Category: COVID-19

Includes manual and computer processes for donor, patient, and IT

My Opinion: Issues in Transfusion Medicine Software and Component Production

drzeyd

I anticipate that there are several innovations coming or in the process of coming to mainstream blood component production and software.  Some of these I have already addressed in some of my previous posts:

Pathogen inactivation:  We have had this for over a decade.  However, with new emerging pathogens, this will become more important so I expect it will be adopted in many centers where it is not currently being used.  I expect we will close the loop and pathogen-inactivated RBCs will be available so all components will be treated.  Still, the first-generation pathogen-inactivated RBCs may have reduced shelf life compared to regular, untreated units.

Automated component production:  Although this is expensive, it does provide excellent GMP production.  It is fast and may provide higher yields, especially for platelets.  I expect more centers will adopt this technology, especially in combination with pathogen inactivation.

Blood bank computer software:  This software must be considered as dynamically changing, and considerable resources are needed to keep in compliance with ever-changing international regulations and the latest epidemiologic data.  Production rules can be strictly and mercilessly enforced by a dedicated blood bank computer software.  It can also ensure that the final ISBT label is not applied unless all the production rules (registration, collection, processing, and testing) are met.  Manual processing is extremely risky nowadays with all the parameters to be monitored.

Patient Blood Management:  Current blood bank software does not adequately address the need for prospective review of component orders.  I expect that collaboration will occur between laboratory and blood bank software vendors to fill this gap.

Refrigerated platelets:  The pendulum swings back to this component which was used over 40 years ago.  Refrigerated platelets suspended in additive solution may be effective up to 14 days for hemostasis in the trauma setting.  These platelets are activated so standard 20-24C stored platelets may be preferred for prophylactic transfusions.

Low-titer group A universal plasma:  This is already available, but its use will increase because of the low numbers of group AB units available and increased demand.  This includes its production for COVID convalescent plasma.  Your transfusion medical director must decide what “low titer” means.  Also you need a robust way of performing anti-B titers, this may require use of an immunohematology analyzer with titration built-in.

Low titer group O whole blood:  Use of this product may reduce the need for components in massive transfusion settings but it requires performing anti-A and anti-B titers on large numbers of units.  Your transfusion medical director must decide what “low titer” means.  Also you need a robust way of performing anti-A and anti-B titers, this may require use of an immunohematology analyzer with titration built-in.  Also, you must decide whether to leukodeplete the whole blood units:  few whole blood filters are platelet-sparing.

CCP COLLECTION AND EXPOSURE TO COVID VACCINES

drzeyd

Principle:

Donor criteria for COVID convalescent plasma collection have been updated by the US FDA.  This policy has adapted them to our practice setting.

Policy:

  1. Donors who donated CCP prior to COVID-19 vaccination may donate following vaccination if they meet remaining donor eligibility criteria.
  2. Donors who did NOT have symptoms and a positive diagnostic test for COVID-19 prior to vaccination are ineligible to donate plasma after COVID -19 vaccination.
  3. Individuals may donate CCP for up to 6 months after resolution of COVID-19 symptoms regardless of what their antibody levels are at 6 months.
  4. Only high-titer units (as defined by the reagent manufacturer) may be used for patient treatment.

Reference:

Regulatory Update:  FDA Officials Provide Insight on High-Titer CCP, Donor Eligibility Following Vaccination, 9/2/21, AABB, Bethesda, MD, USA

COVID-19 Donor Qualification

drzeyd

Principle:

This is the latest update on donor qualifications during the COVID-19 pandemic and addresses issues about COVID-19 vaccination, COVID convalescent plasma use and donation, return of donors into the donor pool after COVID-19 vaccination.  All of this information is subject to change as new regulations are released.

Policy:

  1. All donors must be in good health and meet all donor eligibility criteria at the time of the donation.
  2. Individuals diagnosed with COVID-19 or who are suspected of having COVID-19, and who had symptomatic disease, must refrain from donating blood for at least 14 days after complete resolution of symptoms.
  3. Individuals who had a positive diagnostic test for SARS-CoV-2 (e.g., a nasopharyngeal swab), but never developed symptoms, must refrain from donating at least 14 days after the date of the positive test result.
  4. Individuals who are tested and found positive for SARS-CoV-2 antibodies, but who did not have prior diagnostic testing and never developed symptoms, can donate without a waiting period and without performing a diagnostic test (e.g., a nasopharyngeal swab).
  5. Individuals who received a non-replicating, inactivated, or mRNA-based COVID-19 vaccine can donate blood without a waiting period.
  6. Individuals who received a live-attenuated viral COVID-19 vaccine, must refrain from donating blood for 14 days after receipt of the vaccine.
  7. Individuals who are uncertain about which COVID-19 vaccine was administered must refrain from donating for 14 days if it is possible that the individual received a live-attenuated viral vaccine.
  8. Individuals who received monoclonal antibodies should be deferred for three months from the last dose.
  9. Donors who have received blood components, including COVID-19 convalescent plasma are deferred for 3 months since the last transfusion.
  10. Recovered COVID-19 patients who are eligible to donate CCP and receive an approved COVID-19 vaccine may donate if they:
    1. Had symptoms of COVID-19 and a positive test result from an approved diagnostic test
    2. Received the COVID-19 vaccine after the diagnosis of COVID-19
    3. Are within 6 months after complete resolution of COVID-19 symptoms

