Clinical blood transfusion


Guideline Developer(s)

Singapore Ministry of Health
Health Sciences Authority, Singapore

Date Released

2011 Feb

Full Text Guideline

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is identified and graded for each recommendation (see the "Major Recommendations" field).

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools

Audit Criteria/Indicators
Quick Reference Guides/Physician Guides
Staff Training/Competency Material

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Clinically appropriate, timely, and rational use of blood products

Potential Harms

Infectious and Non-infectious Risks for Blood Transfusion

The risk of blood transfusion can be divided into infectious and non-infectious risks. These range from common to rare but nevertheless, when it happens, can be life threatening and have severe consequences. Table 1 in the original guideline document illustrates the infectious risk and their estimated frequencies in some developed countries. The risks shown in the table are internationally quoted figures and although may not accurately reflect the situation in Singapore, it nonetheless provides a rough estimation for the infectious risk in blood transfusion. See Section 6 in the original guideline document for additional detail.

Adverse Reactions to Transfusion

  • Each blood or blood component transfused carries a risk of an acute or delayed effect and for this reason, physicians prescribing the transfusion should carefully select patients who will benefit from transfusion therapy according to established criteria. The indication for transfusion should be documented in the medical record.
  • Adverse reactions to transfusion can be categorized into acute (immediate) and delayed. Acute (immediate) reaction usually presents within minutes to hours but usually within 24 hours of the transfusion. Acute reactions can be further divided into subgroups of presenting signs and symptoms: fever and or chills, hives or urticaria, dyspnea, and hypotension.
  • Allergic reactions and febrile non-haemolytic transfusion reactions are common but less serious, whereas acute haemolytic reactions, bacterial contamination, transfusion related acute lung injury (TRALI), and anaphylactic reactions are less common but life threatening.
  • Acute haemolytic reaction is commonly due to misidentification of the patient and therefore positive identification of the patient at the bedside when taking blood for crossmatch and before commencing transfusion is the most important step in the prevention of this complication.
  • Delayed transfusion reactions usually manifest days or weeks after the completion of blood transfusion. Recognition of signs and symptoms and correlation with an earlier transfusion can aid in the correct management of the patient and in some cases even reduce the potential complications.

See Section 7 in the original guideline document and Table "Categories and Management of Acute and Delayed Adverse Reactions to Transfusion" in the Major Recommendations field for more information.

Rating Scheme for the Strength of the Recommendations

Grades of Recommendation

Grade Recommendation
A At least one meta-analysis, systematic review of randomised controlled trials (RCTs), or RCT rated as 1++ and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
B A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
GPP
(good practice points)
Recommended best practice based on the clinical experience of the guideline development group

Qualifying Statements

Qualifying Statements
  • These guidelines are not intended to serve as a standard of medical care. Such standards are determined on the basis of all clinical data available for an individual case and are subject to change as scientific knowledge advances and patterns of care evolve.
  • The contents of this publication are guidelines for clinical practice, based on the best available evidence at the time of development. Adherence to these guidelines may not ensure a successful outcome in every case. These guidelines should neither be construed as including all proper methods of care, nor exclude other acceptable methods of care. Each physician is ultimately responsible for the management of his/her unique patient, in the light of the clinical data presented by the patient and the diagnostic and treatment options available.
  • This set of guidelines aim to increase awareness amongst clinicians and healthcare workers about the benefits and risks of blood component therapy. They are however not intended for rigid prescription of care.
  • Evidence based clinical practice guidelines are by nature constantly evolving. New, emerging evidence could always supersede these guidelines and users need to be aware of this. The workgroup advises that these guidelines be scheduled for review in 3 years after publication or if it was felt that new evidence was available that would require substantive amendments to the current set of guidelines.
  • The practical aspects and actual administration of blood products are not covered in this set of guidelines. Each institution should have its own policies of checking blood and patient identity to ensure safety as well as the requisite monitoring of patients when receiving any blood product. These would usually come under the purview of the individual hospital transfusion committees.

Methodology

Methods Used to Collect/Select the Evidence

Searches of Electronic Databases

Description of Methods Used to Collect/Select the Evidence

Searches were run on PubMed (1966-2010), EMBASE (1947-2010), and the Cumulative Index to Nursing & Allied Health (CINAHL) database (1984-2010) for searching evidence related to clinical blood transfusion. Additionally both the Cochrane Library (2010, Issue 5) and Centre for Reviews and Dissemination databases (DARE, NHS EED and HTA) were searched for systematic reviews and cost effectiveness studies. The guideline developers also performed Internet search on websites of guidelines agencies and professional societies that published clinical practice guidelines and consensus evidence on the given condition. These include the search for the last five years of the existing clinical practice guidelines (2006-2010) from sources of overseas guidelines agencies and professional bodies, e.g., National Guideline Clearinghouse, National Health Service (NHS) National Library of Guidelines, the Guidelines International Network, Agency for Healthcare Research and Quality (AHRQ), Canadian Medical Association (CMA) Clinical Practice Guidelines, New Zealand Guidelines Group, Australia's Clinical Practice Guidelines Portal websites.

Inclusion/exclusion criteria were used specific to the clinical questions to be answered. In general, search filters were used to further focus the type of studies to randomised controlled trials and systematic reviews of randomised controlled trials. If there is a paucity of higher level evidence, lower level evidence may be considered.

