BLOOD TRANSFUSION AND ITS COMPONENTS

PRESENTED BY: DR.ANKITA MADAN MODERATER : DR. ANUMEHA JAIN

Characteristics of ideal blood substitute could be defined by the following terms:• Easily available• Oxygen carrying capacity : Good capacity or even better than biological

blood• Volume expansion• No major toxic or physiological effects• No chemical reaction with oxygen, activation of complement system• Metabolized and eliminated by the body• Universal compatibility: Elimination of cross matching• Pathogen free: Elimination of blood borne disease• Minimal side effects• Survivability over a wider range of storage temperatures• Long shelf life• Maintains arterial blood pressure and pH• Cost efficient

The Principle Aims of Blood Transfusion are to:-

(1) Improve oxygen carrying capacity of blood.

(2) Symptomatic improvement.

(3) Reduce hypovolaemia.• 1 UNIT of Blood should

increase the Hb by approx.1g/dL.

• If no improvement or reduction in Hb – think about ongoing blood loss or destruction.

• You need to treat the underlying cause.

Blood Transfusion -Guidance and Regulations

• WHO recommendations• safe and adequate blood supply• also clinical transfusion process • Appropriate use of blood• Collection samples, patient ID• compatibility testing• Administration of blood • Adverse event reporting• Hospital transfusion committee

• ‘Better Blood Transfusion’

• Council of Europe• 47 member countries

Blood safety/ Transfusion safety

SAFE TRANSFUSION

PROCESS

SAFE BLOOD COMPONENT

BLOOD GROUPING• Landsteiner described ABO system in 1900.• In ABO grouping both red cells and serum are tested as the

serum contains isohaemagglutinins to those group specific substances which are not present on the red cells.

• Rhesus grouping is usually done to determine the presence or absence of the D antigen.

CROSS - MATCHING• Cross – matching of patients serum against donor red cells by

various method.

• Cells and serum are incubated in saline at room temperatures and 37˚c for 2 hours with the addition of albumin. Incompatibility is indicated by lysis or agglutination of the red cells.

Indications for Blood Transfusion

Acute Anaemia(1) Symptomatic hypovolaemia and blood loss.(2) Peri-operative – ‘replacing losses’(3) Haemolysis (treat the underlying cause)(4) Severe, critical illness.

Blood Transfusion Indications

Acute Anaemia

• To Increase oxygen carrying capacity of blood- Young adults can tolerate 30 – 40% volume loss with adequate crystalloid replacement alone- Weiskopf et al (1988) – Euvolaemic anaemia in healthy volunteers (and patients) down to Hb ≥5g/dL (!) – No demonstrable inadequate tissue oxygenation- I.e. Only for symptomatic hypovolaemia

‘Keep the Hb ≥ 10 g/ dL’

(2) Peri -operative

• Much quoted by Surgeons still - ‘Keep the Hb ≥ 10 g/ dL

(3) Severe and critical illness

• Oxygen delivery is dependent on:(a) Cardiac output (c.o.)(b) Oxygen content of blood

However there is very little change in C.O. until Hb ≤ 7 g/dL.Herbert et al, 1999 – recommended this was the level taken for transfusion in the critically ill unless other factors were present.

Recommendations for Transfusion

• Bracey et al, 1999≤ 9 g/dL – CABG operation ≤ 8 g/ dL – Symptomatic anaemia and blood loss≤ 7g/dL – Critically ill (Herbert et al)

But: on-going and further blood loss must be taken into consideration as must the clinical situation and co-morbidity!

Chronic Anaemia • Transfuse according to

- Symptoms- Co-morbidities- Level of Activity• Correct underlying cause and deficiencies• ‘Beware the ‘well patient’ with the macrocytic

anaemia, Hb of 2g/dL – ‘Slowly down – Slowly up’; Remember their blood may be ‘see through’ but they are essentially euvolaemic. A large, rapid transfusion will cause fluid overload and pulmonary oedema.

Replacing blood loss

• Average blood volumes

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Age Blood volumes

Neonates

Premature 95mL/kg

Full term 85mL/kg

Infants 80mL/kg

Adults

Men 75mL/kg

Women 05:37 AM13

Estimation of allowable blood loss

• Estimate blood volume (from the table)• Estimate red blood cell volume (RBCV) at the preoperative

hematocrit (RBCVpreop)• Estimate RBCV at a hematocrit of 30% (RBCV30%)• Calculate the red cell volume lost when hematocrit is 30%;

RBCVlost = RBCVpreop — RBCV30%

• Allowable blood loss = RBCVlost 3

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Example• An 85 kg woman has a preoperative hematocrit of 35%. How much

blood loss will decrease her hematocrit to 30%? • Estimated blood volume = 65mL/kg85 kg = 5525 mL• RBCV35% = 552535% = 1934mL• RBCV30% = 552530% = 1658mL• Red cell loss at 30% =1934 — 1658 = 276mL• Allowable blood loss = 3276mL = 828mL

Therefore, transfusion should be considered only when this patient’s blood loss exceeds 800mL.

