This power point is dedicated to deliver history of transfusion, its biology, Procedures for safe transfusion, Indications ,complications and their management.

1. PRESENTER: DR.MELAKU .Y (YEAR I RESIDENT)
MODERATOR:DR.SISAY AYANSA(CONSULTANT
INTERNIST, ASSISTANT PROFESSOR OF MEDICINE)
Transfusion Biology and Therapy
AHMC, Department of Internal
Medicine
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2. Outline
 Introduction
 Transfusion biology
 Procedures for safe transfusion
 Blood components
 Indications and guidelines of transfusion
 Transfusion Complications and Mgt
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3. Intro…
 The process of receiving blood products into one's circulation
intravenously.
 Andreas Libavius (1546–1616) proposed blood transfusion when in
1615 &he wrote:
Let there be a young man, robust, full of spirituous blood, and also
an old man, thin, emaciated, his strength exhausted, hardly able to
retain his soul. Let the performer of the operation have two silver
tubes fitting into each other. Let him enter the artery of the young
man, and put into it one of the tubes, fastening it in. Let him
immediately open the artery of the old man and put the female tube
into it, and then the two tubes being joined together, the hot and
spirituous blood of the young man will pour into the old one as it
were from a fountain of life, and all of this weakness will be
dispelled.
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4. Introduction
 J.Blundell, pioneer of human blood transfusion, 1829
 K.Landsteiner, ABO blood grouping, 1900
 P.Levine and R.Stetson, Rh grouping, 1939
 Goal-directed component therapy, 1970s
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5. Intro…
Important advances in history of blood transfusion:
 understanding blood groups and the identification of hundreds of
specific red cell antigens;
 the development of the plastic bag system for blood collection and
separation;
 plasma fractionation for the production of blood derivatives,
especially factor VIII;
 improved red cell preservation;
 platelet preservation and transfusion;
 understanding hemolytic and febrile transfusion reactions;
 expanded testing for transmissible diseases;
 and the recognition of leukocyte and platelet antigen systems.
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6. Intro…
 In Ethiopia, National Blood Transfusion Services (NBTS)
was established in 1969 by Ethiopian Red Cross Society
(ERCS)
 Since 2004 it has been referred to Federal Ministry of
Health (FMoH)
 Administratively, the regional blood banks (serving 8-12
hospitals each in a radius of about 100 km), are under
their respective regional health bureaus’
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7. Biology
Blood group antigens and antibodies
 Antigens systems important in transfusion medicine comprise red blood
cell (RBC), platelet, neutrophil, and human leukocytes (HLA) antigens.
 Antigens, either carbohydrate or protein, are assigned to a blood group
system based on the structure and similarity of the determinant epitopes.
 Other cellular blood elements such as platelets and plasma proteins are
also antigenic and can result in alloimmunization
 These antibodies, called alloantibodies, can comprise anti-RBC Abs, anti-
human platelet antigens (HPA) Abs, as well as anti-human leukocytes
antigens (HLA) Ab
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8. Bio…
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9. Bio…
 Antibodies directed against RBC antigens may result from
“natural” exposure,
 Autoantibodies (antibodies against autologous blood group
antigens) arise spontaneously or as the result of infectious
sequelae (e.g., from Mycoplasma pneumoniae) and are also
often IgM.
 Autoantibodies can also arise in an autoimmune setting with
most often an IgG isotype.
 Antibodies that result from allogeneic exposure, such as
transfusion or pregnancy, are usually IgG.
 IgG antibodies commonly bind to antigen at warmer
temperatures and may hemolyze RBCs
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10. Bio…
 IgG directed against HPA antigens on platelets that can
lead to fetal or neonatal immunization and result in
intracranial hemorrhage.
 Recipient alloimmunization to leukocytes, platelets, and
plasma proteins may also result in transfusion
complications.
 Can result in a severe lung disorder called transfusion-
related acute lung injury (TRALI).
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11. Bio…
ABO Antigens and Antibodies
 The first blood group antigen system, recognized in 1900, was
ABO, the most important in transfusion medicine.
 The major blood groups of this system are A, B, AB, and O.
 H substance is the immediate precursor on which the A and B
antigens are added.
 This H substance is formed by the addition of fucose to the
glycolipid or glycoprotein backbone.
 The subsequent addition of N-acetylgalactosamine creates the
A antigen, while the addition of galactose produces the B
antigen.
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12. Bio…
 The ABO blood group system is important because
essentially all individuals produce antibodies to the ABH
carbohydrate antigen that they lack.
 The “naturally” occurring anti-A and anti-B antibodies are
termed isoagglutinins
 Thus, type A individuals produce anti-B, while type B
individuals make anti-A.
 Neither isoagglutinin is found in type AB individuals,
while type O individuals produce both anti-A and anti-B.
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13. Bio…
RH System:
 The Rh system is the second most important blood
group system in pretransfusion testing.