References:

  1. Summary:  Donation of CCP, Blood Components, and HCT/Ps Following COVID-19 Vaccines or Treatment with CCP or Monoclonals, Updated 3/2/21, AABB, Bethesda, MD, USA
  2. Updated Information for Blood Establishments Regarding COVID-19 Pandemic and Blood Donation, US FDA, 19/1/21
  3. Toolkit for COVID-19 Convalescent Plasma (CCP) Under Emergency Use Authorization Issued 02 04 21 Revision 12/2/21, AABB, Bethesda, MD, USA

My Ten Years of Experience with Mirasol

drzeyd

I originally adopted this technology because of the plethora of new emerging pathogens.  In addition, I have been concerned about unknown pathogens that have not yet been discovered.  It is not what we know, it is what we don’t know that bothered me.

It is now 10 years since I started using riboflavin-based pathogen inactivation.  Our adoption of the technology was as follows:

  • 2010 pooled buffy coat and apheresis platelets, both suspended in plasma
  • 2012 whole-blood derived plasma and apheresis plasma
  • 2015 pooled buffy coat and apheresis platelets, both suspended in platelet additive solution PAS

Buffy coat platelet pools and whole-blood-derived plasma were both prepared with automated blood component technology, originally with the Terumo Atreus and later with Terumo Reveos system.  We were the first site worldwide to use automated production with the Mirasol system.

After 10 years and over 300,000 donor collections, no documented infectious agent transmission has been noted.  Our average platelet loss has been 4%.  There has been no increase in adverse reactions to plasma or platelets compared the time before we adopted these technologies.  Physicians accepted the products readily.

Mirasol adoption allowed us to discontinue irradiation of platelets and extend our outdate to 7 days.  We did not need a specific bacterial detection system.  Pending regulations in the USA will require stringent bacterial detection processes that are not necessary if a pathogen-inactivation system is being used.

Terumo sent its own engineers to set up and validate the system.  They also trained all the staff in the actual pathogen-inactivation processes and helped us to perform the validations.

When adopting pathogen inactivation, we compared Mirasol with its competitor and selected it for the following reasons:

  • Loss of platelets is low (about 4%)—lower than its competitor product.
  • There is no need to remove the riboflavin from the final product.

In our system, our goal was rapid processing of units.   With Mirasol, we did not have remove the riboflavin from the final product.  The competitor product requires at least 6 hours post-treatment to remove the psoralen agent.  We could immediately use the Mirasol product after treatment!

In our Reveos-Mirasol system, we can process whole blood into packed red cells in SAGM, buffy coat platelets, and plasma in a total of 5 hours including all testing with Mirasol treatment and platelet additive solution PAS.

We originally used the system manually, but in 2013, Terumo in conjunction with Medinfo Hematos IIG developed an interface to the Mirasol illuminator.  The latter device would transmit the successful completion of the illumination to the software.  Any errors in the illumination would block release of the blood component from Medinfo.  Medinfo also monitored the component volumes to prevent treatment of units outside Terumo’s recommendation ranges.

Adoption of platelet additive solution PAS gives us a final product with minimal residual plasma which potentially can reduce plasma reactions and TRALI/TACO.  It also minimizes our need to reduce the volume of platelet components for pediatric patients, especially in cases with ABO-incompatible plasma

Adopting any system of pathogen inactivation requires meticulous monitoring of component volumes to ensure they are within the range for the treatment.  The use of a blood bank software greatly facilitates this.

We make both buffy coat and apheresis platelets. The change from plasma-suspended to PAS-suspended platelets went smoothly.  Special training for Trima apheresis staff to use the new processes was provided by Terumo.

Throughout this time interval, Terumo has provided excellent technical support and educational activities for all staff.  Despite the COVID pandemic, Terumo has been able to deliver supplies to meet our needs so there was no interruption in production.

We started COVID convalescent plasma CCP production at the end of winter 2020.  We set up a parallel but separate quarantine system of collection and processing, originally manual but later controlled by the dedicated blood bank software Medinfo Hematos IIG.  All CCP units have been treated with Mirasol.

In the future, I hope Mirasol will close the loop by providing a pathogen-inactivation process for red blood cells so all components can be treated.  The CE mark for pathogen inactivation of whole blood is exciting and I hope that component preparation from this product will be offered.

In summary, our blood bank system had an excellent, synergistic relationship with Terumo and Medinfo to provide the highest quality product that is currently licensed.  I hope we will all continue to work together to improve the patient care.

