CLINICAL GUIDE TO TRANSFUSION

Chapter 2: Blood Components

Gwen Clarke, MD, FRCPC

BACKGROUND
Whole blood donations are separated into specific cellular (red blood cells and platelets) and plasma products.
This enhances the utilization of individual donations and decreases the need for blood donors. Transfusing the
appropriate combination of blood products effectively provides for the clinical needs of patients and best utilizes
the donated blood.

This chapter describes the manufacturing process for the most commonly prepared blood products: Red Blood
Cells, Pooled Platelets, Frozen Plasma (FP), Apheresis Fresh Frozen Plasma (AFFP), Cryosupernatant Plasma
(CSP) and Cryoprecipitate. Brief descriptions of the indications, contraindications, storage and transportation
requirements, dose, administration and available alternatives are included in the sections below. Further
information may be found in other chapters of this Guide as indicated within the different sections.

In addition, Canadian Blood Services publishes a Circular of Information to provide an extension of the
component label and to provide information regarding component composition, packaging, storage and
handling, indications, warnings and precautions, adverse events, dose and administration.
The Circular conforms to the applicable regulations issued by Health Products and Food Branch, Health Canada.

COLLECTION OF BLOOD PRODUCTS

At Canadian Blood Services, whole blood is collected from donors into a collection pack in which multiple bags
are connected, allowing blood and components to be transferred between bags aseptically during
manufacturing. The collection packs include two different configurations. One, the buffy coat collection set (also
referred to as B1 at Canadian Blood Services), is used in the production of red blood cell, plasma and platelet
products; the other, a whole blood filtration set (also referred to as B2), is used in the production of red blood
cell and plasma products. Figure 1 highlights the main steps of both manufacturing processes. Both collection
sets contain a citrate-phosphate-dextrose (CPD) anticoagulant in the collection bag.

Apheresis technology instead of whole blood collection may also be used for collection of some blood
components, including plasma and platelets. This collection procedure utilizes an automated in-line process in
which whole blood from the donor enters a collection chamber where flow patterns separate the plasma from
cellular blood constituents such as red blood cells and white blood cells. Plasma, or platelets suspended in
plasma, are collected into a bag while the remaining constituents of the blood are returned to the donor.

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

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Chapter 2: Blood Components

Figure 1. The whole blood manufacturing processes used at Canadian Blood Services.

RED BLOOD CELLS

Product manufacturing and description (see Figure 1)
Whole blood collected in CPD anticoagulant is processed by either the B1 or B2 method (Figure 1). In the B1
method, whole blood is centrifuged to separate the red blood cells from the platelets and plasma. The red blood
cells are then leukoreduced (LR) by filtration. In the B2 method, the whole blood is first filtered to remove
platelets and leukocytes (LR), then centrifuged to separate the red blood cells from the plasma. For both B1 and
B2 methods, the red blood cells are then mixed with an additive solution, saline-adenine-glucose-mannitol
(SAGM) and labelled as a red blood cell unit.

Red blood cells LR is the only red blood cell product prepared by Canadian Blood Services. The average volume
of a red blood cell unit issued by Canadian Blood Services is 293 (± 26) ml and it typically contains 56 (± 7) g of
hemoglobin with a hematocrit of approximately 0.68 and has an average residual leukocyte count of 0.18 x 106.
Further modifications of red blood cell products such as washing, deglycerolizing and irradiation are covered in

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

2/14
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Chapter 2: Blood Components

Chapter 15 of this Guide.

Indications
The primary purpose for a red blood cell transfusion is to increase the oxygen-carrying capacity of the blood.
Therefore, red blood cell transfusion is indicated in patients with anemia who have evidence of impaired oxygen
delivery. For example, symptomatic acute blood loss, chronic anemia and cardiopulmonary compromise, or
disease or medication effects associated with bone marrow suppression may be triggers for red blood cell
transfusion. In patients with acute blood loss, volume replacement is often required and, depending on clinical
circumstances, plasma and platelets may also be transfused. See Chapter 11 of this Guide for details on
massive hemorrhage and emergency transfusion.

Effective oxygen delivery depends not only on the hemoglobin level, but also on the cardiovascular condition of
the individual, and the associated ability to compensate for decreased hemoglobin concentration. Patients
without cardio pulmonary compromise, therefore, will typically tolerate lower hemoglobin levels than patients
with limited cardiopulmonary reserve. Similarly, the normal hemoglobin levels of infants and children vary from
those seen in adults and transfusion triggers as well as usual blood component dose will also vary according to
age. See Chapter 13 of this Guide for details on neonatal and pediatric transfusion. Finally, patients who develop
anemia slowly develop compensatory mechanisms to allow them to tolerate lower hemoglobin values than
patients who become acutely anemic.

