CLINICAL BLOOD TRANSFUSION

PROF ALAO, OO

DEPARTMENT OF HEMATOLOGY

BSU/BSUTH

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OUTLINE

• INTRODUCTION
• HISTORY
• BLOOD PROCUREMENT
• DONOR SELECTION
• RECIPIENT/DONOR REACTIONS
• BLOOD PRODUCTS: COMPONENTS & DERIVATIVES
• TRANSFUSION REACTIONS
• CONCLUSION

INTRODUCTION

• The process of blood transfusion aims at the safe transfer of blood component from donor to recipient.
• Blood contains cells and as such is a tissue. So the transfusion of blood should be seen as a form of tissue transplant.
• Like solid organ transplant carries both benefits and risks to the recipients

HISTORY

• Beginning with William Harvey's experiments on the circulation of blood in 1616.
• Richard Lower performed the first blood transfusion between animals 1665.
• The first blood transfusion from animal to human was administered by Dr. Jean-Baptiste Denys. 1667

• Dr. James Blundell performed the first successful transfusion of human blood to treat postpartum hemorrhage 1818
• Samuel Armstrong Lane, aided by Dr. Blundell, performed the first successful whole blood transfusion to treat haemophilia.1840

• The modern era of blood transfusion started in 1901 with the discovery of blood group by Karl Landsteiner.
• Sodium citrate as an anticoagulant. 1914
• The First World War acted as a catalyst for the rapid development of blood banks and transfusion techniques

BLOOD PROCUREMENT

• Blood donation shall in all circumstances be voluntary. Financial profit must never be a motive for the donor or for those collecting the donation. WHO
• However, in a number of countries worldwide, blood donation IS STILL remunerated.

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• In developed countries an organised blood supply system that sources blood from donors (voluntary) in the community exist.
• Approx 100% of whole blood used in the US comes from voluntary donor.
• There is a national blood transfusion policy in Nigeria. Implementation is very poor. >99% of whole blood comes from paid donors and family replacement.

Donor Selection

• All blood component and blood products originate from blood donors, so the safety of blood transfusion begins with careful selection of donors.
• The guiding principles should be to protect both the donor and recipient from any ill effects of donation.
• The ideal donor should be a healthy , voluntary , non-renumerated individual

Donor recruitment

• Ideally each donor is afforded the opportunity for self exclusion with the use of appropriate literature and questionnaire which explain the donation process, the testing that will be carried out on their blood, and the obligatory requirement for reporting certain test results to appropriate authorities.
• Full medical examination is performed on the donor prior to phlebotomy

• Much reliance is placed on answers to questions about general health, medical history, medications and lifestyle practices / risk factors for transfusion transmissible diseases which have crucial implications for the donation process.

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• Measures to protect the donor.
• Age 17 – 65 years
• Weight above 50 kg
• Haemoglobin > 13 g/dL for men, 12 g/dL for women
• Minimum donation interval of 12 weeks (16 weeks advised) and three donations per year maximum
• Pregnant and lactating women excluded because of high iron requirements
• Exclusion of those with:
• Known cardiovascular disease, including hypertension
• Significant chest disorders
• Epilepsy and other CNS disorders
• Gastrointestinal disorders

- diabetes

• Chronic renal disease
• Ongoing medical investigation or clinical trials
• Exclusion of any donor returning to occupations such as driving bus, plane or train, heavy machine or crane operator, mining, scaffolding, etc. because delayed faint would be hazardous

Tests performed on blood donations

• Tests for infectious markers including syphilis, HBsAg, anti-HCV, anti-HIV-1 and -2, HIV-1 p24 antigen, anti-HTLV (in some countries)
• Haemoglobin estimation
• Copper sulphate
• Colorimetric test using filter paper

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• Blood group determination and antibody detection
• ABO and Rh(D) grouping are performed . Donors are tested for the presence of D and weak D antigens.
• Testing may also be performed for unexpected red cell antibodies

Donation process

• Normal vital signs : temperature, pulse, BP
• Volume of donation: about 450 mls of blood; not > 13% of estimated blood volume to prevent vasovagal attacks.
• Standard skin preparation and phlebotomy. Examine arms for signs of intravenous drug use.

