Fresh Frozen Plasma and Cryoprecipitate in Transfusion ( Adults, Children and Neonates ) - Guideline for the Use of

Publication: 31/10/2010  --
Last review: 04/10/2017  
Next review: 04/10/2020  
Clinical Guideline
CURRENT 
ID: 2326 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2017  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for the Use of Fresh Frozen Plasma & Cryoprecipitate in Transfusion (Adults, Children and Neonates)

  1. Introduction 
    1.1 Rationale for guideline
    1.2 About Fresh Frozen Plasma
    1.3 About Pathogen Reduced Plasma
    1.3.1 Methylene Blue treated FFP
    1.3.2 Solvent-detergent FFP
    1.4 Thresholds and Targets
    1.5 About Cryoprecipitate
  2. Storage and Shelf life
    2.1 FFP & Cryoprecipitate
    2.2 Pathogen Reduced Plasmas
    2.2.1 MBFFP
    2.2.2 SDFFP (Octaplas)
  3. Compatibility recommendations
    3.1 Compatibility table for adults
  4. Clinical Indications for the use of FFP and cryoprecipitate 
    4.1 Single Factor Deficiencies
    4.2 Multiple Factor Deficiencies / Disseminated Intravascular Coagulation
    4.3 Massive Transfusion
    4.4 Liver Disease
    4.5 Thrombotic Thrombocytopenic Purpura
  5. Dosage
  6. Administration of FFP and Cryoprecipitate
  7. Children and Neonatal use of FFP and cryoprecipitate
    7.1 Compatibility table for Paediatrics and Neonates
    7.2 Neonatal and children < 1 year – indications for use
  8. Risks associated with the use of FFP
    8.1 Transfusion Transmitted Infections
    8.2 Transfusion Associated Graft versus Host Disease
    8.3 Transfusion Related Acute Lung Injury (TRALI)
    8.4 Allergic reaction and anaphylaxis
    8.5 Transmission of variant Creutzfeldt-Jacob Disease
  9. Written Informed Consent for Transfusion of FFP
  10.  Requesting & Documentation

For guidance on the Indication Codes for the use of red cells, fresh frozen plasma, cryoprecipitate, platelets and prothrombin complex concentrate issued by the National Blood Transfusion Committee, supported by NICE NG24 2015

1. Introduction

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1.1   Rationale for guideline

The purpose of this document is:

  • To give general guidance to clinical staff about the appropriate and safe use of FFP and cryoprecipitate transfusion.
  • To give guidance on the correct procedures for prescribing, requesting, ordering and administering FFP and cryoprecipitate.

NB: FFP is not indicated for the reversal of warfarin therapy – prothrombin complex is safer and more effective.

For information on the management of Warfarin Reversal go to:

LTHT Guidelines for Warfarin Reversal

British Society for Haematology (2011).
Guidelines on oral anticoagulation (warfarin): 4th edition
British Journal of Haematology, 132, 227 - 285

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1.2 About Fresh Frozen Plasma (FFP)

FFP is donor plasma that has been frozen rapidly to -30oC and contains fibrinogen, Factor VIII and other clotting factors – but only in the concentrations present in the original donor plasma. FFP unit volume varies between 180 - 400ml (usually approximately 275ml) and is available as single unit packs containing 1 donation per pack.3

Constituents of FFP2

 

White Blood Cells (WBC)

< 5 x 106 / unit

Fibrinogen

2-5mg/ml

Factor VIII

>0.7IU/ml in >75% packs

Other clotting factors

Variable

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1.3 About Pathogen Reduced Plasmas (PRP) (which are a type of FFP)

All children born since 1st January 1996 should be treated with imported, pathogen reduced plasma (PRP) imported from a country with low risk of Bovine Spongiform Encephalopathy (BSE).2 This is a vCJD risk reduction measure mandated by the Department of Health.