Operational Effects of the COVID Pandemic–My Experience in Qatar

drzeyd

The COVID-19 pandemic imposed new challenges to our system.  In general, these could be divided into:

  1. Decreased donors
  2. COVID vaccine effects
  3. Decreased available staff
  4. Shortages of supplies
  5. More demands on donor apheresis staff—CCP
  6. More demands on donor processing staff—CCP
  7. More demands on hospital transfusion service/blood bank staff—CCP

There were fewer donors in the early phase and the nurses also had to add a large number of donor plasmapheresis collections for COVID convalescent plasma CCP.  Still they had to maintain all donor and therapeutic apheresis services with no increase in staff.  Although elective procedures had been cancelled, there were still obstetrical, oncologic, and trauma services in full action.

Many of our staff were on leave when the borders were closed.  Some had to wait months before they could return to work.  Others had COVID-19 infection and were quarantined for several weeks.  This further reduced staffing.  We could not just hire outside staff since considerable training is involved in these processes.

I dedicated a separate donor collection space for the CCP program away from the regular donors as well as a quarantine processing area.  Similarly, the CCP plasma was kept segregated from the regular plasma supply and a specially designed location was identified for release of this product.  Working for this program diverted resources from blood collection to this special project, again without increasing resources.

With disruptions to shipments of supplies, including the Reveos whole blood kits and Trima donor apheresis sets, we had to rely on our large in-home inventory until the situation stabilized.  We prescreened the CCP donor candidates before we would collect them to avoid wastage of kits.

Fortunately, our throughput was minimally affected because our equipment and processes had always stressed speed.  We used single-well NAT testing to minimize the need of additional runs.  Also, we used Reveos automated component processing to greatly speed production (one Reveos can process four whole blood units in about 23 minutes or about 12 units in 75 minutes.)  One technologist could operate all 4 of our machines simultaneously and perform other tasks while the machines were working.

In the system I developed in Qatar, we could complete processing into components (RBCs, buffy coat platelet pools, leukodepleted plasma), all marker and immunohematology testing, leukoreduction of the pools and RBCs, Mirasol pathogen inactivation, and platelet additive solution in as little as five hours.

In rapid turn-around events, it is most helpful to have a robust blood bank computer system that can scale to the challenge.  Also, it must mercilessly enforce all the rules starting with donor qualification, screening, collection through testing and production.  At times of emergency, it is difficult to meet Good Manufacturing Processes manually.

I had built parallel separate donor collection, donor processing, and transfusion service/hospital blood bank processes specifically for CCP and had to staff them with available personnel, limited our capability to process regular donors.  The blood bank computer software restricted CCP use to designated physicians and transfusing locations.  For those interested, there is a separate series of posts about the CCP project and its implementation in the dedicated blood bank Medinfo HIIG.

COVID-19 vaccinations should have minimal effect in donor qualification since mRNA or antigen-based ones do not cause donor deferral.  Live attenuated COVID vaccines will defer donors for 2 weeks by current rules—the same as other live vaccines.  Donors who had previously received CCP will be deferred for three (3) months after last receiving this product.

In summary, the COVID pandemic reduced staffing and affected donor recruitment.  We had production mitigations to maximize throughput.  The system was stressed by the reduced staffing and special demands to produce CCP.  However, the extent of our automation allowed us to maintain throughput throughout the crisis.

Updated COVID-19 Donor Eligibility Requirements

drzeyd

Principle:

This policy is based on the 19/1/21 CBER document Updated Information for Blood Establishments Regarding COVID-19 Pandemic and Blood Donation.

Policy:

  1. There is no COVID-19 laboratory testing requirement for routine blood donor screening.
  2. Donors must be in good health and meet all blood donor eligibility criteria on the day of donation.
  3. The blood establishment’s responsible physician must evaluate prospective donors and determine eligibility according to the blood donor criteria.
  4. Donors with a diagnosis of COVID-19 or who are suspected of having COVID-19 and who had symptomatic disease should refrain from blood donation for at least 14 days after COMPLETE resolution of symptoms.
  5. Donors who had a positive diagnostic test (RT-PCR SARS-CoV-2 or equivalent) but never developed symptoms, should refrain from blood donation for at least 14 days after the date of the positive test result.
  6. Donors who are positive for SARS-CoV-2 antibodies but did not have prior diagnostic testing and never developed symptoms can donate WITHOUT a waiting period and WITHOUT a diagnostic test (RT-PCR).
  7. Vaccination deferrals are as follows:
    1. Recipients of nonreplicating, inactivated, or mRNA-based COVID-19 vaccines can donate blood WITHOUT a waiting period if #2 above applies.
    2. Recipients of live attenuated viral COVID-19 vaccines should be deferred for 14 days after receipt of the vaccine.
    3. Recipients who are uncertain which COVID-19 vaccine was administered, should wait 14 days.

Note that these rules do not address the special case of COVID-19 convalescent plasma donors.

References:

Updated Information for Blood Establishments Regarding the COVID-19 Pandemic and Blood Transfusion, CBER, US FDA, 19/1/21