 The Rh antigens are found on a 30- to 32-kDa RBC
membrane protein that has no defined function.
 The RHD gene codes for the RhD protein.
 The RHCE gene codes for RhCE proteins expressing C
and/ or c, and E and/or e antigens.
 The presence of the D antigen confers Rh “positivity,”
while persons who lack the D antigen are Rh negative.
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14. Bio…
 The D antigen is a potent alloantigen.
 About 15% of individuals lack this antigen.
 Exposure of these Rh-negative people to even small
amounts of Rh-positive cells, by either transfusion or
pregnancy, can result in the production of anti-D
alloantibody
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15. Are these the only blood
group systems?
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16. Bio…
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17. Procedures for safe transfusion
Governing Principles of blood
transfusion service in Ethiopia?
Ethical issues during blood donation
and transfusion?
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18. Procedures…
Governing Principles of the national blood
transfusion service:
Article 1:There shall be an established national blood transfusion
service
Article 2:Blood and its products must strictly be used under medical
supervision for medical therapeutics
Article 3: Blood its products must be collected with full consent of the
donor without compensation by qualified health worker
Article 4: Any healthy person age 18-65,weight not less than 45 kg could
become a donor
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19. Procedures…
Governing Principles…
 Article 5:Blood transfusion center shall effect the collection,
processing , preservation and distribution of blood and blood products
 Article 6: Blood and its products must be preserved under
supervision of registered and trained medical doctor or transfusion
specialist
 Article 7:The actual cost of processing, analyzing or preserving blood
and its products shall be recoverable and shall not occasion any profit
 Article 8:The MOH shall set and enforce standards on blood
transfusion services
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20. Procedures…
Ethical issues of Blood donation & transfusion:
1. Blood donation shall, in all circumstances be
voluntary
2. Patients should be informed of the known risks and
benefits of blood transfusion.
3. In the event that the patient is unable to give prior
informed consent, the basis for treatment must be in
the best interest of the patient.
4. A profit motive shouldn't be the basis for the
establishment and running of a blood service.
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21. Procedures…
Ethical Issues:
5. Anonymity between donor and recipient must be ensured except in special
situations and the confidentiality of donor information assured.
6. The donor should understand the risks to others of donating infected blood and
his or her ethical responsibility to the patient.
7. Blood donation must be based on regularly reviewed medical selection criteria
and not entail discrimination of any kind, including gender, race, nationality or
religion.
8. Blood must be collected under the overall responsibility of a suitably qualified,
registered medical practitioner.
9. All matters related to whole blood donation and hemapheresis should be in
compliance with appropriately defined and internationally accepted standards.
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22. Procedures…
Ethical issues…
10.Donors and recipients should be informed if they have been harmed.
11. Genuine clinical need should be the only basis for transfusion
therapy.
12. Blood is a public resource and access should not be restricted.
13. As far as possible the patient should receive only those particular
components (cells, plasma, or plasma derivatives) that are clinically
appropriate and afford optimal safety.
14. Wastage should be avoided in order to safeguard the interests of all
potential recipients and the donor.
15. Blood transfusion practices established by national or international
health bodies and other agencies competent and authorized to do so
should be in compliance with these principles of ethics.
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23. Procedures…
Collection of Whole Blood
Eligiblity to donate in Ethiopia:
 In Ethiopia, the range of age to donate blood is from 18-65 years
with >45 kg of body weight.
 The required quantity of blood to be donated in a single donation is
from 350 ml to 450 ml.
 Greater than 12 gm/dl of hemoglobin level for female while 13 gm/dl
for male is another eligibility criterion to donate blood.
 The last but not the least criteria are having 110-160 mmHg systolic
and 70-95 mmHg diastolic blood pressures.
 About 5-7 minutes are enough for drawing blood from your vein .
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24. Procedures…
Collection…
 Labeling
 Blood Containers
 Anticoagulant preservative solutions
 Selection of vein and preparation of the venipuncture site
 Blood Collection
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25. Procedures…
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26. Procedures…
Pretransfusion Testing:
 Pretransfusion testing of a potential recipient consists of the
“type and screen.”
 The “forward type” determines the ABO and Rh phenotype of
the recipient’s RBC by using antisera directed against the A, B,
and D antigens.
 The “reverse type” detects isoagglutinins in the patient’s serum
and should correlate with the ABO phenotype, or forward type.
 Molecular typing is increasingly used to predict the RBC
phenotype and facilitate the selection of a compatible blood
component.
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27. Procedures…
 Cross-matching is ordered when there is a high probability that
the patient will require a packed RBC (PRBC) transfusion.
 Blood selected for cross-matching must be ABO compatible
and lack antigens for which the patient has alloantibodies.
 In the case of Rh (D) -negative patients, every attempt must
be made to provide Rh-negative blood components to prevent
alloimmunization to the D antigen.
