Transfusion is Unnatural

Reaction is Natural
Recognise
React
Report
OBSERVE
Blood Pressure, Temperature, Pulse, Respiratory
Rate
Baseline
15 minutes
Hourly from commencement time
Stop time

Remember most transfusion reactions occur
within the first 15 mins of transfusion

TRANSFUSION RATES
The infusion rate for blood products depends on the
clinical context, age and cardiac status of the patient.
In stable, non-bleeding adult patients typical
administration durations are:
Red cells 60-180 minutes per unit
Platelets 15-30 minutes per standard adult dose
FFP 30 minutes per unit
Cryoprecipitate 30-60 minutes

Note in an emergency you are limited only by the size of the
cannula


TIME LIMITS
Commence transfusion within 30 minutes of
arrival from Blood Bank
If returned to the BB within 30mins it can be returned to the
fridge and then released to any other patient as required.
Once it has been at room temp for >30mins it cannot then be
used for any other patient

Transfusion must be complete within 4 hours
Risk of bacterial proliferation greatly increases when unit is at
room temp for >4 hours

FILTERS
Integral in-line filter is essential
This filter (170-200 micron) removes clots and small clumps of
debris that may form during collection and storage.
In all advanced countries all red cells and platelets issued by the
Blood Service are leucocyte depleted. Therefore additional
bedside leucocyte depletion filters are NOT required.
Microaggregate filters (pore size 20-40 microns) are intended to
remove microscopic debris from stored red blood cells. There is
no evidence from controlled trials that they offer clinical benefit
and their use is not generally recommended.


IV LINES
Primed with normal saline or the blood component
Must not be piggy-backed onto another line
Attachment to extension tubing on an IV cannula/multi-
lumen venous access device is acceptable
Must be changed when transfusion is complete/every 12
hours if not yet complete
reduce the risk of bacterial growth occurring
still

TRANSFUSION REACTIONS
Mild Reactions
Fever, rash,

Moderate to Severe reactions
Hypotension / Shock or hypertension,
tachycardia, tachypnoea, wheeze, stridor,
rigors or chills, nausea, vomiting or pain (local,
chest, back)
If UNCONSCIOUS
Temperature rise more than 1
0
C
Pink or red urine (hemoglobinuria)
Increased operative bleeding
Hypotension
Reduced urine output
Tachycardia or bradycardia

Immunologic Non-Immunologic Infectious
Alloimmunization Volume Overload Hepatitis
Hemolytic
Transfusion Rxn
Massive Transfusion:
Metabolic,
Hypothermia,
Dilutional, Pulmonary
Microembolism
HIV, HTLV
Febrile Transfusion
Rxn
CMV, EBV
TRALI Bacterial
Allergic Transfusion
Rxn
Syphilis
Posttransfusion
Purpura
Parasites
Immunosuppressive
Effects
Risks of Non-Infectious
Complications
Reaction (Selected) Risk
Fever without hemolysis 1:100 1:200
TRALI 1:5000 -1:7500
Acute Hemolysis 1:6000 (1:500,000 are fatal)
Alloimmunization; serologic,
delayed hemolysis
1:1500
Alloimmunization; clinically
symptomatic, delayed hemolysis
1: 4000
CLASSIFICATION
Transfusion reaction
acute delayed
Immunologic Nonimmunologic
Immunologic Nonimmunologic

Immunologic
Acute Hemolytic
Febrile Non-hemolytic
Anaphylaxis
Urticaria
Noncardiogenic Pulmonary Reaction

Acute Hemolytic
Transfusion Reaction

Signs and Symptoms
Fever
Hemoglobinuria
Chills
Shock
Chest pain
Generalized Bleeding
Hypotension
Oliguria or anuria
Nausea Back pain Flushing Pain at infusion site
Dyspnea
Anxiety

Etiology:
Red Cell Incompatibility
Therapy
Stop transfusion immediately
Maintain IV line
Institute therapeutic measures to:
maintain blood pressure
promote adequate renal blood flow