• Phlebotomy site should be properly sterilized and free of skin lesion
• Blood is collected in a single use sterile container
• 450ml(+/-45ml) of blood is collected in 63-70ml of CPDA anticoagulant over 7-10 min

Hazards of blood donation �(To the Donor)

• Fainting
• Infection
• Bruising of site
• Hematoma at the site of venopuncture
• Arterial puncture
• Trauma to the nerves in the arm
• Aneurysms and arteriovenous fistulae

Anticoagulants used in transfusion

• Citrate glucose first anticoag used in blood transfusion and blood banking, able to keep blood viable for 14days.
• Acid citrate dextrose (ACD) use was limited due high acid content, keeps blood viable for 21days
• Citrate phosphate dextrose (CPD) keeps blood viable for 21days
• Citrate-phosphate-dextrose with adenine (CPDA-1) 35days
• Heparin is used for special purpose and blood collected in it must be used within 24hours.

Storage of blood

• Blood can be stored in liquid state(2-6 C) or can be frozen and stored at sub zero(-80 or -150⁰C) temperature.
• When blood is stored in a liquid state there is a progressive loss of viability of the red cells.
• Some biochemical changes have been noted in stored blood i.e
• Decrease in pH
• Build up of lactic acid
• Decrease in ATP level
• Low 2,3-DPG level
• High potassium level

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BLOOD COMPONENTS

• Blood components refer to the specific cellular and plasma components into which a whole blood donation may be separated to enhance the utilization of individual donations. Transfusing the appropriate combination of components effectively provides for the patient’s clinical needs.

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Examples

• Whole blood
• Red cell concentrates
• Washed red cells
• Neocyte-enriched red cells
• Leukocyte-reduced red cells
• Frozen/deglycerolized red cells
• Platelets
• Fresh frozen plasma
• Cryoprecipitates
• Others eg albumin, immunoglobulin

Whole blood

• Indications – appropriate for use if both enhanced O2 carrying capacity AND blood volume replacement are needed concurrently. Eg cardiopulmonary bypass, actively bleeding patients
• Storage – must be refridgerated as soon as possible after collection.

Temperature maintained at 2- 6 C (during storage)

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Disadvantages

• indiscriminate use of whole blood can reduce the availability of components to multiple patients.

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Red cell concentrates (packed red cells)

• Description: whole blood is centrifuged to separate the red cells from the plasma components. A typical unit has a volume of 240 – 340 ml and haematocrit 80%. May undergo further processing before transfusion to patients eg: washing, leucocyte depletion, freezing. Freezing is done in liquid nitrogen... With addition of glycerol (a cryoprotective agent)
• Indications : primarily to augment the O2 carrying capacity of the blood.

- patients with chronic blood loss

- patients who lack normal bone marrow activity

- patients who cannot tolerate increased blood volume eg CCF.

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Red cell concentrates (packed red cells)

• Storage : 2- 6C during storage, 2 – 10 C during transportation

*Shelf life is dependent on the anticoagulant/additive solution used. Manipulation of the unit, including washing or irradiation, alters the shelf life.

• Advantages – RCC minimise circulatory overload because of reduced volume.

- reduced volume of anticoagulants and electrolytes

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• Disadvantages

– actual transfusion of packed cells is slower than whole blood because of increased viscosity

- transfusion of RCC when whole blood is indicated necessitates additional transfusion of FFP thus increasing the risk of exposure to blood borne diseases

- cost to the patient is increased.

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• Contraindications: RCC should not be given for volume replacement or for any other reason than correction of acute or chronic anaemia when non-transfusion alternatives have been assessed and excluded.