 Rh-negative women of childbearing age who are transfused
with products containing Rh-positive RBCs should receive
passive immunization with anti-D (RhoGam or WinRho) to
reduce or prevent sensitization
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28. Procedures…
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29. Procedures…
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30. Blood Components
 Blood products intended for transfusion are routinely
collected as whole blood (450 mL) in various
anticoagulants.
 Most donated blood is processed into components:
PRBCs, platelets, and fresh-frozen plasma (FFP) or
cryoprecipitate.
 Whole blood can be first separated into PRBCs and
platelet-rich plasma by slow centrifugation.
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31. Blood Components
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32. Procedures…
 The platelet-rich plasma is then centrifuged at high speed
to yield one unit of random donor (RD) platelets
(subsequently pooled) and one unit of FFP.
 Alternatively, whole blood can undergo high speed
centrifugation to separate a PRBC, a FFP and a “buffy-
coat” containing leukocytes and platelets.
 The buffy coat then undergoes pooling and is centrifuged
at low speed to produce pooled platelets.
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33. Blood components…
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34. Blood Components…
 The leukocyte level of blood products can be lowered by an additional
filtration step after which they are referred to as leukoreduced (or
leukodepleted) (<1 to 5 × 106 leukocytes per product).
 Cryoprecipitate is produced by thawing FFP to precipitate the plasma
proteins, then separated by centrifugation.
 Apheresis technology is used for the collection of multiple units of
platelets from a single donor.
 These single-donor apheresis platelets (SDAP) contain the equivalent of at
least five units of RD platelets and before eventual leukoreduced, have
fewer contaminating leukocytes than pooled RD platelets
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35. Blood Components…
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36. Whole Blood
 Whole blood provides both oxygen-carrying capacity and
volume expansion.
 It is the ideal component for patients who have sustained
acute hemorrhage of ≥25% total blood volume loss.
 Whole blood is stored at 4°C to maintain erythrocyte
viability, but platelet dysfunction and degradation of some
coagulation factors occur.
 2,3- bisphosphoglycerate levels fall over time, leading to
an increase in the oxygen affinity of the hemoglobin
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37. Packed RBCs
 This product increases oxygen-carrying capacity in the anemic
patient.
 PRBC are stored in additive solution up to 35–42 days at 4°C.
 Adequate oxygenation can be maintained with a hemoglobin
content of 70 g/L in the normovolemic patient without cardiac
disease
 The decision to transfuse should be guided by the clinical
situation and not by an arbitrary laboratory value.
 In most patients requiring transfusion, levels of hemoglobin of
80 g/L are sufficient to keep oxygen supply from being
critically low
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38. Packed…
 The majority of cellular blood products are now
leukocyte-reduced and universal prestorage leukocyte
reduction has been recommended.
 Plasma, which may cause allergic reactions, can be
removed from cellular blood components by washing.
 Patients with hemoglobinopathies such as sickle cell
disease may undergo RBC exchange
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39. Platelets
 Platelets are stored in plasma or in additive solution up to
5–7 days at 20–24°C and under permanent motion.
 The threshold for prophylactic platelet transfusion is
10,000/ μL
 In patients without fever or infections, a threshold of
5000/ μL may be sufficient to prevent spontaneous
hemorrhage.
 For invasive procedures, 50,000/ μL platelets is the usual
target level.
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40. Platelets…
 Platelets are given either as pools of 4 to 6 prepared RDs or as
SDAPs from a single donor.
 In an unsensitized patient without increased platelet
consumption ,two units of transfused RD per square-meter
body surface area (BSA) is anticipated to increase the platelet
count by ~10,000/ uL
 Patients who have received multiple transfusions may be
alloimmunized to many HLA- and platelet-specific antigens
and have little or no increase in their posttransfusion platelet
counts.
 Patients who may require multiple transfusions are best served
by receiving leukocyte-reduced components to lower the risk
of alloimmunization.
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41. Platelets…
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42. Platelets
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43. Platelets…
 The platelet count performed 1 h after the transfusion is
acceptable if the CCI is 10 × 109/mL, and after 18–24 h an
increment of 7.5 × 109/mL is expected.
 Patients who have suboptimal responses are likely to have
received multiple transfusions and have antibodies directed
against class I HLA antigens.
 Refractoriness can be investigated by detecting anti-HLA
antibodies in the recipient’s serum.
 Patients who are sensitized will often react with 100% of the
lymphocytes used for the HLA-antibody screen, and HLA-
matched SDAPs should be considered for those patients who
require transfusion.
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44. Platelets…
 Although ABO-identical HLA-matched SDAPs provide
the best chance for increasing the platelet count, locating
these products is difficult.
 Platelet cross-matching is available in some centers.
 Additional clinical causes for a low platelet CCI include
fever, bleeding, splenomegaly, DIC, or medications in the
recipient.