The searches used keywords and MeSH headings or the controlled vocabulary specific to the databases for the condition specified.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence

Weighting According to a Rating Scheme (Scheme Given)

Rating Scheme for the Strength of the Evidence

Levels of Evidence

Level Type of Evidence
1++ High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias
1+ Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
1- Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias
2++ High quality systematic reviews of case control or cohort studies. High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
2+ Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
2- Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3 Non-analytic studies, e.g., case reports, case series
4 Expert opinion
Methods Used to Analyze the Evidence

Review of Published Meta-Analyses
Systematic Review

Description of the Methods Used to Analyze the Evidence

In assessing the evidence, different study designs were considered including randomised controlled trials, cohort studies, case control studies, uncontrolled clinical trials, and expert opinions. Best practice guidelines important in transfusion medicine were also included.

Methods Used to Formulate the Recommendations

Expert Consensus

Description of Methods Used to Formulate the Recommendations

This guideline was developed by a workgroup appointed by the Singapore Ministry of Health. Its members comprised experts in their individual fields from the personnel involved in the production and availability of the blood components to clinical haematologists and major end users represented by surgeons and obstetricians. In addition, as much of red cell transfusion is based on the principle of restoring physiological carriage of oxygen, an expert in anaesthesiology also formed part of the workgroup. The nursing and primary health care sectors were also represented.

The workgroup formulated this clinical practice guideline by reviewing published international guidelines and current evidence available in the research and clinical practice literature. Specific recommendations intrinsic to the local situation and context have also been considered (for example, refer to the Rhesus negative section in the "Major Recommendations" field).

Cost Analysis

See Section 8 in the original guideline document for a discussion of cost-effectiveness issues.

Method of Guideline Validation

Comparison with Guidelines from Other Groups

Description of Method of Guideline Validation

This clinical practice guideline provides current evidence-based clinical practice recommendations on blood transfusion. These have been compared and cross-referenced to numerous other international published guidelines on the same subject. The concordance of such guidelines aims to instil consistency and appropriateness of transfusion practice in Singapore as well as being comparable to international evidence-based practices.

Identifying Information and Availability

Bibliographic Source(s)

Singapore Ministry of Health. Clinical blood transfusion. Singapore: Singapore Ministry of Health; 2011 Feb. 90 p. [177 references]

Adaptation

Not applicable: The guideline was not adapted from another source.

Source(s) of Funding

Singapore Ministry of Health

Guideline Committee

Workgroup on Clinical Blood Transfusion

Composition of Group That Authored the Guideline

Workgroup Members: Dr Mickey Koh Boon Chai, Division Director, Patient Services, Blood Services Group, Health Sciences Authority, Director, Stem Cell Transplant Programme, Senior Lecturer & Consultant, St George's Hospital & Medical School, London, United Kingdom; Dr Diana Teo Lay Tin, Group Director & Senior Consultant, Blood Services Group, Health Sciences Authority; Dr Tan Hwee Huang, Division Director, Blood Supply Division, Blood Services Group, Health Science Authority; A/Prof Lee Lai Heng, Head & Senior Consultant, Dept of Haematology, Singapore General Hospital, Clinical Associate Professor, Yong Loo Lin School of Medicine, National University Singapore, Adjunct Associate Professor, Duke-NUS Graduate Medical School; Dr Lim Lay Cheng, Senior Consultant, Dept of Haematology, Singapore General Hospital; Dr Ting Wen Chang, Haematologist, Haem-Onc Clinic Pte Ltd; Dr Ng Heng Joo, Senior Consultant, Dept of Haematology, Singapore General Hospital; SNM Chong Lai Ling, Senior Nurse Manager, Ward 72, Singapore General Hospital;. Dr Tan Lip Kun, Senior Consultant, Dept of Haemaology Oncology, National University Health System; A/Prof P. Kuperan, Head & Senior Consultant, Dept of Haematology, Tan Tock Seng Hospital; Prof Alex Sia, Head & Senior Consultant, Dept of Women's Anesthesia, KK Women's & Children's Hospital; Dr Yong TZE Tein, Senior Consultant, Obstetrics & Gynaecology, Singapore General Hospital; A/Prof Tay Kiang Hiong, Head & Senior Consultant, Dept of Diagnostic Radiology, Singapore General Hospital; Dr Philip Iau, Senior Consultant, Dept of Surgery, National University Hospital; A/Prof Goh Lee Gan, Associate Professor, Head, Division of Family Medicine, University Medicine Center, President, College of Family Physicians, Singapore

Financial Disclosures/Conflicts of Interest

Not stated

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available from the Singapore Ministry of Health Web site.

Print copies: Available from the Singapore Ministry of Health, College of Medicine Building, Mezzanine Floor 16 College Rd, Singapore 169854.

Availability of Companion Documents

The following is available:

  • Clinical blood transfusion. Executive summary of recommendations. Singapore: Singapore Ministry of Health; 2011 Jan. 22 p. Electronic copies: Available in Portable Document Format (PDF) from the Singapore Ministry of Health Web site.

Self-assessment questions and clinical quality improvement parameters are also available in the original guideline document.

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on March 21, 2013.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions. Please contact the Ministry of Health, Singapore by e-mail at MOH_INFO@MOH.GOV.SG.

