Bacterial Contamination of Cellular Blood Products

Introduction

Bacterial sepsis from a contaminated blood component is a rare but potentially serious complication of blood transfusion.   Timely recognition and appropriate management of a septic transfusion reaction can be critical to the well being of the patient.

Background

Several precautions are routinely taken to minimize the risk of collection or transfusion of a bacterially contaminated blood product. Standard procedures performed include:  assessment of the donor’s health by history and physical examination; sterilization of the venipuncture site; sterile collection and processing techniques; and a visual check of the product by blood bank personnel prior to issuance of the product.  Despite these measures, bacterial contamination of packed red cells and platelets does occasionally occur.

The estimated rate of bacterial contamination of a unit of packed red blood cells ranges from 1 per 31,000 to less than 1 per 1 million units (1,2).  Red cells are stored at 1- 4°C for up to 42 days; organisms that survive at cold temperatures in the presence of heme and dextrose are the usual pathogens.  Yersinia enterocolitica is the most common organism associated with septic reactions to red cells. Several case reports of septic transfusions due to Yersinia enterocolitica have shown asymptomatic blood donors to be the most likely source.  Organisms which survive in red cells are most often gram negative types which can produce endotoxins.  Besides Yersinia, these include Serratia, Pseudomonas, and Enterobacter species.  Because of these endotoxins, transfused patients may rapidly develop septic shock. Twenty-one episodes of transfusion-related sepsis reported between 1987 and 1997 were due to Yersinia enterocolitica.  The fatality rate in these cases was 52%.  Other organisms reported in cases of red cell transfusion-related sepsis, such as Serratia liquefaciens, have an even greater fatality rate.

A key point to remember is that autologous donation has the same risks of bacterial contamination as allogeneic donation.  The literature reports a few cases of Yersinia sepsis in patients who donated autologous blood and then became septic with transfusion of the product (3). In one case, the patient was hospitalized in the interim between blood donation and surgery with Yersinia sepsis.  Because the transfusion service was not informed of this, the unit was later transfused. If a patient has a known episode of bacteremia, sepsis, or complications from an ongoing infection and has recently donated autologous blood for an upcoming surgery, the blood bank should be notified so that the unit of blood may be appropriately evaluated and, if necessary, discarded.

The rate of bacterial contamination from a platelet product is estimated to be 1 in 1000 to 1 in 3600 units (1,4), while the risk of symptomatic sepsis or septic complications due to bacterial contamination of platelets is between 1 in 2000 and 1 in 12000 random donor units (2).  Fatalities due to bacterial contamination of blood components occurs three times more often with a platelet product than a unit of red cells (2).  Random donor platelets have a statistically greater risk of contamination both because the product is pooled from four or more donors, and because the pooling process requires an open system. Platelet products are stored at room temperature (20-24°C) for up to 5 days. Organisms which proliferate in platelets are most often skin commensals such as Staphylococcus epidermis and Bacillus species.  These organisms may be acquired by skin plugs that are collected at the time of venipuncture into the platelet product. Gram negative organisms have been reported and include Klebsiella pneumoniae, Serratia marcescens, Salmonella species, Escherichia coli and Pseudomonas aeruginosa.  Contamination by these organisms is most often due to asymptomatic bacteremia in the donor.  Fatalities due to platelet contamination implicate gram positive and gram negative organisms in relatively equal numbers.

Recognition and management of a transfusion reaction due to bacterial contaminated blood product

The severity of the reaction may depend on several factors, including the organism involved and the ability to produce endotoxin, the immune status of the patient, and whether or not antibiotics are already being administered.  In general, reactions to contaminated red cells tend to be rapid and severe. The patient may develop circulatory collapse and signs of endotoxic shock during or immediately following the transfusion.  Reactions from contaminated platelets can be much more variable in their severity, and may manifest during the transfusion, or up to 4 hours after the unit has been transfused.

Any patient who has a reaction during infusion of a blood product that includes fever (often greater than 2°C above baseline), rigors, and/or nausea should be evaluated, and the transfusion should be stopped. Vomiting or diarrhea may be present.  Dyspnea or cyanosis may rarely be seen.  Hypotension may accompany the reaction.  The patient’s vital signs should be recorded frequently, with monitoring for the development of oliguria or hypotension.  The blood product and appropriate samples should be sent for a transfusion reaction evaluation.  The degree of severity of the reaction, as well as the changes in vital signs, should be conveyed to the blood bank. Such communication will assist the transfusion medicine physician in deciding if bacterial cultures of the blood product are warranted, and in guiding the clinician in appropriate management of the transfusion reaction.

If evidence of circulatory collapse is present, intravenous hydration with normal saline should be maintained at a rapid rate to support renal perfusion.  Cultures on the patient’s blood should be drawn, and then antibiotic coverage for both facultative gram negative and gram positive organisms should be initiated as soon as possible.  The patient may need to be transferred to an intensive care unit for close monitoring and blood pressure support.  Obtaining a baseline PT, PTT, fibrinogen, and platelet count is appropriate, and frequent monitoring of these parameters may be necessary if signs of DIC develop.  All supportive measures used for a patient in septic shock should be initiated.

Past and future efforts to prevent transfusion of a bacterially contaminated cellular product

Many studies have been undertaken to determine if a test could be used to consistently detect bacterial contamination of a cellular blood product.  Tests evaluated have included gram stain and culture, indicator strips to detect changes in glucose and pH within individual units, endotoxin assays, and chemiluminescence –linked universal bacterial rRNA probes.  Each of the tests has been found to have limitations, with regard to one or more of the following: sensitivity, rapid availability, ease, and cost (4).  Use of antibiotic-labeled probes and microvolume fluorimetry to detect bacteria in blood products is still in experimental stages, but may prove useful in the future (5).

More recently, attention has been focused on ways to reduce or eliminate bacteria from a cellular blood product.  A simple method currently used in Europe is to divert the first 30 mL of a collection into a sampling pouch.  Preliminary data suggest a 75% reduction in risk of bacterial contamination using this method (6).  Psoralen compounds  (particularly S-59) and long-wavelength ultraviolet light, when used in combination, appear to result in photochemical inactivation of viruses and bacteria.   Initial studies with platelets indicate that the treatment effectively inactivates high doses of bacteria, and does not significantly compromise in vitro or in vivo platelet function (7).  A multicenter clinical trial with this treatment is ongoing. In Europe, researchers are investigating whether methylene blue derivatives will prove to be suitable photodynamic antimicrobial agents in blood products.  Although the technology of photoinactivation is still in an experimental phase, it may ultimately eliminate the risk of bacterial contamination of a cellular blood product, and supplant the need for detection.  Until that time, however, ongoing recognition and management of a septic transfusion reaction is the most powerful tool in minimizing the morbidity from such an occurrence.

1. Barrett B.B., Andersen J.W., and Anderson K.C.   Transfusion 1993; 33: 228-233. 

2. American Association of Blood Banks Bulletin, #96-6, Aug 7, 1996.  

3. MMWR  1997; 46: 553-555.

4. Mitchell K.T. and Brecher M.E. Transfusion Med Reviews 1999; 13: 132-144.   

5. Brecher M.E. et. al. Transfusion 2000; 40: 411-413.

6. Bruneau C. et al. Transfusion 2001; 41: 74- 81. 

7. Lin L et al. Transfusion 1997; 37: 423-435. 

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