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45. Fresh Frozen Plasma(FFP)
 FFP contains coagulation factors and plasma proteins:
fibrinogen, antithrombin, albumin, as well as proteins C and S
 Indications for FFP include correction of coagulopathies,
including the rapid reversal of warfarin; supplying deficient
plasma proteins and TTP.
 In the latter case, therapeutic plasma exchange allows both the
removal of the autoantibody and the supplementation of the
depleted enzyme (ADAMTS13).
 Other auto-immune diseases such as Guillain-Barré syndrome
and myasthenia gravis may benefit from plasma exchange.
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46. FFP…
 FFP should not be routinely used to expand blood volume.
 FFP is an acellular component and does not transmit
intracellular infections, e.g., CMV.
 In addition to FFP, pre-thawed or never frozen plasma as
well as freeze-dried plasma are increasingly used to insure
immediate availability when required.
 Patients who are IgA-deficient and require plasma support
should receive FFP from IgA-deficient donors to prevent
anaphylaxis
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47. Cryoprecipitate
 Cryoprecipitate is a source of fibrinogen, factor VIII, and
von Willebrand factor (vWF).
 It is ideal for supplying fibrinogen to the volume sensitive
patient.
 When factor VIII concentrates are not available,
cryoprecipitate may be used since each unit contains ~80
units of factor VIII.
 Cryoprecipitate may also supply vWF to patients with
dysfunctional (type II) or absent (type III) von Willebrand
disease.
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48. Plasma derivatives
 Plasma from thousands of donors may be pooled to derive
specific protein concentrates, including albumin,
intravenous immunoglobulin, antithrombin, and
coagulation factors.
 In addition, donors who have high-titer antibodies to
specific agents or antigens provide hyperimmune
globulins, such as anti-D (RhoGam, WinRho), and
antisera to hepatitis B virus (HBV), varicella-zoster virus,
CMV, and other infectious agents.
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51. Indications for PRBC
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53. Indications
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54. Indications for Platelets
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55. Indications for Platelets…
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56. Indications( FFP, Cryo, Factor concentrates)
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57. Complications
 Adverse reactions to transfused blood components occur
despite multiple tests, inspections, and checks.
 Fortunately, the most common reactions are not life
threatening
 Some reactions can be reduced or prevented by modified
(filtered, washed, or irradiated) blood components.
 Blood product pathogen reduction is an option for platelets
and plasma, and underway for whole blood and PRBC.
 When an adverse reaction is suspected, the transfusion should
be stopped and reported to the blood bank for investigation.
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58. Complications…
 Immune Mediated reactions
 Non- immune mediated reactions
 Infectious Complications
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59. Complications…
Immune Mediated reactions:
 Acute hemolytic transfusion reaction
 Delayed hemolytic and Serologic transfusion reactions
 Febrile non hemolytic transfusion reaction
 Allergic reactions
 Anaphylactic reaction
 Graft-Vs-Host disease
 Transfusion related acute lung injury
 Post transfusion Purpura
 Alloimmunization
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60. Complications…
Nonimmunologic reactions:
Fluid Overload
Hypothermia
Electrolyte toxicity
Iron overload
Hypotensive reactions
Immunomodulation
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61. Complications…
Infectious Complications:
 Viral
 Hepatitis C
 HIV
 Hepatitis B
 CMV
 HTLV 1
 Parvo virus B-19
 Bacterial contamination
 Other infectious agents
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63. Acute hemolytic transfusion reaction
 are almost always caused by the immune-mediated
destruction of ABO-incompatible transfused blood.
 Estimated to occur in one in 38,000 to one in 70,000 RBC
transfusions.
 Isohemagglutinins can activate the complement and
coagulation systems.
 C3a and C5a can activate white blood cells to release
inflammatory cytokines
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64. Acute hemolytic…
 The presence of antigen-antibody complexes and activated
complement on donor RBCs may lead to bradykinin
generation.
 Capillary permeability and arteriolar dilatation causing a fall in
systemic blood pressure.
 Disseminated intravascular coagulation.
 Renal failure
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65. Acute hemolytic…
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66. Acute hemolytic…
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67. Acute hemolytic…
Clinical Presentation
 The most common presenting symptom is fever with or without chills or
rigors.
 In mild cases with abdominal, chest, flank, or back pain, whereas dyspnea,
hypotension, hemoglobinuria, and eventually shock can be seen in severe
cases.
 Bleeding, caused by the consumptive coagulopathy, can occur.
 Hematuria can be the first sign of intravascular hemolysis.
 Approximately 47 percent of the recipients of ABO incompatible blood
show no effects,, 41 percent show symptoms of AHTR, and mortality is
approximately 2 percent.
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68. Acute hemolytic…
Laboratory Evaluation
 Involves checking for technical and identification errors,
examine a posttransfusion specimen for hemolysis, and
perform a DAT to detect antibody-coated red cells.