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Washed red blood cells

• Washed red blood cells are usually obtained from whole blood.
• Packed red cells are washed with and suspended in saline.
• Frozen red cells are also source of washed red cell.
• Washed RBC must be used within 24hrs

Indication for washed RBC

• Hypersensitivity to plasma
• Patients with IgA deficiency
• Neonatal transfusion
• PNH Patients

Leukocyte-reduced red cells

• Unit of RBC containing less than 5*10⁶ WBC
• Indications
• Febrile non-hemolytic transfusion reaction
• Prevention of transfusion associated cytomegalovirus infection
• Aplastic anaemia and bone marrow transplant patient ( bcos of CMV)
• Fetal and neonatal transfusion ( Bcos of CMV)

• Methods of preparation
• Filtration
• Centrifugation and removal of buffy coat
• Washing of red cells
• Freezing and thawing of red cells
• Apheresis with leucodepletion

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RECIPIENT

• Assess need for transfusion- Careful assessment of clinical and lab indications:
• Blood loss
• Haemolysis
• Cardiorespiratory state and tissue oxygenation
• Assessment of anaemia- clinical/lab
• Patient’s tolerance to anaemia/ blood loss
• Anticipated need for blood

Decision on transfusion

• Confirm need for transfusion- ask yourself the following questions-
• What improvement am I aiming to achieve?
• Can I minimize blood loss?
• Are there any treatment I should give?
• What are the specific indications for transfusion?
• What are the risks/ benefits?
• What other options are there if no blood is available in time?
• Will a trained person monitor transfusion?
• Have I recorded my decision and reasons for transfusion?

Indications for transfusion

• Severe haemorrhage
• Shock
• Surgery
• Burns
• Anaemia

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Types of transfusion

• Allogeneic transfusion
• Autologous transfusion
• Pre operative collection and storage for variable time..... PRE DEPOSIT
• Immediate pre operative phlebotomy with haemodilution.
• Intra operative collection with filtration and transfusion

Compatibility testing ( cross - match)

• The ABO and RhD groups of all potential recipients should be determined before transfusion
• The donor red cells are routinely tested against the recipient serum or plasma in order to detect any potential incompatibilities
• This can be done manually or electronically (automated).

PACKED CELLS Compatibilities

Route of administration

• Intravenous
• Intra arterial
• Intra peritoneal

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• The target is to commence transfusion within 30min of dispatch from the blood bank and to complete transfusion within 4hours

TRANSFUSION REACTION

Definition

Any adverse event which occurs as a direct

consequence of blood transfusion.

• It occurs in 1 to 6% of all blood transfusions
• More frequent (10%) in patients with haematologic and oncologic diseases

The “classic” blood transfusion reactions are immunologic in nature, and results from interaction between host’s and transfused

foreign proteins

Transfusion reaction can be classified as

• Immunologic and Non-Immunologic
• Immediate (usually < 24 hrs) and Delayed (>24 hrs)
• Haemolytic and Non-Haemolytic

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• Hazards of transfusion.
• Immediate (less than 24hours)
• Non - immune complications
• Bacterial: acute sepsis or endotoxic shock
• Hypothermia
• Hypocalcaemia ( ↓ Ca 2+ ) worse in neonates, infants, and patients with liver disease (impaired hepatic Citrate metabolism due to liver disease or hepatic immaturity of neonates and infancy) and massive Blood TransfudionS
• Immune complications
• Febrile non- haemolytic transfusion reactions
• Acute haemolytic transfusion reactions: intravascular (IgM), extravascular (IgG)
• Allergic reactions (urticarial)
• Anaphylactic reactions (anti - IgA)
• Transfusion- related acute lung injury
• Transfusion - associated circulatory overload

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• Delayed (days to years)
• Non - immune complications
• HIV, HCV, HBV, CMV
• Others: parvovirus B19, HAV, HEV, dengue, malaria,
• Chagas disease, brucellosis, syphilis, vCJD
• Immune complications
• Delayed haemolytic transfusion reactions
• Post- transfusion purpura
• Transfusion- associated graft- versus- host disease

