Blood transfusion
Introduction
• The transfusion of blood and blood products is life-saving
• Commonplace since the first successful transfusion in 1818.
• Despite low incidence of severe transfusion reactions and
infections in recent years, transfusion of homologous blood
causes immunosuppression, leading to increased morbidity
and decreased survival in certain population groups
(trauma, malignancy).
• Supplies are also limited, and therefore the use of blood
and blood products must always be judicious and justifiable
for clinical need
Indications
• Acute severe hemorrhage
• Severe anemia
• Chronic anemia going for surgery
• Blood clotting disorders
• Extracorporeal circulation
• Exchange blood transfusion
• Significant bleeding during major op
Selection of donor
• Fit – 18-65yrs
• > 51kg in weight
• Hb >13.5g/dl in males, >12.5g/dl in females
• No major op in last 6 months
• No blood donation in last 6 months
• No pregnancy in last 12 months
• No blood transfusion, tissue or organ transplantation
within the past 12 months.
• No clinical evidence of malaria
• Free from severe HTN, splenomegaly, hepatomegaly,
bleeding disorder or allergies such as asthma
• No recent unexplained weight loss of 4.5kg or more.
• Unvaccinated within last 3 weeks
Selection of donor
• Not had tattoos, ear or skin piercing, acupuncture
or accidental needle-stick injury within the past 12months.
• Free of hx or clinical evidence & not carriers of viral
hepatitis, HIV, syphilis, trypanosomiasis, brucellosis
• must not belong to any of the risk groups for HIV infection
e.g homosexuals, IV drug abusers or commercial sex
workers and their clients
Collection/Storage
• Strict asepsis in sterile bag with 50 - 60mls of
anticoagulant
• Anticoagulants- Citrate Phosphate Dextrose
(21days), Citrate Phosphate Dextrose Adenine
(35), Saline Adenine Glucose-Manitol (42days)
• Blood bank refrigerator @ 2-6 oC.
– Platelets @ 22°C. Fresh Frozen Plasma &
Cryoprecipitate are stored frozen (-40°C).
• Shelf-life: Platelets- 5days, FFP/Cryoppt-1yr,
Albumin- 4yrs, Factor concentrates- 2yrs
Effect of stored blood (2-6 C) 0
• Fresh blood (blood used within 3h of
collection) has all its constituents preserved.
• Red cell changes
– Swell and lose potassium to plasma
– Reduced viability (1%/day of storage)
– Reduced 2,3DPG after 1 week of storage
• Increased affinity of haemoglobin for oxygen
• Depressed oxygen release at the tissue level.
• Recovery takes place within 24h after transfusion
• WBC
– not viable after 24h of storage.
– Even fresh leucocytes survive for only 30-90min in
the recipient's blood.
• Platelets
– Non- viable after 24h of storage
• Electrolytes
– Plasma potassium rises at the rate of about
1mmol/day
– Plasma sodium is increased because of the sodium
citrate in the CPD anticoagulant.
– Depleted ionized calcium
• Clotting Factors:
– Factor VIII and Factor V declines rapidly after 24h
of storage, with little activity after 7 days.
– Factor X loses its activity after 7 days
– Factor IX declines rapidly after 7 days and there is
no activity after 14 days.
– Factor VII declines only after 14 days.
– Fibrinogen and factor XI are stable for 21 days
• pH
– Falls due to rising lactic acid concentration from
red cell glycolysis.
• Plasma haemoglobin levels rise due to leakage
of Hb from cells
• The ammonia concentration also rises.
Tests
• ABO & Rh grouping
• Serological tests for syphilis, HBsAg, HCV,
HTLV1 & 2, HIV 1 & 2
• Thick & thin film for malaria
• Cross-matching for compatibility
ABO grouping
• Blood group O is the universal donor type as it contains no antigens to provoke a
reaction.
• Conversely, group AB individuals are ‘universal recipients’ and can receive any ABO
blood type as they have no circulating antibodies
Rhesus system
• The rhesus D (Rh(D)) antigen is strongly
antigenic
– present in majority of the population.
• Antibodies to the D antigen are not naturally
present in the serum of the remaining
individuals
– formation may be stimulated by the transfusion of
Rh-positive red cells, or acquired during delivery
of a Rh(D)-positive baby.
