Clinical applications of blood products

 

According to one estimate, by the time they reach the age of 75 years, at least 75 % of all Americans will, at some time in their lives, have required a blood transfusion or consumed at least one unit of a blood derived product [1]. While this figure may simply reflect stereotypical American consumer behaviour that may not be replicated elsewhere in the world, it does demonstrate the potential that blood has of being consumed by a wide range of patients, even if, like other clinical inputs, its true necessity depends on factors such as the availability of alternate treatment options and the experience and views of different medical practitioners with regards to the use of blood products.

In this section, we look at how the blood products and derivatives that were examined in the previous section are used to treat patients with a variety of ailments. Where possible, figures of the quantities and types of product required to treat specific medical cases will be provided, along with estimates of how the demand for such products is expected to change in future.

 

i) Surgical procedures

Blood products, especially when provided as whole blood transfusions, are often required when operating on people. This is because during many surgical procedures, tissue and veins must be severed if surgeons are to reach those locations requiring their attention, resulting in the spillage of blood from the damaged area. To compensate for this blood loss, and to ensure an optimum recovery in the post-operative phase, transfusions that restore the blood level of a patient to their standard range are required.

Several factors have increased the demand for surgical intervention, and by association, the demand for blood. As technology has developed, the number of new medical techniques that have been implemented to deal with specific problems has increased greatly, with surgeons now having the ability to correct conditions that, until recently, were deemed to be untreatable. Related to this has been an increase in the number of medical specialists capable of using such technologies, along with significant improvements in medical infrastructure, such as the substantial rise in the quantity and quality of hospitals with operating theatres and intensive care wards. While these are largely medical supply factors, the introduction of new funding mechanisms, such as public and private medical insurance, has increased demand by moving surgery away from being seen as merely an option for the wealthy, to being an alternative available to everyone. At the same time, the number of potential candidates qualifying for surgery has risen, with children, the elderly, and other “poor risk” patients benefiting from the increased safety margins within which this form of intervention can be undertaken.

Surgical procedures can be used to correct a range of bodily ailments, with one of the more obvious applications being open-heart surgery. For this type of operation to succeed, the flow of blood to the heart must be temporarily bypassed in order to allow the surgeons to work on this delicate organ while it is not in operation. While this diversion of blood is successfully accomplished by pumping a patient’s blood through a heart-lung machine, several units of blood need to be utilised in order to prime this machine for operation, plus spillage may occur as blood seeps out of the chest area. Due to such factors, the average blood requirement for a cardiovascular operation is 6 units of whole blood and a similar number of platelet extracts [2], although complications obviously push this figure upwards, sometimes by a factor of 10 [3]. In recent decades, the number of South Africans with heart problems has increased dramatically – while many sufferers may be treated via alternative means, it is likely that increasing numbers may have to resort to operations such as cardiovascular surgery or angioplasty for recovery, in which case greater volumes of blood products will be needed.

Another surgical field with a vast blood requirement is that of transplant surgery, where replacement organs such as hearts and kidneys are transplanted into recipients with defective original organs. As each organ has different characteristics and involves different operating techniques, so the quantity and type of blood product needed will differ, although the general rule is that those transplants that involve organs with major blood related functions invariably require the use of more blood. As a guideline though, a standard transplant operation may require the use of 40 units of whole blood, 30 units of platelets, 25 units of plasma, and 20 bags of cryoprecipitate, while a bone marrow transplant necessitates the use of 20 units of whole blood and up to 120 units of platelets [4]. While the demand for transplantation is always high, the number of these operations that are actually performed is constrained by the number of organs supplied, so any major increase in blood requirements in this area is only likely to arise if there is a sustained increase in the number of organs available for transplantation.

Finally, one area where surgery plays an important yet largely overlooked role is in the eradication of cancer. If a portion of tissue becomes infected with a cancerous growth, then to prevent the disease from becoming malignant and spreading throughout the body, the offending tumour may need to be removed by means of a surgical procedure. This is, for example, often the policy when a woman has breast cancer, where a mastectomy is performed, whereby part or all of her breast tissue is removed as a precursor to the initiation of regular cancer treatment such as chemotherapy and radiotherapy [5]. While such surgical interventions require the use of only a couple of units of blood (2-3 units with simple tumour removal, but about 5 units in the more difficult case of prostrate cancer) [6], the number of such operations is significant and likely to rise further due to evolving risk factors such as changing demographics, greater industrialization and toxic pollution.