 If AHTR is strongly suspected, repeat ABO and Rh typing of
the patient and the transfused blood and repeat antibody screen
and crossmatch may be helpful.
 A negative DAT occurs in rare cases when all transfused RBCs
are lysed.
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69. Acute hemolytic…
Management
 Immediate discontinuation of transfusion should always be the first step in
any transfusion reaction.
 Maintaining vascular access with slow infusion of normal saline,
monitoring vital signs, and assessing urine output are key early steps.
 A blood specimen should be collected immediately for laboratory
evaluation
 The component bag should be returned to the blood bank
 If severe hemolysis has occurred, therapy focuses on management of
hypotension, coagulation disorders, and renal function
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70. Acute hemolytic…
Mgt…
 A urine output of approximately 100 mL/h for 24 hours should
be maintained in adults without contraindications.
 In simple cases, normal saline infusion may be sufficient;
however, diuretics may be necessary in some cases.
 Intravenous administration of furosemide (40 to 80 mg)
promotes diuresis and improves blood flow to the renal cortex.
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71. Acute hemolytic…
Mgt…
 In severe cases of hypotension, intravenous dopamine, which dilates
renal vasculature and increases cardiac output, can be used.
 Patients with coagulopathy and active bleeding may require
administration of platelets, fresh-frozen plasma, or cryoprecipitate.
 The most common basis for AHTRs is a clerical error resulting from
mistakes in identifying the patient, labeling the pretransfusions
sample, or identifying the correct red cell unit for the patient
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72. Delayed Hemolytic transfusion reactions(DHTR)
 Occur when a previously immunized patient receives red cells
containing the corresponding antigen but are compatible in the
crossmatch because of a low titer of circulating alloantibody.
 DHTRs occur in 0.2 to 2.6 percent of patients.
 It is vanishingly rare in infants younger than 4 months of age,
and more common in chronically transfused patients.
 Approximately 30 to 40 percent of alloantibodies become
undetectable months to years after their initial identification.
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73. DHTR…
 However, a patient previously immunized by transfusion or
pregnancy may develop a secondary immune response after
reexposure to a blood group antigen.
 Decreasing Hct or failure to see the typical 1 g/dL Hgb/3
percent Hct increment following transfusion may be noted
within several days to weeks of a blood transfusion, as well as
an unexplained fever.
 Hemolysis from DHTR is typically extravascular, without
dramatic clinical symptoms and signs, although some classes
of IgG bind complement and will cause intravascular
hemolysis.
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74. DHTR…
 Hemolysis in DHTRs is usually mild and gradual, however,
when antibodies are produced against antigens in the Kidd
blood system, the hemolysis may be rapid, intravascular, and
may be severe.
 The appearance of spherocytes and reticulocytes on peripheral
blood film, increases in total and unconjugated bilirubin, and
increased LDH.
 The DAT is usually positive but may be negative if all the
transfused RBCs have been eliminated from the circulation.
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75. DHTR…
 The antibody screen is usually positive and the antibody can
be identified.
 No specific management is usually needed as these reactions
are usually subtle and clinically silent.
 In cases of intravascular hemolysis, clinical support measures
are similar to those described for an acute hemolytic
transfusion reaction.
 If transfusion is necessary donor red cells negative for the
offending antigen may be selected.
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76. Febrile nonhemolytic transfusion reaction
 A febrile nonhemolytic transfusion reaction (FNHTR) is
defined, arbitrarily, as a temperature increase of 1°C or more
during or up to 4 hours after transfusion.
 Other possible symptoms include increases in respiratory rate,
anxiety, and, more unusually, nausea or vomiting.
 FNHTRs are one of the most commonly encountered
transfusion reactions
 Leukocyte reduction decreases the incidence of FNHTRs with
both whole-blood derived and apheresis platelets.
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77. Febrile nonhemolytic…
Clinical Presentation:
 Fever is triggered by the action of cytokines (e.g., IL-1, IL-6,
TNF-α).
 Fever should not be solely attributed to FNHTR until other
potential life-threatening transfusion reactions or patient-
related factors have been excluded.
 Past transfusion reaction history should be reviewed to
determine if additional measures should be implemented for
future transfusions.
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78. Febrile nonhemolytic…
Laboratory Evaluation
 Should concentrate on ruling out a septic transfusion reaction.
 Rapid qualitative immunoassay tests (e.g., Verax or BacTx) are
highly sensitive for most commonly encountered bacterial
contaminants and may be used
 In cases with a high index of suspicion, the unit should be
cultured.
 If all results are negative and the patient’s presentation is
consistent with a mild FNHTR, no additional testing is
required.
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79. Febrile nonhemolytic…
Management:
 FNHTRs are typically benign, and usually resolve completely within 1 to
2 hours after the transfusion is discontinued.
 The remainder of the transfused unit and a posttransfusion blood sample
from the patient should be sent to the laboratory for investigation.
 Antipyretics may be administered to shorten the duration of the fever and
provide analgesia.
