Lecture 7 - Blood transfusion & blood products
24
Blood transfusion
is the process of transferring blood or
blood-based products from one person (donor) into the
circulatory system of another (recepient). Blood
transfusions can be life-saving in some situations, such as
massive blood loss due to trauma
Blood is made up of various parts, including red blood
cells, white blood cells, platelets, and plasma.
Every person has one of the following blood types: A, B,
AB, or O. Also, every person's blood is either Rh-
positive or Rh-negative. So, if you have type A blood,
it's either A positive or A negative.
The blood used in a transfusion must work with your
blood type. If it doesn't, antibodies (proteins) in your
blood attack the new blood and cause a reaction.
Type O blood is safe for almost everyone. People who
have this blood type are called universal donors. Type O
blood is used for emergencies when there's no time to test
a person's blood type.
People who have type AB blood are called universal
recipients. This means they can get any type of blood.
If you have Rh-positive blood, you can get Rh-positive or
Rh-negative blood. But if you have Rh-negative blood,
you should only get Rh-negative blood.
The indication for B.T. in surgical practice are;
1) 1-Trauma in which there have been severs blood loss.
2) 2-Haemorrhage from pathological lesions, ex.from GIT.
3) 3-Following severe burns, there may be associated
hemolysis
4) 4-Pre-operatively in cases of chronic anaemia in which
surgery is indicated urgently.
5) 5-During major operative procedures in which a certain
amount of blood loss is inevitable, ex.
abdominal operations & cardiovascular operations.
6) 6-Post-operatively in a patient who has become severly
anaemic.
7) 7-To arrest hemorrhage or as a prophylactic measure prior
to surgery in patient with a haemorrhigic state
ex.thrombocytopenia, haemophilia or liver disease.
Preparation of blood products for transfusion
Its important that blood donor should be fit, No evidence
of infection especially hepatitis & HIV infection.
Donated Blood is collected in a sterile bag, with a needle
& plastic tube attached in a complete, closed sterile unit.
15 G needle is introduced into the median cubital vein &
410 ml of blood is aspirated into the bag containing 75 ml
of anticoagulant (citrate,phosphate,dextrose;CPD).blood
can be stored for up to 42 days
During collection, the blood is constantly mixed with the
anticoagulant to prevent clotting.
All blood should be stored in special blood bank
refrigerator at 4C +/-2C.
Prolong storage may cause the following changes;
Leakage of intracellular K
Reduced level 2,3-DPG
Degeneration of functional granulocytes and platelets
Deterioration of clotting V and VIII
Ammonia concentration rises
Decrease in PH
Decrease in RBC deformability and viability
Component separation:
Red cells, plasma and platelets are separated into different
containers and stored in appropriate conditions so that
their use can be adapted to the patient's specific needs.
Red cells work as oxygen transporters, plasma is used as a
supplement of coagulation factors, and platelets are
transfused when their number is very scarce or their
function severely impaired. Blood components are usually
prepared by centrifugation.
Leukoreduction, also known as Leukodepletion is the
removal of white blood cells from the blood product by
filtration. Leukoreduced blood is less likely to cause
alloimmunization (development of antibodies against
specific blood types), and less likely to cause febrile
transfusion reactions.
Blood fractions
Some fractions are more appropriate than whole blood for
some clinical conditions.
1) packed red cells
Advisable in patients with chronic anaemia, elderly, small
children & patients in whom large volume of fluid may
cause cardiac failure. Packed RC is obtained by letting the
blood sediment & removing the plasma or by
centrifugation of whole blood for 15-30minutes.
2) platelet-rich plasma
Suitable for patient with thrombocytopenia.Prepared by
centrifugation of freshly donated blood for 15-30min.
3) platelet-concentrate
For patients with thrombocytopenia.Prepared by
centrifugation of platelet-rich plasma for 15-20 min.
