Guidelines / Advice

Alternatives to allogeneic transfusions

There are a number of alternatives to allogeneic blood transfusion. Some of these options are conventionally offered by the blood transfusion services themselves, whereas others such as acute normovolaemic haemodilution and autotransfusion of recovered blood are largely the domain of the anaesthetist and surgeon. The same is true for the use of hemostatic drugs and agents. This section will therefore focus on transfusion service controlled alternatives and the reader should refer to other texts for more detail regarding pharmacologic or auto¬recovery strategies.

It is also important to note that many of the measures outlined below require careful planning, and are not possible in emergency settings at short notice. Since there is a lot more time and attention required for the extra clerical requirements, special handling (additional labels, separate storage in the blood bank etc.) and the fact that blood that is not transfused is generally wasted, the costs for autologous and similar procedures are significantly higher than for standard allogeneic components.

9.1. Pre-operative Autoloqous Donations (PAD)

This is an option for patients who are undergoing elective surgery and whose intra-operative blood requirements can be reasonably accurately predicted (e.g. knee and hip joint arthroplasty). The patients should be in good general health and fall broadly within the criteria required for allogeneic blood donors.

Suitable candidates must be able to tolerate the standard donation withdrawal of 450-500ml of blood and the longer term reduction in haemoglobin levels. They must weigh >50kgs, have a haemoglobin level of 11 g/dl or more (lower level than allowed for allogeneic donors) and be between 16 and 70 years of age. Older or younger patients may be accepted after consultation and examination by the medical staff.

It is theoretically possible to collect up to 5 autologous units in a healthy donor, but in practice it is seldom that more than 2 units are collected. Autologous donations may be collected up to 72 hours pre-operatively and all donors are given iron supplementation during and after the collection process.

Contra-indications to admission to the autologous programme include severe cardiac disease, severe pulmonary disease and bacteraemia. Conditions such as insulin dependent diabetes mellitus and other systemic disorders will be assessed carefully in consultation with the referring physician.

The patient's practitioner should initiate requests for autologous donations and refer the patient to the local blood transfusion service in good time before the operation. Autologous donations are reserved exclusively for the patient who donates the unit and will not be made available for another patient. All autologous donations are also tested for markers of transfusion transmissible infections.

9.2. Designated Donations

This is not, strictly speaking, an allogeneic transfusion alternative as it is itself allogeneic. Also, the donation comes from the general population and theoretically would carry the same statistical risk as the general donor population. Furthermore, with family and friends there may be subtle exertion of pressure by the prospective recipient with negative effects on the self-deferral process. Nevertheless, in a country where there is a high prevalence of viral disease with potential transfusion transmission, the motivation to have a known family member or friend as a donor is difficult to refuse and the services provide designated donor options.

All designated donors must conform to the accepted voluntary allogeneic donor criteria. Since blood from family members may have the same HLA haplotypes as the recipient there is a greater risk of transfusion-associated graft-vs-host disease (TA-GVHD) read more. Therefore all blood from family donors must be gamma-irradiated prior to transfusion.

9.3. Acute Normovolaemic Haemodilution (ANH)

This entails the removal of blood from a patient before or shortly after induction of anaesthesia and simultaneous replacement with appropriate volumes of acellular fluid (crystalloid/colloid) followed by the return of the blood as dictated by the intra-operative blood loss. ANH is the responsibility of the anaesthetist and the transfusion service will have little role to play other than possibly provision of suitable blood collection systems.

9.4. Blood Recovery (Autotransfusion)

• a. Intra-operative
  • Suitable for any surgical procedure associated with significant blood loss from clean wounds e.g. cardiac and vascular surgery, orthopaedic procedures. The most commonly used technique is to employ so-called cell savers that aspirate the shed blood, saline wash the blood and return it to the patient. If topical haemostatic agents such as thrombin or microfibrillar collagen have been used, recovered blood from these sites should not be used as microthrombi may embolise to critical organs. Other adverse effects of intra-operative salvage that have been reported include air embolism and coagulation disturbances such as disseminated intravascular coagulation.
• b. Post-operative
  • Blood may be collected from the mediastinum or joint spaces, usually limited to the first 6 hours post-operatively. Various bag systems are available e.g. Sorensen system.

9.5. Pharmacologic interventions

There are topically applied agents and systemically administered drugs that may in specific settings, decrease blood loss.

Examples are:

Collagen haemostat pads, thrombin sprays and fibrin glue
These products are applied directly to the wound (sprayed or in powder form).

Desmopressin (DDAVP)
This is a vasopressin analogue classically used to increase Factor VIII in mild haemophilia A and von Willebrands disease (vWD). Trials of DDAVP in reducing blood loss in cardiac surgery have given mixed results.

Aminocaproic acid and tranexamic acid
A couple of trials have been published demonstrating efficacy in reducing blood loss post-cardiac surgery when these antifibrinolytic agents have been administered.

Aprotinin
This is a serine protease inhibitor and has been used successfully to reduce blood loss in cardiac surgery in a number of clinical trials. However, there are toxicity and other safety problems and careful monitoring is required.

Haemoglobin-based oxygen carriers (HBOC)
Despite 2-3 decades of development, the number of products that have reached clinical trials status is limited. Hemopure (a polymerized bovine haemoglobin) is registered in South Africa for the treatment of surgical anaemia in adults for the purpose of eliminating, delaying or reducing the need for allogeneic red cells. It has been used successfully in a number of patients in an uncontrolled surveillance program.

Safety in pregnant women and in children has not been established. Reported adverse events include increases in blood pressure requiring pharmacologic intervention, and severe rebound anaemia, although in the latter, timing of dosage may have been a factor. Following infusion, the plasma and total haemoglobin (Hb) concentrations increase but the haematocrit may decrease as a result of haemodilution. Haematocrit measurements should therefore not be used to assess red cell 02-carrying capacity.

Red colourisation of the plasma or serum by infused Hemopure may lead to colourimetric interferences with serum chemistry and communication with the pathology laboratory is important. Hemopure has a short half-life(16-24 hours), however, and is therefore useful as an 02 bridge in acute blood loss situations. It may also be considered for patients who for religious reasons will not accept blood transfusions.

Hemopure can be stored at room temperature for up to 3 years and is universally compatible. Cost is a consideration as it is relatively costly.

Erythropoietin
It is the recommended treatment for the anaemia of renal disease; also effective for the anaemia induced by anti-retroviral agents and has been used widely for chemotherapy-induced anaemia, but there have been recent safety concerns.

Recombinant Factor VIla (rVIIa)
rVIIa is registered and approved for use in haemophiliacs with inhibitors and for Factor VII deficiency. In addition a number of clinical trials have shown efficacy in:

• Intracranial haemorrhage in premature neonates.
• Post partum haemorrhage.
• Cardiac surgery.
• Trauma with massive blood loss.

It is, however, extremely costly.

Parenteral Iron Preparations
It needs to be remembered that in patients who have documented iron deficiency but who, for various reasons, cannot take or tolerate oral iron compounds, the option of parenteral iron is available before resorting to transfusion. There are two registered preparations: an iron polymaltose compound for intramuscular injection and an iron sucrose compound for intravenous use. Both can cause allergic reactions including anaphylaxis.