 Acetaminophen 325 to 650 mg orally for adults or 10 to 15 mg/kg/dose
orally for children is effective for this purpose.
 Transfusing leukoreduced RBCs and/or platelets stored in additive solution
will significantly reduce the risk of FNHTRs.
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80. Allergic transfusion reaction
 Ranges from mild forms characterized by localized pruritus and/or
urticaria, to severe anaphylactic or anaphylactoid reactions.
 The mild forms of allergic transfusion reaction (ATR) occur in 1 to 3
percent of transfusions of plasma-rich components and in 0.1 to 0.3
percent for red cells.
 Severe anaphylactic reactions are much less frequent and estimated at one
in 20,000 to 50,000 transfusions.
 The majority of ATRs are immediate (type 1) hypersensitivity reactions,
 Severe anaphylactic reactions may occur after transfusion of blood
products to IgA-deficient patients who have anti-IgA antibodies.
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81. Allergic…
 The rare patient with complete IgA deficiency (<0.05
mg/dL) may develop anti-IgA antibodies and thus might
experience anaphylaxis with transfusion.
 Anaphylactoid reactions are similar to anaphylaxis but
clinically less severe and caused by non–IgE-mediated
activation of mast cells.
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82. Allergic…
Clinical Presentation
 Within an hour of starting a transfusion, but may not become
evident until several hours later.
 Common findings include urticaria, rash, pruritus, and flushing.
 More severe reactions occur sooner and may include angioedema,
chest tightness, dyspnea, cyanosis, hoarseness, stridor, or
wheezing.
 In addition, gastrointestinal symptoms such as abdominal pain,
nausea, vomiting, and diarrhea may also occur
 Anaphylaxis occurs immediately after starting the transfusion.
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83. Allergic…
Laboratory Evaluation
 There is no need for laboratory investigation with simple urticarial
and/or localized pruritus.
 However, the incident should be reported to the blood bank to
update the patient’s record for any future transfusions.
 In anaphylactic reactions, the patient should be tested for complete
IgA deficiency; however, a history of anaphylactic reactions
mandate use of washed red cells and platelets and avoidance of
plasma transfusions regardless of the results of these tests.
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84. Allergic…
Management
 Most ATRs are mild, self-limited and respond well to transfusion
discontinuation and, if indicated, administration of antihistamine
(diphenhydramine hydrochloride, usually orally).
 In cases limited to urticaria, the transfusion may be resumed immediately after
symptoms resolve.
 However, transfusion should never be resumed when there is a severe reaction.
 In acute anaphylaxis, fluid resuscitation may be needed to maintain blood
pressure followed by administration of subcutaneous or intramuscular
epinephrine (0.3 mL of 1:1000 dilution), as well as airway management and
intensive care.
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85. Allergic…
Mgt…
 In case of shock, a higher concentration of intravenous epinephrine
(3 to 5 mL of a 1:10,000 dilution) can be administered.
 Steroids are usually not helpful in acute crises.
 Prevention Patients with a history of mild ATRs should not be
premedicated with an antihistamine, as this does not reduce the
overall risk of ATRs.
 Platelets stored in additive solution may be used to reduce the risk
of a reaction.
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86. Graft-Versus-Host Disease
 Mediated by donor T lymphocytes that recognize host HLA antigens
as foreign and mount an immune response
 Development of fever, a characteristic cutaneous eruption, diarrhea,
and liver function abnormalities.
 marrow aplasia and pancytopenia.
 TA-GVHD is highly resistant to treatment with immunosuppressive
therapies.
 Clinical manifestations appear at 8–10 days, and death occurs at 3–
4 weeks posttransfusion.
 TA-GVHD can be prevented by irradiation of cellular components
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87. Transfusion related acute lung injury(TRALI)
 A syndrome of acute hypoxia attributable to noncardiogenic
pulmonary edema that occurs within 6 hours of a transfusion.
 Has been the leading cause of transfusion-related fatalities for
several years.
 There are two main hypotheses regarding the capillary leak
seen in TRALI.
 The two-hit hypothesis
 The second hit
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88. TRALI…
 The mediators are often antibodies specific for either class II
HLA or for human neutrophil antigens (HNAs).
 There are also cases in which no antibody was detected, which
are thought to be a result of proinflammatory mediators,
bioactive lipids, and CD40 ligand that accumulate in the blood
product during storage
 Specific patient factors (first hits) that are associated with a
greater risk of TRALI include patients on mechanical
ventilation, sepsis, chronic alcohol abuse, severe liver disease,
hematologic malignancy, and others.
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89. TRALI…
 It is not known whether the risk is determined by the patient’s condition,
or by a greater transfusion requirement.
 The two-hit hypothesis accounts for critically ill patients who develop
TRALI; however, there are reports of TRALI in reasonably healthy
patients.
