By Katharine Sedivy-Haley, PhD Candidate, Hancock Lab

Thanks to their dramatic lifesaving effects, blood transfusions have become commonplace in modern medicine. However, it is only in the last two decades that clinicians have begun to assess whether transfusions actually improve patient outcomes under the existing standards and procedures. The results: blood transfusions may be “too much of a good thing”¹ for patients with less severe blood loss.

The risk of infection from blood-borne pathogens² is a familiar one. Currently, this risk is reduced (though not eliminated) using both donor questionnaires to select for donors with low pathogen risk and biological tests to detect pathogens. While biological testing is effective, testers need to know what types of pathogens to look for. For example, in the early 1980s, public health officials did not recognize that HIV could be transmitted through blood transfusions until an infant had been infected by contaminated blood³. Even after a blood-borne pathogen has been identified, a screen must be developed to properly assess donated blood. When the Zika virus first emerged, a screen was not available and blood banks in at-risk areas were forced to stop taking donations completely. Prions – misfolded proteins which cause diseases such as Creutzfeldt-Jakob – are also difficult to detect in the blood supply. In circumstances where a proven screen is in place, the added cost of testing can still lead to insufficient screening. The parasite Babesia microti is one such example and has caused at least 27 deaths since 1979 through contaminated transfusions. A screen was developed in 2012 but is still not widely used, as it can increase the cost per unit of donated blood by 7-10%. Uninfected blood platelets can also become contaminated with bacteria during handling, resulting in potentially fatal sepsis in the recipient.

To remove pathogens we don’t know how to look for, pathogen-reduction systems can often be effective. This emerging technology removes all known and unknown bacterial, viral, and parasitic contaminants from donated blood. Samples are treated with a molecule that binds nucleic acids and, when exposed to UV light, forms cross-links which prevent cells from reading their DNA and RNA. This process does not damage plasma, platelets, or red blood cells, which all lack DNA and RNA. However, the technique fails to remove prions and does kill DNA and RNA-containing white blood cells. Thus, it cannot be used in transfusions containing this cell type. While this new technique is useful in reducing the risk of infection, its scope is limited, and the methods require refinement.

Transfusions can also carry risks beyond those associated with blood-borne pathogens. Researcher Majad Rafaai from the University of Rochester, says that whole blood should be considered a “liquid organ,”¹ as it contains a variety of heavily regulated and specialized cells. Introducing foreign cells via a blood transfusion can have harmful effects, similar to those observed in solid organ transplantation. The age of donated blood may also prove detrimental in blood transfusions, though the research is not yet conclusive. During storage, red blood cells can become misshapen and rigid, impeding proper circulation through small blood vessels. Stored cells may also deteriorate, releasing substances such as iron, which feeds bacteria and increases the risk that invading bacteria will proliferate.

Considering the multitude of complications that may arise, transfusion is an unnecessary risk for many patients. The AABB (formerly the American Association of Blood Banks) has recently revised its guidelines⁴ based on 31 clinical trials investigating outcomes such as mortality, infection, and stroke. To reduce the risk of adverse outcomes, the AABB now recommends that for most patients, red blood cell transfusions should only be administered when the patient’s hemoglobin drops to 7-8 grams per decilitre (compared to the previous standard of 9-10 grams per decilitre). For some patients, alternatives to blood transfusion may be available. Anemic patients may be treated with intravenous iron, and measures can be taken to reduce blood loss during surgery. In contrast, some patients have a greater need for the oxygen that blood provides. Patients with heart or brain injuries, or chronic illnesses may still need more liberal transfusions.

With blood transfusions being an integral part of many areas of medicine, more research is needed in order to better understand the principles of transfusion and assess the needs of different patient populations. Eliminating unnecessary transfusions will not only reduce patient risk, but ultimately simplify patient care and decrease stress on blood banks.

1. Nogrady, B. Transfusion: Too much of a good thing. Nature 549, S22–S23 (2017).
2. Willyard, C. Screening: In the blood. Nature 549, S19–S21 (2017).
3. HIV And The Blood Supply: An Analysis Of Crisis Decisionmaking. (National Academy Press, Washington, DC, 1995).
4. Carson, J. L. et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA 316, 2025 (2016).