TRANSFUSION Volume 32
September 1992
Number 7
Editorials
Yersinia enterocolitica and white cell filtration of storage. This study demonstrates that even very small degrees of Yersinia species contamination may lead to significant bacterial growth, and that there is an approximately 3-week lag period between the start of blood storage and accelerated Yersinia species proliferation. These observations are consistent with what has been observed of clinically in Yersiniu species transmission by transfusion: the blood donor is reasonably healthy at the time of donation (i.e., has a low level of contamination), and the blood has been in storage for about three weeks before the recipient is at risk. published in this issue of The other four TRANSFUSION evaluate whether units of blood deliberately contaminated with Y. enterocolitica soon after collection can be “cleansed” by reduction by filtration of WBCs early in the storage period. The rationale for all these studies is based on the following series of simple premises of how Yersinia contamination develops in the clinical setting. 1) Y. enterocoliticu is present in the donor’s blood at the time of collection. 2) The donor’s phagocytic cells ingest the bacteria rapidly or have already ingested them in the donor’s circulation. 3) The bacteria, or some of the bacteria, although inside or attached to the phagocytic cells, remain viable. 4) After some time in storage (perhaps a few days or less), the phagocytic cells die, releasing the microorganism into the plasma. 5 ) Yersinia species, which are psychrophilic and iron-dependent, then begin to proliferate after a lag period of a few weeks, and they reach significant numbers after about 3 weeks’ storage. If this sequence of events is correct, then the removal of the Yersinia species-laden WBCs early in the storage period- not too early and certainly not too late-would remove these microorganisms as well. All four studies apparently show this to be the case. A prior study by Hogman et al.12 lends support to the premises outlined above. In that study, it was demonstrated that if microorganisms (not Yersinia species) are inoculated into blood or buffy coats after reduction by filtration of WBCs, their growth is generally far greater
The merging of two separate subjects that have aroused great interest during the past few years-the heightened interest in white cell (WBC) reduction of blood by filtration on one hand and the apparent increased incidence of Yersinia enterocoliticu contamination of blood on the other-has led to the publication of five related studies WBC reduction by in this issue of filtration has been the subject of a number of recent editorials that discussed the various potential and real advantages in reducing the WBC load in blood components and the technical issues related to WBC reduct i ~ n . Y. ~ -enterocolitica ~ contamination of blood has also been the subject of recent and Hoppe” summarized discussions held by the Food and Drug Administration Blood Products Advisory Committee in which the various options for preventing Y. enterocolitica transmission were analyzed. Among these options, the routine filtration of all units of blood early in the storage period was mentioned, but no decision was taken on the desirability of this approach. From most of the articles published on this subject in this issue of it now appears that the filtration of blood soon after collection to remove WBCs may be valuable in reducing, if not eliminating, Yersinia species microorganisms in blood obtained from infected donors. The purposes of this editorial are to point out the similarities and differences among the studies presented in this issue of TRANSFUSION, to indicate problems that still require clarification, and to put the issue of Y. enterocolitica and filtration within the broader context of bacterial contamination of blood. The study of Franzin and Gioannin? sets the stage for the other four studies published here. Those authors found that, of 10 units of blood collected in CPDA-1 that were immediately contaminated with very small inocula of Yersinia species microorganisms (0.1 colony-formingunits [CFU]/mL of blood), 3 showed growth to lo9 CFU per mL over 41 days of storage at refrigerator temperature. Significant growth was observed in 1 of the units after 20 days of storage and in the other 2 units after 26 days
597
598
TRANSFUSION
EDITORIAL
than if the inoculation is done without WBC reduction. Thus, phagocytic cells present in the donor’s blood have a “mopping-up” function during the early hours of blood storage. All four filtration studies published here used similar protocols. Technical details of these protocols are summarized in Table 1. Donor blood was inoculated with Y. enterocolitica soon after collection. The units of blood were then held at room temperature for a number of hours, after which WBCs were removed by filtration. The units were then stored up to 42 days at 5°C. Samples for bacterial culture were taken at various times before and after filtration and during the storage period. Controls consisted of units of blood treated similarly but not subjected to filtration. All studies showed that cultures taken from the filtered units showed no growth (or markedly reduced growth) of Y. enterocolitica,while cultures from the unfiltered control units showed proliferation of Y. enrerocolitica to very high levels, especially after 2 to 3 weeks of storage. Despite the general agreement, there are a number of important differences among the studies, as well as uncertainties and opportunities for further investigation that merit discussion. Inoculum