Scope

Disease/Condition(s)

Diseases or conditions requiring clinical blood or blood component transfusion

Guideline Category

Evaluation
Management
Prevention
Risk Assessment
Treatment

Clinical Specialty

Anesthesiology
Emergency Medicine
Family Practice
Hematology
Infectious Diseases
Internal Medicine
Obstetrics and Gynecology
Surgery
Thoracic Surgery

Intended Users

Advanced Practice Nurses
Allied Health Personnel
Hospitals
Nurses
Physician Assistants
Physicians
Public Health Departments

Guideline Objective(s)
  • To guide the user on the international evidence-based practices for blood transfusion, thereby allowing a better understanding on the science in ensuring appropriate transfusion practices in Singapore
  • To assist medical practitioners in the appropriate and rational use of blood and blood components
  • To provide current evidence-based clinical practice recommendations on blood transfusion
  • To increase awareness amongst clinicians and healthcare workers about the benefits and risks of blood component therapy
Target Population

Patients in Singapore who may require clinical blood transfusion, including red blood cells transfusion, platelet transfusion, fresh frozen plasma transfusion, and cryoprecipitate transfusion

Note: Infants, children, and patients in special clinical settings (e.g., liver transplantation, thalassemias) are beyond the scope of this guideline. Principles guiding the decision to administer blood products for children above 4 months of age are largely similar to adults, bearing in mind that younger children below 2 years of age may have lower normal haemoglobin (Hb) values.

Interventions and Practices Considered
  1. Red blood cell transfusion
    • Use of packed red cells for allogeneic transfusion
    • Management of transfusion needs during acute blood loss including trauma and gastrointestinal bleeding
    • Perioperative transfusion
    • Red cell transfusion in chronic anaemia
    • Red cell transfusion in the critical care setting
    • Transfusion of leucodepleted or irradiated blood products
    • Pre-transfusion compatibility testing
    • Selection of ABO Rhesus (Rh)(D) red cells
    • Management of Rh(D) negative patients
    • Blood transfusion in major blood loss
  2. Platelet transfusion
    • Use of ABO compatible platelets
    • Platelet transfusion for haemostasis and platelet dysfunction
    • Prophylactic platelet transfusion to prevent bleeding
  3. Fresh frozen plasma transfusion: dosage and compatibility
  4. Cryoprecipitate transfusion: dosage and compatibility
  5. Safety issues related to transfusion
    • Ensuring that donors are safe
    • Testing blood for evidence of infections
  6. Management of transfusion-related adverse reactions
Major Outcomes Considered
  • Effectiveness of clinical blood transfusion strategies
  • Safety
  • Rate of adverse effects
  • Effectiveness of measures to prevent adverse effects
  • Cost-effectiveness

Recommendations

Major Recommendations

Definitions of the levels of evidence (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) and the grades of recommendations (A, B, C, D, and Good Practice Point [GPP]) are provided at the end of the "Major Recommendations" field.

Red Blood Cells Transfusion

Principles

D - Patients should not be transfused so as to achieve a 'normal' haemoglobin (Hb) concentration. (Grade D, Level 4)

D - In general, packed red cells should be provided for allogeneic transfusion. (Grade D, Level 4)

Trigger for Red Cell Transfusion

A - When haemoglobin >10 g/dL – there is usually very little indication for red cell transfusion. (Grade A, Level 1+)

C - When haemoglobin <7 g/dL – red cells transfusion may be beneficial particularly in symptomatic patients or ongoing blood loss is expected. (Grade C, Level 2+)

C - When haemoglobin is between 7 and 10 g/dL – transfusion should be guided by clinical signs and symptoms, coexisting medical or surgical problems (e.g., >65 years, cardiovascular disease, respiratory disease, ongoing blood loss, coagulopathy). In asymptomatic patients with chronic anaemia and where other specific treatment is available, the need for blood transfusion should be carefully weighed. (Grade C, Level 2+)

GPP - The eventual decision for transfusion should be based on clinical judgement. Avoid transfusion if the indication is unclear or there is minimal or weak evidence for benefit. (GPP)

Management of Transfusion Needs during Acute Blood Loss (Including Trauma and Gastrointestinal Bleeding)

D - Red cells should not be used as a volume expander and initial volume replacement should be with colloids or crystalloids to ensure that the patient is euvolemic. (Grade D, Level 4)

D - In assessing the need for transfusion:

  • For estimated volume loss (EVL) of <15% of blood volume (<750 ml in a 70 kg adult), fluid or blood replacement is usually unnecessary unless blood loss is superimposed on pre-existing anaemia or the patient is compromised by severe reduction in cardio-respiratory reserve.
  • EVL between 15% and 30% (750-1500 ml in a 70 kg adult), replacement by crystalloids/colloids is needed while red cell transfusion is generally unnecessary unless clinical assessment reveals reduced cardio-respiratory reserve or continuing blood loss.
  • EVL of 30% to 40% (1500-2000 ml in a 70 kg adult), red cell transfusion will probably be needed in addition to rapid volume replacement with crystalloids/colloids.
  • EVL >40% (>2000 ml in a 70 kg adult), both fluid and red cell replacement are needed.

(Grade D, Level 4)

The treatment of ongoing bleeding is not blood transfusions but haemostasis by the most expedient means available.

