Transfusion in low-resource settings

INTRODUCTION

Blood transfusion can be a life-saving measure for patients who experience haemorrhage, have severe anaemia or who are undergoing major surgery and cancer therapy.  In high-income countries, the blood supply and associated resources are generally sufficient.  However, in LMICs, the supply is far from secure to support the demand.  Given the resource needs, time dependencies, and cold-chain requirements necessary to support a sustainable, safe and sufficient blood supply, attention to the health sector infrastructure is crucial (Box 1).   

The blood supply relies on a system of interconnected parts that work in concert to assure safety and adequacy.  From collections to testing to transfusion at the bedside, there are many parts that must work together to be effective.  Blood systems may operate at a national level, where blood collection is coordinated under a centralized programme to manage the supply to many hospitals, or a single hospital may maintain a blood programme where it collects, tests and distributes blood to patients being cared for at the facility.  However, even hospital-based blood programmes coordinate across multiple disciplines and apply a systems-thinking approach in order to ensure safety and availability.  We reference blood systems, whether applied at a national or local level, to reinforce the continuous dynamic that is necessary to mitigate shortages, ensure accessibility, and improve safety no matter the scale.   The WHO supports countries to develop nationally coordinated blood services, including implementing a national blood policy. Not all nations are yet able to achieve this, and in many cases blood supplies are still dependent on fragmented systems, with varying safety and quality standards  [1].

DONOR RECRUITMENT

The challenges of blood transfusion systems in LMICs start with blood procurement and voluntary donor recruitment. Donor engagement is fundamentally based on raising public awareness through education campaigns as well as having equipment and motivated staff to work at blood drives and collection centres [2]. Often, secondary school students are targeted to be volunteer blood donors, which is advantageous because they are available and perhaps not yet sexually active, although when the school is not in session, the supply can be impacted. Another potential challenge for volunteer donation in some countries is that, in some regions, blood donation may be unfamiliar, depending on the cultural norms and the communities’ experience with healthcare. There are examples of using social media and church communities to engage and retain blood donors, although more research is needed in this area, including in LMICs [3, 4].  
Because of the difficulty in maintaining adequate blood inventory of donations from voluntary non-remunerated repeat blood donors, many regions also use replacement donation which uses friends and family members as blood donors to replace the blood units used by a patient. Replacement donation models may not supply enough units, and - with their dependence on convenience donors - often will not yield a robust inventory that is available when needed to support emergency transfusions in patients with large blood needs or to support medical and elective surgical programmes. The WHO strongly supports a global framework for action to achieve 100% voluntary non-remunerated repeat blood donation and for countries to phase out family/replacement approach to donation [5]. Thus, in these settings, the ultimate aim should be to maximize conversion of low-risk voluntary and replacement donors into regular donors since those who are successful repeat donors have the best safety profile [6]. The ideal blood donor is a person who is healthy, and motivated to voluntarily donate repeatedly, irrespective of whether mandatory replacement is the official model of blood donation. 

BLOOD COLLECTIONS

The collection of blood requires donor selection and deferral criteria to achieve the safest donors possible; this is best when standardized at the national level. The blood collection model will reflect the size and complexity of the recruitment model, which in turn depends on the projection of blood needs for the population served.  Blood collections can occur at fixed sites (buildings) or via mobile collections such as specialized blood collection buses, or teams of collection staff that use space inside of other facilities. The process depends on many factors, including having appropriately trained staff resources [7]. Furthermore, in LMICs, ensuring the appropriate amount and type of collection equipment (needles, blood collection scales, beds or chairs), collection bags, sample tubes, labelling systems, storage at appropriate temperatures can be challenging, and can lead to having low collections when a key piece of equipment is not available or is broken [8]. Once whole blood is collected, manufacturing blood components, such as platelets, plasma and cryoprecipitate also depends on having the necessary equipment and supplies. Even when efficiencies of scale can be found, such as centralizing the procurement of blood bags, or location of blood product processing after collection, there must be a cold chain that can uphold temperature control requirements, monitoring and security of the supply. Production and supply chains also rely on the local infrastructure, weather conditions and geography.  

