Principles of appropriate use of blood and blood products, and patient blood management

Ideally, a hospital blood bank, sometimes also called a hospital transfusion service, manages the inventory and issues blood and blood components to hospital wards. The blood and blood components are usually supplied by the blood establishment, which is responsible for the collection of blood and ensures that the collected blood is safe and tested for infectious markers and for key quality indicators. However, in some situations, the hospital blood bank can also have the function of collecting, testing, qualifying and preserving blood.  In this case, this is known as a hospital-based blood establishment [1].

An adequate safe blood supply can be defined by the following criteria:

• The number of blood products in the blood bank inventory covers the daily needs (clinical demand) in the hospital, including the capacity to respond to emergencies, and are of the appropriate ABO and Rh groups;
• Blood components are safe regarding infectious risks, in particular, human immunodeficiency virus (HIV)-1/HIV-2, hepatitis B virus (HBV), syphilis, and hepatitis C virus (HCV), human T lymphotropic virus (HTLV; in exposed settings), malaria, and Chagas disease (in exposed settings);
• Blood components are correctly preserved and stored in the blood bank, at appropriate temperatures to minimize bacterial contamination and degradation of the contents.

A transfusion committee is a key clinical governance element for oversight and delivery of safe transfusion within the hospital; its activities should align with national or regional transfusion committees where these exist. Hospital transfusion committees are multidisciplinary groups that have the overarching responsibility to maintain safe hospital transfusion practice and for the implementation of PBM initiatives. 

In particular, the role and activities of the committee are:

• Developing systems for the implementation of national guidelines within the hospital;
• Developing hospital standard operating procedures for all steps in the transfusion process;
• Drafting transfusion protocols and decision trees where needed;
• Oversight of training for all hospital staff involved in transfusion;
• Oversight of education and informed consent processes for patients who may require transfusion;
• Liaison with the blood transfusion service (blood establishment) to ensure the availability of required blood and blood products at all times;
• Developing a hospital blood ordering schedule;
• Liaison with relevant departments to ensure a reliable supply of intravenous replacement fluids and other alternatives to transfusion at all times;
• Oversight of the hospital blood bank’s activities to ensure that it complies with national and local safety and quality standards;
• Monitoring the usage of blood and blood products within the hospital;
• Oversight of PBM activities;
• Monitoring and investigation of severe adverse effects or errors associated with transfusion, taking any corrective and preventive action required, and reporting through the haemovigilance system to the national committee on the clinical use of blood.

A World Health Organization (WHO) Aide-Memoire for National Health Programmes on the Clinical Use of Blood (2004) is available at: https://apps.who.int/iris/handle/10665/330085 

Haemovigilance (sometimes referred to as biovigilance) systems aim both to monitor, report, investigate and analyse adverse events and reactions related to donation, processing and transfusion of blood, and to develop and implement recommendations to prevent their occurrence or recurrence.

The ultimate goal of a haemovigilance system is continuous quality improvement of the transfusion chain through corrective and preventive actions to improve patient safety and outcomes, enhance donor safety and reduce wastage.

To allow the maximum benefit and to minimize the risks associated with blood transfusion, five key factors are:

1. The safety of the collected blood and components;
2. Safe processing, storage and distribution of blood components;
3. Evaluating whether the recipient will benefit from the transfusion;
4. The surveillance of the transfusion process or the so-called transfusion chain and biovigilance programmes;
5. Implementing all elements of quality systems, such as good practice guidelines, in the process from the selection of blood donors through to the administration of the product to the patient [6].

A WHO summary guidance document on blood safety can be downloaded for more information from:  https://apps.who.int/iris/handle/10665/66698

The quality and safety of all blood and blood components must be assured throughout the process from the selection of blood donors through to the administration of the product to the patient. This requires a planned programme of regular blood donations by voluntary non-remunerated donors, the screening and processing of donated blood by trained staff working to national standards and the appropriate use of blood. It also requires:

• National standards and specifications for blood products and a system of good manufacturing practice to ensure these standards are maintained at all times;
• The development and correct use of standard operating procedures;
• The training of all blood transfusion service staff and clinicians to develop and maintain their knowledge and skills;
• The monitoring and evaluation (audit) to check that the correct procedures are being used correctly by all staff at all times;
• An effective system of independent inspection and accreditation of the facilities that collect, process and distribute blood products.

Whatever the local system for the collection, screening and processing of blood, clinicians must be familiar with it and understand any limitations that it may impose on the safety or availability of blood.

A WHO Aide-Memoire document on safe blood components and on quality systems for blood safety can be found at:

https://apps.who.int/iris/handle/10665/69152 and https://apps.who.int/iris/handle/10665/67384.

Recently, the WHO provided an Action Framework Guidance document for universal access to safe, effective and quality-assured blood: https://apps.who.int/iris/handle/10665/67384.