GPP - Source of bleeding should be identified early and appropriate action should be taken immediately, including endoscopic or surgical control of bleeding. (GPP)

Red Cell Transfusion in the Peri-operative Setting

Preoperative Evaluation

D - Where possible, preoperative evaluation should be done well in advance to correct or plan for the management of risk factors associated with transfusions. (Grade D, Level 4)

GPP - Preoperative evaluation should include:

  • Review of previous medical records
  • Interview of the patient or family
  • Physical examination of the patient
  • Review of laboratory test results including haemoglobin and coagulation profiles

(GPP)

Preoperative Preparation

D - If a patient admitted for elective surgery or an invasive procedure is found to have thrombocytopenia or an abnormal coagulation screen, the procedure should be postponed until the cause of the abnormality is identified. (Grade D, Level 4)

Discontinuation or Modification of Antiplatelet and Anticoagulation Therapies

D - Aspirin and clopidogrel should be discontinued at least 7 days prior to planned surgery unless there is a strong contraindication for stopping it. (Grade D, Level 4)

D - Vitamin K or another warfarin antagonist should be used for reversal of warfarin to potentially avoid transfusion of fresh frozen plasma. (Grade D, Level 4)

D - The risk of thrombosis versus the risk of increased bleeding should be considered when altering anticoagulation status. (Grade D, Level 4)

Administration of Prophylactic Pharmacologic Agents

D - Administering pharmacologic agents prophylactically should be considered to promote coagulation and minimise blood loss (e.g., tranexamic acid). (Grade D, Level 4)

D - Specific attention should be paid to the detection, investigation and appropriate treatment of anaemia in advance of major elective surgery. (Grade D, Level 4)

D - Correction of haemoglobin before surgery with measures other than red cell transfusion (e.g., iron replacement or erythropoietin) should be considered where appropriate. (Grade D, Level 4)

D - Erythropoietin may be administered in anemic patients to reduce the need for allogeneic blood in selected patient populations (e.g., chronic renal insufficiency, anaemia of chronic disease, refusal of transfusion). (Grade D, Level 4)

D - Where suitable and indicated, autologous blood donation should be considered. (Grade D, Level 4)

D - Liaise with blood bank to ensure that blood and blood components are available for patients when significant blood loss or transfusion is expected. (Grade D, Level 4)

Red Cell Transfusion in Chronic Anaemia

D - The cause of anaemia should be established before red cell transfusion. (Grade D, Level 4)

D - Red cell transfusion should be reserved for patients with significant signs and symptoms requiring medical intervention. Even then, the patient should be transfused to a level just above that needed to ameliorate the symptoms of anaemia. (Grade D, Level 4)

D - Where appropriate, specific pharmacological agents (iron, vitamin B12, folate) should be used to correct the anaemia in order to reduce exposure to allogeneic transfusion. (Grade D, Level 4)

A - Erythropoietin should be considered when it is indicated, e.g., chronic renal failure, anaemia of chronic illness, haematologic malignancies. (Grade A, Level 1++)

D - Congenital haemoglobinopathies, such as thalassemias and sickle cell disease, are treated according to specific disease-related protocols. (Grade D, Level 4)

Red Cell Transfusion in Critical Care Setting

A - Maintaining haemoglobin level between 7 and 9 g/dL is recommended in critically ill patients. (Grade A, Level 1++)

Transfusion of Leucodepleted or Irradiated Blood Products

Leucocyte Reduction of Red Cells

B - Leucodepleted red cells transfusion is recommended in the following situations:

  • Patients who require multiple transfusions to reduce rate of human leucocyte antigen (HLA) alloimmunisation
  • Non-hepatic solid transplant organ candidates to reduce rate of HLA alloimmunisation
  • Patients experiencing two or more non-haemolytic febrile transfusion reactions
  • As a means of reducing cytomegalovirus (CMV) transmission and CMV disease in immunocompromised patients

(Grade B, Level 2++)

Irradiation of Blood Components (Red Cells, Platelets)

B - Irradiated blood components are required in the following situations:

  • Blood components from 1st and 2nd degree relatives
  • HLA-compatible blood components
  • Intra-uterine transfusions
  • Neonatal exchange transfusions subsequent to intra-uterine transfusions
  • Congenital T-cell immunodeficiency defects
  • Autologous or allogeneic stem cell transplant patients
  • Patients treated with fludarabine or related purine analogue
  • All granulocyte products

(Grade B, Level 2++)

B - Irradiated blood components are recommended in the following situations provided that it does not cause a clinically significant delay:

  • Neonatal exchange transfusions (no prior intra-uterine transfusion)
  • Hodgkin's disease patients

(Grade B, Level 2++)

Pre-transfusion Compatibility Testing

D - Blood group typing and antibody screening is recommended for patients undergoing major surgery and also during the antenatal workup. This is to prevent delays in obtaining blood should transfusion become necessary. (Grade D, Level 4)

Selection of ABO Rh(D) Red Cells

GPP - Due to stock availability, in clinical practice ABO-compatible red cell rather than ABO-identical units may be transfused. (GPP)

D - Non-identical but compatible packed red cells can be used for transfusion, e.g., group O donor packed cells to group A, B, or AB recipient (refer to table below). (Grade D, Level 4)

Patient ABO Group Compatible Donor Red Cells
O Only group O whole blood and red cells.
A Group A whole blood and red cells.
Group O red cells if group A blood not available.
B Group B whole blood and red cells.
Group O red cells if group B blood not available.
AB Group AB whole blood and red cells. Group A or B red cells if group AB blood not available.
Group O red cells as a last alternative.

