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BLOOD PRODUCTS
AND
MASSIVE BLOOD
TRANSFUSION
Dr Naveen Kumar A,
Dept. of General Surgery,
MMHRC.
BLOOD PRODUCT:
Any therapeutic substance prepared from human blood.
WHOLE BLOOD:
Unseparated blood collected into an approved container containing an
anticoagulant-preservative solution.
BLOOD COMPONENT:
A constituent of blood, separated from whole blood,
such as:
Red cell concentrate
Red cell suspension
Platelet concentrates
Fresh Frozen Plasma
Cryoprecipitate
PLASMA DERIVATIVE:
Albumin
Coagulation factor concentrates
Immunoglobulins
WHOLE BLOOD
 A 450 ml whole blood donation contains Up to 510 ml total
volume (volume may vary in accordance with local policies)
450 ml donor blood
63 ml anticoagulant-preservative solution
Haemoglobin approximately 12 g/ml
Haematocrit 35%–45%
No functional platelets
No labile coagulation factors (V and VIII)
 Infection risk: capable of transmitting any agent which has not
been detected by routine screening including HIV-1 and HIV-2,
hepatitis B and C , syphilis, malaria.
 Storage is between +2°C and +6°C.
 Shelf life ACD/CPD - 21 days CPDA-1: 35 days
SAG-M (saline+adenine+glucose+mannitol)- 42
 Transfusion should be started within 30 minutes of removal
from refrigerator
 Indications: Red cell replacement in acute blood loss with
hypovolaemia
Exchange transfusion
Patients needing red cell transfusions where red cell
concentrates or suspensions are not available
 Contraindications: Risk of volume overload in patients with
Chronic anaemia
Incipient cardiac failure
 Must be ABO and RhD compatible with the recipient
 Complete transfusion within 4 hours of commencement
A unit of whole blood ( approximately 350ml) will increase haemoglobin
by about 0.75g/dl
 while a unit of 450 ml by 1g/dl in an adult patient of about 60-70 kg
who is not actively bleeding.
 In pediatric patients the transfusion of 8ml/kg will increase the
haemoglobin by approx. 1g/dl
RED CELL CONCENTRATE (‘Packed red
cells’, ‘plasma-reduced blood’)
150–200 ml red cells from which most of the plasma has been
removed
Haemoglobin approximately 20 g/100 ml (not less than 45 g
per unit)
Haematocrit 55%–75%
 Infection risk & Storage: Same as whole blood
 Indications: Replacement of red cells in anaemic patients
Use with crystalloid replacement fluids or colloid solution in
acute blood loss
RED CELL SUSPENSION
 150–200 ml red cells with minimal residual plasma to which
±100 ml normal saline, adenine, glucose, mannitol solution (SAG-
M) or an equivalent red cell nutrient solution has been added
Haemoglobin approximately 15 g/100 ml (not less than 45 g
per unit)
Haematocrit 50%–70%
 Infection risk, Storage: Same as whole blood
 Shelf life – 42 days
 Indications: Same as red cell concentrate
LEUCOCYTE-DEPLETED RED CELLS
 A red cell suspension or concentrate containing <5 x 106 white
cells per pack, prepared by filtration through a leucocyte-depleting
filter
 Haemoglobin concentration and haematocrit depend on whether
the product is whole blood, red cell concentrate or red cell
suspension
 Leucocyte depletion significantly reduces the risk of
transmission of cytomegalovirus (CMV)
 Infection risk : same as whole blood
 Storage: 4+/-2 °C for 35 days
 Minimizes white cell immunization in patients receiving repeated
transfusions
 Indicated in patients who have two or more previous febrile
reactions to red cell transfusion
PLATELET CONCENTRATES
1) Random donor platelets (prepared from whole blood donations)
Single donor unit in a volume of 50–60 ml of plasma should contain:
At least 55 x 109 platelets
<1.2 x 109 red cells
<0.12 x 109 leucocytes
Pooled unit: platelets prepared from 4 to 6 donor units ‘pooled’ into one
pack to contain an adult dose of at least 3 × 1010 platelets in 150-200 ml
plasma.