• Acquired rhesus antibodies are capable,
during pregnancy, of crossing the placenta
– if present in a Rh(D)-negative mother may cause
severe haemolytic anaemia and even death
(hydrops fetalis) in a Rh(D)-positive fetus in utero.
• Thus rhesus positive blood should not be
given to a rhesus negative woman
Cross-matching
• To prevent transfusion reactions, all
transfusions are preceded by ABO and rhesus
typing of both donor and recipient blood to
ensure compatibility.
• The recipient’s serum is then mixed with the
donor’s cells to confirm ABO compatibility and
to test for rhesus and any other blood group
antigen–antibody reaction.
• Full cross-matching of blood may take up to 45
minutes in most laboratories.
• In more urgent situations, ‘type specific’ blood
is provided which is only ABO/rhesus matched
and can be issued within 10–15 minutes.
• Where blood must be given emergently, group
O (universal donor) blood is given (O− to
females, O+ to males).
Fractions of blood in use
• Whole blood
• Packed red cells
• Platelet concentrate
• Fresh frozen plasma
• Cryoprecipitate
• Granulocyte concentrates
• Factor concentrates
• Plasma protein solutions
• Indications for whole blood transfusion are:
– To restore blood volume in cases of sudden loss of
25% or more of the blood volume.
– Patients undergoing exchange transfusion.
– Patients who continue to bleed after receiving 4
units of packed red blood cells.
• Packed RBC
• The blood is centrifuged at 3000 revs/min for 5 mins and
most of the plasma removed to give a Hct of 50 -75%
• Each unit is approximately 330 mL and raises the Hb by
approximately 1g/dl in a 70kg adult
• Advocated for transfusion in all anaemic patients.
• Used when whole blood may overload the circulation e.g.
in chronic anaemia, renal, liver or cardiac failure.
• Washed packed cells
– patients awaiting transplantation
– those with known allergic or febrile non-haemolytic transfusion
reaction.
• Platelet concentrate
• The precipitate after platelet – rich plasma is centrifuged
at 3000rev/min for 5 mins
• Platelet-rich plasma is the supernatant plasma after
whole blood is centrifuged at 1000rev/min for 3 mins
• It is used in the short-term management of severe or
life-threatening thrombocytopaenia or
thrombocytopathy.
• One unit of platelet concentrate raises the platelet count
by approximately 5-10 x 109/L in an adult.
• Platelets are stored at room temperature (20–24°C) and
are kept rotated or agitated mechanically throughout
the storage period of 5 days.
• Fresh frozen plasma (FFP)
• It is the supernatant liquid portion that is separated and
rapidly frozen by immersion in a mixture of carbon dioxide
and ethyl alcohol within 8h of collection when fresh blood
is centrifuged at 3000 rev/min for 7mins.
• Stored at −40 to −50°C with a two-year shelf life.
• It contains plasma proteins that maintain oncotic pressure
and immunity, all components of coagulation,
fibrinolytic and complement systems, fats, carbohydrates
and minerals.
• FFP is an effective volume expander because of the plasma
proteins and helps in correcting certain disorders of
haemostasis
• Indications for use of FFP:
– deficiencies of coagulation factors or inhibitors of
coagulation for which specific concentrates are not
available
– Emergency treatment of warfarin overdose and Vit. K
deficiency when factor IX complex concentrate is not
available.
– Treatment of thrombotic thrombocytopaenic purpura.
– Treatment of disseminated intravascular coagulation.
• Cryoprecipitate
• It is the precipitate when fresh frozen plasma is
allowed to thaw at 4°C and the supernatant
plasma removed.
• Rich in Factors II, VIII and XIII, fibrinogen and von
Willebrand's factor and is stored at -30 to - 4O"C.
• It is used in haemophilia, hypofibrinogenaemia
and von Willebrand's disease.
• The volume of each unit of cryoprecipitate is
15ml and contains 80-100 IU of Factor VIII and a
minimum of 150mg of fibrinogen.
• Granulocyte concentrate
• It is usually prepared by leukophoresis.
• The volume is 220ml and contains
approximately
• 1.0 x 1010 granulocytes/unit.