GPP - In the rare event that whole blood is to be transfused, it must be ABO group identical with the recipient. (GPP)

GPP - In the rare event or emergency setting, when the patient's ABO group cannot be determined, group O red cells must be selected. (GPP)

GPP - All donor and recipient blood must be ABO and Rhesus D typed. (GPP)

Management of Rh(D) Negative Patients

D - D negative whole blood and red cells must be given to all D negative patients with anti-D present or who have previously been demonstrated to have anti-D. (Grade D, Level 3)

D - When two or more units of D positive blood have been transfused, a red cell exchange transfusion should be considered to reduce the load of D positive red cells in circulation. (Grade D, Level 3)

D - D negative whole blood and red cells should be considered in D negative patients who will receive repeated transfusions, or are likely to become transfusion-dependent, e.g., patients with haemoglobinopathies, aplastic anaemia, myelodysplasia. (Grade D, Level 3)

GPP - D negative patients who have been or will be transfused with D positive blood and blood components must be informed and counseled regarding the implications of possible alloimmunisation. (GPP)

D - Where there will be subsequent interventions such as anti-D immunoglobulin and red cell exchange, the patient must also be informed of the implications of such treatment. (Grade D, Level 4)

C - D negative whole blood and red cells must be given to D negative females with child-bearing potential. Where there has been inadvertent transfusion of D positive blood to D negative females with child-bearing potential, anti-D immunoglobulin should be given at the appropriate dose. (Grade C, Level 2+)

C - Where D positive platelet concentrates are transfused to a D negative patient of child-bearing potential, it is recommended that anti-D immunoglobulin should be given as prophylaxis against possible D alloimmunisation. A dose of 250 iu anti-D immunoglobulin will be sufficient to cover up to five adult therapeutic doses of D positive platelets within a 6-week period. (Grade C, Level 2+)

D -Intramuscular administration of Anti-D should be avoided in thrombocytopenic patients. (Grade D, Level 4)

D - In females with no child-bearing potential and adult males in whom no anti-D is present, D positive whole blood and red cells may be used in large volume replacement or when D negative blood is in short supply. (Grade D, Level 3)

C - D negative platelet concentrates should be given where available to D negative patients. Where this is not available or would cause unacceptable delay, it may be necessary to transfuse D positive platelet concentrates. (Grade C, Level 2+)

D - It is not necessary to give D negative plasma products to D negative patients, provided that such products are free of red cells. (Grade D, Level 4)

Blood Transfusion in Major Blood Loss

D - Where there is a significant degree of blood loss, measures should be taken towards:

  • Identifying the source of haemorrhage and taking the necessary actions, including prompt surgical intervention
  • Preserving haemostasis
  • Maintaining an adequate Hb level

(Grade D, Level 4)

D - Normothermia should be restored and coagulopathy should be corrected with judicious use of blood component therapy. (Grade D, Level 4)

D - A full blood count (FBC) and coagulation profile (prothrombin time [PT], activated partial thromboplastin time [APTT], fibrinogen) should be done and repeated to guide therapy and blood product replacement. (Grade D, Level 4)

B - One should aim to maintain:

  • PT/APTT: Target value <1.5x reference value
  • Fibrinogen: target value >1.0g/L
  • Platelets: target value >50 x 109/L
  • Hb: target value >7g/dL in otherwise fit individuals

(Grade B, Level 2++)

GPP - Platelet transfusions as well as replacement of clotting factors and fibrinogen with fresh frozen plasma (FFP) and cryoprecipitate should be considered before the following values:

  • PT/APTT: 1.5x reference value
  • Fibrinogen: 1.0 g/L
  • Platelets: 50 x 109/L
  • Hb: 7g/dL in otherwise fit individuals

(GPP)

D - Recombinant activated factor VII (rFVIIa) transfusion under the guidance of transfusion specialist or haematologist may be considered in those who fail conventional therapy. (Grade D, Level 3)

D - The principles of management of massive haemorrhage should be incorporated into an institutional algorithm that denotes a logical, sequential approach to resuscitation. (Grade D, Level 4)

See Table 2 in the original guideline document for a summary of key recommendations on management of massive blood loss.

Platelet Transfusion

General Considerations

GPP - Platelet transfusions should be given as close to the procedure as possible for the best haemostatic effect. (GPP)

D - Platelet count levels should not be used as the only indicator for transfusion and the bleeding time is not a good indicator for risk of bleeding. (Grade D, Level 4)

GPP - The cause of thrombocytopenia should always be established before considering platelet transfusion unless there is life threatening bleeding. (GPP)

D - If platelet transfusion is administered in certain conditions such as heparin-induced thrombocytopenia, thrombotic thrombocytopenic purpura, or haemolytic uraemic syndrome, there can be possible exacerbation of the clinical situation. In these conditions, platelet transfusion should only be given after the risks associated with transfusion have been considered and only when the benefits outweigh the risks. (Grade D, Level 4)

Platelet Compatibility

B - As ABO antigens are present on platelets, it is preferable to transfuse with ABO compatible platelets. (Grade B, Level 2++)

GPP - ABO incompatible platelets may be administered only if ABO compatible platelets are not available and there is an urgent clinical need. In this situation, it is preferable to use group A platelets for group B patients, and vice versa. Group O platelets are not advisable in other blood groups unless in an emergency. (GPP)

D - For paediatric recipients (of less than or equal to 45 kg body weight), ABO specific platelets should be ensured whenever possible. Cross matching of platelets is not necessary. (Grade D, Level 4)

C - The concomitant administration of at least 250 IU of anti-D is recommended in case of transfusion of Rh(D) positive platelets to a Rh(D) negative patient in order to prevent Rh(D) alloimmunisation. (Grade C, Level 2+)

B - Apheresed platelets are recommended to prevent HLA alloimmunisation and platelet refractoriness in patients who require prolonged platelet support. (Grade B, Level 1+)

Indications for Therapeutic Platelet Transfusion

For Haemostasis

B - For critically ill patients with thrombocytopenia who are bleeding and where thrombocytopenia is considered as a major contributing factor, platelet transfusion is indicated regardless of the platelet count. (Grade B, Level 2++)

