What are some of the risks of blood product transfusions?

Here follow several important risks that should be communicated to patients, along with explanation of how the blood services in South Africa try to mitigate these:

Transmission of infection from the donor to the patient

What infections do the blood services in South Africa test for?

  • Blood services in South Africa currently test all blood donations for HIV-1, HIV-2, hepatitis B, hepatitis C and syphilis , however there are many other infections that can potentially be transmitted in blood and blood products, such as cytomegalovirus, human T-lymphotropic virus, malaria and parvovirus B19.
  • Individual donor nucleic acid amplification testing (ID-NAT) was introduced in the South African blood services for HIV and Hepatitis B and C screening in 2005, and has dramatically reduced the risk of disease transmission. This advanced technology significantly decreases the window period compared to serology (antibody) or antigen testing alone – refer to the figures as follows: The HIV NAT window period is 4.5 days, whereas, the antibody test window period is 15 days. The Hepatitis B NAT window period is 16.3 days, whereas, the surface antigen test window period is 38.3 days. The Hepatitis C NAT window period is 2.2 days, whereas, the antibody test window period is 58.3 days.
  • Serology testing is still performed for the tested infections as an added safety measure.

What is the risk of acquiring HIV or hepatitis in a blood product transfusion in South Africa?

Since implementation of ID-NAT in 2005, confirmed transmission of HIV or hepatitis has been less than 1 in 10 million transfusions. Because of this it is very difficult to calculate the actual residual risk of such transmissions, so statistical modeling must be used. The blood services in South Africa use the Window Period Ratio Model to calculate this by looking at the rate of infection for a particular disease in the blood donor population. This calculation looks at the length of the ‘window period’, the length of time between NAT positivity and serology positivity for detecting a particular disease, and the number of infected donations identified solely by ID-NAT. It must be stressed that this is a theoretical risk assessment and does not mean that there will in fact be any transmissions.

What other ways do the blood services mitigate transmission of infection from donor to patient?

  • The blood services keep abreast of disease risks by conducting donor prevalence studies for specific infections, in order to determine whether it would be cost-effective to add testing for these infections to our protocols.
  • It would be very costly to test for additional infections, so large emphasis is placed on donor screening through the detailed self-exclusion questionnaire and individual donor interviews. These methods aim to identify donors who are at higher risk of having transmissible infection through enquiry into lifestyle practices (eg. recent or multiple sexual partners), potential needle-sharing (eg. recreational drug use, unsterile piercings or tattoo art) or travel to areas with endemic infection, such as malaria. Donors are typically deferred for at least three months from the time of engaging in high risk behaviour to avoid being tested during the ‘window period’ of the virally transmissible diseases.
  • Blood collection services in South Africa recruit only voluntary, non-remunerated people who are not incentivised to donate for material or monetary gain. It has also been shown that repeat blood donors carry a smaller risk of carrying transfusion transmissible infection, hence our drive to retain a regular donor base through marketing campaigns.

Receiving an ABO-incompatible blood product transfusion

  • The term ‘misdirected transfusion’ is used by the blood services to describe incidents where patients receive blood products not prescribed nor cross-matched for them. This typically results from human error on the part of the medical staff who take a cross-match sample from the incorrect patient or erroneously verify the identity of the patient prior to starting the transfusion, otherwise due to an administrative error or sample mix-up on the part of the blood bank staff.
  • If there is ABO blood group incompatibility between the blood product and the patient, this can potentially have life-threatening consequences due to a haemolytic transfusion reaction – see the Clinical Guidelines for the Use of Blood products in South Africa (5th Edition) for explanation and management of acute and delayed haemolytic transfusion reactions.

What do the blood services do to avoid this?