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Blood and Blood Product Transfusion• Whole Blood• Packed Cells• Platelets• Fresh Frozen Plasma (FFP)• Cryoprecipitate

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Red Cells Whole Blood Platelets (also apheresis) Fresh Frozen Plasma

Plasma Cryoprecipitate Paediatric FFP

Paediatric Cryo Fractionation

Factor concentrates egFVI I I , FI Xs

SD plasma Immunoglobulin

Albumin, Anti D (Universal leucodepletion (Non UK Plasma) in UK since 1998)

Fractionation of whole blood• Separation of cellular constituents

within blood can be achieved by a process known as differential centrifugation.

• Acceleration force is adjusted to sediment certain cellular constituents and leave others in suspension.

• Blood sample is separated into two phases; cellular sediment and a supernatant that may be either cellular or cell-free.

3 Types of differential centrifugation processes:

• Soft spin: platelet rich plasma

• Heavy spin: red cells

• Buffy coat layer: WBCs & larger platelets.

Whole blood componentsComponent Content Volume (ml) Shelf life

Packed Erythrocytes

Erythrocytes, Leucocytes,Clotting factors.

300 35days (CPDA1)45days (Adsol)

Platelet Concentrates

Leucocytes (limited)Erythrocytes (limited)Plasma

50 1-5 days

Fresh Frozen Plasma

Clotting factors 225 Frozen 1yearThawed (6hrs)

Cryoprecipitate Factor VIII Lyophilized powder

Determined by manufacturer

Factor IX Concentrate

Factor IX (II,VII &X limited)

Lyophilized powder

Determined by manufacturer

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Component Content Volume (ml) Shelf life

Granulocyte Concentrates

LeucocytesPlateletsErythrocytes (limited)

50-300 24 hrs

Albumin 5% Albumin25% Albumin

250 or 50050 or 100

3 yrs

Plasma Protein Concentrates

AlbuminAlpha globulinsBeta globulins

500 3 yrs

Immunoglobulins Gamma globulins 1-2 3 yrs

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Packed Erythrocytes

• Goal is to increase oxygen-carrying capacity in the absence of pre-existing hypovolemia• Whole blood minus most of the

plasma• Resulting volume ~ 300 mL• Hematocrit = 70% to 80%• Decreased likelihood of allergic

transfusion reactions, compared with whole blood• Stored at 1 – 6 ⁰C

• Citrate-phosphate dextrose preservative + Adenine (CPDA-1; CPD-A) Storage time 28 days 35 days Increased erythrocyte survival by allowing cells to

resynthesize ATP needed to fuel metabolic reactions

• Citrate-phosphate-dextrose + extra nutrients (adenine, glucose, mannitol, sodium chloride) Adsol Increased storage time (42 days). Contains about 100 mL of additional saline hematocrit 55% rather than 70%

• May be used to replace blood loss that is <1,500 mL in an adult• One unit of packed erythrocytes typically increases the hematocrit 3%

or hemoglobin concentration 1 g/dL in a 70kg non-bleeding adult

Hb conc: >10 g/dL - transfusion rarely indicated < 6 g/dL - almost always indicated, especially when anemia is acuteIntermediate concentrations (6 to 10 g/dL) – transfusion depends on the

patient's risk for complications of inadequate oxygenation

• Administration is facilitated by reconstituting them with crystalloid solutions to decrease viscosity. 5% glucose in 0.9% saline 0.9% saline Normosol

• Lactated Ringer's solution should probably not be used - calcium ions present could induce clotting

• Hypotonic diluent (glucose solutions) osmotic lysis of infused erythrocytes

Platelet Concentrates

Platelets for transfusion are collected in two ways: • Pooled platelets: This is a two-step procedure. Firstly, one

unit of platelets is produced from a unit of whole blood. Then, 4-6 of these units (from different donors) are ‘pooled’ together in a single pack to be given to a thrombocytopenic patient.

• Apheresis platelets: These have the advantage of being collected from a single donor (to reduce the risk of disease transmission). As blood cycles through the apheresis machine, platelets are removed and all other blood constituents are returned to the donor. The amount of platelets collected with this procedure represents the equivalent of 4-6 units of random donor platelets.