INFECTIOUS DISEASE TESTING

The human immunodeficiency virus (HIV) epidemic in the late 20th century ushered in an era with enhanced focus on the prevention of transfusion-transmitted diseases.  However, blood transfusion services in LMICs encounter many problems that impact the ability to perform testing, such as lack of funding, insufficient training, poor management, or failure in supply of reagents and consumables, and breakdown of the cold chain (mostly related to frequent electricity shortages). Supported by the WHO and other partners, there has been an international effort to provide testing for pathogens that are transmitted by blood transfusion and have a public health impact: HIV, hepatitis B (HBsAg), hepatitis C virus (HCV) and syphilis [9]. The prevalence of these diseases varies by region and by country, with high-income countries generally having lower rates than low-income countries (Table 1). Some centres in regions with a high prevalence of disease have attempted pre-donation screening in an attempt to save consumables, with mixed results that may depend on the setting and financial pressures specific to each region [10, 11]. The risk for bacterial contamination in platelets has also been documented in low-resource settings [12].    
A potential future approach to improving the safety of the blood supply worldwide is pathogen reduction technology. By combining pathogen reduction technology with standard donor testing for infectious disease, the overall safety profile of the blood supply may be improved [13]. The decision to transfuse blood products is always a risk–benefit decision based on the patient’s clinical condition as well as the risk of infectious disease and other potential hazards of transfusion, the availability of blood, and costs of care. 

CLINICAL USE OF BLOOD

The care of patients needing and undergoing transfusion in LMICs can present significant challenges [14]. Blood shortages in sub-Saharan Africa can lead to preventable morbidity and mortality in children: in one study, 52% of severely anaemic children who did not receive blood transfusions died within 8 h of hospital admission, 90% died within 2.5 h [15]. The leading cause of maternal mortality is postpartum haemorrhage, accounting for 33.9% of maternal deaths, which the WHO estimates could be significantly decreased by improving the availability of blood [16, 17]. Blood shortages in LMICs are attributed to a combination of inadequate numbers of donations, blood wastage, inappropriate use of blood and blood components, and inadequate access to and use of pharmacological and nonpharmacological alternatives to allogeneic blood [18]. A substantial number of transfusions worldwide may be inappropriate: reports suggest that 23–52% of the transfusions in children and up to 90% of adult transfusions may be unnecessary [19, 20]. Needless transfusions compromise the availability of blood for patients who require it, and also expose patients to the risk of serious adverse transfusion reactions and transfusion-transmissible infections [21]. Inappropriate blood use can be caused by inadequate knowledge of the clinicians, leading to poor decision-making, as well as lack of access to alternative therapies.  

The establishment of hospital transfusion committees can be pivotal in the support and supervision of transfusion services. Areas of focus for the committee may include developing and/or adapting evidence-based transfusion guidelines and pocket or electronic handbooks so they are readily available to clinicians, who should adhere to them in practice. For instance, there is now strong evidence that the early use of tranexamic acid (TXA) offers a survival benefit in bleeding patients who have been traumatically injured or are experiencing obstetric haemorrhage [22, 23].  TXA is inexpensive and safe. The use of TXA should be incorporated into local practice guidelines and should be readily available for rapid access and timely administration in critical bleeding scenarios.  

Auditing and feedback of adherence to guidelines and bleeding management algorithms can be used as a tool to improve clinical care.  An example of questionable common practice is the routine use of diuretics after transfusion; this may be inappropriate since the majority of patients who need transfusion present with hypovolaemia rather than heart failure as previously presumed [24].  Another example is that under-transfusion may be related to using a conservative transfusion policy, irrespective of haemoglobin threshold by guidelines.  A recent randomized controlled trial found that immediate transfusion for African children with severe anaemia does not appear to impact long-term survival [25].  Further, there was no long-term survival effect when African children with severe anaemia <6 g/dL were randomized to a dose of blood (20 mL/kg vs. 30 mL/kg), although, in the presence of fever (>37.5°C) those transfused with the 30-mL/kg dose had lower survival compared to those transfused with a 20-mL/kg dose   [26].These studies show that additional research is needed to generate local evidence to drive practice on a number of these unresolved clinical questions. To evolve practice, translating evidence into policy and practice and effective engagement with clinicians about the clinical use of blood are important goals.

The bedside administration of blood, observation and clinical monitoring during the transfusion, and management of any adverse events due to transfusion are also important practices tied to transfusion safety [27, 28]. The availability of trained clinical staff - doctors, nurses, midwives, surgeons, anaesthesiologists, obstetricians, critical care and support staff - is important to provide appropriate management of a patient who is receiving a transfusion.  Hospitals should have policies and procedures to direct the staff to carry out safe practices. Because modern transfusion devices are often lacking in under-resourced settings, it may be practical to consider alternatives. For instance, in settings where infusion pumps are not available, it is recommended to use a gravity infusion procedure to administer blood, and to ensure that the rate is approximately 5 mL/kg/h and completed within 4 h. However, there are instances where no alternatives may be appropriate, such as when blood infusion sets with a filter for small clots are not available. Under such difficult circumstances, clinicians should perform individualized risk–benefit assessment and transfuse in the safest manner possible.  