• It is useful in selected patients with sepsis and
severe neutropaenia.
• It has to be irradiated to prevent post
transfusion graft-versus-host disease in
neonates and immunocompromised recipients.
• The shelf-life is 24hr
• Factor concentrates
– Factor VIII concentrate
– Factor IX complex concentrate
– Fibrinogen concentrates.
• Recombinant factor VIII and IX are available
but are very expensive. However, they are free
from diseases transmitted by blood derived
concentrates.
• Protein solutions
– Human plasma protein fraction
– Albumin concentrate
– immune and hyperimmune globulins
– antithrombin III and protein concentrate.
• The latter two fractions are used to correct
hereditary deficiency states which predispose
to thrombophilia
Types of blood transfusion
• Homologous – blood obtained from a donor
• Autologous – collection and subsequent re-infusion of
the patient's own blood.
– prevents transmission of diseases such as HIV
– avoids immunological complications such as
alloimmunization and transfusion reactions
– very useful in centres with limited or absent blood
transfusion service especially in emergencies
• Preop autologous blood donation
• Acute isovolaemic haemodilution
• Intraop blood salvage
• Postop blood salvage
• Preoperative Autologous Blood Donation (PABD)
– Effective method for patients for elective surgery.
– Patient donates preoperatively, 1-5 units of his
blood.
– Donations should be 3-7 days apart and the last one
should not be within 72hrs of surgery
– Patient’s haemoglobin should be over 10g/dl and the
PCV over 30%.
– The patient is given haematinics and Recombinant
human erythropoietin
– Patients with bacteraemia, serious cardiac disease
and sickle cell disease should be excluded
• Acute lsovolaemic Haemodilution (AIVH)
– 1-4 units of the patient's own blood are removed
immediately prior to the commencement of
operation
– replaced simultaneously with a crystalloid (3.0ml
for every 1.0ml of blood collected) and/or colloid
(1.0ml for every 1.0mI of blood collected) to
maintain the circulating blood volume.
– Blood is collected from one venous line while
simultaneous replacement with fluid is carried out
via a second venous line
– The autologous blood collected is re- infused if
excessive bleeding occurs or preferably after
major bleeding has been controlled, during or
after the operation.
– Patient's initial haemoglobin and PCV should be >
12g/dl and 36% respectively and must not fall
below 9 g/dl and 27% respectively after
haemodilution
• Intra-operative Blood Salvage
– Shed blood from a wound or body cavity during
surgery is collected and subsequently re-infused
into the same patient.
– Useful in ruptured ectopic pregnancy, ruptured
spleen, penetrating injuries, haemothorax.
cardiovascular surgery and some orthopaedic
operations.
– Shed blood in a body cavity is collected with a
laddle or gallipot into a kidney dish or large bowl
containing an anticoagulant.
– The blood is filtered into a bottle through 4-6
layers of sterile gauze placed in a funnel.
– The bottle is then sealed and the blood re-infused.
– Process can be automated with use of a machine
– May lead to coagulopathy due to loss of clotting
factors in shed blood
– In blood salvage, haemolyzed or infected blood
should not be used.
– Contra-indicated in patients undergoing tumour
resection because of concern about re-infusing
tumour cells
• Postoperative Blood Salvage
– Considered when post-operative blood loss is likely
to cause haemodynamic instability and require
homologous blood transfusion.
– Blood is salvaged from body cavities and joint
spaces and reinfused.
– Useful in cardiac surgery, penetrating chest injuries
and some orthopaedic procedures.
– The precautions indicated for Intraoperative Blood
Salvage also apply for this type of blood salvage
World War II syringe for direct interhuman
blood transfusion
Principles
• Obtain consent
• Transfuse only when necessary
• Use of required fraction of blood
• Group specific blood
• Double checking of patient’s data
• Warm blood before commencement
• Close monitoring of vital signs
• Avoid top-up transfusion
Transfusion trigger
• Historically, patients were transfused to achieve a
haemoglobin >10 g/dL.
• This has now been shown to not only be unnecessary but
also to be associated with an increased morbidity and
mortality compared to lower target values.
• A haemoglobin level of 6 -7g/dL is acceptable in patients
who are not actively bleeding, not about to undergo major
surgery and are not symptomatic.