There are two types of Pathogen Reduced Plasma:

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1.3.1 Methylene Blue treated FFP
Methylene blue treated FFP (MBFFP) is a pathogen reduced “single donor” blood component produced from US male donors and distributed by the National Blood Service. It is treated with methylene blue and light as a viral inactivation method and is primarily intended for use
in patients born since Jan 1st 1996.

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1.3.2 Solvent-detergent FFP
Solvent detergent treated FFP (SDFFP) is a commercially available manufactured blood product prepared from pools of plasma donations (Octaplas™). It is treated with solvent and detergent to inactivate viral and bacterial pathogens. The units contain a standardised dose of coagulation factors (but this is not a factor concentrate). Each pack exposes the patient to
380-2500 donations 2 SD FFP is now recommended for high volume plasma exchange in patients with Thrombotic Thrombocytopenic Purpura (TTP) because of its increased efficacy compared to standard FFP in this setting. This product may also be used as a substitute for MBFFP.

1.4 Thresholds and Targets

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1.4.1 Only consider fresh frozen plasma transfusion for patients with clinically significant bleeding but without major haemorrhage if they have abnormal coagulation test results (for example, prothrombin time ratio or activated partial thromboplastin time ratio above 1.5).

1.4.2 Do not offer fresh frozen plasma transfusions to correct abnormal coagulation in patients who:

  • Are not bleeding (unless they are having invasive procedures or surgery with a risk of clinically significant bleeding)
  • need reversal of a vitamin K antagonist

1.4.3 Consider prophylactic fresh frozen plasma transfusions for patients with abnormal coagulation who are having invasive procedures or surgery with a risk of clinically significant bleeding.

Doses

1.4.4 Reassess the patient’s clinical condition and repeat the coagulation tests after fresh frozen plasma transfusion to ensure that they are getting an adequate dose, and give further doses if needed.

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1.5 About Cryoprecipitate

Cryoprecipitate is obtained by thawing FFP at 4OC. The cryoprecipitate remains the supernatant plasma as a gel like precipitate; this is then rapidly frozen to -30C. It consists of the cryoglobulin fraction of plasma containing the major portion of Factor VIII and fibrinogen. It is issued by National Heath Service Blood & Transplant (NHSBT) and primarily used as a concentrated source of fibrinogen.

Constituents of Cryoprecipitate2

 

WBC count

<5x106 / unit

Fibrinogen

150-300 ml/pack

Factor VIII

80-120 u/pack

Von Willebrand Factor

80-120 IU/pack

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1.5.1 Methylene Blue treated Cryoprecipitate
Methylene blue treated Cryoprecipitate is a pathogen reduced component processed from whole blood or apheresis plasma from male donors imported from the USA. It is treated with methylene blue and light as a viral inactivation. Methylene Blue treated cryoprecipitate is not
available in Group AB. This should be used for patients born since Jan 1st 1996.

Thresholds and targets.

1.5.1 Consider cryoprecipitate transfusions for patients without major haemorrhage who have:

  • clinically significant bleeding and
  • a fibrinogen level below 1.5g/litre.

1.5.2 Do not offer cryoprecipitate transfusions to correct the fibrinogen level in patients who:

  • are not bleeding and
  • are not having invasive procedures or surgery with a risk of clinically significant bleeding.

1.5.3 Consider prophylactic cryoprecipitate transfusions for patients with a fibrinogen level below 1.0g/litre who are having invasive procedures or surgery with a risk of clinically significant bleeding.

Doses

1.5.4 Use and adult dose of 2 pools when giving cryoprecipitate transfusions (for children, use 5- 10ml/kg up to maximum of 2 pools)

1.5.5 Reassess the patient’s clinical condition, repeat the fibrinogen level measurement and give further doses if needed.

2. Storage and shelf life

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2.1 FFP & Cryoprecipitate

FFP and Cryoprecipitate have a shelf life of 3 years if kept at -30OC or colder. Thawing takes approximately 30 minutes. Once thawed the component must not be refrozen and should be transfused as soon as possible but at least within 4 hours.