C - Platelet transfusion is indicated where platelet count is less than 50 x 109/L. In such patients, a higher platelet threshold should be considered if there is clinical evidence of microvascular haemorrhage. (Grade C, Level 2+)

D - Platelet transfusion is indicated in patients undergoing cardiopulmonary bypass surgery where bleeding is associated with acquired platelet dysfunction, secondary to the bypass surgery or the presence of anti-platelet agents such as aspirin, ticlopidine, or clopidogrel. (Grade D, Level 4)

For Patients with Platelet Dysfunction

GPP - Platelet transfusion should be given in the event of acute life threatening bleeds or just before major surgery. (GPP)

C - In renal failure and uraemia, the following recommendations should be implemented to avoid platelet transfusion if possible:

  • Correct the hematocrit to >0.30.
  • Consider the use of desmopressin.
  • Consider the use of dialysis, which also have hemostatic benefits in this situation.
  • Only use platelet transfusions where the above methods are inappropriate or ineffective.

(Grade C, Level 2+)

D - In drug induced platelet dysfunction such as use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or antiplatelet drugs, the following recommendations should be followed.

  • Discontinue drugs with anti-platelet activity where possible.
  • Consider platelet transfusion in acute bleeding situation.

(Grade D, Level 4)

Prophylactic Platelet Transfusion (to Prevent Bleeding)

Prophylactic platelet transfusion is recommended in the following conditions:

  • B - In patients with impaired bone marrow function when platelet count is less than 10 x 109/L and there are no other risk factors. (Grade B, Level 1+)
  • C - In patients with impaired bone marrow function when platelet count is less than 20 x 109/L and there are concomitant risk factors (e.g., sepsis, rapid fall of platelet count, or coagulation abnormalities). (Grade C, Level 2+)

D - More liberal approach to prophylactic platelet transfusion should be practised. A transfusion trigger at platelet count of 30 x 109/L is acceptable. Consultation with the haematologist or transfusion specialist is advised in individual cases where bleeding is thought to be a major risk factor. (Grade D, Level 4)

C - For patients undergoing surgery or invasive procedures (e.g., epidural, lumbar puncture, renal biopsy, liver biopsy, central line insertion) when the platelet count is less than 50 x 109/L and there are no other associated coagulopathies. (Grade C, Level 2+)

D - Neurosurgical and ophthalmic procedures may benefit from a higher prophylactic platelet transfusion threshold (100 x 109/L). (Grade D, Level 4)

Contraindications

B - Platelet transfusion is contraindicated if the thrombocytopenia is due to platelet activation. (Grade B, Level 2++)

D - Platelet transfusion is usually not indicated when thrombocytopenia is related to immune mediated platelet destruction, such as autoimmune thrombocytopenia, drug-induced thrombocytopenia and post transfusion purpura. Platelet transfusions are only indicated when there is significant and/or potentially life threatening bleeding in such conditions. (Grade D, Level 4)

GPP - Expert advice should be obtained before platelet transfusion is given in any of the contraindicated conditions. (GPP)

FFP Transfusion

General Considerations

D - Routine and timely tests for coagulopathy such as the PT or international normalised ratio (INR), APTT, platelet counts, and fibrinogen level as well as haemoglobin/haematocrit should be obtained to guide decisions on plasma transfusion. These results should be integrated with a thorough assessment of the patient's clinical condition and the presence or risk of bleeding. (Grade D, Level 4)

B - Abnormal PT/INR or APTT results should not be the sole reason for transfusing plasma as they do not correlate well with bleeding risk and only a small proportion of patients with abnormal results will experience bleeding manifestations. (Grade B, Level 2++)

GPP - All attempts must be made to identify the underlying cause of a coagulopathy and manage this appropriately together with efforts to correct such abnormality with plasma transfusion if necessary. (GPP)

GPP - A comprehensive personal and family history of bleeding is the best pre-operative screen for bleeding in surgical patients. In the event that preoperative PT and partial thromboplastin time (PTT) tests are performed and found to be abnormal, its significance should be carefully considered and if necessary, further discussed with a haematologist. (GPP)

Indications for FFP

FFP is recommended for the following situations:

B - Massive blood transfusion, especially with evidence of microvascular bleeding and associated with significant (>1.5x midpoint of normal range) abnormalities in PT and APTT. When PT and APTT cannot be obtained in a timely fashion, it is reasonable to give FFP after replacement of one blood volume while waiting for results. (Grade B, Level 2++)

B - If immediate reversal of warfarin effect is required. Intravenous vitamin K should be concurrently given for sustained reversal of warfarin effect. (Grade B, Level 2++)

C - Acute disseminated intravascular coagulation (DIC) associated with microvascular bleeding and abnormal coagulation profile. (Grade C, Level 2+)

D - Bleeding due to coagulopathy associated with chronic liver diseases. (Grade D, Level 4)

A - Plasma exchange for thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS). Cryosupernatant may also be considered as an alternative. (Grade A, Level 1+)

C - Bleeding associated with clotting factors deficiency if no alternative processed products or specific factor concentrates are available. (Grade C, Level 2+)

Fresh frozen plasma is not justified in the following situations:

D - As a volume expander in hypovolaemia (Grade D, Level 4)

D - As replacement for albumin or immunoglobulin. Specific albumin and immunoglobulin preparations are available (Grade D, Level 4)

D - Replacement for any clotting factors unless processed and virally inactivated products are unavailable (Grade D, Level 4)

B - Reversal of warfarin effect in the absence of bleeding. Oral or intravenous vitamin K should be the therapy of choice in this instance (Grade B, Level 2++)