 

ii) Medical emergencies and accidents

In the previous paragraphs, we dealt only with cases of elective surgery, where surgical operations are planned in advance, thereby allowing for any anticipated blood requirements to be acquired before the operation occurs. Not all medical procedures are of this type though, as there are many dramatic emergencies where blood may be urgently required at a moments notice. In such cases, a form of “surgical rationing” [7] that disrupts normal hospital operations may be practiced, where blood intended for planned operations is diverted to an emergency ward, where the medically determined need for it is more pressing [8]. This occurs because irrespective of the cause of the accident, an emergency patient is deemed to have a greater priority to whatever blood is available than scheduled patients who, despite the inconvenience caused, are unlikely to die very soon from a massive loss of blood that can only be staunched through transfusion.

While the victims of such accidents may not be identifiable ex ante, we can, with some confidence, establish the probability with which such emergencies will arise. However, this may provide little comfort to blood banks, as they may also need to know the right time when such events will take place in order to stock up on the necessary quantities and types of blood product before such events actually occur. Indeed, some blood banks have warned that when their stocks are low, they may have difficulty providing sufficient blood to meet the needs of all potential recipients should a major disaster, such as an earthquake, occur at an inopportune moment [9].

Many of the more common emergencies arise due to the internal and external injuries caused to people involved in transport accidents, or as a result of violent acts such as stabbings and shootings. While the circumstances under which these injuries are inflicted vary, they are all similar in that when they are so severe that patients must be rushed to trauma units for emergency treatment, they will invariably require massive blood transfusions due to the scale of their wounds. In the case of motor vehicle accidents, for example, up to 50 units of whole blood along with several units of platelets may be required to treat patients[10], with similar needs being expressed for victims of serious assault. While blood demand as a result of criminal activity is directly proportional to the incidence of violent crime and will therefore only fall if society becomes safer, with transport related emergencies, any per capita improvements due to better road safety awareness and transport infrastructure may be offset by an increase in the absolute number of vehicles operating on our national roads [11].

While childbirth is an activity that usually proceeds without any major complications, some women may have difficulties before or during labour. One of the most serious problems is that of haemorrhage, where rapid transfusions of blood may be required to prevent miscarriage or the death of the mother. While the rate of normal gynaecological and obstetric incidents where transfusions are required has followed a downward trend over time (due to improved maternity facilities and relatively healthier expectant mothers), the increased availability of abortions and advanced delivery techniques, such as caesarean sections, has meant that the number of potential complications that could lead to the use of blood has actually risen [12].

Finally, we have a range of common, everyday accidents that can occur at any time or place, such as scalds and burns at home, as well as industrial accidents at work. While each accident may be unique and require the use of different blood products, we can get an idea of how much blood is needed by simply considering the case of the burn wounds that can be caused by fires, where upwards of 20 units of platelets may be required to treat a single patient [13]. While extra safety precautions to prevent the occurrence of such events can always be undertaken, it is likely that they will always remain a feature of daily life, so the potential demand for blood as a result of normal accidents can be expected to remain at a constant per capita level over time.

 

iii) Specialised blood products

So far, we have only reviewed those cases where blood recipients receive transfusions in a surgical theatre for once off events. However, there are many cases where blood can regularly be consumed outside a hospital, especially when provided to patients as part of an ongoing treatment regimen. In such cases, whole blood is rarely transfused, with the standard procedure being rather to provide a product containing only the particular blood element needed by the patient.

While the intensive use made of red cell products in operating theatres is well documented, what often goes unmentioned is that they also play an important role in managing ailments outside such venues. Amongst these illnesses are anaemia (where the red cells of recipients are deficient in substances such as iron) and sickle cell disease (a disease common in Africa that results in the occurrence of strokes and chest ailments), although arguably their most important use concerns the treatment of leukaemia and cancer patients (whose bone marrow is unable to manufacture the cellular blood components that they require) [14]. Indeed, patients who suffer from bone marrow failure are considered to be amongst the biggest users of blood products, since they must continue receiving regular transfusions of blood products for as long as their own bone marrow fails to function or until they can get a bone marrow transplant. Not only must these particular patients supplement their red cell counts with transfusions, but they also need to consume platelets, with a considerable portion of all the platelet donations that are made being dedicated entirely to them, with their average consumption of such products standing at about 6-10 units per day [15]. 