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2.2 Pathogen Reduced Plasmas

2.2.1 MBFFP
MBFFP has a shelf life of 3 years if kept at -30OC or colder. Thawing takes approximately 30 minutes. Once thawed the component must not be refrozen and should be transfused as soon as possible but at least within 4 hours.

2.2.2 SDFFP (Octaplas)
SDFFP (Octaplas™) has a shelf life of 4 years if kept at -30OC or colder. Thawing takes approximately 30 minutes. Once thawed the component must not be refrozen and should be transfused as soon as possible but at least within 4 hours4.

3. Compatibility recommendations

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3.1 FFP and Cryoprecipitate compatibility table for adults
(see Section 7.1 for Paediatric compatibility table)

Recipient Group

O

A

B

AB

1st choice

O

A

B

AB

2nd choice

A

AB

AB

A*

3rd choice

B

B*

A*

B*

4th choice

AB

-

-

-

*only suitable for emergency use.

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4. Clinical indications for the use of FFP and Cryoprecipitate

NB: FFP is NOT indicated for use in Warfarin reversal.

For management guidelines of Warfarin reversal go to:
LTHT Guideline for Warfarin Reversal

The indications covered under this section are relevant for adults and children.

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4.1 Single Clotting Factor Deficiencies

FFP should only be used for single clotting factor deficiencies for which no virus safe fractionated concentrated product is available (currently mainly Factor V). Pathogen reduced plasma should be considered for these patients as well as vaccination against Hepatitis A and B to safeguard against transmission of viral infection in a high use group.

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4.2 Multiple Factor Deficiencies / Disseminated Intravascular Coagulation (DIC)

FFP is indicated for the treatment of bleeding associated with multiple clotting factor deficiencies, for example in DIC, liver failure, massive haemorrhage and transfusion. FFP is not indicated for “prophylaxis” in patients with abnormal coagulation results or DIC with no evidence of bleeding. There is no evidence that prophylactic replacement regimens prevent DIC or reduce transfusion requirements.

Cryoprecipitate may be indicated if the plasma fibrinogen is <1g/l although there is no clear threshold for clinically significant hypofibrinogenaemia. Use of Cryoprecipitate should be guided by clinical picture and / or Thromboelastogram (TEG) results. Remember that each unit of FFP contains more fibrinogen than a unit of cryoprecipitate, albeit in a higher transfusion volume.

For further information on the management of DIC go to:
Guidelines for the diagnosis and management of disseminated intravascular coagulation

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4.3 Massive Transfusion

In post-surgical haemorrhage, coagulation factor deficiency is the primary cause of coagulopathy during massive transfusion because of dilution of coagulation factors following volume replacement with crystalloid or colloid and transfusion of plasma-poor red cells. Administration of blood components should be guided by coagulation test results or Thromboelastogram (TEG) where possible.

Major haemorrhage due to trauma is often accompanied by early “traumatic coagulopathy” with consumption of clotting factors, later complicated by dilution after transfusion of plasma expanders and plasma-poor components.

Traditional guidelines suggest that FFP should be considered after one blood volume is replaced by transfusion and then guided by regular measurement of coagulation tests.

Non-randomised studies have shown significant improvement in trauma patient survival when early intensive replacement of FFP (and platelets) is administered in a 1:1 ratio to red cells6, 11. Four units of pre-thawed group A FFP are available upon request from Blood Bank during the event of a Massive Haemorrhage. Guidelines incorporating this into the management plan for massive haemorrhage are available at:

LTHT Guideline for the Generic Transfusion Management of Adult Massive Haemorrhage
detail.aspx?ID=2275

LTHT Guideline for the management of Massive Transfusion during Major ObstetricHaemorrhage
detail.aspx?ID=2146

LTHT Guideline for Massive Transfusion Management (Paediatric Patients Birth to 16 years)
detail.aspx?id=2412

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4.4 Liver disease

There is now very good evidence that routine laboratory tests of coagulation do not reliably predict the risk of haemorrhage in liver disease and that many patients are “prothrombotic” despite prolongation of PT and APTT7. There is no evidence to support the use of FFP to treat prolonged clotting times in non-bleeding patients. Global tests of coagulation, such as TEG or ROTEM are likely to be of more benefit in stratifying bleeding risk and guiding management.

