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Volume (Plasma) Reduced Platelet

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We hold to a pretty strict ABO compatible platelet transfusion policy (anyone else still out there ;)) ... Most of our platelets are volume reduced for this reason.  Most literature states a 4 hour expiration date, but we use a closed system to process and there doesn't seem to be a determination of the maximum allowable storage for this?

Does anyone have any advice for me on this?  Thank you!!!

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I am not familiar with using volume reduced platelets, but if the unit is not entered in any way, i do not see why the expiration would change.  But this is a question for AABB.

Scott

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2 hours ago, SMILLER said:

I am not familiar with using volume reduced platelets, but if the unit is not entered in any way, i do not see why the expiration would change.  But this is a question for AABB.

Scott

Thanks Scott! 

In the newest AABB Tech manual:  Method 6-13 Removing Plasma from Platelets:

Notes #2:  If a sterile connection device is used for removing plasma from a hemapheresis component or individual platelet concentrate, the unit is considered functionally closed and it is not necessary to impose a 4-hour expiration interval required for entered platelets.  However, no data exist to support storage of reduced-volume platelet concentrates: therefore, it is preferable to transfuse them as soon as possible.   

Wouldn't it be easier if they could just tell me an exact acceptable expiration? haha

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In my experience, if the platelet product is removed from the original container, the expiration period may be affected by the new storage container's ability to maintain optimal storage conditions. Apheresis platelets are collected in bags that are gas-permeable - if product is transferred to another type of bag (not validated for platelet storage),  this should be considered when assigning the expiration date/time even if you volume-depleted using a sterile connecting device. 

I also consider this when removing the supernatant from CPDA or AS red blood cells (as in intrauterine or exchange transfusions) - you can do everything in a functionally closed system but when you remove the "food", the red cells do not exist in the same environment and cannot be expected to maintain the same functionality.

The reason that the Technical Manual is not going to specify is that everything depends on the validation of functional survival of the stored platelet and there isn't data available to make a valid claim.

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I seem to remember that the concentration of platelets in plasma is an important part of QC for the 5 day expiration, something about pH changes over time I think, which may be why platelets come as singles, doubles and triples? I would check/clarify with your blood bank/supplier. As applejw said; you are changing the environment, which may impact the functional survival of the stored platelets.

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22 hours ago, applejw said:

In my experience, if the platelet product is removed from the original container, the expiration period may be affected by the new storage container's ability to maintain optimal storage conditions. Apheresis platelets are collected in bags that are gas-permeable - if product is transferred to another type of bag (not validated for platelet storage),  this should be considered when assigning the expiration date/time even if you volume-depleted using a sterile connecting device. 

I also consider this when removing the supernatant from CPDA or AS red blood cells (as in intrauterine or exchange transfusions) - you can do everything in a functionally closed system but when you remove the "food", the red cells do not exist in the same environment and cannot be expected to maintain the same functionality.

The reason that the Technical Manual is not going to specify is that everything depends on the validation of functional survival of the stored platelet and there isn't data available to make a valid claim.

Thank you for the info!  Yeah, the data doesn't seem to be there - but I still wish they would just give us a definite outdate requirement haha.

I did find some information in The Bethesda Handbook of Clinical Hematology that says Platelets must be used within 4 hr of volume reduction because of decrease in amount of plasma/volume remaining for optimal platelet metabolism.  I just happened to run across that online...

When we volume reduce, the platelet do stay in the same container.  The excess plasma is expressed into a transfer bag and heat sealed/removed.  When we prep syringes for babies we do decrease the outdate to 4 hours no matter what product it is.

It definitely makes sense, I'm just trying to milk all the time I can out of these.  So finding something that will give us a definite more than 4 would be ideal :) 

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11 hours ago, Ensis01 said:

I seem to remember that the concentration of platelets in plasma is an important part of QC for the 5 day expiration, something about pH changes over time I think, which may be why platelets come as singles, doubles and triples? I would check/clarify with your blood bank/supplier. As applejw said; you are changing the environment, which may impact the functional survival of the stored platelets.

Thank you!  That makes total sense and correlates with what I found in The Bethesda Handbook of Clinical Hematology online...  I will check with my supplier and see if they can provide some feedback as well.  Good idea!