All four studies used the 0 : 3 strain of Y. enterocolitica; one study4 also used the 0:8 strain. Other strains were not studied, although it is known that other strains of Y. enterocolitica, as well as Y. pseudotuberculosis,
Vol. 32, No. 1-1992
also proliferate in stored bl00d.~While most cases of fatal Yersinia species sepsis and endotoxemia have been adassociated with the 0:3 stain of Y. entero~olitica,’~ ditional studies are needed to evaluate the ability of WBCreducing filters to eliminate other Yersinia species microorganisms from blood as well. The size of the inoculum used in the studies varied from a low dose of less than 1 CFU per mL to a high dose of 150 CFU per mL of donor blood. To the best of this reviewer’s knowledge, however, it must be noted that, there is no good informtion as to the size of the contamination that exists when blood is donated by an asymptomatic carrier, although it has been assumed that contamination is usually at the level of about 1 CFU per mL of blood or less. Thus, we do not know whether an experimental high-dose inoculation is analogous to the usual or worst-case scenario that may occur clinically. This point is critical, as, in a number of instances where the inoculum was high, Yersinia species organisms could be detected even in units of blood that had been filtered. Timing and Temperature
After inoculation of a unit of blood with Y. enterocolitica (or in the clinical setting, the period of time after a contaminated unit is collected), the WBCs present in the unit should be permitted the amount of time necessary to ingest all contaminating microorganisms without disturbing the quality and quantity of any of the useful components in the blood such as platelets, anti-hemo-
Table 1. Comparison of experimental design of four studies Studies Varlable lnoculum serotype lnoculum slze (CFWmL) Timehemperature between donation and inoculation Component inoculated Tlmehemperature between lnoculatlon and component production Tlmehemperature between component production and flltratlon Component filtered Type of filter
Hogman et al.’
Kim et al.*
0:3, 0:8 0.7-1 32 (0:3) 0.3-98.8 ( 0 : 8 ) < 1 hourlRT
0:3 65
0:3 10-1 50
4 hourslRTt
5-6 hourslRT
ImmediatelRT
WBS/Bufty coat 5 hours/RT
WB
5-6 hourslRT
WB 3 hourslRT
WB 7 hours/RT
NA§
< 70 minutes
OvernighWC
Overnight/5’C
WBIBufiy coat Sepacell PL-5N
PRBCs BPF4
PRBCs Sepacell R-500
Antlcoagulant= preservative
CPD
WBCll removal (loglo)
2->3
2-4
‘Colony-formlng units per mL. Room temperature. *Whole blood.
Buchholz et al:
0:3 100
PRBCslI Leukotrap Leukotrap RC Leukotrap RC-300 Nutricel AS-3
t
Wenz et aL3
8 Not applicable. 11 Packed red cells. ? White l cell.
Adsol AS-1 Nutricel AS-3 Not stated
CPD/AdSOl AS-1
> 1.9-2.3
TRANSFUSION 1992-Vol. 32. No. 7
599
EDITORIAL
philic factor, or the red cells themselves. However, a holding time that is too long might permit the WBCs to begin to deteriorate, thereby releasing into the plasma the still-viable microorganisms that were previously ingested. In the studies published in this issue of TRANSFUSION, a holding time of 3 to 7 hours at room temperature was used, undoubtedly in an attempt to mimic various existing practices in many blood processing lab~ . additional ~ period of stororatories. In two ~ t u d i e s ,an age in the refrigerator was permitted after component preparation. No attempt was made in any of the investigations to determine the optimal amount of time or the optimal temperature needed to achieve the desired effect of Yersinia species ingestion. The matter is complicated further by the need to separate blood into various components during this period. In three of the studies presented in this i s s ~ e ,component ~-~ preparation was done before filtration; only afterwards were the concentrated red cells filtered. Thus, if the proposed mechanism of Yersinia species removal is correct, units of plasma and platelets separated from the contaminated units of whole blood would still contain Yersinia species-laden WBCs that may be hazardous to patients receiving these components, as these components had not undergone filtration. Platelet contamination especially deserves consideration, as it accounts for a substantial number of the reported cases of bacterial sepsis after tran~fusi0n.l~ Whether it is possible to filter whole blood prior to component preparation without compromising the efficacy of the resulting components, while still achieving optimal WBC and