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Immunologic Complications

This can be classified into

haemolytic

non-haemolytic

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Haemolytic transfusion reaction

This is premature destruction of transfused red cells reacting with antibodies in the recipient , or less commonly the destruction of recipient red cells by the transfused antibodies....THE LAST EXAMPLE COMMONLY OCCURS WITH DANGEROUS UNIVERSAL DONORS

• The haemolysis can be acute, which is usually

intravascular, or delayed which is usually

extravascular

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Acute Haemolytic Transfusion Reaction

• usually due to ABO incompatibility
• most commonly due to clerical error, particularly in operating room
• usually severe, but the severity of the reaction depends on the amount of blood transfused
• it accounts for over 50% of deaths related to blood transfusion

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Pathology

• Rapid rbc destruction results from binding of preformed antibodies which are usually IgM, mainly anti-A or B, to red cell antigens capable of fixing complement
• Leading to intravascular hemolysis from MAC , a major product of complement activation and intravascular hemolysis results in DIC as a direct result of activation of coagulation pathways by thromboplastin like materials released from haemolysed red cells

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• the anaphylatoxins C3a and C5a that are liberated during complement activation, cause the release vasoactive amines and hydrolases from mast cell, basophils and granulocytes... Anaphylatoxins typically mediate /cause hypotension and acute renal failure
• The cytokines interleukin (IL) - 1, IL - 8 and TNF are released.

Factors that affect the clinical features

• whether the red cells are destroyed within the circulation or in the mononuclear phagocytic system
• The strength, class and subclass of the antibody
• the nature of the antigen
• the number of incompatible red cells transfused
• the clinical state of the patient.

Signs and symptoms

• Typically, within less than 1 hour of the start of the transfusion,
• the patient complains of heat or pain in the cannulated vein
• throbbing in the head
• Flushing of the face
• chest tightness
• Nausea
• lumbar pain.

• Tachycardia
• hypotension.
• Shock
• renal failure.
• Rigor
• pyrexia
• Intravascular destruction of red cells brings about liberation of thromboplastin - like substances that activate coagulation and lead to DIC.

• When asked to void, dark coloured urine is passed (haemoglobinuria)
• Oozing in the surgical field(DIC)

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Immediate step

• Stop transfusion but leave IV line in-situ
• Begin infusion of Normal Saline.
• From the other arm, collect sample for investigations
• Collect urine sample
• Check for clerical errors and alert the blood Bank

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Investigations

• Full blood count; Baseline parameters, red cell agglutinates on film
• Plasma/urinary Hb, haptoglobin, bilirubin; Evidence of intravascular or extravascular haemolysis
• Blood group of patient and units transfused; Compare with retested pretransfusion sample, to detect ABO error Unexpected ABO antibodies may arise from transfusion of incompatible plasma. Rechecking labels is often sufficient

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• DAT; Positive in majority. Compare with retested pretransfusion sample. May be negative if all incompatible cells destroyed
• Compatibility testing; Repeat antibody screen and compatibility testing on pre - and post - transfusion samples.

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• Urea, electrolytes and creatinine; Baseline renal function
• Coagulation screen Detection and monitoring of DIC
• Blood cultures of patient and units; In event of possible septic reaction caused by bacterial contamination of unit

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Management

• Transfusion may be stopped permanently or managed conservatively
• If transfusion is stopped, replace with normal saline[avoid the use of hypotonic solution to avoid haemolysis]
• Institute supportive management: maintain airways, monitor urine output, pulse rate, BP

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• When haemolysis is severe, urgent re-grouping, cross-matching and transfusion, FFP, and platelet transfusion may be necessary

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Delayed Haemolytic Transfusion Reaction

Usually:

• mild compared to acute transfusion reaction
• due to an anamnestic response occurring after re-exposure to a foreign red cell antigen previously encountered by
• Transfusion,
• Transplantation, or
• Pregnancy

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Pathology

It is usually due to atypical (unexpected) antibodies...

