ADDENDA Jan. 3, 2002

9. A blood banker in a large urban area wrote that they see "an unacceptably high number of hemolyzed leukoreduced units". They report seeing hemolysis both in units they receive from their community blood supplier and in ones they draw and leukoreduce themselves. They use leukoreduction filtersets that are docked to the unit for filtering and they have contacted the filter set manufacturer numerous times about what could be wrong with their process that leads to this hemolysis. The responding blood banker laments that they have not gotten a complete answer from the filter manufacturer, so that there is still incomplete resolution of the problems. The responding blood banker comments that they have changed some steps in the leukoreduction procedure such as: never squeezing units to initiate the blood flow; always filtering in the cold and filtering fresh units only. These changes have helped some. A bigger concern for the responding blood banker is that when they return hemolyzed RBC units to the community blood supplier, they get back a response like "unit was not hemolyzed when issued to hospital" ....which suggests to the responding blood banker that the blood supplier believes that the hospital does something to cause the hemolysis (such as wrong storage temperature or other product mishandling) and is concerned that the blood supplier might not be investigating the root cause of this problem.

ADDENDA Jan. 7, 2002

10. A blood banker reports that a similar situation of apparent gross segment hemolysis occurred with some of our colleagues in Canada. Several factors appeared to play a role in segment hemolysis. One factor was perception of color in the segment and another was the sealing technique and equipment used. As far as the responding blood banker was aware, no strict and/or validated criteria are used to determine what color of the supernatant is 'bad'. Therefore, different hospital centers may use different pink to red color criteria to censor RBC units. Additionally, two abstracts presented at the 2000 AABB meeting #SP68 and #SP86 (Transfusion 40;10S: 62S and 66S) studied segment hemolysis in pre-storage whole blood and red cell filter systems and found high variability in segment color with no correlation to actual bag hemolysis. A finding corroborated by the group at University of British Columbia in an abstract reported at the 2001 ASH meeting and by the individual reporting this phenomenon. The responding blood banker added that another factor affecting segment color is the type of bag system used to collect the whole blood. Some systems will have red cell concentrate (RCC) segments with low hematocrits while other systems produce RCC with high hematocrits. Therefore, two segments from two RCC with the same red cell mass and hemolysis values will have differing color with the higher hematocrit segment having higher supernatant hemoglobin value and deeper pink or red color. The responding blood banker is curious if all RCC units returned are from RCC filter systems and not from whole blood filter systems? Some blood centers dramatically reduced segment hemolysis by switching from a metal head segment sealer to a ceramic head sealer. Apparently, the ceramic head sealer is more tolerant of repeat sealing. The responding blood banker has learned that a paper is to be published this month in Transfusion Medicine Reviews (TRM) entitled "Red Blood Cell Hemolysis During Processing" TRM. Vol.16 (1). January 2002. The responding blood banker believes that this article should give an in depth and informative discussion of the factors involved in red cell storage hemolysis.

ADDENDA Jan. 8, 2002

11. A blood Banker from the Basque Blood Transfusion Center in Spain wrote: "I would like to add some observations that we made in our blood center: We started universal leukoreduction in August 1999 using two kinds of bags: 1) with a single filter in line to obtain filtered whole blood from which was then obtained red cells in additive solution and plasma, or 2) with two filters in line in order to obtain filtered PRP and red cells; red cells are then mixed with additive solution and filtered. By these methods two kinds of lines with segments were obtained: those containing whole blood and those containing red cells suspended in additive solution. We never saw signs of hemolysis in the former but frequently in the second. We also suspected that the hemolysis could be related to the electronic sealer, an so we planned an observation: We sealed 50 bags with a standard electronic sealer and another 50 bags with standard hand sealer clips (Fenwall). All the lines contained red cells in additive solution. The results were: None of the 50 bags in which hand sealer clips were used presented signs of hemolysis in their segments, but 48 out of 50 in wich an electronic sealer was used presented signs of hemolysis. In summary, electronic sealers may cause hemolysis only when applied to segments with red cells suspended in a low-protein medium, but this does not happen if hand sealer clips are used. The fact that a low protein medium is prone to produce hemolysis is very well known; this phenomenon may be averted by the addition of traces of mannitol as usually is included in most standard red cell additive solutions. Perhaps in a stressful condition for red cells such as the contact with an electronic sealer may induce hemolysis, whereas in whole blood red cells may be protected by a protein-rich medium."