Procedure
• Strict asepsis
• Personal details of patient cross-checked with blood
to be transfused
• Pre-transfusion vital signs
• IV access secured, large bore needle
• Initial rate 20-30 drops i.e 2-3ml/min
• If there is blood loss the rate of infusion should be
rapid, squeezing if necessary the plastic bag
containing the blood
• IV frusemide given (pt @risk of circulatory overload)
• Parenteral Antihistamine/steroid, antipyretics should
be available in case of transfusion reaction
• Close monitoring of vital signs
Complications
• Immediate
– Febrile non-haemolytic reaction
– Allergic/anaphylactic reaction
– Haemolytic reaction
– Bacterial contamination
– Cardiac arrest/arrhythmias
– Circulatory overload
– Air embolism
– Transfusion related acute lung injury (TRALI)
• Febrile non-haemolytic transfusion reaction
– Quite common
– most often due to incompatibility between
antigens on the donor white cells and antibodies
in the recipient's plasma formed as a result of
previous transfusions or pregnancies.
– may also be due to endotoxin or pyrogens in the
transfusion set or blood.
– Features are:
• Rigors and fever
• Nausea and vomiting
– Management
• Stop transfusion temporarily.
• Give antipyretics eg Aspirin or paracetamol.
• The condition settles after a few hours.
• If severe, it is investigated to exclude a haemolytic
reaction, septicaemia or malaria.
• Subsequent transfusions should be with leucocyte-
depleted blood products.
• Allergic Reaction
– Occurs in 2% of transfusions and a few may be
fatal.
– More common in patients receiving repeated
transfusions and those with IgA deficiency.
– Due to allergens, usually plasma proteins, in the
donor plasma and so is less likely to occur with
packed red cells.
– Symptoms include
• Urticaria.
• Myalgia and arthralgia.
• Bronchospasm, oedema of the face and/or larynx, in
severe cases with anaphylaxis.
• Chest pain, hypotension, abdominal cramps, diarrhoea
and shock in cases with anaphylaxis
• Pyrexia
– mediated by histamines and leukotrienes.
– Management
• Transfusion should be stopped anti-histamine and
corticosteroid given.
• If symptoms are severe IV adrenaline should be
administered.
• Subsequently, such patients should have premedication
with antihistamines before transfusion or be given a
plasma-free componen e.g. washed packed RBC for
treatment of anaemia
• Haemolytic Reactions
– The haemolysis of donor cells by antibodies in the
recipient's plasma.
– Occurs in about 0.05% of transfusions and has a
mortality of 10-50%.
– Results from wrong identification of blood and
recipient.
– Natural ABO antigen-antibody incompatibility is the
commonest and most important cause and the
reaction occurs instantaneously.
– Rh incompatibility is infrequent and the reaction
takes hours or days.
– Features
• Develop during or at times some hours after
transfusion
• Sensation of heat and pain along the vein being used
for transfusion soon after transfusion has begun;
tingling of the limbs.
• Headache or fullness in the head.
• Rigors and fever:
• Dyspnoea and constricting pain in the chest due to
histamine-induced bronchiole and vessel constriction.
• Pain in the loins.
• Shock with hypotension. tachycardia, sweating and
restlessness in severe cases.
• Haemoglobinuria (coca-cola coloured urine).
• Jaundice after some hours.
• In the anaesthetized, hypotension in spite of adequate
correction of blood loss and diffuse oozing of blood
from the operation site due to consumption
coagulopathy
• Progressive oliguria to anuria due to toxic action of free
haemoglobin and inadequate renal perfusion following
shock and fibrin deposition in the small vessels.
– Management
• Stop transfusion
• Remaining donor and the patient's blood taken for
further grouping and crossmatching.
• Bedside clerical checks should also be done
• Some blood is taken for culture as bacterial
contamination may be the cause of the symptoms.
• Laboratory confinnation.
– Haemoglobinaemia - Free haemoglobin may be
confirmed chemically.
– Methaemalbumin in the plasma.
– Plasma bilirubin is elevated.
– Saline suspension of recipient's blood may show
agglutinated red cells microscopically.
• Establish diuresis to flush the renal tubules of
haemoglobin and prevent their blockage.