4) plasma
By centrifugation of whole blood
Lecture 7 - Blood transfusion & blood products
25
5) human albumin 4.5%
Repeated fractionation of blood by organic fluids
followed by heat treatment result in this plasma fraction
which is rich in protein.Albumin may be stored for
several months at 4C & are suitable for protein
replacement ex. In severe burns
6) Fresh-frozen plasma (FFP).
Plasma removed from fresh blood within 4 hrs , rapidly
frozen by immersing in a solid Co2 & ethyl alcohol
mixture.This stored at -40 to -50C.Its good source for all
the coagulation factors, albumin & Ig.
Its indicated for surgical patient with abnormal
coagulation due to severe liver failure.Intial dose 12-15
ml/kg (one unit contain200-250ml).It should not be used
as a plasma expander in hypovolemia.
7) Cryoprecipitate.
By thawing FFP at 4C, removing supernatant plasma.The
cryoprecipitate is a very rich source of factorVIII. Its
stored at -40C,its good for haemophilic patients, also
good source of fibrinogen in patient with
hypofibrinogenemia
8) factorVIII&IX concentrate.
These are available in freeze dried form
9) Fibrinogen.
By liquid fractionation of plasma & stored in a dried form
. Used for patients with DIC or congenital
afibrinogenemia, however it carries a high risk of
hepatitis.
10) SAG-Mannitol blood.
All plasma is removed & is replaced with 100 ml of
crystalloid solution containing; Nacl, Adenine, Glucose &
Mannitol. This maintains good cell viability, but contain
no protein (albumin).
Blood grouping & cross-match.
RBCs have many different Ag on their surface.2 main
groups of major importance;
A. Ag of the ABO blood groups;
These are strongly antigenic & are associated with
naturally occurring Abs in the serum.4 different ABO cell
groups;
Red cell group serum contains;
A Anti-B Antibody
B Anti-A Antibody
AB No ABO Antibody
O Anti-A&Anti-B Antibody
B. Ags of the rhesus blood groups
The important Ag in this group is Rh (D) which is
strongly Antigenic & is present in 85% of the population
& Abs to the D Ag are not naturally present in the
remaining 15% but their formation may be stimulated by
the transfusion of Rh +ve.
Such acquired Abs are capable during pregnancy of
crossing the placenta& may cause severe hemolytic
anaemia & even death (hydropes fetalis) in a Rh +ve fetus
in utero.
Incompatibility
If Abs present in the recipients serum are incompatible
with the donors cells ,a transfusion reaction will result
because of agglutination & hemolysis of the donated
cells,leading in sever cases to acute tubular necrosis &
renal failure.So for this reason all transfusion should be
preceeded by;
1-ABO & Rh grouping of the recipient & donor cells , so
that only ABO&Rh(D) compatible blood is given
2-Direct matching of the recipients serum with the donor
cells to confirm compatibility
Blood grouping & cross-matching take 1 hr. If emergency
, blood volume may be restored by
saline,gelatin(ex,haemaccel),dextran or human albumin
4.5%.Alternatively O-ve should be given.
Giving blood.
1) Selection & preparation of the site
2) Checking of the donor blood; compatibility label ,
patients name, hospital reference , ward & blood group
3) Insertion of needle or cannula
4) Giving written instruction, ex, rate of flow. In emergency
it may be necessary to increase rate of flow,its preferable
to give one or two unit in 30 min using a pressure cuff
around a plastic bag of blood
Warming blood.
During rapid major blood transfusion,the blood must be
warmed before reaching the patient by blood warming
unit to reduce the risk of cardiac arrest.
Autotransfusion
Transfusion of patients own blood,ex. In ruptured ectopic
pregnancy when blood is collected from peritoneal cavity
& put in sterile container to give to the patient after
filtering it.