Routine use of FFP prior to a liver biopsy to prevent bleeding in patients with a prolonged PT is also controversial and practice varies widely between clinical units. Again, global coagulation assays such as thrombin generation and thrombelastography (TEG) may provide a more accurate estimate of underlying coagulopathy and bleeding risk7.

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4.5 Thrombotic Thrombocytopenic Purpura (TTP)

SDFFP (Octaplas) is now advocated for use in plasma exchange for the treatment of TTP.

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5. Dosage

The recommended therapeutic dose of FFP is 12 - 15 ml/kg2 for adults and children. Each unit contains approximately 275 ml. In most adult patients this corresponds to at least 4 donor units (calculated on basis of approximately 300ml per unit). Subtherapeutic dosing is common and exposes the patient to the significant risks of FFP administration without clinical benefit. This dose may have to be exceeded in massive bleeding and is dependent on the clinical situation and coagulation results. Response should be monitored by repeat coagulation tests.

In Thrombotic Thrombocytopenic Purpura (TTP), at least 1 plasma volume (2.5-3 litres) should be transfused daily in conjunction with plasma exchange.

Cryoprecipitate is issued in bags containing 5 pooled donations. The usual adult dose is two bags (equivalent to 10 single donor units). Children born since Jan 1st 1996 receive Methylene Blue treated Cryoprecipitate which is available in single donor units.

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6. Administration of FFP and cryoprecipitate

FFP and Cryoprecipitate must be administered using an administration set with a 200 micron filter.

For full administration guidance go to:
LTHT Policy for Safer Transfusion Procedures: Administering Blood and Blood Components detail.aspx?ID=1864

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7. Children and neonatal use of FFP and cryoprecipitate

To prevent the risk of disease transmission the Department of Health have recommended that all children born since Jan 1st 1996 must be given FFP which has been obtained from an area free from Bovine spongiform encephalopathy (BSE) and subject to pathogen-reduction procedures – i.e. either MB-FFP or SD-FFP (Octaplas).

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7.1 Compatibility table for the use of MBFFP and SDFFP in Paediatrics and Neonates12

Recipient group

O

A

B

AB

Ist choice

O

A

B

AB

2nd choice

A

AB

AB

A*

3rd choice

B

-

-

-

4th choice

AB

-

-

-

*only for use in an emergency

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7.2 Neonatal and children < 1 year - indications for use:

  • Treatment of disseminated vascular coagulation with bleeding (DIC)
  • Vitamin K dependent bleeding
  • Inherent deficiencies of clotting factors where no specific concentrate is available
  • Pre-procedure in well babies with abnormal clotting – discuss individual cases with senior clinician.

There is NO evidence to support to use of FFP for:

  • Volume replacement or corrective hypotension
  • Prevention of intraventricular haemorrhage
  • Routine correction of abnormal coagulation tests if clinically fit

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8. Risks associated with FFP and cryoprecipitate & management of adverse events

For Management Guidelines of Adverse Effects go to:

LTHT Policy for Safer Transfusion Procedures: Reactions to Transfusions
detail.aspx?ID=1864

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8.1 Transfusion Transmitted Infections

Bacterial contamination is unlikely because the freezing process inactivates bacteria. The removal of cellular components also removes cell associated bacteria and cell associated viruses.

There is a small risk of transmission of Hepatitis E Virus (HEV) infection to immunosuppressed patients from FFP and cryoprecipitate. Current guidelines recommend transfusion of HEV negative blood and blood components for these patients. All blood and blood components provided from the NHSBT are HEV negative.
For further information please refer to the LTHT guideline
detail.aspx?ID=3157
detail.aspx?ID=3834

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8.2 Transfusion Associated Graft versus Host Disease (TaGvHD)

This is not applicable; FFP does not need to be irradiated as there have been no case reports of FFP associated GvHD.

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8.3 Transfusion Related Acute Lung Injury (TRALI)

TRALI is most strongly associated with the transfusion of FFP. It usually occurs within 6 hours of transfusion and presents clinically as acute respiratory distress with hypoxia, pulmonary oedema and infiltrates or ‘white out’ on chest X-ray. It is caused by antibodies in the donor plasma (mainly HLA antibodies) reacting with the recipient’s leucocytes leading to their sequestration in the lungs and breakdown of the intravascular/alveolar barrier. TRALI has a mortality of up to 40%, but appropriate management, usually with temporary ventilatory support leads to high survival rates. Since 2003, the Blood Services have sourced FFP predominantly from male donors, with a marked fall in the incidence of TRALI.
If Transfusion Related Lung Injury is suspected stop the transfusion immediately and manage the acute respiratory distress, inform Blood Transfusion Laboratory, take chest x-ray and all necessary bloods as requested by the Transfusion Laboratory. Recovery is usual within 48 hours.

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8.4 Allergic reaction and anaphylaxis

FFP has the highest association with severe allergic reactions of any blood component12. Urticaria and/or itching may occur. For patients sensitive to Immunoglobulin A (IgA), plasma deficient in IgA is available on request. If an allergic or anaphylactic reaction is suspected stop the transfusion and inform the Transfusion Laboratory.

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8.5 Transmission of Variant Creutzfeldt-Jakob Disease (vCJD)

Variant CJD is a fatal neurological disease caused by the same prion agent that causes BSE in cattle. There have been 4 confirmed transmissions of vCJD by blood transfusion in the UK. In common with many prion diseases, vCJD may have an incubation period of many years after transmission so the true extent of the clinical problem remains unknown. As of October 1999, all manufactured plasma products, including Factor VIII and Factor IX concentrates, immunogloblins and albumin have been derived from donors outside the UK.  UK-derived FFP and cryoprecipitate are still used for adult patients, although this is currently being reviewed by the Department of Health. The UK blood services have been required to take a number of measures to try to reduce the risk of transmission of variant CJD by blood, plasma and tissue products these include;

  • Withdrawal and recall of any blood components obtained from any individual who later develops variant CJD.
  • Importation of plasma from countries other than the UK for fractionation to manufacture plasma derivatives.
  • Leucodepletion of all blood components.
  • Importation of clinical FFP for patients born since Jan 1st 1996.
  • Exclusion of whole blood donors who state that they have received a blood component transfusion in the U.K. since 1 January 1980.
  • Promotion of appropriate use of blood and tissues products and alternatives throughout the NHS.

The risk of vCJD transmission by UK FFP is unknown and probably low but, like all blood components, it should only be used when there are clear clinical benefits that outweigh the risks.

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9. Written informed consent for transfusion of FFP

In LTH NHS Trust ALL patients are required to give their written informed consent before transfusion of any blood or blood component (wherever clinically possible). This consent and the discussion of the risks explained to the patient must be recorded on consent form 1 (adults) and consent form 2 (paediatrics - to be signed by the parent) either on the pre-printed ‘blood/blood components’ version or on the consent form being used for the patient’s surgery / invasive procedure. This consent process should be backed up with the offer of a Patient Information Leaflet on transfusion (available in all clinical areas or from the Hospital Transfusion Team) where appropriate.
In emergency situations where the patient requires blood component therapy, information regarding the risks and benefits may be given retrospectively.

For further information on written informed consent for transfusion go to:

LTHT policy on obtaining written informed consent for blood / blood components:
detail.aspx?ID=1217

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10. Requesting & documentation

As with all blood components the clinical reason for transfusion should be documented in the case notes.

All FFP and Cryoprecipitate must be prescribed on a LTHT Transfusion Prescription form (order code WPG602). Requests for FFP and Cryoprecipitate must be made via a telephone call to the Transfusion Laboratory LGI – 23398, SJUH - 65559).