– Give normal saline infusion
– IV frusemide 40-80mg or 50ml of 20% (or 100ml of
10%) IV mannitol in 5 minutes.
• The urine output should be 1ml/kg/hr
– Established acute tubular necrosis is treated by
peritoneal- or haemo- dialysis until tubular function is
restored.
– IV sodium bicarbonate makes the urine alkaline,
enhancing the solubility of haemoglobin and prevent
its deposition in the tubules.
– Fresh compatible blood may be necessary to correct
shock.
– Low doses of dopamine 4-5ug/kg/minute may also be
given to increase the cardiac output in hypotensive
patients.
– If the patient is undergoing surgery and oozing of
blood is severe, fresh frozen plasma and platelets
• Circulatory Overload
– leads to pulmonary oedema or congestive cardiac
failure.
– particularly likely to occur in the elderly and
debilitated and in patients with chronic anaemia,
congestive cardiac failure, pulmonary, hepatic or
renal disease.
– Such patients are best given packed red cells; but if
whole blood must be given then it should be
transfused slowly - 1 unit in 4-6hr.
– A diuretic may be given at the same time so that
the excess fluid is excreted by the kidneys.
– may also occur in massive transfusion.
– The symptoms and signs are
• Dyspnoea, orthopnoea, cough and cyanosis.
• Frothy sputum.
• Raised jugular venous pressure.
• Rales in both lungs.
• Rapid and weak pulse.
– Treatment
• The transfusion is stopped and the patient propped up.
• IV frusemide removes the excess fluid.
• In an emergency, phlebotomy is done to relieve the
overload.
• Digitalization is done to improve myocardial function.
Complications
• Delayed
– Thrombophlebitis
– Delayed haemolytic reaction
– Post-transfusion thrombocytopenic purpura
– Transmission of blood-borne diseases
– Iron overload
– Immunosuppression
Massive blood transfusion
• Transfusion of >1/2 blood vol in 1hr or >total
blood volume in <24hrs
• Estimation of total blood volume
– ADULTS - 70mls/kg body weight or 7% of ideal body
weight
– CHILDREN - 80 to 90mls/kg body weight or 8-9% of
ideal body weight
• Problems
– Technical & clerical errors
– Circulatory overload
– Cardiac arrhythmias/arrest
• Hyperkalemia, cold blood, hypocalcemia
• Give 10ml of 10% calcium gluconate in a vein other
than the one being used for the transfusion for every
litre of blood transfused
– Respiratory complications
– Reduced oxygen delivery to tissues
• Bleeding diathesis
– Thrombocytopaenia.
– Deficiency of clotting factors V and VIII in banked blood.
– Hypocalcaemia for reasons stated above.
– Patients receiving massive transfusion should, therefore,
be given
• platelet concentrate and fresh frozen plasma (1unit for
5 units of banked blood if clotting factors are not
available) to provide functioning platelets and clotting
factors
• 10% calcium gluconate (10ml for every litre of blood) to
prevent hypocalcaemia.
• In the absence of fresh frozen plasma and platelet
concentrate, 500ml of fresh blood may be given for
every 1500ml of banked blood .
• If necessary, the coagulation status should be
checked and specific deficits corrected
PLASMA SUBSTITUTES
• In the absence of blood, substitutes are used
to replace lost circulating blood volume in
hypovolaemic patients
– Stable plasma protein solution
– Albumin
– Dextran (40, 70, 110)
– Synthetic gelatin colloids (Haemaccel, Gelofusine)
– Hydroxyethyl starch preparations (Hetastarch,
Pentastarch)
– Crystalloids eg Normal saline, ringer’s lactate
RED CELL SUBSTITUTES
• Diaspirin cross-linked haemoglobin solution
– has similar oxygen transport and exchange properties as whole blood.
– It is as effective as whole blood in restoring haemodynamics after
haemorrhagic shock.
• The perfluorocarbons
– also oxygen-carrying solutions.
– They dissolve oxygen which is released to tissues by diffusion
– 100% inspired oxygen is required during their use.
• These substitutes are not yet established in clinical practice.
• Other substitutes under investigation
– stroma-free haemoglobin
– encapsulated haemoglobin
– recombinant DNA derived haemoglobin