Tests

Free Hb in serum
Direct antiglobulin test on post-transfusion specimen
Repeat Grouping & xmatch
Measure unconjugated bilirubin on serum draw 5-7
hours post-transfusion
Look for urine free Hb
Perform tests for unexpected Ab in donor and patient
Make Gram stain of blood smear of unit and culture
unit at 4, 22, and 35-37 degrees C
Evaluate response to transfusion with Hb and Hct
results - 1 unit should increase HB 1 g/dL and Hct by
3%

Complications of AHTRS
Renal failure :- 36 %
Thrombus formation in renal
arterioles
DIC :- 10 %
Other reactions characterized
by hemolysis

1. Autoimmune hemolytic anemia
2. Donor units hemolysed due to
Bacterial contamination
Excessive warming
Erroneous freezing
Addition of drugs or iv fluids
Trauma from extracorporeal devices
Red cell enzyme deficiency
Maintain adequate renal perfusion by
- Fluid challenges
- Frusemide infusion
- If hypovolumic dopamine infusion
Transfer to high dependency area
Repeat coagulation and biochemistry screens ever
2- 4 hrly
Hemofiltration or dialysis m/b required for acute
tubular necrosis
DIC development component therapy may be
required
Tt
Acute Hemolytic TR
Other Considerations
Dont wait for the lab tests if your suspicion
is high treat with HYDRATION to keep
urine output > 100ml-200ml/hour
Remember hyperkalemia is common
cardiac monitoring
Acute Transfusion
Reaction

Immunologic
Acute Hemolytic
Febrile Non-hemolytic
Anaphylaxis
Urticaria
Noncardiogenic Pulmonary Reaction
Post Transfusion Purpura

Febrile Nonhemolytic TR
Signs and Symptoms:
Fever - 1degree centigrade ABOVE
baseline
Tends to be later in the transfusion or up to
2 hours post transfusion
Chills
Missing some of the key findings in
hemolysis, i.e. the laboratory findings.
Febrile Nonhemolytic TR
Related to the amount leukocytes in the
donated product and duration of
storage.
Cytokines in the donated product
generated during the STORAGE of the
products
1-6% of Red cell Transfusions
More with Platelets



Febrile Nonhemolytic
Reactions

Treatment:
stop transfusion
antipyretics
Leukopoor units if >2 febrile reactions

DO NOT RESTART TRANSFUSION

Acute Transfusion
Reaction

Immunologic
Acute Hemolytic
Febrile Non-hemolytic
Anaphylaxis
Urticaria
Noncardiogenic Pulmonary Reaction

Anaphylaxis

Signs and Symptoms
Cough, bronchospasm, respiratory
distress, vascular instability, shock,
diarrhea, nausea, abdominal cramps, loss
of consciousness
lack of fever
occurrence after infusion of a few ml of
blood or plasma

Etiology:
Usually to an unspecified plasma protein
IgA deficient pts more likely at risk (1:300
1:500)

Therapy:
Stop transfusion
Keep IV open
Treat hypotension
Give epinephrine (0.4 mL of l:1000 solution)

Do not restart transfusion
Washed products if further transfusions
required.

Acute Transfusion
Reaction

Immunologic
Acute Hemolytic
Febrile Non-hemolytic
Anaphylaxis
Urticaria
Noncardiogenic Pulmonary Reaction

Urticaria

Soluble allergenic substances in DONOR product
React with RECIPIENT preexisting IgE antibodies.

Bound IgE cross links MAST CELLS and
BASOPHILS mediator release including
histamines
Urticarial Reactions
Signs and Symptoms
Urticaria
Pruritis
NO OTHER SYMPTOMS i.e. no
bronchospasm, hoarseness, hypotension,
etc.
Simple allergic reaction
Treatment
Pause the transfusion
Keep IV open
Administer antihistamines
After symptoms disappear, continue with
transfusion
Patient with frequent reactions may be
premedicated prior to transfusion If patient
has repeated and/or severe reactions,
consider transfusion of washed or
deglycerolized frozen RBCs


Immunologic
Acute Hemolytic
Febrile Non-hemolytic
Anaphylaxis
Urticaria
Noncardiogenic Pulmonary Reaction

Noncardiogenic
Pulmonary Reaction
Signs and Symptoms
Pulmonary edema without cardiac failure
Occurrence after administration of volume
of fluid too small to produce hypervolemia
Can also have:
chills
fever
cyanosis
hypotension