bacterial removal, remains to be studied. Alternatively, it may be necessary to filter platelets (and perhaps plasma as well) individually at some time soon after separation from whole blood to remove WBCs from these components as well. It is evident that WBC reduction by filtration for the removal of Yersinia species might have profound effects on the manner in which blood component laboratories operate in the future, and it might increase costs and delay availability of blood. Filters A variety of different filters were used in the various studies being discussed. All appeared to be capable of achieving the removal of Y. enterocolitica within the conditions specified. Because no attempt was made in any of the studies to compare the effectiveness of the different filters with regard to WBC or Y. enterocolitica removal, no conclusions can be drawn as to whether there are significant differences among them. In addition, in those instances in which a high dose of inoculum was used and filtration failed to protect against later growth of Y. enterocolitica, it is difficult to ascertain whether this was the result of an overwhelming of the phagocytic
capacity of the WBCs or of the incapability of the filters used to remove all the Yersinia species-laden WBCs present in the unit of blood. If the latter possibility is correct, then there would be an advantage in using filters that achieve the greatest degree of WBC removal possible. Complicating matters further is the fact that it has yet to be demonstrated that the effect of Yersinia species removal is directly related or entirely due to WBC removal. The evidence for this is indirect: cultures performed on contaminated units of blood after the holding period, but before filtration, were sterile. (When the inoculum was very high, the colony count was markedly reduced.) This would suggest that the WBCs in the blood had ingested the bacteria (which would then be removed by WBC filtration). It is possible, however, that WBCs kill phagocytosed bacteria during the holding period. If so, filtration would serve to remove directly the extracellular, uningested bacteria only in those instances in which the phagocytic capacity of the WBCs in the unit is exceeded by the number of contaminating microorganisms. Evidence for this is presented by Buchholz et al.,4 who showed that all postfiltration cultures were sterile, even when there were bacteria still present (presumably extracellularly) immediately before filtration. Other investigators2J raise this possibility as well, although some' consider it unlikely or only a minor factor in Yersinia species removal. It would be important to ascertain to what extent, if any, WBC filters directly remove Yersinia species microorganisms from red cells, as this would determine when filtration should occur. Microorganisms
Y. enterocolitica is not the only bacterial pathogen that may contaminate donor blood. Other bacterial species have also been implicated, and the incidence of transfusion-associated deaths due to bacterial sepsis and/or endotoxemia reported to the Food and Drug Administration appears to be inexplicably increasing in recent years. 13-16 Deaths resulting from the transfusion of contaminated platelet concentrates, in particular, have been reported more frequently in recent years.14 Whether reduction of WBCs by filtration of blood early in the storage period would reduce the hazard of transfusion-induced sepsis due to other bacterial species, as it has that due to Yersinia species, remains to be shown. Furthermore, the filtration conditions that are optimal for preventing Yersinia species sepsis may not be optimal for the prevention of sepsis due to other microorganisms. The previously published study by Hogman et aI.** is germane to this question. Those authors demonstrated that WBCs present in units of blood early in the storage period prevent the proliferation of a variety of bacterial species inoculated into the blood. Neverthe-
600
TRANSFUSION
EDITORIAL
less, this protective effect was not of the same magnitude; nor was the kinetics of bacterial removal by the WBCs the same for all species studied. Furthermore, that study also indicated that other non-WBC-mediated bactericidal mechanisms may also be at work for some species of bacteria. The four filtration studies published in this issue of TRANSFUSION represent an important step toward eliminating Y. enterocolitica contamination as a transfusion hazard. There are still many questions, however, that deserve further study. Perhaps most important among these is the need to make sure that the solution to the Yersinia species problem does not unmask other problems that may be lurking in this complex matter. The decision as to whether all units of blood should be filtered routinely after a holding period will ultimately be made, therefore, after all the risks, costs, and benefits of this procedure have been weighed. More data are required to arrive at a fully informed decision. One suspects that these data are being gathered vigorously.