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On 5/10/2018 at 10:13 AM, BloodBanker80 said:

Wouldn't it be easier if they could just tell me an exact acceptable expiration?

Technically, they cannot as they are not a law setting organization like the FDA.

I would not go past the 4 hours, but we do not volume reduce.  Platelets are living, "breathing" cells and you are greatly increasing their concentration and ability to transport oxygen.

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23 minutes ago, Cliff said:

Technically, they cannot as they are not a law setting organization like the FDA.

I would not go past the 4 hours, but we do not volume reduce.  Platelets are living, "breathing" cells and you are greatly increasing their concentration and ability to transport oxygen.

Good point... I should blame FDA then haha.  Thank you!

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If you have access to the 31st edition of the AABB Standards for Blood Banks and Transfusion Services handbook, Reference Standard 5.1.8A is a table that provides the expiration times for a number of blood components (e.g., platelets, RBCs, plasma). This should provide some guidance for the expiration of your volume reduced platelets. Hope this helps!

Kaytee

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15 hours ago, ICCBBA said:

If you have access to the 31st edition of the AABB Standards for Blood Banks and Transfusion Services handbook, Reference Standard 5.1.8A is a table that provides the expiration times for a number of blood components (e.g., platelets, RBCs, plasma). This should provide some guidance for the expiration of your volume reduced platelets. Hope this helps!

Kaytee

No luck :( They conveniently left that product out haha ;)  !  thank you though!!

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Posted (edited)

There are no data.  When we wash platelets or red cells, the outdate is 24 hours because of the open system (ancient COBE/Terumo type 2991s).  Patients do better in terms of key clinical outcomes (mortality, infection, thrombosis) with washed platelets so I'm not concerned about the container, length of storage, etc.  Ultimately clinical outcomes are more important than any of those surrogate in vitro markers.  We routinely wash to remove incompatible ABO antibody and soluble antigen, FYI.  We do not wash red cells more than 21 days of storage due to increased hemolysis, and poorer clinical outcomes with these components (washed >21 days). We currently wash with normal saline, but Plasma-Lyte A (AJCP in press) causes less hemolysis and we will be moving away from normal saline. Hopefully we remove normal saline from use for all transfusion service and clinical uses, due to recent data that normal saline causes increased mortality and renal failure in ICU patients (in NEJM).  See references below.

 

A randomized trial of washed red blood cell and platelet transfusions in adult acute leukemia [ISRCTN76536440].

Blumberg N, Heal JM, Rowe JM.

BMC Blood Disord. 2004 Dec 10;4(1):6.

 

Providing ABO-identical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence.

Henrichs KF, Howk N, Masel DS, Thayer M, Refaai MA, Kirkley SA, Heal JM, Blumberg N.

Transfusion. 2012 Mar;52(3):635-40. doi: 10.1111/j.1537-2995.2011.03329.x. Epub 2011 Sep 2.

 

Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial.

Cholette JM, Henrichs KF, Alfieris GM, Powers KS, Phipps R, Spinelli SL, Swartz M, Gensini F, Daugherty LE, Nazarian E, Rubenstein JS, Sweeney D, Eaton M, Lerner NB, Blumberg N.

Pediatr Crit Care Med. 2012 May;13(3):290-9. doi: 10.1097/PCC.0b013e31822f173c.

 

ABO identical and washed blood transfusions as candidate strategies to reduce early mortality in acute promyelocytic leukemia.

Sahai T, Henrichs K, Refaai M, Heal JM, Kirkley SA, Schmidt AE, Mendler JH, Masel D, Liesveld J, Aquina C, Blumberg N.

Leuk Res. 2017 Nov;62:1-3. doi: 10.1016/j.leukres.2017.09.011. Epub 2017 Sep 23.

 

Improved outcomes in acute myeloid leukemia patients treated with washed transfusions.

Greener D, Henrichs KF, Liesveld JL, Heal JM, Aquina CT, Phillips GL 2nd, Kirkley SA, Milner LA, Refaai MA, Mendler JH, Szydlowski J, Masel D, Schmidt A, Boscoe FP, Schymura MJ, Blumberg N.