Lecture 7 - Blood transfusion & blood products
26
Complications of BT
A. Immune complications
1) Hemolytic
i. acute
ii. delayed
2) non-hemolytic
i. febrile
ii. urticarial
iii. anaphylactic
iv. pulmonary oedema (non-cardiogenic)
v. graft vs. host
vi. purpura
vii. immune suppression
B. non-immune complications
1) complications associated with massive B.T
i. coagulopathy
ii. citrate toxicity
iii. hypothermia
iv. acid-base disturbance
v. change in serum K concentration
vi. iron accumilation
vii. volume overload
2) infectious complications
i. hepatitis
ii. AIDS
iii. Other viral agents(CMV,EBV,HTLV)
iv. Parasites&bacteria
3) Other complications
i. thrombophlebitis
ii. air embolism
A.
Immune Complication
These are primarily due to the sensitization of the
recipient to donor blood cells (either red or white),
platelets or plasma proteins. Less commonly, the
transfused cells or serum may mount an immune response
against the recipient
1) Hemolytic reactions
Usually involve the destruction of transfused blood cells
by the recipient's antibodies. Less commonly, the
transfused antibodies can cause hemolysis of the
recipient's blood cells. There are acute (also known as
intravascular) hemolytic reactions and delayed (also
known as extravascular) hemolytic reactions.
i. acute hemolytic reactions
The majority of hemolytic reaction are caused by
transfusion of ABO incompatible blood.,eg group A,B or
AB cells to agroup O patient. Most hemolytic reaction are
the result of human error such as error in labeling or
checking the specimen
This type of reaction has been reported to occur
approximately 1 in 25,000 transfusions but it is often very
severe and accounts for over 50% of reported deaths
related to transfusion. The severity of the reaction often
depends in the amount of blood given.
Non-immune hemolysis of RBCs in the blood container
or during administration can occur due to physical
disruption (temperature changes, mechanical
forces,non-isotonic fluid)
The pt. develops chills, fever, nausea chest pain and
flank pain,pain along iv line hypotension, dark urine,
uncontrolled bleeding due to DIC in awake pt.. In
anasthetized pt., you should look for rise in temperature,
unexplained tachycardia, hypotension, hemoglobin
urea, oozing in the surgical field,DIC, shock and renal
shutdown.
Management of acute hemolytic reaction
These patients usually require ICU support and therapy
includes vigorous treatment of hypotension and
maintenance of renal blood flow The unit should be re-
checked. Blood from the recipient patient should be
drawn to test for hemoglobin in plasma, repeat
compatibility testing and coagulation tests. A foley
catheter should be placed to check for hemoglobin in the
urine. Osmotic diuresis with mannitol(or frusemide) and
fluids should be utilized (low-dose dopamine may help
renal function and support blood pressure).dialysis may
be necessary. With rapid blood loss, platelets and fresh
frozen plasma may be indicated.
Prevention:
Proper identification of the pt. from sample collection
through the blood admimistration, proper labeling of
samples and products is essential. Prevention on non-
immune hemolysis requires adherence to proper handling,
storage and administration of blood products
ii. Delayed hemolytic reactions
Pts may develop Abs to red cells Ags (Ab. To non-D Ag
of the Rh system or to the kell,duffy or kidd Ags).
Antibodies can occur naturally, or may arise as a
consequence of previous transfusion or pregnancy. .
Following a normal, compatible transfusion there is a 1-
1.6% chance of developing antibodies to these foreign
antibodies (alloimmunisation). This takes weeks or
months to happen - and by that time, the original
Lecture 7 - Blood transfusion & blood products
27
transfused cells have already been cleared. Re-exposure to
the same foreign antigen can then cause an immune
response.
Most delayed haemolytic reactions produce few
symptoms and may go unrecognised, however, there may
be malaise, jaundice, fever, a fall in Hematocrit despite
transfusion, and an increase in unconjucated bilirubin.