JACOBNUSBACHER,MD Director, Blood Bank Meir Hospital Kfar Saba, Israel Visiting Professor of Medicine Sackler School of Medicine Tel Aviv University Ramat Aviv, Israel
Vol. 32. No. 7-1992
References 1. Hogman CF, Gong J, Hambraeus A, Johansson CS, Eriksson L. The role of white cells in the transmission of Yersinia enterocofitica in blood components. Transfusion 1992;32:654-7. 2. Kim DM, Brecher ME, Bland LA, et al. Prestorage removal of Yersiniu enferocoIifku from red cells with white cell-reduction filters. Transfusion 1992;32:658-62. 3. Wenz B, Burns ER, Freundlich LF. Prevention of growth of Yersinia enterocolitica in blood by polyester fiber filtration. Transfusion 1992;32:663-6. 4. Buchholz DH, AuBuchon JP, Snyder E, et al. Removal of Yersinia enfemofiticu from AS-1 red cells. Transfusion 1992;32:66772. 5. Franzin I, Gioannini P. Growth of Yersinia species in artificially contaminated blood bags. Transfusion 1992;32:673-6. 6. Snyder EL. Clinical use of white cell-poor blood components (editorial). Transfusion 1989;29:568-71. 7. Heal JM, &hen HJ. Do white cells in stored blood components reduce the likelihood of posttransfusion bacterial sepsis? (editorial). Transfusion 1991;31:581-3. 8. Nemo GJ, McCurdy PR. Prevention of platelet alloimmunization (editorial). Transfusion 1991;31:584-6. 9. Dzik WH. White cell-reduced blood components: Should we go with the flow? (editorial). Transfusion 1991;31:789-91. 10. Aber RC. Transfusion-associated Yersinia enferocoliticu (editorial). Transfusion 1990;30:193-5. 11. Hoppe PA. Interim measures for detection of bacterially contaminated red cell components. Transfusion 1992;32:199-201. 12. Hogman CF, Gong J, Eriksson L, Hambraeus A, Johansson CS. White cells protect donor blood against bacterial contamination. Transfusion 1991;31:620-6. 13. Tipple MA, Bland LA, Murphy JJ, et al. Sepsis associated with transfusion of red cells contaminated with Yersiniu enterocolitica. Transfusion 1990;30:207-13. 14. Goldman M, Blajchman MA. Blood product-associated bacterial sepsis. Transfus Med Rev 1991;7:73-83. 15. Honig CL, Bove JR. Transfusion-associated fatalities: review of Bureau of Biologics reports 1976-1978. Transfusion 1980;20:65361. 16. Sazama K. Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion 1990;30:583-90.
September 1992
Number 7
Editorials
Yersinia enterocolitica and white cell filtration of storage. This study demonstrates that even very small degrees of Yersinia species contamination may lead to significant bacterial growth, and that there is an approximately 3-week lag period between the start of blood storage and accelerated Yersinia species proliferation. These observations are consistent with what has been observed of clinically in Yersiniu species transmission by transfusion: the blood donor is reasonably healthy at the time of donation (i.e., has a low level of contamination), and the blood has been in storage for about three weeks before the recipient is at risk. published in this issue of The other four TRANSFUSION evaluate whether units of blood deliberately contaminated with Y. enterocolitica soon after collection can be “cleansed” by reduction by filtration of WBCs early in the storage period. The rationale for all these studies is based on the following series of simple premises of how Yersinia contamination develops in the clinical setting. 1) Y. enterocoliticu is present in the donor’s blood at the time of collection. 2) The donor’s phagocytic cells ingest the bacteria rapidly or have already ingested them in the donor’s circulation. 3) The bacteria, or some of the bacteria, although inside or attached to the phagocytic cells, remain viable. 4) After some time in storage (perhaps a few days or less), the phagocytic cells die, releasing the microorganism into the plasma. 5 ) Yersinia species, which are psychrophilic and iron-dependent, then begin to proliferate after a lag period of a few weeks, and they reach significant numbers after about 3 weeks’ storage. If this sequence of events is correct, then the removal of the Yersinia species-laden WBCs early in the storage period- not too early and certainly not too late-would remove these microorganisms as well. All four studies apparently show this to be the case. A prior study by Hogman et al.12 lends support to the premises outlined above. In that study, it was demonstrated that if microorganisms (not Yersinia species) are inoculated into blood or buffy coats after reduction by filtration of WBCs, their growth is generally far greater