 This observation led to the threshold model of TRALI
 In this paradigm, a threshold, or tipping point, must be surpassed to induce
TRALI.
 Conversely, a critically ill patient with primed neutrophils can be tipped
into TRALI with a lower titer of antibody
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90. TRALI…
Clinical Presentation and DDx
 It is often impossible to fully distinguish TRALI from other
causes of respiratory distress.
 The typical presentation of TRALI is the sudden development
of dyspnea, severe hypoxemia (O2 saturation <90 percent in
room air) hypotension, and fever that develop within 6 hours
of transfusion and usually resolves with supportive care within
48 to 96 hours.
 Although hypotension is considered one of the important signs
in diagnosing TRALI, hypertension can occur in some cases.
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91. TRALI…
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92. TRALI…
Clinical ….
 In addition to new or worsening oxygen desaturation, TRALI
is characterized by chest x-ray findings of bilateral diffuse
patchy pulmonary densities without cardiac enlargement.
 TRALI can be ruled out by the presence of rales and jugular
venous distention on physical exam and/or dilated pulmonary
arteries on chest x-ray
 Transient leukopenia, which follows the reaction within few
hours, can also distinguish TRALI from TACO.
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93. TRALI…
Management and Prevention:
 Supportive care is the mainstay of therapy in TRALI, including
oxygen supplementation and aggressive respiratory support plus
intravenous fluid and vasopressors for hypotension, if indicated.
 It has been suggested that diuretics, which are indicated in TACO
management, are not efficacious and should be avoided in TRALI.
 Glucocorticoids may provide benefit.
 HLA alloimmunization has been directly correlated with the number
of times a woman is pregnant and plasma from multiparous women
has been implicated as a risk factor in TRALI.
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94. TRALI…
Management and…
 To reduce this risk, blood banks attempt to collect plasma from
males, nulliparous females, and/or females tested and found to be
negative for HLA antibodies.
 TRALI continues to be the leading cause of transfusion-related
fatalities.
 Pooled plasma may also be used for TRALI mitigation because
antibody titers drop due to dilution.
 No cases of TRALI resulting from transfusion of pooled solvent
detergent treated plasma have been reported.
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95. Posttransfusion Purpura
 Thrombocytopenia, 7–10 days after platelet transfusion
 Platelet-specific antibodies are found in the recipient’s serum, and
the most frequently recognized antigen is HPA-1a found on the
platelet glycoprotein IIIa receptor.
 The delayed thrombocytopenia is due to the production of
antibodies that react to both donor and recipient platelets.
 Additional platelet transfusions can worsen the thrombocytopenia
and should be avoided.
 Treatment with intravenous immunoglobulin may neutralize the
effector antibodies, or plasmapheresis can be used to remove the
antibodies.
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96. Transfusion associated circulatory overload(TACO)
 Occurs when patients are unable to effectively process the expansion in
intravascular volume from a blood transfusion.
 Circulatory overload may be the consequence of the infusions rates, the
volume of infused blood product, and/or an underlying cardiac, renal,
and/or pulmonary pathology.
 The fluid volume transfused may be less important than the infusion flow
rate and the patient’s ability to process the fluid.
 The incidence of TACO is difficult to ascertain, as there are inconsistent
case definitions, passive reporting systems and poor clinical recognition.
 Approximately 1 percent of orthopedic patients developed TACO
postoperatively, compared to 6 percent of patients in an ICU setting.
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97. TACO…
 TACO is seen more in younger and advanced age patients.
 Additional risk factors include:
 Female sex,
 A history of congestive heart failure,
 Hemodialysis,
 Mechanical ventilation,
 Recent vasopressors,
 And positive fluid balance.
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98. TACO…
Clinical Presentation
 Symptoms of TACO may include dyspnea, orthopnea,
cough, headache, and hypoxemia, which are not specific.
 However, signs such as rales, hypertension, and jugular
vein distention may differentiate TACO from TRALI.
 These signs and symptoms usually present within 2 hours
of the onset of transfusion, but may be up to 6 hours or
even 24 hours after the onset of transfusion.
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99. TACO…
Laboratory Evaluation
 Oxygen saturation may decrease along with the partial pressure of
oxygen in the arterial blood.
 New bilateral infiltrates on chest x-ray is characteristic for TACO;
however, it is also seen in TRALI.
 Elevated levels of B-type natriuretic peptide (BNP) and N-terminal
pro-BNP (NT-proBNP) are both useful markers for TACO, but NT-
proBNP may be more useful as it has a longer in vivo and in vitro
half-life.
 Unfortunately neither peptide was found to be useful in
distinguishing TACO from TRALI in critically ill patients
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100. TACO…
Management:
 Intravenous fluids should be restricted, followed by the administration
of supplemental oxygen and a diuretic
 Placing the patient in a sitting position can also be helpful.
 In severe cases, mechanical ventilation may be required.