Transfusion Related
Acute Lung Injury
Serious, more frequent
30 min 2 hours after the start of
transfusion
Sudden respiratory distress, hypoxemia,
pulmonary edema
Normal Central Venous Pressure,
Normal Cardiac Function
Exclusion of other precipitating causes
Coarse
Alveolar
Infiltrates &
Normal
cardiac
Contours
TRALI
Mechanism
Endothelial Cell activation Increased
adhesion of neutrophils to pulmonary
endothelium. Neutrophil activation and
release of cytokines (Pts in Sepsis)
Donor antibody to recipient leukocytes or
reverse- Leucocytes trapped in Lung vas
Clinically and mechanistically looks like
ARDS
Better prognosis than ARDS
TRALI
Treatment
STOP TRANFUSION
Supplemental Oxygen
Confirm diagnosis pulmonary imaging,
rule out alternative diagnoses
Critical Care Support
Leucodepleted products if required later.

NONIMMUNOLOGIC
Fever with Shock
a. High fever
b. Abdominal cramps
c. Shock
d. Diarrhea
e. Hemoglobinuria
h. Vomiting
i. DIC
j. Generalized muscle pain
k. Renal failure

Etiology: Bacterial contamination gram-
negative bacteria

Therapy
Stop transfusion
Keep IV open
Administration of antibiotics IV
Treat shock
vasopressors
steroids
Work-up
Inspect bag for purple color , hemolysis, and/or
clots in bag
Gram stain
Aerobic and anaerobic culture at refrigerator,
room, and body temperatures

Congestive Heart Failure

Etiology - volume overload

Therapy
Stop tranfusion
Keep IV open
Diuretics
Oxygen
Postural changes
?Phlebotomy



Prevention
Packed cells instead of whole blood.
Packed cells given slowly over 4 hours. ( usual
about 200 ml per hour. In patient at risk rate of
100 ml per hour or less are appropriate.)
Diuretics should be given at the start of the
transfusion
Only one or two units of concentrated red cells
should be transfused in any 24 hour period.
Blood transfusion should be given during the
daytime, Overnight transfusion avoided
Delayed Adverse Events
Immune-Mediated
RBC alloimmunization
HLA alloimmunization
Post-transfusion
purpura (PTP)
Transfusion-
associated GVHD
Immunomodulation /
Immune suppression
Non-Immune
Iron overload
Blood-borne pathogens
Bacterial diseases
Viral diseases
Parasitic diseases
Delayed Transfusion
Reactions-Immune
Mechanism
Antibodies that exist in low titers prior to the
transfusion
Typically to the Kidd or Rh system
Upon re exposure, titer increases
Clinical Picture:
Decrease in Hb, fever?, unconjugated bilirubin,
spherocytosis
Happens 2-10 days post transfusion
DHTR
Treatment
As long as clinically mild, no treatment
necessary
Monitor renal function, Hb
PREVENT it from happening the next time
Ab screening
Post Transfusion
Purpura
Very rare
Mostly occurs in women
Severe thrombocytopenia
Develops 5 to 10 days following transfusion
Delayed antibody response to platelets
IVIG if very thrombocytopenic

Immune destruction of platelets
common in Multiple transfusions
HLA antigens and donor leucocytes are
the common culprits
??? Over enthusiastic Transfusions
GVHD
Rare, but always fatal
Severe diarrhoea, liver failure, skin desquamation, bone marrow
failure & death weeks to months post transfusion

Immunosuppressed-
Stem Cell Transplant patients
On chemo
Fetus - if needs intra-uterine transfusion
Congenital immunodeficiency conditions
If donor happens to be HLA matched
If donor is homozygous for an HLA haplotype the patient has

Or blood from 1st degree relatives
Other Reactions
NON-Immune
Volume Overload
Toxic reactions to the citrate in the
components during pheresis or
exchange
Iron Overload need for chelation
therapy
Bacterial / Viral Infections
Massive transfusion dilutional
coagulopathies
Cytomegalovirus
Post transfusion CMV infection is not uncommon.
Fever spleenomegaly, and atypical lymphoid cells in the
peripheral blood.
Due to its benign course, screening for past infection
among donors are not necessary.
If screened rejection rate will be very high

In UK, incidence of CMV antibodies in adult population is
50 to 60 %.

