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 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 (see comparisons below). Serology testing is still performed as an added safety measure.

Infection Serology (antibody) Window Period ID-NAT Window Period
HIV 15 days 4.5 days
Hepatitis B 38.3 days 16.3 days
Hepatitis C 58.3 days 2.2 days


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

Since implementation of ID-NAT in 2005, WCBS has not had any confirmed cases of HIV or hepatitis transmission via a blood product reported to our haemovigilance office. The prevalence statistics of these infections in new and repeat blood donors are monitored very carefully and reported each year. The blood services in South Africa use a residual risk calculation to determine the theoretical likelihood of transmitting HIV or hepatitis through a blood product transfusion despite the multiple safety strategies that we currently employ. This is estimated to be about 1 in 10 million transfusions although it must be stressed that this is a theoretical risk 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 donating 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 regular blood donors carry a lower risk of having 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 accidentally 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 mistake the identity of the patient prior to starting the transfusion. This can also be 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 an acute haemolytic transfusion reaction – see the Clinical Guidelines for the Use of Blood and Blood Products in South Africa (6th 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 a patient’s blood group with previous records if they have been transfused before.

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 false 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 and Blood Products in South Africa (6th 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 and Blood Products in South Africa (6th Edition) for detailed explanations of the types, pathophysiology and management of ATRs.

How do the blood services 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 the 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’).

Irradiation

This refers to the exposure of a 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. For other indications for irradiated products, refer to the Clinical Guidelines for the Use of Blood and Blood Products in South Africa, 6th Edition.

The WCBS irradiators are currently located at Groote Schuur and Tygerberg Hospitals in Cape Town. There is an additional charge for this service and the issuing time may be prolonged if the products need to be transported between hospitals.

Platelet additive solution (PAS)

PAS is a nutrient media that replaces about 60-70% of human plasma in both random donor (pooled) platelet products and single donor (apheresis) products at WCBS. The use of PAS reduces allergic transfusion reactions in recipients as there are fewer plasma proteins to instigate this response.

Male-only fresh frozen plasma (FFP)

FFP is made only from male donors at WCBS in order to reduce the risk of TRALI. Multiparous female donors are more likely to have human neutrophil antigen and/or HLA Class 1 and Class II antibodies that are believed to be responsible for this reaction if the antigens on the patient’s white cells are corresponding.  HLA antibody testing is not performed for female donors at WCBS due to the prohibitive cost.

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 and allergic-related reactions.

Severely immunocompromised people (eg. bone marrow transplant recipients) are at risk of TA-GvHD and should receive irradiated blood products following the start of induction chemotherapy.

The elderly, young and patients with cardiovascular disease are more at risk of volume overload from blood product transfusions and TACO.

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.