• One unit of platelet concentrate will increase the platelet count 5,000 to 10,000 cells/mL3

• Usual therapeutic dose is one platelet concentrate per 10 kg of body weight• Storage is limited to 5 days – to minimize risk of sepsis• Contain only a few erythrocytes, but large amounts of

plasma (leukocytes) administration on the basis of ABO compatibility is desirable. • Small quantity of erythrocytes present can cause Rh

immunization if platelets from an Rh-positive donor are administered to an Rh-negative recipient Rh - compatible platelets should be used in women of child-bearing age.

Indications:

• Surgical and obstetric patients with platelet count <50,000 cells/mL3

• >100,000 cells/mL3 - rarely require therapy

• Intermediate platelet counts (50,000 to 100,000 cells/mL3) - based on the patient's risk for more significant bleeding.

• In nonsurgical patients, spontaneous bleeding is uncommon with platelet counts of >10,000 cells/mL3.

Fresh Frozen Plasma• FFP is collected as the supernatant after centrifuging a donation of whole

blood.

• It is frozen within 8 hours and may be stored for up to 1 year at —30 ˚C.

• Under these conditions, the loss of Factors V and VIII is kept to a minimum.

• Frozen packs are brittle and should be handled with care.

• The frozen plasma can be thawed using a dry oven (10minutes), microwave (2—3 minutes) or a water bath (20 minutes).

• Thawed FFP is best used immediately but may be stored at 4˚C and infused within 24 hours, provided it is kept at this temperature or returned to the blood bank for storage within 30 minutes of being removed from a 4˚C fridge.

• Contains all procoagulants except platelets in a concentration of 1 unit/mL, as well as naturally occurring inhibitors.

• Compatibility for ABO antigens is desirable, but cross-matching is not necessary.

• Life-threatening allergic reactions, and the transmission of diseases (HBV / HIV) possible

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• Usual starting dose is two units (400 to 500 mL) or one plasmapheresis unit to treat active bleeding due to a congenital or acquired deficiency of coagulation factors as confirmed by

PT >1.5 times normal (usually >18 s),

Partial Thromboplastin Time >1.5 times normal (usually >55 to 60 s), or

Coagulation factor assay of <25% activity

Indications of FFP• Correction of excessive microvascular bleeding in the

presence of a PT greater than 1.5 times normal, an INR greater than 2.0, or an aPTT greater than twice normal.

• Correction of excessive microvascular bleeding that is secondary to coagulation factor deficiency in patients receiving massive transfusion (approximately 70ml/Kg) and when PT or INR and aPTT are not available on time.

• Urgent reversal of warfarin therapy when human prothrombin complex is unavailable (5-8ml/kg iv)

Indications of FFP

• Correction of known coagulation factor deficiencies for which specific coagulation factor concentrates are unavailable.

• Heparin resistance (antithrombin III deficiency) in a patient requiring heparin.

• Not recommended for hypovolemia or hypoalbuminemia

Cryoprecipitated Antihemophilic factor (factor VIII)

• Fraction of plasma that precipitates when fresh frozen plasma is thawed.• Stored at room temperature; to be used within 3 hours.• Mainly intravascular• Elimination half time 12 hrs.• Only approved component that has fibrinogen in concentrated form.

Cryoprecipitated Antihemophiliac Factor (Factor VIII)

USES

• Hemophilia A [high concentrations of factor VIII (80 to 120 units) in a

volume of only about 10 ml]

• In non bleeding patients with congenital fibrinogen deficiency or Von Willebrands disease not responding to desmopressin.

• Bleeding patients with VWD.

• In massively transfused patients with fibrinogen concentrates <80-100 mg/dl.

Adverse reactions

• Hyperfibrinogenemia

• Greater risk of viral transmission eg. Hepatitis (commercial preparations derived from multiple donors)

• Hemolytic anemia (if given to individuals with A, B or AB erythrocyte antigens)

Factor IX Concentrate

• Can be infused without typing or cross – matching

• Concentrated nature; small amount of fluid needed for administration Hypervolemic reactions do not occur

• Pooled origin Significant potential to cause hepatitis • High concentrations of prothrombin and factor X that result from

factor IX High risk of thrombotic complications

Granulocyte Concentrates

• Obtained either by continuous-flow or intermittent-flow leukopheresis or by filtration leukopheresis

• Indicated in severely leukopenic (<500/mm3 ) patients with evidence of septicemia and fever.

• Functional viability of 48 hrs.• To be ABO and Rh compatible• Should be administered through a filter and should be

administered slowly over 2 to 4 hours• Rapid infusion pulmonary insufficiency (sequestration in

pulmonary capillaries)• Transfusion is often accompanied with fever can be ameliorated

by the administration of an antihistamine and an antipyretic• Risk of CMV transmission

Blood Transfusion - Acute Complications Complication Cause Incidence / Likely timing with

regard transfusionTreatment

Acute Intravascular haemolysis

ABO incompatibility(Commonest cause is administrative!)