The decision to transfuse anemic patients should be made in each individual case. There is no uniformly
accepted hemoglobin value below which transfusion should always occur. However, many studies and
guidelines support the use of a restrictive transfusion strategy, including in the intensive-care unit (ICU) setting
and with postoperative anemia.1

Red blood cells should not be given for volume replacement or for any reason other than correction of acute or
chronic anemia when non-transfusion alternatives have been assessed and excluded. The decision to transfuse
should not be based on a single hemoglobin or hematocrit value as a trigger without considering all critical
physiologic and surgical factors affecting oxygenation and clinical status in that patient. See the Choosing
Wisely Canada website for more information about transfusion guidelines.2

Dose and administration

One unit of red blood cells usually increases the hemoglobin concentration by approximately 10 g/l in an
average size, non-bleeding adult. For pediatric or neonatal patients, as well as for adult patients who cannot
tolerate a transfusion rate that would allow for infusion of the total volume within four hours, small volume or
“split” units may be provided by some hospital transfusion services.

Reading of chapters 8 and 9 of this Guide is recommended for detailed information on pre-transfusion testing
and administration, respectively. Chapter 13 of this Guide is also recommended for guidelines on neonatal and
pediatric transfusion.

If transfusion of the red blood cell unit will not be initiated promptly after removal from the temperature-
controlled blood product refrigerator or storage/transportation device, it should be returned immediately to
prevent waste. Blood products may be returned to inventory only if the bag is intact, passes a visual inspection
and has maintained an acceptable temperature or the red blood cells have not been out of a temperature
controlled environment for more than 60 minutes (See CSTM Standard 5.8.7.1 for more information).3

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

3/14
CLINICAL GUIDE TO TRANSFUSION
Chapter 2: Blood Components

Storage and transportation

The proper storage and transportation of blood products are critical for safe transfusion. As a biological product,
blood carries a risk of bacterial contamination if stored improperly. Improper storage may also affect the
efficacy of blood products.

The shelf life of a red blood cell unit issued by Canadian Blood Services is 42 days from collection. Manipulation
of the unit, including washing or irradiation, alters the shelf life. The expiry date is documented on the label of
each unit. If the blood product is opened without the use of a sterile connection device, the shelf life is limited to
24 hours if stored at 1–6°C (or the original expiry date, whichever is sooner), or to four hours if stored above
6°C. Units selected for irradiation at Canadian Blood services must be less than or equal to 14 days after
collection and following irradiation, the units may be stored for an additional 14 days. This change occurred on
2017-08-14 and aligns Canadian Blood Services with the British Committee for standards in Hematology.4 Red
blood cell products must be stored at 1–6°C in a temperature-controlled storage device with an alarm system,
air-circulating fan and continuous monitoring device. Records must be kept during storage and transportation
that maintain the chain of traceability, in order to follow blood products from their source to final disposition and
to ensure that appropriate conditions were present throughout this time frame.

Maintaining proper storage temperature during transportation is essential. Transportation time should not
exceed 24 hours. Blood products with a required storage temperature of 1–6°C should be transported under
validated conditions of 1–6°C; however, if the transit time is 24 hours or less, a transport system validated to
maintain an environmental temperature of 1–10°C is allowable. Visual inspection of each blood product to be
shipped must be performed and documented. Validated shipping containers and standardized packing
procedures are critical to this process. Some hospitals and regions use temperature-monitoring devices, in one
or more shipping containers in each shipment of blood and blood products, to ensure the correct temperature
during transportation.

When red blood cell units accompany a patient, the issuing hospital transfusion service is responsible for
notifying the receiving hospital transfusion service, which is then responsible for the final disposition
documentation.

Further details about the red blood cell units manufactured by Canadian Blood Services can be found in the
relevant Circular of Information.

Available alternatives
Depending on the underlying cause of anemia, alternative treatments that may be considered include oral iron,
intravenous iron, vitamin B12, folic acid, and erythropoietin stimulating agents. Monitoring the hemoglobin
while treating the underlying condition(s) contributing to anemia may be an alternative to transfusion for some
patients.2

PLATELETS
Product manufacturing and description (see Figures 1 and 2)
At Canadian Blood Services, there are two types of platelet preparations: Pooled Platelets and Apheresis
Platelets.