ADDENDA Jan. 10, 2002

12. A blood banker who works for a major blood collection agency submitted a follow up question for comment #10 above. The comment is "As far as the responding blood banker was aware, no strict and/or validated criteria are used to determine what color of the supernatant is 'bad'. Therefore, different hospital centers may use different pink to red color criteria to censor RBC units." The blood banker who questions comment #10 would like to know if some uniform standard has been established to determine acceptable color criteria? If so, are their comparative charts available from any manufacturer? (Editor's note: At least one laboratory has made up their own hemoglobin standards using food coloring. The color and intensity of these standards was matched with actual hemolyzed specimens with measured amounts of hemoglobin, as part of a validation study for a piece of chemistry equipment some years ago).

13. A blood banker from Southern California wrote that her donor collection center is seeing hemolysis in their leukocyte-reduced RBCs, and that this is a new observation. They received 20 cases of Leukocyte Reduction filters (all from the same lot) this December, and after using 11 of these cases, they observed 11 hemolyzed units. The hemolyzed units were discovered either during labeling or in distribution before shipment. The filter manufacturer was contacted and a formal complaint was filed. According to the blood banker, she was told that no other complaints had been lodged on that lot number. The filter manufacturer sent the donor center guidelines to review with their staff. Among the guidelines was a recommendation to avoid shaking a unit hard after adding Adsol to it, as such shaking might damage red cell membranes, causing them to lyse when the unit is run through a leukocyte reduction filter. Another recommendation was to perform irradiation AFTER leukocyte reduction (not irradiation and then leukocyte reduction), to avoid running irradiated cells through a leukocyte reduction filter.

ADDENDA Feb. 20, 2002

14. A blood banker from a blood center in California reports that when they began leukoreducing units they were seeing more hemolysis than with non-leukoreduced units. The reporting center states that they sterile dock the filters to the packed cell units. The filter manufacturer assessed their procedures and suggested more plasma be left on the units (to the shoulder of the original bag). With that change they report seeing an increase in hemolysis only as the units near expiration. No specific percentages were reported, but the reporting blood banker states that the percentage of hemolyzed leukocyte-reduced units does not seem to be much higher that with non-leukoreduced units. The Adsol (AS-1) units do seem to show less hemolysis than non-Adsol units. As with others who have reported increased hemolysis with leukocyte-reduced RBCs, the actually cause of the hemolysis is not known.

ADDENDA Dec. 11, 2004

15. Editor's note: The FDA/CBER Safety Information: Potential Hemolysis in Red Blood Cells and Whole Blood Leukocyte Reduced Products Manufactured with the Pall BPF4 Filter may be germane to this discussion.

ADDENDA Dec. 18, 2004

16. Editor's note: Please see the new AABB Alert, FDA/CBER update to the above Safety Info & Recall of Leukocyte Reduction BPF4 High Efficiency Filter

ADDENDA Feb. 26, 2005

17. The Editor wishes to advise colleagues of the latest recall update here.

ADDENDA Mar. 9, 2005

18. A colleague in California reports that her blood collection center is aware of the problem of hemolysis of RBC and the recall of certain lots of filters. Her center has made two procedural changes to cut down on the chances of shipping hemolyzed RBCs to customer hospitals.

• They leuko-reduce the RBCs within 3 to 5 days of collection, then let the units rest (settle) for a period of time (not disclosed)
• They check the units for hemolysis before issue using a color comparator (from Haemonetics). If on inspection a unit looks suspicious for hemolysis, it is not shipped.

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator