May 4, 1999
This is to alert you to the possibility that patients who receive blood products transfused through a bedside leukocyte reduction filter may develop a precipitous drop in blood pressure. These reactions have a rapid onset. In some cases, patients also develop respiratory distress and shock. In most situations, the reactions resolve when the transfusion is discontinued and when appropriate medical intervention is performed.
Since 1994, FDA has received over 80 reports of patients developing significant hypotensive events while receiving blood products transfused through a bedside leukocyte reduction filter. It is estimated that approximately 20 million bedside leukocyte reduction filters were used during this period. Although some sources have attributed several of these events to the use of angiotensin converting enzyme (ACE) inhibitors and the use of negatively charged filter surfaces, FDA’s analysis of these reports indicated that neither ACE inhibitor therapy nor exposure to negatively charged filter surfaces were consistently associated with these events. The reactions occurred with a variety of blood products, although the majority of events occurred during platelet transfusions. The common variable in almost all of the hypotensive events appeared to be bedside leukocyte reduction filtration.
It was also noted that there are almost no adverse event reports associated with the use of in-process, leukocyte-reduced blood products, i.e., blood products that are leukocyte-reduced by blood collection centers or laboratories at the time of collection or after the product was stored. This may be because the longer storage time allows more time for bradykinin to break down before the product is transfused.
Cause of problem
A review of the literature indicates that many authors believe these reactions occur more frequently in patients receiving ACE inhibitor therapy. It is hypothesized that these reactions are due to the ACE inhibitors' tendency to retard degradation of bradykinin, a potent vasodilator. Some authors have shown evidence that bradykinin may be generated as a result of filtration at room temperature or when the storage period for filtered blood is insufficient to inactivate bradykinin. Others have discussed the possibility that these reactions occur when the negatively charged membranes in these filters activate Factor XII, one of the blood clotting factors, which triggers a production of bradykinin. However, there have also been adverse events reported with the use of positively charged filters.
Based on the current scientific knowledge, FDA recommends the following:
- Watch for a precipitous drop in blood pressure. The primary clinical manifestation of the reaction is the sudden onset of a severe hypotensive episode within one hour of transfusing blood or blood components through a bedside leukocyte reduction filter. The hypotension may be associated with respiratory distress, facial flushing, abdominal pain and nausea, and loss of consciousness.
- Immediately stop the transfusion. Should the patient develop signs of a leukocyte reduction blood filter reaction, immediately stop the transfusion. A rapid resolution of the symptoms is usually seen once the transfusion is discontinued. Follow your institution’s protocol for treatment of transfusion reactions.
- Use blood products leukocyte-reduced at the time of collection or during laboratory storage if available. Whenever feasible, should the patient’s condition require such products, use blood products leukocyte-reduced during the time it was collected or during its laboratory storage period.
Reporting adverse events to FDA
FDA is interested in additional data on adverse events involving the use of leukocyte reduction filters. Healthcare providers employed by health care facilities that are subject to FDA’s user facility reporting requirements should follow the reporting procedures established by their facility. All other providers may submit their reports to MedWatch, FDA’s voluntary reporting program. The reports can be submitted by phone at 1-800-FDA-1088; by fax at 1-800- FDA-0178; via the MedWatch website, or by mail to MedWatch, FDA, HF-2, 5600 Fishers Lane, Rockville, Maryland 20852-9787.
Getting more information
If you have questions regarding this letter, please contact Leslie Holness, M.D., Center for Biologics Evaluation and Research, FDA, 1401 Rockville Pike, Mail Stop HFM-375, Rockville, MD 20852-1448, by fax at 301-827-3534; or by e-mail at HOLNESS@cber.fda.gov.
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Kathryn C. Zoon, Ph.D.
Elizabeth D. Jacobson, Ph.D.
Janet Woodcock, M.D.
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