  • There are meticulous processes in place at the blood banks to ensure that mix-up of patient samples does not occur, along with verification of patients’ blood groups with previous records if these exist.
  • The blood services advocate that two medical staff check the details on the issued blood product with the patient information at the bedside prior to starting a transfusion.
  • A useful tip is to ask the patient’s name (‘What is your name?’), rather than asking them to confirm that their name is correct (‘Are you John Brown?’), as incorrect information may be affirmed due to language barriers, poor hearing or confusion on the part of the patient – see the Clinical Guidelines for the Use of Blood Products in South Africa (5th Edition) for further information about the correct and safe administration of blood products

Adverse transfusion reactions (ATR)

  • These can be acute (occurring within 24 hours after the start of the transfusion) or delayed (occurring after 24 hours of the start of the transfusion) and are attributable to either immunological or non-immunological causes.
  • Immunologically mediated reactions include haemolytic transfusion reactions, febrile non-haemolytic reactions, allergic or anaphylactic responses to blood products, and transfusion related acute lung injury (TRALI).
  • Non-immunological ATRs include transmission of infection, iron overload from chronic transfusions, metabolic changes associated with blood products and hypothermia.
  • ATRs are not common, although it is difficult to obtain accurate rates of occurrence in the South African context due to under-reporting of adverse reactions.
  • Febrile non-haemolytic and allergic reactions are the most commonly reported adverse incidents but life-threatening reactions such as TRALI, acute haemolytic reactions, anaphylaxis, transfusion associated graft versus host disease (TA-GvHD), and acute sepsis from bacterially contaminated blood products can occur.
  • Refer to the Clinical Guidelines for the Use of Blood Products in South Africa (5th Edition) for detailed explanations of the types, pathophysiology and management of ATRs.
  • The blood services offer several methods to reduce the risk of ATRs:
  • Leucocyte-reduction of blood products
  • White blood cells are often implicated in immune-mediated transfusion reactions so physical filtration of products can reduce the remaining white cell count volume to <1 x 106. There is a definite reduction in risk of febrile non-haemolytic transfusion reactions, transmission of cytomegalovirus and platelet refractoriness when products are leucocyte-reduced.
  • Leucocyte-reduction must be requested when ordering blood products and this has an additional charge (see blood product pricing under ‘Blood products and services’).
  • Gamma-irradiation
  • This refers to the exposure of blood product to 25 – 50 Gy of irradiation in an irradiator.
  • The purpose of this is to eliminate donor T-lymphocytes that can cause TA-GvHD in severely immunocompromised patients. Designated blood donations for family members should also be irradiated to prevent this complication due to potential sharing of HLA haplotypes.
  • Platelet additive solution (PAS) in random donor (pooled) platelet products
  • PAS is a substance that has replaced the use of human plasma in pooled random donor platelet products, which reduces the risk of alloimmunisation (antibody formation).

What are the risk factors for ATRs?

Patient factors

  • Multi-transfused patients and multiparous women are more susceptible to febrile and haemolytic transfusion reactions.
  • Multiparous women and IgA deficient people with anti-IgA antibodies are also more prone to haemolytic transfusion reactions and allergic-related reactions.
  • Severely immunocompromised people (eg. bone marrow transplant recipients) are at risk of TA-GvHD and should receive gamma-irradiated blood products.
  • The elderly, young and patients with cardiovascular disease are more at risk of volume overload from blood product transfusions.

Type of blood products

  • Platelet products are stored at room temperature so are more at risk of bacterial contamination than red cell or plasma products that are refrigerated or frozen.
  • Plasma-containing products are associated with higher risk of allergic and anaphylactic reactions due to the presence of plasma proteins.

Transfusion Related Immunomodulation (TRIM)

  • The concept of TRIM suggests that non-leucocyte-reduced allogeneic red cell transfusions can result in immunosuppression in the recipient.
  • This phenomenon was first described in the 1970s where it was seen that the survival rate of patients with transplanted kidneys was significantly higher in people who received red cell transfusions, presumably due to the immunosuppressive effect.
  • Several studies confirm that red cell transfusions are associated with an increase in nosocomial infections, cancer recurrence and organ dysfunction through dysregulation of the immune system by a variety of mechanisms.
  • Although there is a lot of research to confirm that allogeneic red blood cells interact with and modulate the recipient’s immune system, the clinical implications of this are controversial.