2) Apheresis Platelets: Obtained by apheresis.
One apheresis platelet concentrate is equivalent to 6 random donor
platelet concentrates and hence the number of donor exposures is
reduced.
Apheresis platelets contain 3 × 1011 platelets in 150-300 ml of plasma
 Infection risk : Same as whole blood. Bacterial contamination affects
 Storage: Up to 72 hours at 20°C to 24°C. Do not store at 2°C to 6°C.
 Indications :Amegakaryocytic thrombocytopenia, Drug or radiation
induced hypoplasia, functional platelet abnormalties, viral diseases
associated with thrombocytopenia e.g. Dengue, Disseminated
intravascular coagulation
 Dosage
Random Donor Platelets:
Adult: 1 unit/10 kg body weight ( minimum 6 units)
1 unit raises 5000-10,000 platelets/ul
Child: 1 unit/10 kg body weight
1 unit raises 20,000 platelets/ul
Neonate: 1 unit/2.5 kg body weight
1 unit raises 75,000-1,00,000 platelets/ul
Apheresis platelets:
Adult: 1 unit , raises 25000-30,000 platelets/ul
 To be infused generally within 4 hours, because of the risk of bacterial
proliferation. Must not be refrigerated before infusion as this reduces
platelet function.
FRESH FROZEN PLASMA
 Pack containing the plasma separated from one whole blood donation
within 6 hours of collection and then rapidly frozen to –25°C or colder
 FFP of 175-250 ml contains
70-80 units/dl of factor VIII, factor IX, vWF and other clotting factors.
Fibrinogen 200-400 mg
 Infection risk : If untreated, same as whole blood
Very low risk if treated with methylene blue/ultraviolet light inactivation
Storage: At –25°C or colder for up to 1 year
Before use, should be thawed in the blood bank in water which is
between 30°C to 37°C.
 Dosage: Initial dose of 15 ml/kg.
 Labile coagulation factors rapidly degrade; use within 6 hours of
thawing
Indications: Replacement of multiple coagulation factor
deficiencies: e.g.
— Liver disease
— Warfarin (anticoagulant) overdose
— Depletion of coagulation factors in patients receiving
large volume transfusions
Disseminated intravascular coagulation (DIC)
Thrombotic thrombocytopenic purpura (TTP)
CRYOPRECIPITATE
 Prepared from fresh frozen plasma by collecting the precipitate
formed during controlled thawing at +4°C and resuspending it in
10–20 ml plasma
 10-20 ml contains Factor VIII 80 – 120 IU, Fibrinogen 150 – 250
mg
Von-Willebrand Factor 40 – 70 % 0f original FFP, Fibronectin
55 mg, Factor XIII 20 – 30 % 0f original.
Infection risk: As for plasma, but a normal adult dose involves
at least 6 donor exposures
 Storage: At –25°C or colder for up to 1 year
Must be infused within 6 hours of thawing
Each unit of Cryo raises Factor VIII by 2%, to achieve plasma
factor VIII rise of 20%, 10units/kg have to be infused
Indications: As an alternative to Factor VIII
concentrate in the treatment of inherited deficiencies
of:
— von Willebrand Factor (von Willebrand’s disease)
— Factor VIII (haemophilia A)
— Factor XIII
As a source of fibrinogen in acquired coagulopathies:
e.g. disseminated intravascular coagulation (DIC)
PLASMA DERIVATIVES
ALBUMIN:
 Preparations
Albumin 5%: contains 50
mg/ml of albumin
Albumin 20%: contains 200
mg/ml of albumin
Albumin 25%: contains 250
mg/ml of albumin
 Indications:
nephrotic syndrome
liver disease with fluid
overload
IMMUNOGLOBULINS
 Concentrated solution
of the IgG antibody
component of plasma
 Indications
 Idiopathic autoimmune
thrombocytopenic purpura
 Treatment of immune
deficiency states
 Hypogammaglobulinaemia
 Prevention of specific
infections
FACTOR VIII CONCENTRATE
 Factor VIII ranges from 0.5–20
iu/mg of protein.
 Vials of freeze-dried protein
labelled with content, usually
about 250 iu of Factor VIII.
 +2°C to +6°C up to stated expiry
date
Indications:
• Treatment of haemophilia A
 Treatment of von Willebrand’s
disease: use only preparations
that contain von Willebrand
Factor
Factor IX
• Vials of freeze-dried protein
labelled with content, usually
about 350–600 iu of Factor IX
• +2°C to +6°C up to stated
expiry date
Indications
• Treatment of haemophilia B
(Christmas disease)
 Immediate correction of
prolonged ✔
 prothrombin time
MASSIVE OR LARGE VOLUME BLOOD
TRANSFUSIONS
 Replacement of one entire blood volume within 24h
 Transfusion of >10 units of packed red blood cells (PRBCs) in
24 h
 Transfusion of >20 units of PRBCs in 24 h
 Transfusion of >4 units of PRBCs in 1 h when on-going need is
foreseeable
 Replacement of 50% of total blood volume (TBV) within 3 h.
MASSIVE TRANSFUSION PROTOCOL
designed to interrupt the “lethal triad”
HYPOTHE
-RMIA
ACIDOSIS
COAGULO
-PATHY
 Massive transfusion protocols are activated by a clinician in
response to massive bleeding.
Generally this is activated after transfusion of 4-10 units.
 Massive transfusion protocols have a predefined ratio of RBCs,
FFP/cryoprecipitate and platelets units (random donor platelets)
(e.g. 1:1:1 or 2:1:1 ratio) for transfusion.
COMPLICATIONS OF MASSIVE TRANSFUSION
Problems secondary to volume resuscitation
 Inadequate resuscitation: Hypoperfusion leads to lactic
acidosis, systemic inflammatory response syndrome (SIRS),
disseminated intravascular coagulation and multiorgan
dysfunction.
 Transfusion Associated Circulatory Overload: This is a well-
known condition that occurs due to rapid transfusion of blood or
blood products.
Dilutional coagulopathy:
During haemorrhagic shock, there is fluid shift from the
interstitial to the intravascular compartment that leads to dilution
of the coagulation factors. This is further accentuated when the
lost blood is replaced with fluids.
Citrate toxicity:
• 80 ml of citrate phosphate dextrose adenine solution present in
each blood bag
contains approximately 3 g citrate. A healthy adult can metabolise
this load in 5 min.
• Hypoperfusion or hypothermia associated with massive blood
loss can decrease this rate of metabolism leading to citrate
toxicity.
• Unmetabolised citrate can then lead to hypocalcaemia,
hypomagnesemia and worsen the acidosis.
• Hypocalcaemia can lead to myocardial depression that
• Calcium supplementation is thus required in most cases.
Hyperkalaemia:
 Potassium concentrations in PRBCs can range from 7 to 77
mEq/L depending on age of stored blood.
 Development of hyperkalaemia will depend on the underlying
renal
function, severity of tissue injury and rate of transfusion.
 At transfusion rates exceeding 100-150 ml/min, transient
hyperkalaemia is frequently seen.
Hypothermia:
 Factors contributing to hypothermia include infusion of cold
fluids and blood and blood products.
 Hypothermia leads to decreased citrate metabolism and
decreased platelet function contributing coagulopathy.
Hypomagnesemia: Citrate also binds to magnesium and can
lead to hypomagnesaemia which can further accentuate effects of
hypocalcaemia
Acidosis
 Acidosis directly reduces activity of both extrinsic and intrinsic
coagulation pathways.
 A pH decrease from 7.4 to 7.0 reduces the activity of FVIIIa and
FVIIa by over 90% and 60% respectively.
Late complications
Respiratory failure
 Transfusion related acute lung injury (TRALI): The risk of TRALI
increases with the number of blood and blood products transfused.
SIRS
Sepsis
Thrombotic complications
Targets of resuscitation in massive blood loss
 Mean arterial pressure (MAP) around 60 mmHg, systolic
arterial pressure 80-100 mmHg (in hypertensive patients one
may need to target higher MAP)
 Hb 7-9 g/dl
 INR <1.5; aPTT <42 s
 Fibrinogen >1.5-2 g/L
 Platelets >50 × 10 /L
 pH 7.35-7.45
 Core temperature >35.0°C
THANK YOU

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Blood products and massive blood transfusion

  • 1. BLOOD PRODUCTS AND MASSIVE BLOOD TRANSFUSION Dr Naveen Kumar A, Dept. of General Surgery, MMHRC.
  • 2. BLOOD PRODUCT: Any therapeutic substance prepared from human blood. WHOLE BLOOD: Unseparated blood collected into an approved container containing an anticoagulant-preservative solution. BLOOD COMPONENT: A constituent of blood, separated from whole blood, such as: Red cell concentrate Red cell suspension Platelet concentrates Fresh Frozen Plasma Cryoprecipitate PLASMA DERIVATIVE: Albumin Coagulation factor concentrates Immunoglobulins
  • 3. WHOLE BLOOD  A 450 ml whole blood donation contains Up to 510 ml total volume (volume may vary in accordance with local policies) 450 ml donor blood 63 ml anticoagulant-preservative solution Haemoglobin approximately 12 g/ml Haematocrit 35%–45% No functional platelets No labile coagulation factors (V and VIII)  Infection risk: capable of transmitting any agent which has not been detected by routine screening including HIV-1 and HIV-2, hepatitis B and C , syphilis, malaria.  Storage is between +2°C and +6°C.  Shelf life ACD/CPD - 21 days CPDA-1: 35 days SAG-M (saline+adenine+glucose+mannitol)- 42  Transfusion should be started within 30 minutes of removal from refrigerator
  • 4.  Indications: Red cell replacement in acute blood loss with hypovolaemia Exchange transfusion Patients needing red cell transfusions where red cell concentrates or suspensions are not available  Contraindications: Risk of volume overload in patients with Chronic anaemia Incipient cardiac failure  Must be ABO and RhD compatible with the recipient  Complete transfusion within 4 hours of commencement A unit of whole blood ( approximately 350ml) will increase haemoglobin by about 0.75g/dl  while a unit of 450 ml by 1g/dl in an adult patient of about 60-70 kg who is not actively bleeding.  In pediatric patients the transfusion of 8ml/kg will increase the haemoglobin by approx. 1g/dl
  • 5. RED CELL CONCENTRATE (‘Packed red cells’, ‘plasma-reduced blood’) 150–200 ml red cells from which most of the plasma has been removed Haemoglobin approximately 20 g/100 ml (not less than 45 g per unit) Haematocrit 55%–75%  Infection risk & Storage: Same as whole blood  Indications: Replacement of red cells in anaemic patients Use with crystalloid replacement fluids or colloid solution in acute blood loss
  • 6. RED CELL SUSPENSION  150–200 ml red cells with minimal residual plasma to which ±100 ml normal saline, adenine, glucose, mannitol solution (SAG- M) or an equivalent red cell nutrient solution has been added Haemoglobin approximately 15 g/100 ml (not less than 45 g per unit) Haematocrit 50%–70%  Infection risk, Storage: Same as whole blood  Shelf life – 42 days  Indications: Same as red cell concentrate
  • 7. LEUCOCYTE-DEPLETED RED CELLS  A red cell suspension or concentrate containing <5 x 106 white cells per pack, prepared by filtration through a leucocyte-depleting filter  Haemoglobin concentration and haematocrit depend on whether the product is whole blood, red cell concentrate or red cell suspension  Leucocyte depletion significantly reduces the risk of transmission of cytomegalovirus (CMV)  Infection risk : same as whole blood  Storage: 4+/-2 °C for 35 days  Minimizes white cell immunization in patients receiving repeated transfusions  Indicated in patients who have two or more previous febrile reactions to red cell transfusion