 If a patient is at risk for TACO and blood transfusion is imperative,
blood should be administered slowly at a rate of 1 to 4 mL/kg/h.
 Close monitoring of the patient’s vital signs throughout the transfusion
may also help in decreasing the development of TACO.
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101. Hypothermia
 Refrigerated (4°C) or frozen (−18°C or below) blood
components can result in hypothermia when rapidly
infused.
 Cardiac dysrhythmias can result from exposing the
sinoatrial node to cold fluid.
 Use of an in-line warmer will prevent this complication
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102. Electrolyte Toxicity
 Hyperkalemia
 Hypocalcemia
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103. Iron Overload
 Each unit of RBCs contains 200–250 mg of iron.
 Endocrine, hepatic, and cardiac function are
common after 100 units of RBCs have been
transfused (total-body iron load of 20 g)
 Preventing this complication by using alternative
therapies
 Chelating agents
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104. Hypotensive Reactions
 Transient hypotension may be noted among
transfused patients who take angiotensin-converting
enzyme (ACE) inhibitors.
 Since blood products contain bradykinin that is
normally degraded by ACE, patients on ACE
inhibitors may have increased bradykinin levels that
cause hypotension in the recipient.
 The blood pressure typically returns to normal
without intervention.
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105. Immunomodulation
 Transfusion of allogeneic blood is immunosuppressive
 Multiply transfused renal transplant recipients are less likely
to reject the graft, and transfusion may result in poorer
outcomes in cancer patients and increase the risk of
infections.
 Transfusion-related immunomodulation is thought to be
mediated by transfused leukocytes.
 Leukocyte-depleted cellular products may cause less
immunosuppression, though controlled data are unlikely to be
obtained as the blood supply becomes universally leukocyte-
depleted
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106. Transfusion related sepsis
 Transfusion-related sepsis when it occurs is usually from
platelet units that are stored at room temperature.
 Red cells, stored at refrigerator temperatures, are very
rarely contaminated by unusual cold-growing organisms
(e.g., Yersinia, Serratia, Pseudomonas).
 The rate of fatal transfusion- transmitted bacteremia from
red cells has been estimated to be 0.13 per million units
transfused in the United States.
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107. Transfusion related…
Clinical Presentation&Mgt
 The infusion of large numbers of Gram- negative
microorganisms may lead to fever (>38.5°C), rigors, marked
hypotension, abdominal pain, vomiting, diarrhea, and the
development of profound shock.
 Gram-positive contaminants may cause fever and rigors, but
are not associated with the severe symptoms produced by
Gram-negative toxins.
 Laboratory Evaluation Rapid diagnosis usually may be made
via Gram stain of the residual donor blood; however, a culture
of the transfused component is necessary.
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108. Alternatives to transfusion
 Alternatives to allogeneic blood transfusions that avoid
homologous donor exposures with attendant immunologic and
infectious risks remain attractive.
 Autologous blood remains an option when transfusion is
anticipated.
 However, the cost-benefit ratio of autologous transfusion
remains high.
 No transfusion is a zero-risk event; clerical errors and bacterial
contamination remain potential complications even with
autologous transfusions.
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109. Alternatives…
 Additional methods of autologous transfusion in the surgical
patient include preoperative hemodilution, recovery of shed
blood from sterile surgical sites, and postoperative drainage
collection.
 Directed or designated donation from friends and family of the
potential recipient has not been safer than volunteer donor
component transfusions.
 Such directed donations may in fact place the recipient at
higher risk for complications such as GVHD and
alloimmunization.
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110. Alternatives…
 Granulocyte and granulocyte-macrophage colony-stimulating
factors are clinically useful to hasten leukocyte recovery in
patients with leukopenia related to high-dose chemotherapy.
 Erythropoietin stimulates erythrocyte production in patients
with anemia of chronic renal failure and other conditions, thus
avoiding or reducing the need for transfusion.
 This hormone can also stimulate erythropoiesis in the
autologous donor to enable additional donation.
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111. Alternatives…
 Gene therapy approaches in patients with sickle cell or
major thalassemia offers the potential of dramatically
reducing their transfusion needs.
 Stem cell-derived blood cells such as RBCs or platelets
may in the future become a suitable alternative to very
rare blood donors.
 Lastly, optimizing the use of blood products through
patient blood management programs can improve the
therapeutic index of transfusion medicine
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112. References
 Harrison’s Principles of Internal Medicine,20th edition
 Williams Hematology,9th edition(2016)
 Handbook of transfusion Medicine,5th edition
 Ethiopian national blood transfusion services strategy,2005
 Uptodate,2018
 American Society of Hematology(ASH), Transfusion
guideline,2013
 Transfusion Medicine(Jeffrey McCullough) ,4th Edition
 Guide to the preparation, use and quality assurance of blood
components(European committee for blood transfusion),2017
 Strategic framework of blood safety and availablity,WHO,2016
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113. Thank you!
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