Which are antibodies other than anti A and anti B.... eg anti Kell,anti Duffy, or anti Kidd anti D antibodies... These are IgG antibodies that develop following allo immunization via previous Transfusion or pregnancy

• these Antibodies to these other antigens are not routinely screened for and are not usually detected during routine cross match because their concentration is usually too low
• Pathogenesis :
• Following a normal ‘compatible’ blood transfusion, antibodies [IgG] to these antigens

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may develop after some weeks or months: by

this time, the transfused blood had been cleared

• Re-exposure to the same antigen leads to destruction of the transfused cells by the existing antibodies in the recipient (anamnestic response). This destruction usually occurs between 2 to 21 days after transfusion
• Destruction is usually extravascular in the RES cells

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Symptoms

Generally mild and include

• malaise,
• jaundice,
• Fever
• Fall in haematocrit despite transfusion,
• Increase in unconjugated bilirubin
• A positive Coombs test confirms diagnosis

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Treatment

Screen and identify the antibody and avoid

transfusion of blood containing such antigens in

future

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Reactions due to white cell and platelet antibodies

1. Febrile non-haemolytic transfusion reaction (FNHTR)

Clinical presentation FNHTRs consists of:

• Fever with temperature rise of > or =1^oC above the pre-transfusion temperature
• sometimes headaches, chill and rigor back pain
• Mild dyspnoea within 6hrs of transfusion of red cells or platelets
• it is common in multi-transfused or multiparous women

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Pathology

FNHTRs are caused by cytokines such as

Interleukin 1,

Interleukin 8, and

Tumour Necrosis Factor-α

• which are generated and accumulate during the storage of blood components
• Interaction of donor leukocytes and recipient antibody can also lead to IL-1 release from donor leukocytes or recipient monocytes

-IL-1 can cause fever by stimulating PGE₂ production in the hypothalamus

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Clinical features

-the reaction is relatively common, found in 1 –

3 % of all transfusions

-there is fever, with a rise in temperature of at

least 1^oC above the pre-transfusion value and

without evidence of haemolysis

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Treatment

• Antipyretic
• Transfusion can be continued at a slower rate
• In patients with previous history, leukocyte-poor blood and blood products should be transfused

Transfusion- related acute lung injury

• TRALI consists of non - cardiogenic pulmonary oedema with bilateral pulmonary infiltrates on chest radiography, accompanied by chills, fever, cough and dyspnoea with low oxygen saturation and low or normal central venous pressure.....PRESENTATION SIMILAR TO ARDS
• this develop very rapidly, usually within 1 – 2 hours,or up to 6 hours after infusion of a plasma – containing component.....LEUKOAGGLUTININS IN TRANSFUSED PRODUCT REACT WITH RECEPIENT LEUCOCYTES, FORMING LEUKO-AGGREGATES THAT LODGE IN PULMONARYVASCULATURE.........MULTIPAROUS FEMALE DONORS IMPLICATED....
• It has a high mortality
• Management is essentially symptomatic

Post- t ransfusion purpura

• sudden onset of severe thrombocytopenia 7 – 10 days after the transfusion of platelet - containing blood components, usually red cells.
• The patient always has a history of previous blood transfusions or pregnancies.
• Caused by presence of antibodies against platelet specific antigen in the recipient eg anti-HPA-1a, anti-HPA-5b

• Both donor and recipient platelets are destroyed
• The disease is self - limiting,
• In severe cases therapy with intravenous immunoglobulin or plasma exchange is indicated.
• Platelet transfusion is not recommended.