Pooled Platelets are prepared from whole blood collected into a buffy coat collection set (B1 method) with CPD
anticoagulant (Figure 1). The whole blood donations are rapidly cooled to room temperature after collection.
After transportation to the production site, the blood components are separated by centrifugation. The top

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

4/14
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Chapter 2: Blood Components

layer, containing the plasma, and the bottom layer, containing the red blood cells, are extracted. The buffy coat
layer between the red blood cells and plasma contains platelets and white blood cells. The buffy coat layers
from four donations of the same ABO blood group, along with plasma from one of the same four donations
(generally a male donor), are pooled together and further processed, including LR by filtration, in order to
produce Pooled Platelets (Figure 2). The pool is labeled as Rh negative only when all the donor units within the
pooled product are Rh negative. The Pooled Platelets units are produced within 28 hours of collection and have
a unique pool number identifier. Pooled Platelets have an average volume of 342 (± 15) ml and a typical
platelet count of 298 (± 68) x 109 per unit. The shelf life is seven days from the time of collection. The typical
unit of Pooled Platelets has an average residual leukocyte count of 0.09 x 106 and may also contain trace
amounts of red blood cells.

Apheresis Platelets are collected and prepared by an automated in-line process using a chamber with flow
patterns that separate the red blood cells and leukocytes from the platelets and plasma. A typical unit of
Apheresis Platelets issued by Canadian Blood Services contains 370 (± 48) x 109 platelets, with a mean residual
leukocyte count of 0.067 x 106 and an average volume of 242 (± 8) ml.

Figure 2. Pooled Platelets manufacturing at Canadian Blood Services.

Indications
The transfusion of platelets is indicated in the treatment of patients with bleeding due to severely decreased or
dysfunctional platelets. Platelet transfusion may also be useful if given prophylactically to patients with rapidly
falling or low platelet counts secondary to bone marrow disorders or chemotherapy. Platelet transfusions are
not recommended for patients with rapid platelet destruction (e.g. ITP, heparin-induced thrombocytopenia (HIT),
thrombotic thrombocytopenic purpura (TTP)) except in the setting of clinically significant and/or life threatening
bleeding.5

Indications are similar for both Pooled Platelets and Apheresis Platelets. Apheresis Platelets may be selected on
the basis of similar human leukocyte antigen (HLA) typing to the recipient's when a recipient fails to respond to
platelet transfusion because of demonstrated anti-HLA antibodies (alloimmune refractoriness). See Chapter 18
of this Guide for details of treatment and testing for platelet-refractory patients.

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

5/14
CLINICAL GUIDE TO TRANSFUSION
Chapter 2: Blood Components

Dose and administration

The donor plasma in the platelet unit should be ABO compatible (but not necessarily group-specific) with the
recipient’s red blood cells. The same compatibility guidelines are used for platelets and plasma products (Table
1). See chapters 9 and 18 of this Guide for information on dose and administration of platelet products.

Table 1. ABO compatibility for plasma and platelet product recipients

A/B Antigen(s)
A/B Antibodies May receive
Blood group present on Compatible plasma
present in recipient platelets from
of recipient recipient red blood from groups
blood groups
cells
A A Anti-B A, AB A, AB, B, O
B B Anti-A B, AB B, AB, A, O
AB A, B None AB AB, A, B, O
O None Anti-A, Anti-B All (A, B, AB, O) O, AB, A, B

Transfusion of Apheresis Platelets should result in increments similar to those achieved by transfusion of Pooled
Platelets. In practice, the post-transfusion platelet count often does not rise to the expected level. Sepsis,
alloimmunization, fever, immune thrombocytopenic purpura (ITP) or disseminated intravascular coagulation
(DIC) may contribute to a suboptimal response. See Chapter 18 of this Guide for more information.

Storage and transportation

Platelet components must be stored at 20–24°C under continuous agitation. Platelet agitators and incubators
are required for storing platelet products. If the agitator is not contained in a platelet incubator, the ambient
temperature must be recorded manually using a calibrated thermometer every four hours or through use of a
constant room temperature monitoring device as long as platelet products are stored.

Their shelf life is seven days from the date of collection. Once opened, the expiry time is four hours from the
time of opening unless aliquots are prepared using a sterile connection device. Aliquots obtained using such a
device retain the seven day expiry date and must contain a minimum residual volume that is dependent on the
collection pack. For Apheresis Gambro Trima collection packs the minimum volume is 100 ml. For Haemonetics
MCS collection packs the minimum residual volume in the original storage container is 200 ml. The collection
and expiry dates indicated on the platelet unit must be copied to the label of each aliquot pack made from the
original unit.

Further details on the platelet products manufactured by Canadian Blood Services can be found in the Circular
of Information and Chapter 18 of this Guide.

Available alternatives
Apheresis Platelets may be used instead of Pooled Platelets whenever supply and demand allow.

There are no known alternatives to platelet concentrates.