The merging of two separate subjects that have aroused great interest during the past few years-the heightened interest in white cell (WBC) reduction of blood by filtration on one hand and the apparent increased incidence of Yersinia enterocoliticu contamination of blood on the other-has led to the publication of five related studies WBC reduction by in this issue of filtration has been the subject of a number of recent editorials that discussed the various potential and real advantages in reducing the WBC load in blood components and the technical issues related to WBC reduct i ~ n . Y. ~ -enterocolitica ~ contamination of blood has also been the subject of recent and Hoppe” summarized discussions held by the Food and Drug Administration Blood Products Advisory Committee in which the various options for preventing Y. enterocolitica transmission were analyzed. Among these options, the routine filtration of all units of blood early in the storage period was mentioned, but no decision was taken on the desirability of this approach. From most of the articles published on this subject in this issue of it now appears that the filtration of blood soon after collection to remove WBCs may be valuable in reducing, if not eliminating, Yersinia species microorganisms in blood obtained from infected donors. The purposes of this editorial are to point out the similarities and differences among the studies presented in this issue of TRANSFUSION, to indicate problems that still require clarification, and to put the issue of Y. enterocolitica and filtration within the broader context of bacterial contamination of blood. The study of Franzin and Gioannin? sets the stage for the other four studies published here. Those authors found that, of 10 units of blood collected in CPDA-1 that were immediately contaminated with very small inocula of Yersinia species microorganisms (0.1 colony-formingunits [CFU]/mL of blood), 3 showed growth to lo9 CFU per mL over 41 days of storage at refrigerator temperature. Significant growth was observed in 1 of the units after 20 days of storage and in the other 2 units after 26 days
597
598
TRANSFUSION
EDITORIAL
than if the inoculation is done without WBC reduction. Thus, phagocytic cells present in the donor’s blood have a “mopping-up” function during the early hours of blood storage. All four filtration studies published here used similar protocols. Technical details of these protocols are summarized in Table 1. Donor blood was inoculated with Y. enterocolitica soon after collection. The units of blood were then held at room temperature for a number of hours, after which WBCs were removed by filtration. The units were then stored up to 42 days at 5°C. Samples for bacterial culture were taken at various times before and after filtration and during the storage period. Controls consisted of units of blood treated similarly but not subjected to filtration. All studies showed that cultures taken from the filtered units showed no growth (or markedly reduced growth) of Y. enterocolitica,while cultures from the unfiltered control units showed proliferation of Y. enrerocolitica to very high levels, especially after 2 to 3 weeks of storage. Despite the general agreement, there are a number of important differences among the studies, as well as uncertainties and opportunities for further investigation that merit discussion. Inoculum
All four studies used the 0 : 3 strain of Y. enterocolitica; one study4 also used the 0:8 strain. Other strains were not studied, although it is known that other strains of Y. enterocolitica, as well as Y. pseudotuberculosis,
Vol. 32, No. 1-1992
also proliferate in stored bl00d.~While most cases of fatal Yersinia species sepsis and endotoxemia have been adassociated with the 0:3 stain of Y. entero~olitica,’~ ditional studies are needed to evaluate the ability of WBCreducing filters to eliminate other Yersinia species microorganisms from blood as well. The size of the inoculum used in the studies varied from a low dose of less than 1 CFU per mL to a high dose of 150 CFU per mL of donor blood. To the best of this reviewer’s knowledge, however, it must be noted that, there is no good informtion as to the size of the contamination that exists when blood is donated by an asymptomatic carrier, although it has been assumed that contamination is usually at the level of about 1 CFU per mL of blood or less. Thus, we do not know whether an experimental high-dose inoculation is analogous to the usual or worst-case scenario that may occur clinically. This point is critical, as, in a number of instances where the inoculum was high, Yersinia species organisms could be detected even in units of blood that had been filtered. Timing and Temperature
After inoculation of a unit of blood with Y. enterocolitica (or in the clinical setting, the period of time after a contaminated unit is collected), the WBCs present in the unit should be permitted the amount of time necessary to ingest all contaminating microorganisms without disturbing the quality and quantity of any of the useful components in the blood such as platelets, anti-hemo-
Table 1. Comparison of experimental design of four studies Studies Varlable lnoculum serotype lnoculum slze (CFWmL) Timehemperature between donation and inoculation Component inoculated Tlmehemperature between lnoculatlon and component production Tlmehemperature between component production and flltratlon Component filtered Type of filter
Hogman et al.’