Patient at risk of developing fatal pneumonitis or
disseminated CMV infection
Prem baby < 1500g,
BM or and other organ transplant recipient
Pregnant women ( risk to fetus ).

anti CMV free blood & components should be
provided.
Leukodepleted blood may be used.
Human T- cell leukaemia
viruses.
HTLV 1 is associated with tropical spastic paraparesis
and adult T cell leukaemia.
Importance of HTLV II is not clear.

Both HTLV 1 and II are cell associated and not
transmitted in plasma.

Currently available test include ELISA and gelatin
particle assay, but confirmation of positive result are
difficult due to cross reactivity with other retroviruses.
Infectious Risks
Agent (Selected List) Risk
Hep B 1:220,000-1:488,000
Hep C 1:1,935,000
HIV 1:2,135,000
CMV <1% of CMV seropositive
components transmit CMV
Gram + Bacteria 1:1000
1:10,000,000 fatal sepsis
Gram Bacteria
Malaria (plasmodium spp.) 1-5 cases/year. 10% fatal
Massive transfusion
Defined as the replacement of total blood volume
within a 24 hour period.

1. Dilution of platelets.

No functional platelets after 48 hours storage.

Platelet transfusion may be required if platelet count
<10 x 103 /ml or with continous bleeding or surgical
intervention.

2. Dilution of coagulation factors.

Stored Whole blood < 14 days has adequate levels of
most coagulation factors for haemostasis.
If stored blood of more than 14 days, or plasma reduced
blood or red cells in optimal additive solution is used,
replacement of coagulation factors with FFP is necessary.


3. Hypothermia ( defined as core body temperature
less than 35 c ) is associated with large volumes of cold
fluid transfusion. This may results in cardiac irregularities in
particular VF. Therefore the use of blood warmer is
important.






4. Excess citrate
can act on the patients plasma free ionized calcium and
results in hypocalcaemia ( transient ).

Citrate toxicity occur with extremely rapid transfusion ( one
unit every 5 minute

5. Hyperkalemia
Caused by intracellular loss of potassium from
RBC during storage.


The most important consideration in massive
blood transfusion is to replace blood loss
quickly and adequately.
Too little blood , too late has more serious
consequences than massive blood
transfusion itself.
Universal Leucodepletion
Leucocytes in blood components responsible for
many of complications associated with blood
transfusion
Patients receiving standard blood transfusion
receive large numbers of allogeneic leucocytes
Average blood contain 1-3x10
9
leucocytes per
unit
Platelet concentrate contains .5-1x10
9

leucocytes per unit adult therapeutic dose of
platelets.
Leucodepletion
AABB Standards
Each transfusion of a leucodepleted
component should contain < 5X 10
6
leucocytes.
Leucodepleted RBCs should retain 85 % of
original RBCs with leucocyte count reduced to
< 5X 10
6
/unit
Apheresis platelets should contain < 5 X 10
6

leucocytes
The European standards recommend the
residual leucocyte count to be < 1 X 10
6
/unit

Indications
Recommended
FNHTRs
? Reducing graft rejection after haemopoietic cell
transplantation.
Prevention of transmission of viral infections by blood
transfusion.
Fetal/Neonatal transfusions.
Thalassemics
Possible
Platelet refractoriness
Kidney transplants.
Immunomodulation.
Progression of HIV infection.
? Use
TAGvHD
Timing of leucocyte-depletion
With in short time after collection (In lab)
Advantage
Leucocytes are removed before cytokines are
released
Fragments of cell membranes and possible
intracellular viruses removed. HLA
alloimmunization can occur with leucocyte
fragments
Laboratory filtration assures quality monitoring
and also the time of filtration
Filtration is done within 48 hours
One school of thought favors processing of
units after 6 hours as it allows phagocytosis of
any bacteria present
Fetal / Neonatal
transfusion
Fetal / neonatal transfusion often consist
of relatively fresh blood containing
viable leucocytes
Increase risk of transmission of CMV
Presence of viable lymphocytes may
cause TA-GvHD
Recommendations
Leucocyte-depleted blood components should
be used for intra-uterine transfusion and for all
transfusion to infants below 1 year of age
Haemovigilance

Recognise
React
Report