C - Plasma exchange procedures other than for TTP and HUS (Grade C, Level 2++)

D - Treatment of immunodeficiency states (Grade D, Level 4)

D - Nutritional support (Grade D, Level 4)

Dose and Compatibility

D - The recommended dose for FFP is 10-15 ml per kg body weight. It is always useful to have FFP administration guided by coagulation screens. If necessary, these should be repeated and more FFP given, depending on the clinical situation. (Grade D, Level 4)

B - Although small amounts of red cell stroma may be present in FFP, it is less immunogenic than intact red cells and sensitisation following Rh(D) positive FFP to Rh(D) negative patients is unlikely. FFP of any Rh type may be given regardless of Rh status of the patient. (Grade B, Level 2++)

Cryoprecipitate Transfusion

Indications for Cryoprecipitate

C - Cryoprecipitate is rich in factor VIII, von Willebrand factor, factor XIII, and fibrinogen. Use of cryoprecipitate is considered appropriate when there is bleeding associated with hypofibrinogenaemia (fibrinogen level <1.0 gm/L) in the following conditions:

  • Massive blood transfusion
  • Disseminated intravascular coagulation
  • Obstetric emergencies
  • Open heart surgery
  • Congenital hypofibrinogenaemia or documented dysfibrinogenaemia
  • Advanced liver disease associated with low fibrinogen
  • Bleeding associated with thrombolytic therapy

(Grade C, Level 2+)

D - Cryoprecipitate may be used during bleeding in congenital factor XIII deficiency when factor XIII concentrate is not available. (Grade D, Level 4)

Cryoprecipitate is not recommended:

D - For clotting factor deficiency or von Willebrand disease unless processed, virally inactivated products are not readily available (Grade D, Level 4)

D - For preparation of fibrin glue with commercial sources of thrombin. Factor V inhibitors have been reported following exposure to such preparations. Commercially produced fibrin sealants containing human thrombin is preferred. (Grade D, Level 4)

Dose and Compatibility

C - In the management of hypofibrinogenaemia, 1 unit/5 kg body weight - equivalent to 10 units for an average size adult - should be administered. Further therapy should be guided by fibrinogen levels. (Grade C, Level 2+)

Safety Issues Related to Blood and Blood Component Transfusion

Blood Safety

GPP - Before making a donation, the blood donor should be made aware that he or she needs to ensure that the donated blood is safe to be used. (GPP)

GPP - Every unit of donated blood or apheresis component needs to be tested for evidence of the following infections -- hepatitis B, hepatitis C, Treponema palladium, and human immunodeficiency virus (HIV). (GPP)

Ensuring Safe Blood

C - Blood donations should be collected from the safest possible donors, namely regular voluntary donors. (Grade C, Level 2+)

C - Replacement or directed donations should be avoided as far as possible. (Grade C, Level 2+)

D - Irradiated blood components are indicated in bone marrow/stem cell auto- or allo-grafting, and transfusions from relatives or HLA-selected platelet donors. (Grade D, Level 3)

Adverse Reactions to Transfusion

GPP - It is advisable that a policy be in place in each hospital for the management and reporting of adverse events following transfusion of blood and blood components. This should be regularly reviewed by the hospital transfusion committee with an aim to improving transfusion practice. (GPP)

GPP - Institutional policies may vary regarding the initial steps in managing an adverse reaction but the following key elements should be followed:

  1. The transfusion of on-going unit should be discontinued immediately.
  2. Immediately do a clerical check at beside to detect any misidentification and major ABO mismatch.
  3. Monitor patient's vital signs.
  4. The intravenous access should be kept open for treatment if necessary.
  5. The adverse reaction should be reported to the blood bank immediately.
  6. Coordinate with the blood bank regarding the collecting of samples for transfusion reaction investigation workup.
  7. Continue to observe and monitor the patient.
  8. Do not initiate another transfusion without blood bank consultation.
  9. Document all events on appropriate forms and in the patient's chart.

(GPP)

D - Categories and Management of Acute and Delayed Adverse Reactions to Transfusion