1:6x105

Occurs within a few mls of starting transfusion(Mortality 10%)

Shouldn’t happen!STOP THE BLOOD!Supportive treatmentTreat complications – ARF and DIC

Febrile Non-haemolytic reactions

Anti –Leucocyte Ig or Cytokines in platelet transfusionsCommonest in patients receiving

multiple transfusions or previously pregnant

Becoming rarer because of leucocyte depletion in many transfusion practices.Occurs towards the end of or up to hours after transfusion

Unpleasant – but not life threateningParacetamol and cooling.

Urticaria Transfusion contains plasma proteins or allergens causing an acute IgE mediated allergic responseOccurs with plasma and platelet rather than red cell transfusions.

1 – 2% of all transfusionsPeri-transfusionMay occur recurrently

Unpleasant – but not life threateningAnti-histamines –(can be given prophylactically in known patients)

Infective shock Bacterial contamination of transfused blood

Rare; 1:5x 105

First 100mls of blood – ie earlyOften fatal!

That of Septicaemia and shock – fluids, IV antibiotics

Anaphylaxis Anti-IgA antibodies ?othersPatients are often IgA deficient as well!

Extremely rare Life threateningA.B.C / Crash team callIV / IM adrenaline, steroids, aHistamines, OxygenNebulisers.

Blood Transfusion - Acute Complications

Transfusion Related Acute Lung Injury (TRALI)

• Non-cardiogenic Pulmonary oedema• Caused by donor blood containing anti-Leucocyte

antibodies• Occurs at the start of the transfusion• Can be life threatening• Treat for

(a) Acute transfusion reaction(b) Respiratory failure (ARDS), Shock and Pulmonary oedema

Blood Transfusion – Delayed Complications

Complication Cause Incidence / Timing Treatment

Delayed Red cell haemolysis Recipient IgG vs Red cell antigensOccurs in previously transfused or pregnant patients; Initial cross match will not contain IgG but subsequent cross matches should!

5 – 10 days after transfusion

<1:500 red cell transfusions

No treatment per se but Patient will receive less

benefit from transfusion and once present they will cause problems for future transfusions

Transfusion associated Graft versus Host disease(TA-GvHD)

Immune mediated donor T-cell reaction (often occurs in immunodeficient patients)Fever, Rash, MOF, Pancytopaenia

Rare 1:750,000 units of cellular blood components transfused4 – 30 days after transfusion

Usually fatal!Haematology specialist care requiredIn susceptible recipients – blood is subjected to Gamma irradiation

Post Transfusion Purpura Anti-Platelet antibodies(usually aHPA-1a)Immune medicated TCPPrimarily during pregnancy

RHS Rare5 -10 days after transfusionOften severe TCP causing bleeding

Use HPA-1a negative red cell and platelet transfusions or LDBloodHigh dose IV Immunoglobulins for 5 days0.4g / kg

Post Transfusion Viral Infection

Virus (and other infective agents e.g. prions) undetected by UK screening system

HIV <1: 3x 106

HBV and HCV < 1: 2 x 105

Counselling and specialist advice required

Iron overload Multiple transfusions

One unit of blood contains 250mg of iron

Only occurs after several years of blood transfusionse.g. Chronic haemolytic disease

Desferrioxamine – increases iron excretion

BOMBAY BLOOD GROUP• hh blood group or oh is a rare blood group.

• First discovered in bombay by DR.Y.M. BHENDE in 1952.

• The serum contained antibodies that reacted with all red blood cells with normal ABO phenotypes.

• Red blood cells lack all of ABO blood group antigens and have additional antigen that was previously unknown.

MASSIVE BLOOD TRANSFUSION

• >50% of blood volume in 4 hrs

• >1 blood volume in 24hrs

• In children transfusion of >40ml/kg

• It can lead to rapidly drop in recipient’s temperature to low as 27.5˚c which causes fatal dysrhthmias.

• It leads to high plasma citrate level which decreases ionised calcium in blood. It can cause cardiac arrest and impair the blood clotting system.

• The citrate metabolised to bicarbonate producing metabolic alkalosis within 24hrs.

• During storage aggregates of leucocytes and platelets with diameters upto 200 µm are formed. Filter is of 170 µm so there is passage of quite sizeable aggregates. Large volume infused without ultrafiltration can lead to increase in arteriovenous shunting and alveolar arterial oxygen differences.

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