Kim et al.*
0:3, 0:8 0.7-1 32 (0:3) 0.3-98.8 ( 0 : 8 ) < 1 hourlRT
0:3 65
0:3 10-1 50
4 hourslRTt
5-6 hourslRT
ImmediatelRT
WBS/Bufty coat 5 hours/RT
WB
5-6 hourslRT
WB 3 hourslRT
WB 7 hours/RT
NA§
< 70 minutes
OvernighWC
Overnight/5’C
WBIBufiy coat Sepacell PL-5N
PRBCs BPF4
PRBCs Sepacell R-500
Antlcoagulant= preservative
CPD
WBCll removal (loglo)
2->3
2-4
‘Colony-formlng units per mL. Room temperature. *Whole blood.
Buchholz et al:
0:3 100
PRBCslI Leukotrap Leukotrap RC Leukotrap RC-300 Nutricel AS-3
t
Wenz et aL3
8 Not applicable. 11 Packed red cells. ? White l cell.
Adsol AS-1 Nutricel AS-3 Not stated
CPD/AdSOl AS-1
> 1.9-2.3
TRANSFUSION 1992-Vol. 32. No. 7
599
EDITORIAL
philic factor, or the red cells themselves. However, a holding time that is too long might permit the WBCs to begin to deteriorate, thereby releasing into the plasma the still-viable microorganisms that were previously ingested. In the studies published in this issue of TRANSFUSION, a holding time of 3 to 7 hours at room temperature was used, undoubtedly in an attempt to mimic various existing practices in many blood processing lab~ . additional ~ period of stororatories. In two ~ t u d i e s ,an age in the refrigerator was permitted after component preparation. No attempt was made in any of the investigations to determine the optimal amount of time or the optimal temperature needed to achieve the desired effect of Yersinia species ingestion. The matter is complicated further by the need to separate blood into various components during this period. In three of the studies presented in this i s s ~ e ,component ~-~ preparation was done before filtration; only afterwards were the concentrated red cells filtered. Thus, if the proposed mechanism of Yersinia species removal is correct, units of plasma and platelets separated from the contaminated units of whole blood would still contain Yersinia species-laden WBCs that may be hazardous to patients receiving these components, as these components had not undergone filtration. Platelet contamination especially deserves consideration, as it accounts for a substantial number of the reported cases of bacterial sepsis after tran~fusi0n.l~ Whether it is possible to filter whole blood prior to component preparation without compromising the efficacy of the resulting components, while still achieving optimal WBC and bacterial removal, remains to be studied. Alternatively, it may be necessary to filter platelets (and perhaps plasma as well) individually at some time soon after separation from whole blood to remove WBCs from these components as well. It is evident that WBC reduction by filtration for the removal of Yersinia species might have profound effects on the manner in which blood component laboratories operate in the future, and it might increase costs and delay availability of blood. Filters A variety of different filters were used in the various studies being discussed. All appeared to be capable of achieving the removal of Y. enterocolitica within the conditions specified. Because no attempt was made in any of the studies to compare the effectiveness of the different filters with regard to WBC or Y. enterocolitica removal, no conclusions can be drawn as to whether there are significant differences among them. In addition, in those instances in which a high dose of inoculum was used and filtration failed to protect against later growth of Y. enterocolitica, it is difficult to ascertain whether this was the result of an overwhelming of the phagocytic
capacity of the WBCs or of the incapability of the filters used to remove all the Yersinia species-laden WBCs present in the unit of blood. If the latter possibility is correct, then there would be an advantage in using filters that achieve the greatest degree of WBC removal possible. Complicating matters further is the fact that it has yet to be demonstrated that the effect of Yersinia species removal is directly related or entirely due to WBC removal. The evidence for this is indirect: cultures performed on contaminated units of blood after the holding period, but before filtration, were sterile. (When the inoculum was very high, the colony count was markedly reduced.) This would suggest that the WBCs in the blood had ingested the bacteria (which would then be removed by WBC filtration). It is possible, however, that WBCs kill phagocytosed bacteria during the holding period. If so, filtration would serve to remove directly the extracellular, uningested bacteria only in those instances in which the phagocytic capacity of the WBCs in the unit is exceeded by the number of contaminating microorganisms. Evidence for this is presented by Buchholz et al.,4 who showed that all postfiltration cultures were sterile, even when there were bacteria still present (presumably extracellularly) immediately before filtration. Other investigators2J raise this possibility as well, although some' consider it unlikely or only a minor factor in Yersinia species removal. It would be important to ascertain to what extent, if any, WBC filters directly remove Yersinia species microorganisms from red cells, as this would determine when filtration should occur. Microorganisms