Diagnosis may be facilitated by the direct coombs test
which can detect the presence of antibodies on the RBC
membrane
Alloimmunisation to the D andK (Kell) antigens is
prevented by the provision of Rh(D) negative and Kell
negative blood for Rh(D) negative, kell negative pts. This
is important for females with child-bearing potential as
these antibodies can cause sever hemolytic disease of the
newborn during pregnancy
2) Non-hemolytic reaction
Are Due to sensitization of the recipient to donor WBC,
platelets, or plasma proteins. These reactions include;
i. Febrile Reactions
Cause: Fever and chills during transfusion without
evidence of hemolysis are thought to be caused by
recipient antibodies reacting with white cell antigens or
white cell fragments in the blood product or due to
cytokines which accumulate in the blood product during
storage. Fever occurs more commonly with platelet
transfusion (10-30%) than red cell transfusion (1-2%).It is
important to distinguish from fever due to the patient's
underlying disease or infection (check pretransfusion
temperature). Fever may be the initial symptom in a more
serious reaction such as bacterial contamination or
haemolytic reaction.
Management: Symptomatic, paracetamol
If the fever is accompanied by significant changes in
blood pressure or other signs and symptoms, the
transfusion should be ceased and investigated.
Prevention: A proportion of patients who have febrile
reactions will have similar reactions to subsequent
transfusions. Many are prevented by leucocyte filtration
(either bedside or pre-storage).
ii. Urticarial (allergic)reactions
Are characterized by erythema, hives and itching
without fever. on rare occasions it may be associated with
laryngeal oedema and bronchospasm. Again, this is a
relatively common reaction and occurs in about 1% of all
transfusions. It is thought to be due to sensitization
against plasma proteins. The use of packed red blood cells
rather than whole blood has decreased the likelihood of
this problem.
Management; If urticaria occurs in isolation (without
fever and other signs), slow the rate or temporarily stop
transfusion. If symptoms are bothersome, consider
administering an antihistamine before restarting the
transfusion. If associated with other symptoms, cease the
transfusion and proceed with investigation.
iii. Anaphylactic reactions
Are rare and occur in about 1 of 150,000 transfusions.
These are severe reactions that can occur with very small
amounts of blood (a few milliliters). Typically, these
reactions occur in pts with IgA deficiency who have anti-
IgA antibodies. These antibodies react to transfusions
containing IgA.
Anaphylactic and anaphylactoid reactions have signs of
cardiovascular instability including hypotension,
tachycardia, loss of consciousness, cardiac arrhythmia,
shock and cardiac arrest. Sometime respiratory
involvement with dyspnea and stridor are prominent.
IgA deficiency occurs in 1 of 600-800 patients in the
general population. Patients with known IgA deficiency
should receive washed packed red blood cells, or IgA free
blood units
Management by immediately stop transfusion,
supportive care including airway management may be
required. Adrenaline may be indicated. Usually given as
1;1000 solution s.c,i.m or slow i.v.,fluids and
corticosteroids
iv. Transfusion-related acute lung injury
Some pts can develop acute hypoxemia and non-
cardiogenic pulmonary oedema and present with a
picture that looks like adult respiratory distress syndrome
(ARDS) developing within 2-8 hrs hours after a
transfusion. This is a rare (1 in 5000) but serious
complication that is thought to be secondary to cytokines
in the transfused product or from interaction between
donar antileucocyte antibodies with the patient white cells
antigens (or vice versa) causing them to aggregate in the
pulmonary circulation. Subsequent damage to the
alveolocapillary membrane triggers the syndrome.
Treatment involves symptomatic support for respiratory
distress includes oxygen administration and may require
Lecture 7 - Blood transfusion & blood products
28
intubation and mechanical ventilation . symptoms
generally resolves over 24-48 hours.
v. Graft versus Host disease
This seen exclusively in immunocompromised patients
when donor lymphocytes proliferate and damage target
organs especially bone marrow, skin, liver and
gastrointestinal tract. The clinical syndrome comprises
fever, skin rash, pancytopenia, abnormal liver function
and diarrhoea and is fatal in over 80% of cases. The usual
onset is 8-10 days post transfusion, with a longer interval
between transfusion and onset of symptoms in infants.
Prevention: Gamma irradiation of cellular blood products
(whole blood, red blood cells, platelets, granulocytes) for
at risk patients.(pts with hodgkins disease, aplastic
anaemia, AIDS, cytotoxic drugs)
vi. Post-transfusion purpura
is common with the development of platelet antibodies.