Arguably the most important and best-known use of blood derivatives is made in the treatment of haemophilia, which, although relatively uncommon, plays a major role in driving the demand for plasma [16]. Before products such as factor VIII were available, haemophiliacs had an arduous life, as they had no adequate way of responding to their occasional episodes of bleeding. At such times, they would be unable to undertake even the simplest of activities, since they suffered from a painful wastage of their muscles that crippled them, with many suffering a premature death due to this condition. Following the introduction of factor VIII products, their quality of life improved dramatically due to the elimination of pain and restrictions on their freedom of movement. In addition, their life expectancy increased substantially, with British haemophiliacs, for example, moving from an expected lifespan of only 37 years in 1962 to a level much closer to the UK median of around 65 years by 1980 [17].

Despite this, haemophiliacs have not been entirely fortunate in their interactions with these new medical products, since in the developed world at least, they are the ones most at risk of being infected by disease borne within them. This is owing to the quantity of, and frequency with which they need to consume blood products sourced from plasma pools. Until the late 1970s, it had long been recognized that large numbers of haemophiliacs could expect to be infected with hepatitis, but, given the alternative of suffering a short life cocooned in pain, this option was considered to be an acceptable trade-off worth making. In the early 1980s, the hazard of hepatitis infection was compounded by the newly arrived threat of HIV, with the fears and misconceptions about the disease being particularly acute during the two year period between when the virus was first identified (1983) and when definite measures could be taken to prevent its transmission (1985).

While some consideration was given to limiting the quantity of factor VIII distributed, and thereby reducing the number of possible exposures to infection, no action was taken due, in part, to intensive lobbying conducted by organisations representing haemophiliacs. This was since these bodies argued that in light of the limited scientific evidence then available on the virus, any disruption of plasma supplies could only result in unnecessary hardship, not benefit, for their members. Here, it was stated that “throughout the world the opinion of the majority is that the risk of haemorrhage and its complications far outweigh the risk of developing AIDS” [18]. Rather, they argued, concrete action would only be advisable when more was known about the virus, with some authorities confidently predicting that like hepatitis, HIV would be controllable, with at most 10% of all those infected being likely to develop AIDS [19]. Consequently, the provision of these products continued to proceed as normal until, too late, the ultimate fate that was to be suffered by all those who were infected by HIV became known. The end result was that tens of thousands of haemophiliacs around the world were to be in the initial waves of those who died from AIDS. 

Plasma derivatives have also proven their worth in the field of preventative medicine, where immunoglobin is used to produce vaccines against a range of infectious diseases. One way in which these vaccines can be used is in the provision of basic immunological cover to infants and young children as part of a primary health care programme, where protection is offered against diseases such as measles, rubella, smallpox and some types of hepatitis. In addition, a second major area of use is in the provision of vaccinations against diseases that may be encountered while travelling abroad in the relevant risk zones, such as tetanus and yellow fever. In future, the demand for these immunizations can be expected to rise significantly, due to both better and more comprehensive basic immunization programmes, and as a result of the increased numbers of people who are expected to travel the world for business and pleasure [20].

While the aforementioned products are used by relatively large numbers of patients, there are other products that have a limited scope of use, but which remain nonetheless life enhancing. This can be illustrated by considering the example of people with a very rare disease known as chronic inflammatory demyelinating polyneuropathy, where the immune system attacks the nervous system, and thereby prevents the limbs from operating normally [21]. While this disease can be successfully countered through the consumption of a product called Intragram, the problem that exists is that in order to acquire the components necessary for just one dose, blood from about 75 donations needs to be processed (which is not always feasible). To put this into clearer perspective, about 1350 donations of blood need to be collected in order to supply the annual requirements of just one sufferer, with any decrease in the provision of Intragram leading immediately to a marked deterioration in the patients’ state of health. While the number of people with such diseases is relatively low, their blood demands are, nonetheless, entirely out of proportion to their numbers, as the products they consume frequently require the processing of large volumes of blood in order to extract only a few key ingredients. As a hypothetical guess, we can expect the demand for blood products that are aimed at treating rare diseases to increase in future, as scientists develop new methods of treating an ever-expanding range of rare disorders.