A major element of blood safety is blood availability, with processing of blood components and making up an inventory. The constitution of a suitable inventory is highly variable worldwide, as some countries can generally collect and issue as many blood components as needed to serve patients with few restrictions, while other countries can only rely on blood banks to collect blood during emergencies, such as for patients with acute haemorrhage. Blood donation programmes are thus important to ensure an adequate supply of blood products at all times [7]. 

Resolution 28.72 of the World Health Assembly (1975) established the principle that blood donation should be voluntary and non-remunerated (unpaid) [8]. This policy has been adopted by many countries for the collection of whole blood. In some countries, however, the supply of plasma for the manufacture of plasma derivatives is still based on commercial programmes, in which individuals receive payment for regular collections of plasma by plasmapheresis. A system of voluntary non-remunerated blood and plasma donation is regarded as safer because the incidence and prevalence of transfusion-transmissible infections is invariably lower than among family or ‘replacement’ donors and paid donors [9]. It also permits the use of donor education and selection procedures that encourage unsuitable donors to self-defer or self-exclude. 

When blood is in short supply, or if it is not possible or economical to maintain a regular inventory in a blood bank sufficient to meet clinical needs, there can be serious pressure to take short cuts in providing blood for individual patients: for example, the correct selection criteria for donors may be ignored or virological testing may be rushed or even omitted. If this occurs, the risks of transfusion are considerably increased and taking responsibility for deciding whether the transfusion is clinically justified should be balanced with the risks and benefits to the patient.

One way of minimizing these problems is for the blood establishment to maintain a list of donors who can be contacted in an emergency and who agree to be tested regularly so that their blood is more likely to be safe when collected and used in an emergency—a ‘walking blood bank’; certain blood establishments run a pre-donation testing programme, qualifying donors as eligible to donate blood. Rapid screening tests are suitable for then testing blood donated in this kind of situation.

As adjunctive therapy, and especially in the case of unavoidable delay in the delivery of blood, alternatives must be in place, such as fluids and macromolecules, tranexamic acid (an antifibrinolytic agent) and plasma derivatives (which are, however, expensive). Anaesthesiology protocols have also been set up to control bleeding and stabilize the patient [10]. Rapid access to cell salvage can be life-saving in these settings.

Many life-saving transfusion requirements can be met safely and effectively with whole blood. The provision of a safe and adequate supply of blood and blood products for transfusion is expensive. Even the production of whole blood involves significant capital expenditure on laboratory facilities, equipment for screening for infectious agents and refrigeration units. In addition, there are substantial recurrent costs, particularly for trained staff and essential supplies, such as blood collection packs and testing reagents. ‘Costing Blood Transfusion Services’ (WHO 1998; currently under review) provides a step-by-step guide to carrying out a detailed costing analysis of blood transfusion services [11].

Blood component separation and the collection of plasma and platelets by apheresis are more expensive than the processing of whole blood, and plasma derivative production involves very large capital investment and recurrent costs. Blood component production and the availability of plasma derivatives enable a wider range of treatments to be provided for more patients and are usually more cost-effective. However, it is important to remember that the use of whole blood may be more cost-effective where resources are limited, and in some settings may be clinically appropriate [12, 13].

The rationale for testing

Blood donation and/or donor testing is central to blood safety. It has the following main objectives:

• To detect specific, defined markers of infection in donations in order to prevent the release of blood and components donated by individuals with evidence of exposure to defined infectious agents, for clinical use;
• To ensure that the desired therapeutic elements are in a sufficient quantity in each unit to benefit each recipient. Evaluation of constituents of the therapeutic activity and the absence or presence in acceptable quantities of degraded material are part of the quality control of the process; 
• To determine the blood group of the given blood, with additional testing (for example, extended phenotyping) as necessary;
• To minimize harm to donors: for example, to detect anaemia in potential blood donors: A ‘first do no harm’ principle must be applied to blood donation to protect donors’ health.

Screening for transfusion-transmissible infections

The term ‘incidence’ describes the frequency of new infections in a defined population within a defined period of time. The term ‘prevalence’ describes the proportion of a population who, at a given time, have evidence of the infection. The ‘window period’ is the period during the development of a new infection in a previously non-infected person in which the blood of the infected individual may be infectious, but the marker is not yet detectable. The probability of window period infection is high in high-prevalence populations at risk of infection; it can be narrowed as the sensitivity and the quality of the tests and the testing procedures increase [14]. However, the prevalence in the population may nevertheless still be low, at least for a time, because many or most of those at risk will not yet have been exposed to infection.  