Am J Hematol. 2017 Jan;92(1):E8-E9. doi: 10.1002/ajh.24585.

 

Longer RBC storage duration is associated with increased postoperative infections in pediatric cardiac surgery.

Cholette JM, Pietropaoli AP, Henrichs KF, Alfieris GM, Powers KS, Phipps R, Spinelli SL, Swartz M, Gensini F, Daugherty LE, Nazarian E, Rubenstein JS, Sweeney D, Eaton M, Blumberg N.

Pediatr Crit Care Med. 2015 Mar;16(3):227-35. doi: 10.1097/PCC.0000000000000320.

 

Transfus Apher Sci. 2018 Feb;57(1):127-131. doi: 10.1016/j.transci.2018.02.021. Epub 2018 Feb 21.

0.9% NaCl (Normal Saline) - Perhaps not so normal after all?

Crystalloid infusion is widely employed in patient care for volume replacement and resuscitation. In the United States the crystalloid of choice is often normal saline. Surgeons and anesthesiologists have long preferred buffered solutions such as Ringer's Lactate and Plasma-Lyte A. Normal saline is the solution most widely employed in medical and pediatric care, as well as in hematology and transfusion medicine. However, there is growing concern that normal saline is more toxic than balanced, buffered crystalloids such as Plasma-Lyte and Lactated Ringer's. Normal saline is the only solution recommended for red cell washing, administration and salvage in the USA, but Plasma-Lyte A is also FDA approved for these purposes. Lactated Ringer's has been traditionally avoided in these applications due to concerns over clotting, but existing research suggests this is not likely a problem. In animal models and clinical studies in various settings, normal saline can cause metabolic acidosis, vascular and renal function changes, as well as abdominal pain in comparison with balanced crystalloids. The one extant randomized trial suggests that in very small volumes (2 l or less) normal saline is not more toxic than other crystalloids. Recent evidence suggests that normal saline causes substantially more in vitro hemolysis than Plasma-Lyte A and similar solutions during short term storage (24 hours) after washing or intraoperative salvage. There are now abundant data to raise concerns as to whether normal saline is the safest replacement solution in infusion therapy, red cell washing and salvage, apheresis and similar uses. In the USA, Plasma-Lyte A is also FDA approved for use with blood components and is likely a safer solution for these purposes. Its only disadvantage is a higher cost. Additional studies of the safety of normal saline for virtually all current clinical uses are needed. It seems likely that normal saline will eventually be abandoned in favor of safer, more physiologic crystalloid solutions in the coming years.

 

N Engl J Med. 2018 Mar 1;378(9):829-839. doi: 10.1056/NEJMoa1711584. Epub 2018 Feb 27.

Balanced Crystalloids versus Saline in Critically Ill Adults.

BACKGROUND:

Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes.

METHODS:

In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days - a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) - all censored at hospital discharge or 30 days, whichever occurred first.

RESULTS:

Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P=0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P=0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P=0.60).

CONCLUSIONS:

Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779 .).

 
Edited by Neil Blumberg

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1 hour ago, Neil Blumberg said:

There are no data.  When we wash platelets or red cells, the outdate is 24 hours because of the open system (ancient COBE/Terumo type 2991s).  Patients do better in terms of key clinical outcomes (mortality, infection, thrombosis) with washed platelets so I'm not concerned about the container, length of storage, etc.  Ultimately clinical outcomes are more important than any of those surrogate in vitro markers.  We routinely wash to remove incompatible ABO antibody and soluble antigen, FYI.  We do not wash red cells more than 21 days of storage due to increased hemolysis, and poorer clinical outcomes with these components (washed >21 days). We currently wash with normal saline, but Plasma-Lyte A (AJCP in press) causes less hemolysis and we will be moving away from normal saline. Hopefully we remove normal saline from use for all transfusion service and clinical uses, due to recent data that normal saline causes increased mortality and renal failure in ICU patients (in NEJM).  See references below.

 

Just a couple of questions -

How many techs work in your Blood Bank on a daily basis?

How do you keep up with washing units during a surgery?  Or do you wash units before the surgery?

