Things We Do for No Reason™: Routinely Prescribing Transfusion Premedication To Prevent Acute Transfusion Reactions

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 68-year-old woman with a known history of myelodysplastic syndrome is admitted for fatigue and shortness of breath on exertion. Her hemoglobin concentration decreased from 9.1 g/dL to 6.5 g/dL. Her physical examination is unremarkable except for mild tachycardia with a heart rate of 105. She is scheduled to receive her first red blood cell (RBC) transfusion. The hospitalist orders premedication with acetaminophen and/or diphenhydramine to prevent an acute transfusion reaction.

The most frequent complications of blood transfusion are allergic transfusion reactions (ATRs) and febrile nonhemolytic transfusion reactions (FNHTRs), with a combined incidence of approximately 1%-4% per transfusion.¹ ATRs may range in severity from mild urticaria to life-threatening anaphylaxis. FNHTRs manifest as a fever (oral temperature greater than or equal to 38°C/100.4°F and an increase of at least 1°C/1.8°F from pretransfusion values) or chills/rigors. With approximately 17 million blood transfusions, including RBCs, plasma, platelet, and cryoprecipitate components, administered annually in the United States, often to those with severe illnesses, ATRs and FNHTRs confer a substantial public health burden. Currently, the prevalence of premedication to prevent acute transfusion reactions in the United States and Canada is variable, ranging from 1.6% in one Canadian institution to as high as 80% in one large US hospital.^2,3

FNHTRs are thought to be caused by cytokines elaborated by donor leukocytes that remain in blood products and/or by recipient antibodies reacting with donor leukocytes.¹ While the clinical course is self-limited, these reactions can cause patients significant distress. The rationale behind acetaminophen premedication is to blunt the febrile response.

ATRs are usually mild, but anaphylaxis (which may include respiratory compromise, hypotension, and even death) can occur. They are caused by recipient histamine release in response to exposure to donor plasma proteins.¹ This provides the theoretical rationale for antihistamine (eg, diphenhydramine) premedication as a prevention strategy.

Data on pretransfusion medication originate from the mid-20th century. In 1952, Ferris et al. published results showing a significant decrease in both febrile and ATRs when blood bottles were injected with an antihistamine.⁴ This was followed, in 1956, by Winter and Taplin’s further demonstration that both febrile and allergic reactions were significantly reduced when patients received units of blood injected with both oral acetylsalicylic acid and an antihistamine (chlorprophenpyridamine).⁵ These trials notably lacked appropriate controls and blinding, and numerous transfusion practice changes have taken place during the subsequent decades.