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

6/14
CLINICAL GUIDE TO TRANSFUSION
Chapter 2: Blood Components

PLASMA PRODUCTS
Product manufacturing and description
The main types of plasma products produced and distributed by Canadian Blood Services are Frozen Plasma
CPD, Apheresis Fresh Frozen Plasma and Cryosupernatant Plasma CPD. Canadian Blood Services also distributes
solvent detergent treated (SD) plasma produced by Octapharma to specific patients who have conditions
requiring use of this product (Table 2). Canadian Blood Services also produces and distributes Cryoprecipitate,
for which a separate section is identified at the end of this chapter.

Frozen Plasma CPD (FP) is prepared from whole blood collected in CPD anticoagulant that is red blood cell-
reduced by centrifugation. Depending on the processing method, FP is platelet-reduced and leukocyte-reduced
by either centrifugation (B1 method) or filtration (B2 method) (Figure 1). The extracted plasma is frozen within
24 hours of collection and labelled as a Frozen Plasma CPD unit. Although the processing steps inherently
reduce the number of leukocytes to a residual leukocyte level that averages < 5 x 106 per unit, the label for
plasma components does not indicate that leukoreduction has been performed because leukocyte level can be
highly variable.

Apheresis Fresh Frozen Plasma (AFFP) is collected using an automated in-line process in which whole blood from
the donor enters a collection chamber where flow patterns separate the plasma from cellular blood constituents
such as red blood cells and leukocytes. Plasma collected by apheresis is frozen within eight hours of collection
and labelled as an Apheresis Fresh Frozen Plasma unit.

The average volume of FP and AFFP products issued by Canadian Blood Services and their coagulation factors
content are described in Table 2. Coagulation Factors V and VIII, known as the labile coagulation factors, are not
stable in plasma stored for prolonged periods at 1–6˚C; therefore, plasma is stored in the frozen state at -18˚C
or lower. AFFP contains approximately 87% of the Factor VIII present at the time of collection, and according to
Canadian standards must contain at least 0.70 IU/ml of Factor VIII. FP contains Factor VIII levels that are
approximately 70–75% of the levels present at the time of collection, and according to Canadian standards must
contain at least 0.52 IU/ml of Factor VIII. The levels of Factor V, as well as the levels of other coagulation factors,
are not significantly decreased from baseline in plasma frozen within 24 hours of collection.

Cryosupernatant Plasma CPD (CSP) is prepared from slowly thawed FP that is centrifuged to separate the
plasma from the insoluble cryoprecipitate. The insoluble cryoprecipitate is removed and the remaining plasma is
refrozen and labelled as Cryosupernatant Plasma CPD.

Canadian Blood Services also distributes Octaplasma™ to a limited number of patients who meet specific
criteria. This is a solvent detergent (SD) treated, pooled fresh frozen plasma product produced by Octapharma.
Octaplasma™ is filtered to remove cells and debris, which may help reduce adverse events linked to residual
blood cells, and the pooling process dilutes and neutralizes allergens and antibodies, theoretically reducing the
risk of TRALI. The SD treatment destroys enveloped viruses, and the manufacturing process reduces the risk of
infection by non-enveloped viruses and prions, but the possibility of transmission of the latter agents cannot be
eliminated.

Table 2. Description of plasma products distributed by Canadian Blood Services

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

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CLINICAL GUIDE TO TRANSFUSION
Chapter 2: Blood Components

Type Description
Frozen Plasma CPD Approximately 283 ml of plasma separated from an individual unit of whole blood
(FP) collected in CPD anticoagulant and placed in a freezer at <-18˚C within 24 hours
after donation; contains all coagulation factors but has slightly reduced amounts
of clotting Factors V and VIII. On average, FP contains 0.87 IU of Factor VIII per ml.
Apheresis Fresh Plasma collected by apheresis and frozen within eight hours of donation; contains
Frozen Plasma both labile clotting Factors V and VIII, plus non-labile coagulation factors. Sodium
(AFFP) citrate anticoagulated AFFP units have an average volume of 494 ml while ACD-A
anticoagulated AFFP units have an average volume of 249 ml. AFFP units contain
an average of 1.29 IU of Factor VIII per ml.
Cryosupernatant Approximately 273 ml of plasma separated from an individual unit of whole blood
Plasma CPD (CSP) prepared following Cryoprecipitate production; contains all coagulation factors but
has reduced levels of the high molecular weight Von Willebrand factor (vWF)
multimers.
Solvent Detergent (SD) Plasma pooled from many donors, treated with processing steps (solvent
plasma detergent, immune neutralisation, sterile filtration) to remove or inactivate
pathogens, cells, allergens and antibodies. Each unit is 200 ml of cell-free plasma
that contains 9.0–14.0 g of human plasma proteins (45–70 mg/ml). A minimum of
0.5 IU per ml is obtained for all clotting factors.
FP, AFFP and CSP are manufactured and distributed by Canadian Blood Services. SD plasma (Octaplasma™) is produced by
Octapharma and distributed by Canadian Blood Services for specific indications. See product monograph for more details.

Indications
Given the fact that AFFP is no longer used to treat patients with isolated Factor VIII or Von Willebrand factor
deficiencies and that studies have shown that the levels of Factor VIII in FP are only slightly lower than those in
AFFP, in most clinical situations where these products are indicated (Table 3), FP and AFFP may be used
interchangeably.

There is broad general consensus that the appropriate use of AFFP/FP is limited almost exclusively to the
treatment or prevention of clinically significant bleeding due to a deficiency of one or more plasma coagulation
factors. Such situations potentially include the treatment of:

• bleeding patients or patients undergoing invasive • patients with rare specific plasma protein deficiencies
procedures who require replacement of multiple for which no more appropriate or specific alternative
coagulation factors (such as patients with severe liver therapy is available;
disease or DIC); • patients requiring treatment of TTP and adult
• patients with massive transfusion (replacement of hemolytic uremic syndrome (HUS) by plasma
patient’s blood volume in less than 24 hours) with exchange;
clinically significant coagulation abnormalities; • other conditions treated by therapeutic plasma
• patients on warfarin anticoagulation who are exchange where the exchange fluid must include
bleeding or need to undergo an invasive procedure coagulation factors. See Chapter 14 of this Guide.
before vitamin K can reverse the warfarin effect and
for whom prothrombin complex concentrates are not
indicated, or not available;

AFFP or FP may also be used in the preparation of reconstituted whole blood for exchange transfusion in
neonates. See Chapter 13 of this Guide for more information about neonatal and pediatric plasma transfusion.

CSP is used in the treatment of TTP and adult hemolytic uremic syndrome (HUS) by plasma exchange, or may
be used in treatment of multifactor deficiency, particularly when fibrinogen replacement is not required. For
example, CSP may also be used for treatment of patients on warfarin anticoagulation who are bleeding or need

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

8/14
CLINICAL GUIDE TO TRANSFUSION
Chapter 2: Blood Components

to undergo an invasive procedure before vitamin K can reverse the warfarin effect and for whom prothrombin
complex concentrates are not indicated, or not available. AFFP or FP is usually used in these situations when
CSP is not available.

SD plasma (Octaplasma™) is licensed and approved for use in Canada for a number of indications where plasma
might otherwise be used. However, the supply is limited, and only patients with high volume plasma
transfusions who meet criteria identified by the National Advisory Group6 for blood and blood products may be
treated with SD plasma, including patients with:

Thrombotic thrombocytopenic purpura (TTP) or

Hemolytic uremic syndrome (HUS) with associated factor H deficiency or
Clotting factor deficiencies for which specific licensed concentrates may not be readily available (e.g.
Factor V, Factor XI, Factor XIII)

Who also:

Have experienced an allergic reaction to a frozen plasma product (e.g. AFFP, FP) or
Have a pre existing lung disorder or
Need FP but a blood group compatible product is not available in a timely manner.

Table 3. Indications for plasma component transfusion by condition/clinical circumstance

Apheresis
Frozen Fresh Solvent
Cryosupernatant
Condition/Clinical Circumstance Plasma Frozen Detergent
Plasma CPD (CSP)
CPD (FP) Plasma (SD) Plasma
(FFPA)
Reversal of warfarin therapy when X X X
prothrombin complex concentrates and/or
vitamin K is contra-indicated or unavailable
Correction of microvascular bleeding when X X
laboratory testing demonstrates
coagulopathy
Liver disease X X
Massive transfusion X X
Exchange transfusion in neonates X X
TTP or adult HUS plasma exchange therapy X X X
Patients with selected coagulation factor X X
deficiency or rare plasma protein deficiencies
when specific alternative therapy is not
available
Patients who meet the qualifying criteria for X
SD plasma (see above)

Guidelines for reversal of oral anticoagulant therapy using plasma or prothrombin complex concentrates (PCC)
are available from the National Advisory Committee on Blood and Blood products.7 See also Chapter 17 of this

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Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

9/14
CLINICAL GUIDE TO TRANSFUSION
Chapter 2: Blood Components

Guide and/or the relevant Canadian Blood Services Circular of Information for further information.

Contraindications
Plasma transfusion is not indicated for volume replacement alone, or for a single coagulation factor deficiency if
specific recombinant products or plasma-derived virally inactivated products are available. Plasma transfusion is
generally not indicated or effective in reversal of an International Normalized Ratio (INR) below 1.8.8

Hypovolemia without coagulation factor deficiencies should be treated with other plasma volume expanders
such as 0.9% sodium chloride, Ringer’s lactate solution, albumin or hydroxyethyl starches. See Chapter 3 of this
Guide for more details on albumin and therapeutic alternatives to albumin.

Do not use plasma when coagulopathy can be more appropriately corrected with specific therapy such as
vitamin K, prothrombin complex concentrates (PCCs), Cryoprecipitate, or specific coagulation factor
replacement. See Chapter 5 of this Guide for information about coagulation factors available in Canada and
their use.

Do not use cryosupernatant plasma for conditions that require fibrinogen, Factor VIII or Von Willebrand factor
replacement.

Dose and administration

Reading of chapters 9 and 13 of this Guide is recommended for detailed information on blood administration
and on neonatal and pediatric transfusion, respectively.

The volume transfused depends on the clinical situation and recipient size, and when possible should be guided
by serial laboratory assays of coagulation function. In general, the dose to achieve a minimum of 30% of plasma
clotting factor concentration is attained with the administration of 10–15 ml/kg of body weight, except for the
treatment of warfarin reversal in which 5–8 ml/kg body weight will usually suffice (and only in the rare
circumstance where PCCs are contraindicated or unavailable).

Plasma products must be ABO compatible with the recipient’s blood type but not necessarily be group specific
(see Table 1). To be compatible, the plasma product should not contain ABO antibodies that may be
incompatible with the ABO antigens on the patient’s red blood cells. If there is no ABO group available for the
recipient, a typing will be required to determine compatibility or group AB plasma can be used.

Thawing of FP, AFFP and CSP may take 12–30 minutes depending on the product volume, thawing method and
equipment used by the hospital transfusion service. SD plasma should be thawed in the outer wrapper in a
circulating water bath (30–37°C) for 30 to 60 minutes or in a dry tempering system according to manufacturer
instructions; detailed device-specific recommendations are available from Octapharma.

Upon completion of thawing, transfuse immediately or store plasma products in an alarmed, continuously
monitored refrigerator at 1–6°C. Once thawed, plasma products cannot be refrozen; some institutions have a
thawed plasma bank. FP, CSP, and AFFP anticoagulated with ACD-A can be stored up to five days; however,
AFFP anticoagulated with sodium citrate) is collected in an open system and can be stored for only 24 hours (at
1–6°C) after thawing.

If transfusion of the plasma unit will not be initiated promptly after removal from the temperature-controlled
blood product refrigerator or storage/transportation device, it should be returned immediately to prevent waste.
Blood products may be returned to inventory only if the bag is intact, passes a visual inspection and has
maintained an acceptable temperature (See CSTM Standard 5.8.7.1 for more information).3

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

10/14
CLINICAL GUIDE TO TRANSFUSION
Chapter 2: Blood Components

Storage and transportation

Frozen plasma products must be stored frozen at -18°C or colder in a controlled, monitored freezer for a
maximum of 12 months (FP, AFFP, CSP) or four years (Octaplasma™). Product must not be out of the controlled
blood storage freezer for longer than 30 minutes.

Available alternatives
FP and AFFP may be used interchangeably depending on indication, supply and demand.

SD plasma is available for specific indications as described above.

Vitamin K should be used for warfarin reversal when the patient is not bleeding and does not require an invasive
procedure. Patients requiring rapid reversal of warfarin due to bleeding, bleeding risk or an urgent invasive
procedure may benefit from use of a PCC.

Specific plasma protein concentrates are available and are described in chapters 5 and 17 of this Guide.

CRYOPRECIPITATE
Product manufacturing and description
Canadian Blood Services prepares Cryoprecipitate from slowly thawed FP that is centrifuged to separate the
insoluble cryoprecipitate from the plasma. The plasma is removed and the insoluble cryoprecipitate is refrozen
and labelled as Cryoprecipitate. Each 10 (± 2) ml bag of cryoprecipitate contains a mean of 285 (± 88) mg of
fibrinogen.

Indications
Over the last several years a number of factors have changed the clinical indications for the use of
Cryoprecipitate. These factors include a better understanding of the coagulation system; more attention to the
non-factor VIII factors within Cryoprecipitate; concern about viral inactivation; and the development of
alternative products.

The current primary uses of Cryoprecipitate are for fibrinogen replacement in acquired hypofibrinogenemia or
as empiric therapy in a bleeding patient. Generally, a plasma fibrinogen level of less than 1.0 g/l, as might occur
in DIC or fibrinogenolysis, provides an objective basis for Cryoprecipitate therapy. Certain populations have a
higher threshold (e.g. fibrinogen >1.5 g/l is recommended in patients with acute promyelocytic leukemia and in
massively bleeding patients).3, 9, 10

Apart from the historical use of Cryoprecipitate as a Factor VIII concentrate for hemophilia and Von Willebrand
disease, there are no prospective studies demonstrating evidence-based outcomes for the use of
Cryoprecipitate. See the “Available alternatives” section below for information on use of recombinant products
for these conditions.

Despite the paucity of evidence, Cryoprecipitate is widely accepted as one of the products used to treat
bleeding due to hypofibrinogenemia. These conditions include rare cases of hypofibrinogenemia or
dysfibrinogenemia and, more commonly, acquired conditions with multiple factor deficiencies (e.g. DIC, post-
thrombolytics, massive transfusion or liver disease). These are complicated conditions and Cryoprecipitate is
only one part of the clinical management of such patients. Fibrinogen deficiency should be documented, and the

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

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CLINICAL GUIDE TO TRANSFUSION
Chapter 2: Blood Components

product should only be used if there is active bleeding or a planned surgical procedure. While studies
documenting efficacy in these settings are very limited, these are relatively common conditions and there is
considerable clinical experience using Cryoprecipitate. In some cases, fibrinogen concentrates may be
considered an equally effective alternative (see chapters 5 and 8 of this Guide).

Contraindications
Usually, Cryoprecipitate is not indicated unless results of laboratory studies indicate a fibrinogen
concentration of 1.0 g/l or less or in the setting of massive hemorrhage with coagulopathy. Specific factor and/or
recombinant concentrates are preferred, when available, because of the reduced risk of transfusion-
transmissible diseases.

Cryoprecipitate should not be used to make fibrin glue. Virally inactivated commercial products should be
purchased for this purpose.

Cryoprecipitate is not recommended in the treatment of hemophilia A, or in most cases (see below) in the
treatment of Von Willebrand disease.

Dose and administration

Group-specific Cryoprecipitate is not necessary outside of the pediatric setting, and should be considered
according to local policy for pediatric recipients. Reading of chapters 9 and 13 of this Guide is recommended for
detailed information on administration and on neonatal and pediatric transfusion, respectively.

One unit of Cryoprecipitate contains approximately 285 mg of fibrinogen. The amount of Cryoprecipitate
required for transfusion will depend on the severity and nature of the bleeding condition.

The amount of Cryoprecipitate needed to raise the fibrinogen concentration of plasma can be calculated as
follows:

Step 1. Weight of the patient (kg) x 70 ml/kg = blood volume in ml.

Step 2. Blood volume in ml x (1.0 – patient hematocrit) = plasma volume in ml.
Step 3. Desired fibrinogen – actual fibrinogen x plasma volume (ml) = mg fibrinogen required.
Step 4. mg fibrinogen required/285 mg per cryoprecipitate unit = units of cryoprecipitate required.

Many facilities use the generic dose of up to 1–2 units per 10 kg body weight, as required to maintain fibrinogen
above 1 g/l, as directed by the hospital transfusion service medical director for treatment of
hypofibrinogenemia. An order for 10 units of Cryoprecipitate for an average sized patient is typical at many
hospitals, with subsequent requests in increments of 10 units depending on clinical need. The same standards
as for the other blood components concerning prescription, informed consent and addition of medications apply
to Cryoprecipitate.

Cryoprecipitate is often pooled by the hospital transfusion medicine service personnel or may be given
sequentially. Small quantities of normal saline are introduced to rinse each bag in the pooling process. Pooled
Cryoprecipitate may have a single pool number and the label will indicate the number of units in the pool. This
number and the number of units in the pool must be documented. If no pool number exists, each donor unit
number must be documented on the medical record. If the Cryoprecipitate is pooled, all units will have been
opened and must be used within four hours.

Cryoprecipitate may be administered through a blood administration set with a standard blood filter or as a

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

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CLINICAL GUIDE TO TRANSFUSION
Chapter 2: Blood Components

bolus injection by trained personnel. Infusion should be as rapid as can be tolerated by the patient or as
specified by the ordering physician. See the Circular of Information on plasma components for further
information.

Storage and transportation

Cryoprecipitate must be stored frozen at -18°C or colder in a controlled, monitored freezer for a maximum of 12
months. Product must not be out of the controlled blood storage freezer for longer than 30 minutes and cannot
be refrozen. If the transfusion will not be initiated promptly after removal from the temperature-controlled blood
product storage device, the product should be returned immediately to prevent deterioration and waste (CSTM
Standard 5.8.7.1).3

Additional information on storage may be found in the Circular of Information on plasma components.

Available alternatives
The primary use of Cryoprecipitate is for fibrinogen replacement, or empirically in a bleeding patient or patient
with new microvascular bleeding.