If they do not use the units, what can you do with them?  What is your RBC/PLT unit loss rate (washed but not used?)? 



 

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Each manufacturer of platelet bags has validated conditions that must be met for 5 day storage.  The AABB/ FDA cannot give you a standard because each bag is slightly different.  Talk to your supplier to find out the storage requirements for the bag you are using.  (I know Terumo is validated up to a concentration of 2,100,000 and Fenwal has a minimum volume requirement for a range of concentration).  If you're outside of that storage recommendation... you probably will need to short-date those products, or at least test the pH prior to issue to ensure a quality product.

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When we were bringing up a platelet collection system I asked the manufacturer some questions about the bag volume limits (100-400mL) and time spent where the volume was greater than 400mL. This scenario occurs for example when a 500mL intended-double is collected, but stored in one bag until counting/processing begins after the collection. That manufacturer said you could go up to 24 hours "out of range" before you compromised the product. Similar concerns about the storage concentration, the manufacturer has validated an acceptable platelet concentration range, odds are your volume reduction process results in a concentration greater than their validated upper limit.

With your closed system scenario I'd be uncomfortable giving the volume reduced product more than 24 hours without having validation data showing viability past that point. Due to container, volume and [PLT] concerns.

At a previous employer we volume reduced platelets and they were pretty ugly products, my current employer no longer volume reduces platelets, we give multiple divided aliquots instead.

[sorry for reiterating some of the points made earlier. they're good points :)]

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Posted (edited)

"How many techs work in your Blood Bank on a daily basis?"

Typically 9-10 on days, 6-7 on evenings and 3-4 on nights, with fewer on holidays and weekend shifts.  All are full-time transfusion service only licensed medical technologists.  Also 5 supervisory level staff (3 of whom also work at the bench), 2 full-time education/reference specialists, 2 full-time stem cell processing.  

 

"How do you keep up with washing units during a surgery?  Or do you wash units before the surgery?"

We don't. We wash in advance if need be, and if that isn't enough, we do the best we can.  Thanks to the fact that manufacturers have focused on apheresis devices and the 2991 and ACP-215 are much older technology, we do not have a closed system.  In any case, storing washed red cells for more than a few days would defeat the purpose of removing the supernatant containing free hemoglobin, red cell microparticles, etc.

"If they do not use the units, what can you do with them?  What is your RBC/PLT unit loss rate (washed but not used?)?" 

We transfuse 20,000 red cells per year so finding a patient who needs an O or A red cell isn't difficult.  Same for platelets.  On a typical weekday we transfused 80-100 red cells and 10-20 platelet doses. Essentially no losses.  Our platelet outdate rate is consistently about 1-3%, washed or otherwise.  Usually these are for scheduled elective transfusions on both inpatients and outpatients.

As blood bankers/transfusion service personnel we do many inconvenient things, some quite expensive (CMV serotesting--unnecessary and less clinically valuable than leukoreduction), antigen matching for patients with hemoglobinopathies (quite clinically effective but time consuming and expensive), use of apheresis platelets instead of whole blood platelets (an almost totally unnecessary misuse of donor resources in most cases, additional risk to donors,  no clinical advantage of substance,  and fabulously expensive).  I'd gladly give up apheresis platelets (except for HLA matched) and their cost for universal leukoreduction in the USA and selective washing of ABO minor-incompatible platelets and red cells. The latter on rare occasions kills patients, yet we do nothing about it in most transfusion services, and routinely give group O platelets to non-O recipients.  I know these dilemmas are easily ignored and scoffed at, but the facts support these unpopular contentions.  I should add that we see perhaps 3-5 platelet transfusion refractory patients per year out of thousands of platelet transfusion recipients.  This is a benefit of transfusing only ABO identical platelets and red cells (or washed O's) which our group and Robert Carr of the UK demonstrated 25-30 years ago reduces refractoriness by 2-5 fold in the only randomized trials that exist.

 

We have randomized trial evidence that washed red cells and platelets also contribute to improved long term survival in acute myeloid leukemia patients and reduce inflammation in pediatric cardiac surgery patients. Arguing against washing because it's expensive (it's not really all that expensive compared with apheresis platelets), it's inconvenient (it sure is) andis not "essential" doesn't justify subjecting patients to inferior treatment approaches in our view.   Obviously these approaches have not caught on in most places (ABO identical and selective washing) but it's not for lack of data :).