The external purpura signal a reaction that may lead to
profound thrombocytopenia which usually occurs about
one week post transfusion. Plasmapheresis is the
recommended treatment.
vii. Immune suppression
is a debatable complication. The transfusion of leukocyte-
containing blood products appears to be
immunosuppressive causing a decrease in Natural Killer
cell function, decreased phagocytosis and decreased
helper to suppressor cell ratios.
The effect was first seen in renal transplant patients in
whom preoperative blood transfusions appeared to
improve graft survival.
B.
Non-Immune Complications
1) complications associated with massive B.T
Massive Transfusion is usually defined as the need to
transfuse a volume of blood equivalent or exceeding the
patients own volume in a less than a 24-hours period or
replacement of more than one blood volume in 24 hours
or more than 50% of blood volume in 4 hours.(adult
blood volume is approximately 70 ml/kg, in children over
1 months old is approximately 80 ml/kg.
Massive transfusion occurs in settings such as severe
trauma, ruptured aortic aneurysm, surgery and obstetrics
complications.
i. Coagulopathy
Is common with massive transfusion. The most common
cause of bleeding following a large volume transfusion is
dilutional thrombocytopenia(each 10-12 units can
produce a 50% fall in the platelet count, thus, significant
thrombocytopenia can be seen).
Alteration in clotting system may occur, it can be
preexisting or induced coagulopathy. Its usually related to
the effects of acidosis and hypothermia. Acidosis
interfere with the assembly of coagulation factor
complexes involving calcium. Hypothermia reduces the
enzymatic activity of plasma coagulation proteins and
prevent platelets activation
ii. Citrate toxicity
Citrate is the anticoagulant used in blood products. It is
usually rapidly metabolised by the liver. Rapid
administration of large quantities of stored blood(one unit
over five minutes or so ) may cause hypocalcaemia and
hypomagnesaemia when citrate binds calcium and
magnesium. This can result in myocardial depression or
coagulopathy.
Patients most at risk are those with liver disease or
dysfunction or neonates with immature liver function
having rapid large volume transfusion.
Management: Slowing or temporarily stopping the
transfusion allows citrate to be metabolised. Replacement
therapy with intravenous calcium administration may be
required if there is clinical(transient tetany, hypotensiov)
or ECG or lab evidence of hypocalcemia or
hypomagnesaemia
iii. Hypothermia
Rapid infusion of large volumes of stored blood
contributes to hypothermia. Infants are particularly at risk
during exchange or massive transfusion.
Prevention and Management: Appropriately maintained
blood warmers should be used during massive or
exchange transfusion
iv.
v. Acid-Base imbalance
can be seen after massive transfusion. The most common
abnormality is a metabolic alkalosis. Patients may
initially be acidotic because the blood load itself is acidic
and there may be a prevailing lactic acidosis from
hypoperfusion. However, once normal perfusion is
restored, any metabolic acidosis resolves and the citrate
and lactate are then converted to bicarbonate in the liver.
Lecture 7 - Blood transfusion & blood products
29
vi. Potassium Effects
Serum potassium can rise as blood is given. The
potassium concentration in stored blood increases steadily
with time (stored red cells leak potassium proportionally
throughout their storage)..
hyperkalaemia can occur during rapid, large volume
transfusion of older red cell units in small infants and
children.
Prevention: Blood less than 7 days old is generally used
for rapid large volume transfusion in small infants (eg
cardiac surgery,exchange transfusion)
vii. Iron accumulation
Iron accumulation is a predictable consequence of chronic
RBC transfusion. Organ toxicity begins when
reticuloendothelial sites of iron storage become saturated.
Liver and endocrine dysfunction creates significant
morbidity and the most serious complication is
cardiotoxicity which causes arrhythmias, and congestive
heart failure. Patients receiving chronic transfusion
usually have their iron status monitored and managed by
their physician.
