when sufficient antibody has been produced as a
result of an immune response induced by the transfusion
 most DHTRs share these characteristics
– DHTRs generally occur in patients who have been
alloimmunized to RBC antigens by previous transfusions or
pregnancies
– implicated antibody is not detected in pretransfusion
antibody screening or compatibility testing

39. Complication Cont’d
Characteristics of DHTR
– usually suspected 3 to 10 days after transfusion
– DAT and/or a positive antibody screening test in post-
transfusion testing
– Antibodies directed against Rh (CEce) and Kidd (Jka,
Jkb) system antigens are the antibodies most
commonly implicated in DHTR

40. Complication Cont’d
Transfusion-Associated Graft-versus-Host Disease
• usually fatal immunologic transfusion complication
caused by engraftment and proliferation of donor
lymphocytes in a susceptible host
• The engrafted lymphocytes mount an immunologic
attack against the recipient tissues
– hematopoietic cells, leading to refractory pancytopenia with
bleeding and infectious complications

41. Complication Cont’d
Pathophysiology and Manifestations
 Complex and incompletely understood.
 The overall mechanism includes
– escape of donor T lymphocytes present in cellular
blood components from immune clearance in the
recipient and
– subsequent proliferation of these cells, which then
mount an immune attack on host tissues

42. Complication Cont’d
Manifestation
 The rash typically begins as a blanching,
maculopapular erythema of the upper trunk, neck,
palms, soles, and earlobes
 Factors that determine an individual patient’srisk for
TA-GVHD
– degree the recipient is immune status
– the degree of HLA similarity between donor and
recipient, and
– the number and type of T lymphocytes transfused
that are capable of multiplication

43. Complication Cont’d
Post-transfusion Purpura
Pathophysiology and Manifestations
 Uncommon event
 is characterized by the abrupt onset of severe
thrombocytopenia (platelet count usually <10,000/μL)
an average of 9 days after transfusion (range, 1-24 days)
 Most cases (68%) involve patients whose platelets lack
the HPA-1a, HPA-1b and other HPA who form the
corresponding antibody
 Alloantibodies destruction of patient's own platelet

44. Complication Cont’d
 The reason for destruction of the patient’s own platelets
by platelet alloantibody is controversial
• Three mechanisms have been proposed
– formation of immune complexes of patient antibody
and soluble donor antigen that bind to Fc receptors
on the patient’s platelets and mediate their
destruction
– conversion of antigen-negative autologous platelets
to antibody targets by soluble antigen in the
transfused component

45. Complication Cont’d
– cross-reactivity of the patient’s antibodies with
autologous platelets
o the presence of an autoantibody component
Bleeding after transfusion

46. Complication Cont’d
Iron Overload
 Every RBC unit contains approximately 200 mg of iron
 Chronically transfused patients, especially those with
hemoglobinopathies, have progressive and continuous
accumulation of iron
 no physiologic means of excreting it
 Storage occurs initially in reticuloendothelial sites
– when they are saturated, there is deposition in parenchymal
cells
• clinical damage is lifetime exposure to greater than 50
to 100 RBC units in a non-bleeding person

47. Complication Cont’d
• Iron deposition interferes with function of the
– heart, liver, and endocrine glands (eg, pancreatic
islets, pituitary)
 Hepatic failure and cancer, diabetes mellitus, and
cardiac toxicity cause most of the morbidity and
mortality

48. Summary

49. ?