Another option to minimize the reliance on donor blood is the use of cell salvage. The benefit of cell salvage, typically used in the operating room, is that it can be activated quickly, avoids exposure to donated blood and may address bleeding needs if availability of blood products is low or they are not available. The challenge of cell salvage is that trained staff are needed to use specialized equipment and consumables, which can be costly.   
Patient blood management, a programmatic approach to minimize unnecessary transfusion, including through appropriate management of anaemia, offers a paradigm in which low-resource settings may improve the care of patients while also preserving the fragile available blood supply. Table 2 outlines recommended practices and those that should be avoided.

Table 2 Bedside transfusion practices

Quality Systems

Ensuring the quality of blood and safe blood transfusion requires a systems approach that recognizes the integrated nature of the blood system [29].  Competent and capable staff are critical to this process.  Screening of blood donors to protect their health and to prevent disease transmission to patients is of paramount importance. Laboratory testing protocols augment donor screening and should adhere to evidence-based methods or the manufacturer’s package insert. External quality assessment (EQA) or proficiency testing provides a means of independently verifying test system performance for blood typing and infectious diseases [30]. Some programmes offer discounts to participate in EQA for low-resource settings.  If commercial EQA is not available, periodically testing blinded samples between laboratories is an alternative (Table 3).

Since blood comprises living cells and labile proteins, controlling the process of collecting, processing, transporting, and storing blood is critical to the quality of the components that will end up being transfused.  Shipping containers should be appropriate for the environment where they are being used and validated to show the ability to maintain appropriate temperatures.  If not continuously monitored, refrigerator and freezer temperatures should be regularly checked to maintain the quality of the blood.  Documentation is essential to create a record to show that proper procedures were applied, or that corrective actions were taken when a process was found to be out of control. A practice of regularly reviewing such records and auditing activities provides reassurance that standard operating procedures are being followed. Finding and documenting shortcomings offers opportunities to engage in continual process improvement to enhance the safety and reliability of the blood system.  

Examining ways to minimize blood product wastage in low-resource settings can help to conserve scarce resources (Table 4). In addition to expiry due to poor inventory management, in-process wastage can result if blood is not maintained at the appropriate temperature or if transportation over long distances adversely impacts time-dependent component preparation. Evaluating the supply chain for weaknesses and examining where timing constraints can be modified can be an effective tool in LMICs. Additionally, having back-up methods or alternatives assures redundancy in the event that the primary methods are not available.

Recognizing that blood is an integral part of the overall health delivery system, it is beneficial to forecast blood collection goals [31]. For example, if the health system grows oncology care capabilities, the demand for platelets could be anticipated. Connecting blood supply goals with health service projections ensures that the demand for blood, and consequently the supply of blood, is aligned.  

Figure 1. Continuous linkage between blood supply and blood transfusion demand

At the hospital level, governance, process control, education and monitoring are crucial to ensure blood safety. The hospital transfusion committee, which is lacking in many low-resource settings, is crucial to provide a framework for monitoring practice through setting evidence-based policies and taking steps to implement and monitor them to improve clinical practice and patient outcomes [32]. The committee should consist of stakeholders such as clinical care providers (doctors, nurses), laboratory staff, blood supplier staff and hospital administrators to review past performance and current issues. The committee should be chaired by a staff member with authority in the hospital setting to lead and effect necessary changes.

The transfusion committee can use published benchmarks and collaborations through professional transfusion societies as a source for best practice. Other critical activities of the hospital transfusion committee include setting policy and monitoring incident reporting systems for incidents caused by human error as well as adverse reactions caused by product. Hospital-based haemovigilance is a more advanced approach to incident monitoring in which the events can be tallied at the regional or national level for broader understanding of rare events that can, in turn, be used to set improved policies or testing algorithms (in the case of infectious disease transmission). The transfusion audit is a straightforward and low-cost approach to uncover quality issues in practice and documentation.  Audit results should be reviewed by the transfusion committee on a regular basis, and action taken on relevant findings in order to improve practice.

Table 3 Quality systems considerations