Every unit of donated blood should be screened for main transfusion-transmissible infections using the most appropriate and effective tests, in accordance with national policies and the prevalence of the infection in the potential blood donor population. Tests must be accurate and precise; procedures must be conducted in compliance with quality systems. 
Several infectious agents are transmissible by blood transfusion and are potentially dangerous for recipients.
The most common infectious agents that are screened following all donations include: 

• HIV
• HBV
• HCV
• Syphilis bacterium
• Tests of other infectious agents are required based on local epidemiological evidence:
• Chagas disease parasite
• Malaria parasites
• HTLV
• West Nile virus

More information on screening donated blood can be found in the WHO document available at: https://apps.who.int/iris/handle/10665/44202

Some additional infectious pathogens, mainly viruses, may need to be tested for in case an epidemic outbreak affects a geographical area, if it is proved that the infectious pathogens can be transmitted by transfusion by asymptomatic carriers and pose a potential infectious risk to recipients of their donations.

The WHO has produced a document, Protecting blood supplies during disease outbreaks: guidance for National Blood Services, which provides information for Blood Services on dealing with emerging infectious threats and is available at: https://www.who.int/iris/handle/10665/311443 

Every prescriber of blood should be aware of the occurrence, distribution and spread of transfusion-transmissible infections in order to be able to make informed judgements about the risks and benefits of transfusion and to wisely inform patients.

Testing strategies implemented by blood establishments differ among countries and sometimes differ among regions in the same countries. Not all the blood donations in all countries in the world are yet covered by quality-assured testing [15]. The WHO provides guidance on estimation of the residual risk based on data on virus infections in the blood donor population and comparing different testing scenarios [16].

Other than in the most exceptional life-threatening situations, and with the consent of the patient and/or the treating physician, blood should not be issued for transfusion unless it has been obtained from appropriately selected donors and has been screened for transfusion-transmissible infections, in accordance with national requirements.

Every blood establishment should have procedures to phenotype collected blood and the processed components made from this donation. Some blood groups are critical as recipients may have so-called natural (preformed) antibodies that can bind to some antigens present on the transfused red cells (and vice-versa in the case of plasma). Each blood component must thus be typed for its ABO blood groups. Additionally, a number of other blood groups are of variable importance. Of importance to protect the recipient against post-transfusion immunization and female recipients against pregnancy complications are the Rhesus (referred to as Rh or—in the international nomenclature—RH) antigens, and particularly RhD (RH:1); individuals who are positive for this antigen on red blood cells are known as Rh-positive or Rh⁺ or RH:1; individuals lacking this antigen are referred to as RhD-negative, or Rh–, or RH:-1 [17,18].

Every hospital should have standard operating procedures to ensure that blood components to be transfused are compatible with the patient’s red cells and the antibodies in the patient’s plasma.

Transfusion is only one part of patient management. It is essential to remember that the need for transfusion can often be minimized by the following means:

• The prevention or early diagnosis and treatment of anaemia and the conditions that cause anaemia. The patient’s haemoglobin level is usually raised by appropriate diet and iron and vitamin supplementation without the need for transfusion. In chronic anaemia, red cell transfusion is needed only if the anaemia is symptomatic and requires rapid raising of the haemoglobin level.
• The correction of anaemia and replacement of depleted iron stores before planned surgery, and appropriate use of various forms of iron, vitamins, and erythropoietin.
• The judicious (limited) use of intravenous fluid replacement with crystalloids or colloids in cases of acute blood loss.
• Good anaesthetic and surgical management, including:
  • Stopping anticoagulants and anti-platelet drugs before planned surgery, where it is safe to do so;
  • Minimizing the blood taken for laboratory use, both in terms of frequency and volume. Initially designed for children, small-volume sampling may be wisely applied for all patients;
  • Minimizing blood loss during surgery;
  • Salvaging and reinfusing surgical blood losses, when appropriate;
  • Using alternative approaches such as desmopressin, aprotinin, tranexamic acid, etc.

Transfusion, when required, should be used in conjunction with other aspects of patient management [19].

PBM is a personalized, patient-centred initiative that is now applied worldwide in many clinical settings. PBM programmes aim to integrate all aspects of a patient’s care, including planning for procedures and surgery or obstetric care.

PBM is in general common sense and simply the application of the principles of good clinical practice as outlined above, but in many ways PBM challenges some habits and ‘default’ approaches to transfusion that may have developed over time.

PBM has been described, especially in the elective surgical setting, to encompass three pillars:

1. Optimizing the patient’s red blood cell mass;
2. Minimizing blood loss;
3. Managing anaemia and optimizing the patient’s tolerance of anaemia.

These strategies can reduce the need for transfusion and optimize patient outcomes. 

Of note, PBM is now also applied in many medical indications. 

PBM programmes can reduce excessive blood sampling in patients for pathology testing and line flushing, and calls attention to finding alternate solutions, including use of small-volume sample tubes and rationalizing the frequency of blood testing. These manoeuvres can minimize the occurrence and severity of iatrogenic anaemia, and also reduce costs associated with frequent pathology testing. The WHO recently developed a policy brief document in which PBM is outlined in more detail: https://apps.who.int/iris/bitstream/handle/10665/346655/9789240035744-eng.pdf.