Type Incidence/Aetiology Diagnostic Criteria/ Presentation Diagnostic Testing Management
Acute – within 24 hours of transfusion
Allergic Reaction (Mild)/Urticarial
  • Interaction of an allergen with preformed antibodies
  • Morbilliform rash with or without pruritus
  • Urticaria (hives)
  • Flushing
  • Localized angioedema
  • N/A
  • Diphenhydramine
  • Transfusion can be restarted if the symptoms and signs have subsided provided the incomplete unit can be completed within 4 hours of issuance
  • Monitor closely for other signs and symptoms
Anaphylactoid Anaphylaxis (Severe)
  • Antibody to donor plasma protein (immunoglobulin A [IgA], haptoglobin, C4)
  • Mucocutaneous symptoms
  • Hypotension
  • Respiratory signs and symptoms may be laryngeal (tightness in throat, dysphagia, dysphonia, hoarseness, stridor) or pulmonary (dyspnea, cough, wheezing, bronchospasm, hypoxemia)
  • Rule out haemolysis
  • Maintain airway; provide oxygen and ventilatory support
  • Treat hypotension with fluids, dopamine if unresponsive
  • Initiate transfusion reaction workup
  • Do not initiate another transfusion without blood bank consultation
  • Premedicate with diphenhydramine and or steroids
  • Use of washed red cells (and platelets) in severe anaphylaxis
Haemolytic Reaction
  • Incompatible blood transfusion results in antigen/antibody response with activation of complement and subsequent intravascular haemolysis
  • Chills/rigors
  • Fever
  • Back/flank pain
  • Hypotension
  • Haemoglobinuria
  • Oliguria/anuria
  • Disseminated intravascular coagulation
  • Pain or oozing at intravenous (IV) site
  • Clerical check
  • Check for haemolysis
    • Direct Coombs test
    • Visual inspection
    • Repeat patient ABO, pre and post sample
    • Further tests to detect haemolysis (lactate dehydrogenase [LDH], bilirubin, etc.)
  • Maintain airway; provide oxygen and ventilatory support
  • Hydration to maintain urinary output
  • Diuretics to promote renal perfusion
  • Cardiovascular support with pressor agents if needed
  • Treatment of disseminated intravascular coagulation
  • Initiate transfusion reaction workup; inform blood bank
Febrile Non Haemolytic Transfusion Reaction
  • Cytokines
  • Antibody to donor white cells
  • Fever (≥38C or a change of ≥1C from pre transfusion value)
  • Chills/rigors
  • Headache
  • Vomiting
  • Rule out haemolysis
  • Rule out bacterial contamination
  • Initiate transfusion reaction workup; inform blood bank
  • Leucoreduced components
  • Premedication with antipyretics
Transfusion Associated Acute Lung Injury (TRALI)
  • Anti-human leukocyte antigen (HLA) and anti-human neutrophil antigen (HNA) antibodies in donor (occasionally in recipients)
  • Acute respiratory distress within six hours of transfusion
  • Bilateral pulmonary infiltrates on chest x-ray
  • Hypoxemia (02 sat ≤90% on room air or PaO2 ≤300 mm Hg)
  • No evidence of circulatory overload
  • Hypotension (some cases hypertension)
  • Fever
  • Transient leucopenia
  • Rule out haemolysis
  • Rule out cardiogenic oedema
  • HLA antibody screen
  • Chest x-ray
  • Maintain airway; provide oxygen and ventilatory support
  • Treat hypotension
  • Supportive care
  • Initiate transfusion reaction workup; inform blood bank
Transfusion Associated Circulatory Overload (TACO)
  • Volume overload
  • Acute respiratory distress (dyspnea, orthopnea, cough)
  • Tachycardia
  • Hypertension
  • Evidence of left sided heart failure
  • Rule out TRALI
  • Chest x-ray
  • Maintain airway; provide oxygen and ventilatory support
  • Diuretics
  • Initiate transfusion reaction workup; inform blood bank
Transfusion Associated Sepsis (Bacterial Contamination)
  • Sepsis is the result of transfusion of contaminated blood components
  • The bacteria usually originate from the blood donor either from venipuncture (e.g., Staphylococcus, Streptococcus) or unsuspected bacteremia (e.g., Yersinia) but may also result from donor unit processing
  • Fever, often ≥2C rise from baseline
  • Chills/rigors
  • Hypotension
  • Shock
  • Renal failure
  • Unexplained bleeding from mucocutaneous or infusion sites
  • Rule out haemolysis
  • Gram stain
  • Component culture
  • Blood culture on patient
  • Maintain airway; provide oxygen and ventilatory support
  • Hydration to maintain urinary output
  • Diuretics to promote renal perfusion
  • Broad spectrum antibiotics
  • Cardiovascular support with pressor agents if needed
  • Treatment of disseminated intravascular coagulation
  • Initiate transfusion reaction workup; inform blood bank
Delayed – more than 24 hours from transfusion
Delayed Haemolytic Transfusion Reaction
  • Anamnestic immune response to red cell antigens
  • Decrease in haemoglobin
  • Fever
  • Jaundice (mild)
  • Patient may be asymptomatic
  • Antibody screen and identification
  • Direct Coombs test
  • Elution
  • Test for haemolysis
  • Initiate delayed transfusion reaction workup; inform blood bank
  • Transfuse anti-human globulin (AHG) crossmatch compatible blood; antigen negative if indicated
Graft versus Host Disease (GVHD)
  • Donor lymphocytes engraft in recipient and mount attack on host tissues
  • Fever
  • Gastrointestinal symptoms
  • Rash
  • Hepatitis
  • Pancytopenia
  • Skin biopsy
  • HLA typing
  • Molecular analysis for chimerism
  • Immunosuppressive agents
  • Irradiation of blood components for patients at risk

(Grade D, Level 3)

Definitions:

Levels of Evidence

Level Type of Evidence
1++ High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias
1+ Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
1- Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias
2++ High quality systematic reviews of case control or cohort studies. High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
2+ Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
2- Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3 Non-analytic studies, e.g., case reports, case series
4 Expert opinion

Grades of Recommendation

Grade Recommendation
A At least one meta-analysis, systematic review of randomised controlled trials (RCTs), or RCT rated as 1++ and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
B A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
GPP
(good practice points)
Recommended best practice based on the clinical experience of the guideline development group
Clinical Algorithm(s)

None provided

Contraindications

Contraindications
  • Platelet transfusion is contraindicated if the thrombocytopenia is due to platelet activation.
  • Platelet transfusion is usually not indicated when thrombocytopenia is related to immune mediated platelet destruction, such as autoimmune thrombocytopenia, drug-induced thrombocytopenia, and post transfusion purpura. Platelet transfusions are only indicated when there is significant and/or potentially life threatening bleeding in such conditions.
  • Expert advice should be obtained before platelet transfusion is given in any of the contraindicated conditions.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need

Getting Better
Staying Healthy

IOM Domain

Effectiveness
Patient-centeredness
Safety
Timeliness

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