Similarly, in our view,  transfusing  ABO mismatched platelets for our own convenience, inventory purposes and to save outdating does not make sense when there is abundant evidence that this practice seriously harms some patients.  Hence, plasma removal by washing when indicated and feasible. Contrary to 75 years or more of practice and tradition, there is no such thing as "universal donor group O red cells" and "universal donor group AB plasma."  No patient makes red urine with this approach, and it's necessary when the ABO of the patient isn't known, but patients receiving ABO mismatched platelets use 50% more red cells, develop multi-organ failure more often, have more transfusion reactions and higher mortality rates than patients receiving ABO identical platelets(all observational data, but from multiple centers in surgical patients).  O patients receiving AB plasma in large volumes have a 9% increase in mortality rate in Swedish data.  We all know of rare case reports of fatal transfusion reactions from group O red cells given to non-O patients. Washed transfusions make these problems go away, in our experience.

 

Is It Time to Reconsider the Concepts of "Universal Donor" and "ABO Compatible" Transfusions?

Refaai MA, Cahill C, Masel D, Schmidt AE, Heal JM, Kirkley SA, Blumberg N.

Anesth Analg. 2018 Jun;126(6):2135-2138. doi: 10.1213/ANE.0000000000002600. 

 

Zaffuto BJ, Conley GW, Connolly GC, Henrichs KF, Francis CW, Heal JM, Blumberg N, Refaai MA.

Vox Sang. 2016 Apr;110(3):219-26. doi: 10.1111/vox.12354. Epub 2015 Nov 3

 

Improved outcomes in acute myeloid leukemia patients treated with washed transfusions.

Greener D, Henrichs KF, Liesveld JL, Heal JM, Aquina CT, Phillips GL 2nd, Kirkley SA, Milner LA, Refaai MA, Mendler JH, Szydlowski J, Masel D, Schmidt A, Boscoe FP, Schymura MJ, Blumberg N.

Am J Hematol. 2017 Jan;92(1):E8-E9. doi: 10.1002/ajh.24585. 

 

A randomized trial of washed red blood cell and platelet transfusions in adult acute leukemia [ISRCTN76536440].

Blumberg N, Heal JM, Rowe JM.

BMC Blood Disord. 2004 Dec 10;4(1):6.

 

Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial.

Cholette JM, Henrichs KF, Alfieris GM, Powers KS, Phipps R, Spinelli SL, Swartz M, Gensini F, Daugherty LE, Nazarian E, Rubenstein JS, Sweeney D, Eaton M, Lerner NB, Blumberg N.

Pediatr Crit Care Med. 2012 May;13(3):290-9. doi: 10.1097/PCC.0b013e31822f173c.

Edited by Neil Blumberg

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On ‎05‎/‎16‎/‎2018 at 3:04 PM, Eman said:

When we were bringing up a platelet collection system I asked the manufacturer some questions about the bag volume limits (100-400mL) and time spent where the volume was greater than 400mL. This scenario occurs for example when a 500mL intended-double is collected, but stored in one bag until counting/processing begins after the collection. That manufacturer said you could go up to 24 hours "out of range" before you compromised the product. Similar concerns about the storage concentration, the manufacturer has validated an acceptable platelet concentration range, odds are your volume reduction process results in a concentration greater than their validated upper limit.

With your closed system scenario I'd be uncomfortable giving the volume reduced product more than 24 hours without having validation data showing viability past that point. Due to container, volume and [PLT] concerns.

At a previous employer we volume reduced platelets and they were pretty ugly products, my current employer no longer volume reduces platelets, we give multiple divided aliquots instead.

[sorry for reiterating some of the points made earlier. they're good points :)]

Excellent information!  We do try to use the product as soon as possible, but outdate at 24 hours.  You bring up an interesting point, when we combine a 'double bag' into one... the expiration has to be changed to 24 hours.  Although we don't routinely do that ahead of time, we wait until the nurse is here to pick it up. 

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