Blood cell transfusion and bone marrow transplantation

Minimizing the risks of blood transfusion

Because of the possible complications of blood transfusion, it is constantly emphasized that unnecessary transfusions should be avoided. In most cases therapy with blood or blood components is solely a replacement therapy and should therefore be used only when a distinct deficiency of some blood component has been demonstrated; “component blood therapy” is usually preferable to whole blood therapy, providing more specific treatment. Also, the use of autologous transfusions, although not always feasible, seems to be a strategy that might reduce complication rates [ ].

In order to reduce risks to a minimum and at the same time ensure that blood products are of high quality, three measures must be enforced.

• 1.

  Proper selection of blood donors [ ].

• 2.

  Screening of individual donations [ ].

• 3.

  The use of production methods specifically aimed at minimizing the risks of transmitting infectious diseases [ ].

Blood donor selection

Blood donors should be non-remunerated and voluntary, and their health should be checked at regular intervals. A scheme for donor selection may include permanent exclusion criteria, such as previous episodes of jaundice (including laboratory evidence of current or previous infectious hepatitis, especially hepatitis B or C), syphilis or malaria, the presence of anti-HIV antibodies, so-called risk conduct, such as homosexual or bisexual behavior, or treatment with non-recombinant growth hormone. Time-limited exclusion criteria relating to current health status should also be used; these may also include such temporary risk factors as the taking of certain kinds of medicine, a recent blood transfusion, vaccination with live vaccines, a recent pregnancy, and travel to certain geographical areas, for example regions with malaria or a high prevalence of HIV.

In most countries, people with a history of jaundice are excluded from the donor population. However, there is a substantial geographic variation in the prevalence and detection rate of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (HCV) in donors [ , ]. In addition, the type of donor involved influences the risk: commercial (paid) donors carry a much higher hepatitis risk than non-remunerated voluntary donors [ , ].

With respect to the risk of transmission of variant Creutzfeldt–Jakob disease by blood, some countries exclude from donation donors who lived in the UK for more than 6 months between 1980 and 1996 [ ].

Laboratory screening of individual donations

Individual portions of donated blood should be tested for infectious risk whenever possible. The series of assays currently performed in most countries comprises tests for antibodies against HIV-I/-II, HCV, and HTLV-I/II, HBsAg, and a test for syphilis. However, screening for syphilis is no longer mandatory in all countries, as cost-benefit analysis has shown it to be of little value, at least with voluntary non-remunerated donors.

Now that hepatitis C can be tested for, the so-called surrogate tests such as alanine transaminase and antibodies to hepatitis B core antigen (HBcAb) are no longer carried out in all countries, and their relevance has been questioned [ ].

Serological screening of every blood or plasma donation must be performed using the most sensitive techniques available. Screening may be unreliable in cases of HBsAg at low titers, as evidence has accumulated that blood that is HBsAg negative but strongly positive for HBcAg antibody may be infectious [ , ]. However, routine screening for HBcAg antibodies is at present impracticable. There may also be a delay of 1–10 months before antibodies appear in patients infected with HIV or HCV.

In order to increase the sensitivity of screening, so as to minimize the so-called window period during which serological markers will not detect the infectivity marker, methods of detecting nucleic acids from, for example, the virus particle have been developed. Hepatitis C virus nucleic acid testing is obligatory in Europe, the USA, and Japan, and in many countries nucleic acid testing for other viruses has also been implemented. There is nevertheless no doubt that in future PCR-based methods will further increase the safety of blood and blood products.

Preparation of safe plasma-derived products

Infectivity can be reduced by introducing good manufacturing practice (GMP), both in blood banks and in plasma fractionation units. The sterility of the final products is checked and virus inactivation measures (for example heat treatment and/or chemical inactivation) are taken whenever appropriate. At present, virus inactivation procedures are most relevant to non-cellular products, although leukodepletion procedures using filtration have been used for infectious agents that are almost exclusively intracellular.

The virucidal methods currently in use [ ] are based on different rationales. Heat treatment can involve heating solutions, heating lyophilized products, or heating in vapor under pressure, where the actual temperature, duration, and addition of stabilizers vary for the individual products [ , ]. Chemical treatment of products with a mixture of an organic solvent and a detergent (S/D treatment) is highly effective against lipid-enveloped viruses [ , ]. Other methods of removing or inactivating viruses use nanofiltration [ ] or treatment with a combination of a colored photosensitizer and light [ ].

Use of autologous blood transfusion

In some countries there has been a marked increase in the use of autologous blood transfusion, since it is known that blood-borne viruses, such as HIV, can be transmitted by allogeneic blood transfusion [ ].

In 1997, 66 185 units of autologous blood (200 ml) were collected in Japan, 81% using preoperative collection and storage and 19% by perioperative hemodilution or blood salvage [ ]. The total volume of autologous blood collected accounted for 1.1% of the total number of units of whole blood donated in the same year. Of the autologous blood donated before surgery, 78% was used, while more than 70% of the blood that was collected by hemodilution, intraoperative salvage, and postoperative salvage was used. During whole blood donations adverse reactions were reported in 1.6% of cases, and ranged from mild reactions (for example dizziness) to severe reactions, such as angina and asthma. With respect to storage and transfusion, 288 errors or problems were reported, with a frequency of 1 per 455 units during production/storage, 1 per 213 transfusion problems/errors, 1 per 23 hemodilution procedures, and 1 per 54 salvage procedures. In 3.7% of the patients hypotension occurred during hemodilution. Clotting in blood units (0.9%) and bacterial contamination (0.4%) were the most frequent problems associated with blood salvage.

Adverse reactions to massive blood transfusions

Patients who receive massive transfusions are either extremely ill and suffering from prolonged shock or are undergoing major surgery (for example organ transplantation). Patients who receive massive transfusions are exposed to several risks resulting from the addition of anticoagulant, from transfusion of cold blood, and from biochemical, hematological, and other changes in the blood during storage. The complications lead in turn to metabolic disturbances and impaired hemostasis in proportion to the transfused volume.