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U.S. Department of Health and Human Services

Medical Devices

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Hypotension and Bedside Leukocyte Reduction Filters

This is an archived document and is no longer current information.

May 4, 1999

 

Dear Colleague:

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.

 

Reports

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.

 

Recommendations

Based on the current scientific knowledge, FDA recommends the following:

  1. 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.
     
  2. 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.
  3. 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.

FDA Medical Device Public Health Notifications are available on the Internet. You can also be notified through email each time a new Public Health Notification is added to our web page. To subscribe, visit: http://service.govdelivery.com/service/subscribe.html?code=USFDA_39

 

If you have questions about this Notification, please contact FDA's  Division of of Small Manufacturers, International and Consumer Assistance (DSMICA) by e-mail at dsmica@fda.hhs.gov or by phone at 1-800-638-2041 or 301-796-7100
 

Sincerely yours,

 


Kathryn C. Zoon, Ph.D.
Director
Center for Biologics
Evaluation and Research


Elizabeth D. Jacobson, Ph.D.
Acting Director
Center for Devices and
Radiological Health


Janet Woodcock, M.D.
Director
Center for Drug Evaluation
and Research

 

Suggested Reading

Belloni M, Alghisi A, Bettini C, et al. Hypotensive reactions associated with white cell-reduced aphresis platelet concentrates in patients not receiving ACE inhibitors (letter). Transfusion 1998;38:412-13.

Fried MR, Eastlund T, Christie B, et al. Hypotension reactions to white cell-reduced plasma in a patient undergoing angiotensin-converting enzyme inhibitor therapy. Transfusion 1996;36:900-3.

Heddle NM, Klama L, Kelton JG, et al. Investigation of two interventions to prevent acute reactions to platelets. Abstracts of the 24th Congress of the International Blood Transfusion, Abstract SY2BII-05.

Hume HA, Popovsky MA, Benson K, et al. Hypotensive reactions: a previously uncharacterized complication of platelet transfusion? Transfusion 1996; 36:904-9.

Sano H, Koga Y, Hamasaki K, et al. Anaphylaxis associated with white-cell reduction filter (letter). Lancet 1996;347:1053.

Shiba M, Tadokoro K, Sawanobori M, et al. Activation of the contact system by filtration of platelet concentrates with a negatively charged white cell removal filter and measurement of venous blood bradykinin level in patients who received filtered platelets. Transfusion 1997;37:457-462.

Sweeney JD, Dupuis M, and Mega AJ. Hypotensive reactions to red cells filtered at the bedside, but not to those filtered before storage, in patients taking ACE inhibitors (letter). Transfusion 1998;38:410-11.

Yenicesu I, Tezcan I, and Tuncer AM. Hypotensive reactions during platelet transfusions (letter). Transfusion 1998;38:410.