The Transfusion Laboratory requires a blood sample to determine the patients ABO group and Rh factor in order to issue FFP or Cryoprecipitate. Please send a correctly labelled sample for Group and Save to the lab as soon as possible to prevent any delays. Be aware that any FFP or Cryoprecipitate need to be thawed before being issued to a patient and this process can take up to 30 minutes plus transport time to the clinical area.

Transfusion observations must be recorded for each unit transfused.

Following transfusion all FFP and Cryoprecipitate must be positively confirmed as transfused in line with the Blood Safety and Quality Regulations 2005. Full “traceability” of all blood component transfusions is a legal requirement and the Transfusion Laboratory has to retain this information for 30 years. This can be done by using the Blood Track ‘Autofate’ system or by returning the manila tag to the transfusion laboratory.

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Provenance

Record: 2326
Objective:

To provide guidance on the appropriate and safe use of Fresh Frozen Plasma (FFP), Cryoprecipitate and Pathogen Reduced Plasmas (PRP). To guide clinicians on the correct procedures for requesting, prescribing and administering the above.

Clinical condition:

Single coagulation factor deficiencies, multiple coagulation factor deficiencies, thrombotic thrombocytopenic purpura, massive haemorrhage.

Target patient group: Adults, children and neonates with coagulopathy
Target professional group(s): Secondary Care Doctors
Allied Health Professionals
Secondary Care Nurses
Adapted from:

British Committee for Standards in Haematology (2004)
Guidelines for the use of fresh frozen plasma, cryoprecipitate and cryosupernatant

British Journal of Haematology 126, 11-28


Evidence base

  1. NBS (2004)
    Portfolio of Components and Guidance for their Clinical Use
    Specification SPN/PTI/PR/030/03

  2. United Kingdom Blood Services (2007)
    Handbook of Transfusion Medicine
    4th Edition
    London, The Stationary Office

  3. NHS Blood and Transplant (2010)
    A Wealth of Knowledge; Information for developing and experienced transfusion
    Practitioners.
    March Version 2

  4. Octapharma (2005)
    Octaplas: Patient Information Leaflet
    Octapharma Limited 2/5/5

  5. British Society for Haematology (2004)
    Guidelines for the use of fresh frozen plasma, cryoprecipitate and cryosupernatant
    British Journal of Haematology 126, 11-28

  6. British Society for Haematology (2006)
    Guidelines on the management of massive blood loss
    British Journal of Haematology 135, 634-641

  7. Holcomb. J et al (2008).
    Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients.
    Annals of Surgery Vol. 248, No 3, Sept

  8. Roberts. L.N, Patel R.K, Ayra. R, (2010) Haemostasis and Thrombosis in Liver Disease British Journal of Haematology
    148, 507-521

  9. Dzik. H.W, (2005)
    Component therapy before bedside procedures
    Transfusion Therapy: Clinical Principles and Practice, 2nd Edition
    AABB Press

  10. British Committee for Standards in Haematology (2004).
    Transfusion Guidelines for Neonates and Older Children.
    British Journal of Haematology
    124 (4): 433-53

  11. Leeds Teaching Hospitals NHS Trust
    Guideline for the management of massive transfusion in ruptured abdominal aortic aneurism
    detail.aspx?ID=1808

  12. Blood Safety & Quality Regulations (2005) SI 2005/50

  13. Serious Hazards of Transfusion (2008)
    SHOT Annual Report

  14. British Society for Haematology (2011).
    Guidelines on oral anticoagulation (warfarin): 4th edition

  15. Leeds Teaching Hospital NHS Trust
    Policy on obtaining written informed consent for blood / blood components:
     detail.aspx?ID=1217

  16. Leeds Teaching Hospitals.
    Policy for Safer Transfusion Procedures: Reactions to Transfusions
    detail.aspx?ID=1864

  17. Leeds Teaching Hospitals
    Guideline for the Use of Irradiated and HEV negative and CMV negative Blood / Blood Components in Transfusion detail.aspx?ID=3157

  18. Leeds Teaching Hospitals
    Guideline for Blood Component and Blood Product Provision during Solid Organ Transplantation
    detail.aspx?ID=3834

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

Not supplied

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