Management and Prevention: Iron chelation therapy is
usually commenced early in the course of chronic
transfusion therapy
viii. Volume overload
Pts with cardiopulmonary disease and infants are at risk
of volume overload especially during rapid transfusion of
large volume of blood
Management; : Stop the transfusion, administer oxygen
and diuretics as required.its advisable in chronic anaemia
to give packed RC in addition to diuretic.The transfusion
should be given slowly(one unit over 4-6hrs).
2) Infectious complications
Hepatitis May be transmitted from donor & cause sever
hepatitis , usually 3 mths after transfusion. it should be
avoided by screening of the blood donor.
AIDS is a feared disease but the actual risk is quite low.
All blood is tested for the anti-HIV-1 antibody which is a
marker for infectivity. Unfortunately, there is a 6-8 week
period required for a person to develop the antibody after
they are infected with HIV and therefore infectious units
can go undetected
CMV and EBV are usually the cause of only
asymptomatic infection or mild systemic illness.
Unfortunately, some of these people become
asymptomatic carriers of the viruses and the white blood
cells in blood units are capable of transmitting either
virus.
Immunocompromised and immunosuppressed
patients are particularly susceptible to CMV and should
receive CMV negative units only.
Parasitic diseases
Reported to be transmitted via blood transfusion include
malaria, toxoplasmosis, and Chagas' disease.
Bacterial Contamination
Bacteria may be introduced into the pack at the time of
blood collection from sources such as donor skin, donor
bacteraemia or equipment used during blood collection or
processing.or it may results from faulty storage,especially
when donor blood being Left in a warm room for some
hrs before transfusion
Bacteria may multiply during storage. Gram positive and
Gram negative organisms have been implicated. Platelets
are more frequently implicated than red cells.
Symptoms: Very high fever, rigors, profound
hypotension, nausea and/or diarrhoea.
Management: Immediately stop the transfusion and
notify the hospital blood bank.
After initial supportive care, blood cultures should be
taken and broad-spectrum
antimicrobials commenced. Laboratory investigation will
include culture of the blood pack.
Prevention: Inspect blood products prior to transfusion.
Some but not all bacterially contaminated products can be
recognised (clots, clumps, or abnormal colour).
Maintaining appropriate cold storage of red cells in a
monitored blood bank refrigerator is important.
Transfusions should not proceed beyond the
recommended infusion time (4 hours).
Blood substitutes
1) Albumin
Human albumin can be used while cross-matching is
being performed.2-3 units are given IV over 30min.Its
valuable in burns & hypovolemia. Its prepared from
human plasma & heat treated so that neither hepatitis nor
Lecture 7 - Blood transfusion & blood products
30
HIV can be transmitted.Shelf life is one year at room
temp. but 5-yr at 2-8C
Human albumin(4.5%) is valuable in burn&hypovolemia.
Human albumin(20%) concentrated salt poor used in
sever hypoalbuminemia with salt&water overload ex.
Liver failure with ascitis.
2) 2-Dextrans
These are polysaccharide polymers of varying molecular
wt.ex.dextran70 & dextran40.
It produce an osmotic pressure similar to that of
plasma.They induce roulex of the red cells,thus interfere
with blood grouping&cross-matching,so the need of
blood sample before hand.It interfere with platelets
function & may cause an abnormal bleeding,so its
recommended that total volune of dextran should not
exceed 1000ml.It may also cause;
anaphylactic reaction.dextran may also cause;
- simple haemodilution of clotting factors
- Reduced factorVIII activity
- Increased fibrinogen activity
- Increased fibrinolysis
- Reduced clotting strength
- Impairment of platelets function
3) Gelatin(ex.Haemaccel,Gelofusin)
Used commonly as plasma expander.Up to 1000ml of 3.4-
4% solution givenIV.It has low rate of anaphylactic
reaction
4) Hydroxyethyl starches
Many types;Haptostarches,Pentastarches,Tetrastarches.It
has low incidence of anaphylactic reaction.It may cause
intractable itching,coagulopathy may occur due to
reduction in factor VIII& platelets
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