See Chapter 5 of this Guide for information on coagulation factor concentrates available in Canada and their
use. There are fibrinogen concentrates available. In Canada, the current indication is for treatment of congenital
hypofibrinogenemia.

See also Chapter 17 of this Guide for information on how to treat hemostatic disorders including hemophilia and
Von Willebrand disease. Cryoprecipitate does contain fibronectin that has been suggested and used to improve
reticuloendothelial function in critically ill patients with sepsis. There is, however, insufficient information to
recommend its use in this setting.

CONTINUING PROFESSIONAL DEVELOPMENT CREDITS

Fellows and health-care professionals who participate in the Canadian Royal College's Maintenance of
Certification (MOC) Program can claim the reading of the Clinical Guide to Transfusion as a continuing
professional development (CPD) activity under Section 2: Self-learning credit. The reading of one chapter is
equivalent to two credits.

ACKNOWLEDGEMENTS
The author, Gwen Clarke, acknowledges Kathy Chambers, Pat Letendre and Lucinda Whitman as authors of a
previous version of this chapter and Kathryn Webert, MD FRCPC, Tanya Petraszko, MD FRCPC, Robert Skeate,
MD FRCPC, Debra Lane, MD FRCPC, and Michelle Zeller, MD FRCPC, for their review of the current version.

We’re here to answer your questions about the Clinical Guide to Transfusion. We’d also appreciate your ideas on
how to improve the Guide. Please contact us through the Clinical Guide feedback form.

REFERENCES
1. Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, Gernsheimer T, Holcomb JB, Kaplan LJ,
Katz LM, Peterson N, Ramsey G, Rao SV, Roback JD, Shander A, Tobian AA. Clinical Practice Guidelines from the
AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA 2016; 316: 2025-35.
2. Canadian Society for Transfusion Medicine. Transfusion Medicine Recommendations, Choosing Wisely

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

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Chapter 2: Blood Components

Canada2015. https://choosingwiselycanada.org/transfusion-medicine/ (Last accessed July 24 2017).

3. CSTM Standards Committee. CSTM Standards for Hospital Transfusion Services. Published in Ottawa,
Canada by Canadian Society for Transfusion Medicine, 2017.
4. Canadian Blood Services. Canadian Blood Services Customer Letter # 2017-29: Important Information
Regarding Changes to the Expiry Date of Irradiated Red Blood Cells. 2017.
5. Nahirniak S, Slichter SJ, Tanael S, Rebulla P, Pavenski K, Vassallo R, Fung M, Duquesnoy R, Saw CL,
Stanworth S, Tinmouth A, Hume H, Ponnampalam A, Moltzan C, Berry B, Shehata N, International Collaboration
for Transfusion Medicine Guidelines. Guidance on Platelet Transfusion for Patients with Hypoproliferative
Thrombocytopenia. Transfus Med Rev 2015; 29: 3-13.
6. National Advisory Committee on Blood and Blood Products. Framework for Appropriate Use and Distribution
of Solvent Detergent Treated Plasma in Canada. 2015.
7. Canadian National Advisory Committee on Blood and Blood Products. Nac’s Statement Regarding
Appropriateness of Use of Cytomegalovirus (Cmv) Sero Negative Vs Cmv Safe Product.
http://www.nacblood.ca/resources/guidelines/CMV.html (Last accessed August 1 2017).
8. Callum JL et al. Bloody Easy 4: Blood Transfusions, Blood Alternatives and Transfusion Reactions. Published
in Ontario, Canada by Ontario Regional Blood Coordinating Network, 2016.
9. Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ,
Komadina R, Nardi G, Neugebauer EA, Ozier Y, Riddez L, Schultz A, Vincent JL, Spahn DR. The European
Guideline on Management of Major Bleeding and Coagulopathy Following Trauma: Fourth Edition. Crit Care
2016; 20: 100.
10. Stein E, McMahon B, Kwaan H, Altman JK, Frankfurt O, Tallman MS. The Coagulopathy of Acute
Promyelocytic Leukaemia Revisited. Best Pract Res Clin Haematol 2009; 22: 153-63.

https://professionaleducation.blood.ca/en/transfusion/guide-clinique/blood-components
Published: Friday, September 8, 2017
Important disclaimer: This material is an educational tool providing guidelines for the care of patients. These recommendations should thus not be
applied rigidly, since they could result in some patients receiving unnecessary transfusions or experiencing adverse effects from under-transfusion.
The guidelines are mainly for adult patients and may not necessarily apply to the treatment of children.
The recommendations do not replace the need in some cases to consult an expert in Transfusion Medicine to provide optimal patient care.

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