  • 8. PLATELET CONCENTRATES 1) Random donor platelets (prepared from whole blood donations) Single donor unit in a volume of 50–60 ml of plasma should contain: At least 55 x 109 platelets <1.2 x 109 red cells <0.12 x 109 leucocytes Pooled unit: platelets prepared from 4 to 6 donor units ‘pooled’ into one pack to contain an adult dose of at least 3 × 1010 platelets in 150-200 ml plasma. 2) Apheresis Platelets: Obtained by apheresis. One apheresis platelet concentrate is equivalent to 6 random donor platelet concentrates and hence the number of donor exposures is reduced. Apheresis platelets contain 3 × 1011 platelets in 150-300 ml of plasma  Infection risk : Same as whole blood. Bacterial contamination affects
  • 9.  Storage: Up to 72 hours at 20°C to 24°C. Do not store at 2°C to 6°C.  Indications :Amegakaryocytic thrombocytopenia, Drug or radiation induced hypoplasia, functional platelet abnormalties, viral diseases associated with thrombocytopenia e.g. Dengue, Disseminated intravascular coagulation  Dosage Random Donor Platelets: Adult: 1 unit/10 kg body weight ( minimum 6 units) 1 unit raises 5000-10,000 platelets/ul Child: 1 unit/10 kg body weight 1 unit raises 20,000 platelets/ul Neonate: 1 unit/2.5 kg body weight 1 unit raises 75,000-1,00,000 platelets/ul Apheresis platelets: Adult: 1 unit , raises 25000-30,000 platelets/ul  To be infused generally within 4 hours, because of the risk of bacterial proliferation. Must not be refrigerated before infusion as this reduces platelet function.
  • 10. FRESH FROZEN PLASMA  Pack containing the plasma separated from one whole blood donation within 6 hours of collection and then rapidly frozen to –25°C or colder  FFP of 175-250 ml contains 70-80 units/dl of factor VIII, factor IX, vWF and other clotting factors. Fibrinogen 200-400 mg  Infection risk : If untreated, same as whole blood Very low risk if treated with methylene blue/ultraviolet light inactivation Storage: At –25°C or colder for up to 1 year Before use, should be thawed in the blood bank in water which is between 30°C to 37°C.  Dosage: Initial dose of 15 ml/kg.  Labile coagulation factors rapidly degrade; use within 6 hours of thawing
  • 11. Indications: Replacement of multiple coagulation factor deficiencies: e.g. — Liver disease — Warfarin (anticoagulant) overdose — Depletion of coagulation factors in patients receiving large volume transfusions Disseminated intravascular coagulation (DIC) Thrombotic thrombocytopenic purpura (TTP)
  • 12. CRYOPRECIPITATE  Prepared from fresh frozen plasma by collecting the precipitate formed during controlled thawing at +4°C and resuspending it in 10–20 ml plasma  10-20 ml contains Factor VIII 80 – 120 IU, Fibrinogen 150 – 250 mg Von-Willebrand Factor 40 – 70 % 0f original FFP, Fibronectin 55 mg, Factor XIII 20 – 30 % 0f original. Infection risk: As for plasma, but a normal adult dose involves at least 6 donor exposures  Storage: At –25°C or colder for up to 1 year Must be infused within 6 hours of thawing Each unit of Cryo raises Factor VIII by 2%, to achieve plasma factor VIII rise of 20%, 10units/kg have to be infused
  • 13. Indications: As an alternative to Factor VIII concentrate in the treatment of inherited deficiencies of: — von Willebrand Factor (von Willebrand’s disease) — Factor VIII (haemophilia A) — Factor XIII As a source of fibrinogen in acquired coagulopathies: e.g. disseminated intravascular coagulation (DIC)
  • 14. PLASMA DERIVATIVES ALBUMIN:  Preparations Albumin 5%: contains 50 mg/ml of albumin Albumin 20%: contains 200 mg/ml of albumin Albumin 25%: contains 250 mg/ml of albumin  Indications: nephrotic syndrome liver disease with fluid overload IMMUNOGLOBULINS  Concentrated solution of the IgG antibody component of plasma  Indications  Idiopathic autoimmune thrombocytopenic purpura  Treatment of immune deficiency states  Hypogammaglobulinaemia  Prevention of specific infections