Graft versus Host Disease (GvHD)

-This type of reaction is seen mainly in immuno-

compromised patients, particularly transplant

patients and foetuses receiving IU transfusion

-Also seen in patients receiving blood transfusion from close reltives...eg.siblings

-it is caused by donor T lymphocytes that engraft in the recepient and attack recipient host tisssues...esp liver,skin,GIT, and haemopoetic system: there can be pan cytopenia,skin rashes,liver fxn impairment,diarrhoea.

-it is usually fatal in 75% of cases

-Acute GvHD begins between day 4 to day 30

following blood transfusion with symptoms:

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• High fever
• Diffuse erythematous skin rash progressing to erythroderma
• Diarrhoea
• Abnormal liver function
• If not properly managed, patients deteriorate with BM failure and death as a result of overwhelming sepsis

Treatment

-immunocompromised patients should receive

irradiated blood and blood products....irradiation selectively destroys donot T cells

-there must be a genuine need for transfusion

-avoid siblings and close relatives as donors, if you must use them, irradiate the blood.

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Reactions due to plasma protein antibodies

1. Urticarial reactions
1. patient may present with urticaria rash, oedema, dizziness during or after transfusion
2. it occurs in 1% of all transfusions
3. It is mediated by Ig E in the donor unit

Treatment

-the reaction can be prevented by the use of

packed or washed red cells as against whole

blood transfusion

-anti-histamine for symptomatic relief

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ii) Anaphylactic reaction

Is mediated b IgA in the donor unit

• a rare but severe reaction that occurs in IgA-deficient patients that produce anti-IgA
• the anti-IgA reacts to transfusion containing IgA

Treatment

• anti-histamine and adrenalin in severe cases
• known IgA-deficient patient should receive IgA-free blood and blood products (washed rbc and platelet)

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NON - IMMUNOLOGICAL COMPLICATIONS

1. Complications of Massive Blood Transfusion

i) coagulopathy: usually bleeding problems

• common with massive blood transfusion,
• A patient is said to have been massively Transfused when total blood volume is replaced within 24hours or when more than 10 units of blood have been Transfused an adult in less than 24 hours.
• coagulopathy is usually due to dilutional thrombocytopenia

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ii) Citrate toxicity

• common when large volume of blood is being transfused, particularly in neonates
• excess citrate chelates calcium and leads to clinical features of hypo- calcemia
• More pronounced in pt with hepatic dysfunction
• IV calcium will correct symptoms

iii) Hypothermia

• particularly common when large volume of stored blood is transfused
• blood and blood products to be transfused to should be warmed to body temp.

iv) Acid-Base imbalance

• Acidosis: after massive transfusion

v) Hyperkalemia

-common after massive transfusion

-the K+ concentration increases steadily with

time and can be clinically significant when large

volume of blood is transfused

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vi) Volume overload

• Particularly common in patients

with impaired cardiac function

with chronic anaemia

who are transfused with too much fluid, or

are transfused too quickly

• Patients that are prone to volume overload should be transfused slowly with packed red cells
• add pre-transfusion diuretics if necessary

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vii) Transfusion haemosiderosis

-each unit of blood contains approx. 200mg of

elemental iron

-since the elimination route of iron is limited,

multiple transfusion can easily lead to iron

overload over time which can cause damage to

the liver, heart, kidneys, and the pancreas

-transfusion haemosiderosis is particularly

common in thalassemic and sickle cell disease

-use of iron chelating agents increase excretion

viii) Disease transmission

• Viral infections such as HBV, HCV, HIV, HTLV, CMV, CJD
• Bacteria diseases, particularly if the site of phlebotomy is not properly cleaned
• Parasitic disease, particularly, malaria and microfilaria
• Prion, Variant Creutzfeldt – Jakob disease (vCJD),

Conclusion

• Blood transfusion is life saving procedure that carries some risk.
• This risk has been reduced by strict donor selection and deferral procedure, advances in donor screening, blood component preparation and storage.
• Blood transfusion should be appropriate and components given only when the benefits outweigh the risks.