Y. enterocolitica is not the only bacterial pathogen that may contaminate donor blood. Other bacterial species have also been implicated, and the incidence of transfusion-associated deaths due to bacterial sepsis and/or endotoxemia reported to the Food and Drug Administration appears to be inexplicably increasing in recent years. 13-16 Deaths resulting from the transfusion of contaminated platelet concentrates, in particular, have been reported more frequently in recent years.14 Whether reduction of WBCs by filtration of blood early in the storage period would reduce the hazard of transfusion-induced sepsis due to other bacterial species, as it has that due to Yersinia species, remains to be shown. Furthermore, the filtration conditions that are optimal for preventing Yersinia species sepsis may not be optimal for the prevention of sepsis due to other microorganisms. The previously published study by Hogman et aI.** is germane to this question. Those authors demonstrated that WBCs present in units of blood early in the storage period prevent the proliferation of a variety of bacterial species inoculated into the blood. Neverthe-
600
TRANSFUSION
EDITORIAL
less, this protective effect was not of the same magnitude; nor was the kinetics of bacterial removal by the WBCs the same for all species studied. Furthermore, that study also indicated that other non-WBC-mediated bactericidal mechanisms may also be at work for some species of bacteria. The four filtration studies published in this issue of TRANSFUSION represent an important step toward eliminating Y. enterocolitica contamination as a transfusion hazard. There are still many questions, however, that deserve further study. Perhaps most important among these is the need to make sure that the solution to the Yersinia species problem does not unmask other problems that may be lurking in this complex matter. The decision as to whether all units of blood should be filtered routinely after a holding period will ultimately be made, therefore, after all the risks, costs, and benefits of this procedure have been weighed. More data are required to arrive at a fully informed decision. One suspects that these data are being gathered vigorously.
JACOBNUSBACHER,MD Director, Blood Bank Meir Hospital Kfar Saba, Israel Visiting Professor of Medicine Sackler School of Medicine Tel Aviv University Ramat Aviv, Israel
Vol. 32. No. 7-1992
References 1. Hogman CF, Gong J, Hambraeus A, Johansson CS, Eriksson L. The role of white cells in the transmission of Yersinia enterocofitica in blood components. Transfusion 1992;32:654-7. 2. Kim DM, Brecher ME, Bland LA, et al. Prestorage removal of Yersiniu enferocoIifku from red cells with white cell-reduction filters. Transfusion 1992;32:658-62. 3. Wenz B, Burns ER, Freundlich LF. Prevention of growth of Yersinia enterocolitica in blood by polyester fiber filtration. Transfusion 1992;32:663-6. 4. Buchholz DH, AuBuchon JP, Snyder E, et al. Removal of Yersinia enfemofiticu from AS-1 red cells. Transfusion 1992;32:66772. 5. Franzin I, Gioannini P. Growth of Yersinia species in artificially contaminated blood bags. Transfusion 1992;32:673-6. 6. Snyder EL. Clinical use of white cell-poor blood components (editorial). Transfusion 1989;29:568-71. 7. Heal JM, &hen HJ. Do white cells in stored blood components reduce the likelihood of posttransfusion bacterial sepsis? (editorial). Transfusion 1991;31:581-3. 8. Nemo GJ, McCurdy PR. Prevention of platelet alloimmunization (editorial). Transfusion 1991;31:584-6. 9. Dzik WH. White cell-reduced blood components: Should we go with the flow? (editorial). Transfusion 1991;31:789-91. 10. Aber RC. Transfusion-associated Yersinia enferocoliticu (editorial). Transfusion 1990;30:193-5. 11. Hoppe PA. Interim measures for detection of bacterially contaminated red cell components. Transfusion 1992;32:199-201. 12. Hogman CF, Gong J, Eriksson L, Hambraeus A, Johansson CS. White cells protect donor blood against bacterial contamination. Transfusion 1991;31:620-6. 13. Tipple MA, Bland LA, Murphy JJ, et al. Sepsis associated with transfusion of red cells contaminated with Yersiniu enterocolitica. Transfusion 1990;30:207-13. 14. Goldman M, Blajchman MA. Blood product-associated bacterial sepsis. Transfus Med Rev 1991;7:73-83. 15. Honig CL, Bove JR. Transfusion-associated fatalities: review of Bureau of Biologics reports 1976-1978. Transfusion 1980;20:65361. 16. Sazama K. Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion 1990;30:583-90.