  • 15. FACTOR VIII CONCENTRATE  Factor VIII ranges from 0.5–20 iu/mg of protein.  Vials of freeze-dried protein labelled with content, usually about 250 iu of Factor VIII.  +2°C to +6°C up to stated expiry date Indications: • Treatment of haemophilia A  Treatment of von Willebrand’s disease: use only preparations that contain von Willebrand Factor Factor IX • Vials of freeze-dried protein labelled with content, usually about 350–600 iu of Factor IX • +2°C to +6°C up to stated expiry date Indications • Treatment of haemophilia B (Christmas disease)  Immediate correction of prolonged ✔  prothrombin time
  • 16. MASSIVE OR LARGE VOLUME BLOOD TRANSFUSIONS  Replacement of one entire blood volume within 24h  Transfusion of >10 units of packed red blood cells (PRBCs) in 24 h  Transfusion of >20 units of PRBCs in 24 h  Transfusion of >4 units of PRBCs in 1 h when on-going need is foreseeable  Replacement of 50% of total blood volume (TBV) within 3 h. MASSIVE TRANSFUSION PROTOCOL designed to interrupt the “lethal triad” HYPOTHE -RMIA ACIDOSIS COAGULO -PATHY
  • 17.  Massive transfusion protocols are activated by a clinician in response to massive bleeding. Generally this is activated after transfusion of 4-10 units.  Massive transfusion protocols have a predefined ratio of RBCs, FFP/cryoprecipitate and platelets units (random donor platelets) (e.g. 1:1:1 or 2:1:1 ratio) for transfusion. COMPLICATIONS OF MASSIVE TRANSFUSION Problems secondary to volume resuscitation  Inadequate resuscitation: Hypoperfusion leads to lactic acidosis, systemic inflammatory response syndrome (SIRS), disseminated intravascular coagulation and multiorgan dysfunction.  Transfusion Associated Circulatory Overload: This is a well- known condition that occurs due to rapid transfusion of blood or blood products.
  • 18. Dilutional coagulopathy: During haemorrhagic shock, there is fluid shift from the interstitial to the intravascular compartment that leads to dilution of the coagulation factors. This is further accentuated when the lost blood is replaced with fluids. Citrate toxicity: • 80 ml of citrate phosphate dextrose adenine solution present in each blood bag contains approximately 3 g citrate. A healthy adult can metabolise this load in 5 min. • Hypoperfusion or hypothermia associated with massive blood loss can decrease this rate of metabolism leading to citrate toxicity. • Unmetabolised citrate can then lead to hypocalcaemia, hypomagnesemia and worsen the acidosis. • Hypocalcaemia can lead to myocardial depression that • Calcium supplementation is thus required in most cases.
  • 19. Hyperkalaemia:  Potassium concentrations in PRBCs can range from 7 to 77 mEq/L depending on age of stored blood.  Development of hyperkalaemia will depend on the underlying renal function, severity of tissue injury and rate of transfusion.  At transfusion rates exceeding 100-150 ml/min, transient hyperkalaemia is frequently seen. Hypothermia:  Factors contributing to hypothermia include infusion of cold fluids and blood and blood products.  Hypothermia leads to decreased citrate metabolism and decreased platelet function contributing coagulopathy. Hypomagnesemia: Citrate also binds to magnesium and can lead to hypomagnesaemia which can further accentuate effects of hypocalcaemia
  • 20. Acidosis  Acidosis directly reduces activity of both extrinsic and intrinsic coagulation pathways.  A pH decrease from 7.4 to 7.0 reduces the activity of FVIIIa and FVIIa by over 90% and 60% respectively. Late complications Respiratory failure  Transfusion related acute lung injury (TRALI): The risk of TRALI increases with the number of blood and blood products transfused. SIRS Sepsis Thrombotic complications
  • 21. Targets of resuscitation in massive blood loss  Mean arterial pressure (MAP) around 60 mmHg, systolic arterial pressure 80-100 mmHg (in hypertensive patients one may need to target higher MAP)  Hb 7-9 g/dl  INR <1.5; aPTT <42 s  Fibrinogen >1.5-2 g/L  Platelets >50 × 10 /L  pH 7.35-7.45  Core temperature >35.0°C