My Opinion: Issues in Transfusion Medicine Software and Component Production

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.

Reveos Interface to Medinfo Hematos IIG

The Medinfo HIIG interface to the Reveos is a bidirectional interface, which was first developed by the Medinfo team for HMC in Qatar.  It is similar to the Atreus interface but there are 4 units processed simultaneously in each cycle of operation whereas the Atreus only processed 1 unit each cycle.  In Qatar it was used in conjunction with Mirasol riboflavin-based pathogen inactivation.

The process is:

  1. Medinfo controls registration, donor screening, and donor collection of whole blood and apheresis-derived (Trima) components.
  2. Medinfo will assign ISBT specimen labels for the whole blood collected with the Reveos blood kit.
  3. Medinfo will not allow processing of whole blood units not meeting donor criteria (donor screening, volumes, collection time, donor deferral database, etc.)
  4. Reveos will read ISBT specimen labels generated by Medinfo.
  5. Upon processing, Medinfo will receive from the Reveos machine the packed red blood cell, plasma, platelet, and buffy coat volumes for each bucket in the Reveos machine.
  6. If the volumes are within the specified ranges, platelet pooling and Mirasol pathogen inactivation of platelets and plasma may proceed.

For each component, the following information will be collected:

  1. All timestamps in the process
  2. Which Reveos machine used
  3. Which bucket in each machine used
  4. Volumes collected (packed RBCs, buffy coat platelet, plasma volume)
  5. Reveos collection set details
  6. Processing technologist ID

The key point is the complete TRACEABILITY of each component throughout its production.  Should there be a failure in production, we can trace exactly where the problem is and then quarantine this and any other affected units simply in the system.  Additionally, this information is part of the permanent record of the unit so it can retrieved subsequently at any time.

Reveos and Atreus Automated Blood Component Processing: My Experience

This post is about my over 10 years of experience with automated component processing using Terumo equipment, first Atreus and then Reveos at HMC Qatar.  The Reveos system is still in use at that institution.  There is also a previous post about Mirasol riboflavin-based pathogen inactivation.

We were the first place in the world to combine the automated component production Atreus with the Mirasol pathogen inactivation.  Their synergism was very important in the rapid throughput of component production for Qatar.

Terumo has two programs, 2C (C for components) to yield plasma and RBCs and 3C for yielding RBCs, plasma, and platelets.  The 2C program is faster but no platelets are separated.

We used the Atreus since 2010 and later replaced it with the Reveos in 2016.  Both systems use a special blood bag set that collects the whole blood in European CPD.  The kit is carefully placed in the machine.  Atreus machines accepted one blood bag set, the Reveos can accept up to 4 sets.  In both cases, the whole blood is processed to yield packed RBCs, leukoreduced plasma (<1E6 residual WBCs), platelets, and a special WBC bag (i.e. the residual buffy coat, which is not for clinical use.

The Atreus took about 10 minutes to process the one bag set whereas the Reveos processes 4 bag sets in slightly more than 20 minutes.  Thus, the throughput from the Reveos is twice that of Atreus.

We had 4 Atreus and later 4 Reveos machines and these were handled by up to 4 technologists, depending on the number of the units.  While the machines were running, the staff were filtering the RBCs and platelet pools, pooling the platelets, and performing the PAS-Mirasol pathogen inactivation.  The workflow was not hectic and staff were not stressed out by the multiple tasks.  Normally 1 staff member ran the Reveos or Atreus machines at any one time.

When the processing was complete, the RBC bags were filtered with an integral leukodepletion filter designed to leave a residual of <1E6 WBCs in accordance with the CE Standard.  The platelets were combined to give a target yield of >= 2.4E11 absolute number of platelets.  Then the pool was leukodepleted by filtration to a residual of <1E6 WBCs.

Both Reveos and Atreus measured the RBC, platelet, and plasma volume yields.  Additionally, for platelets a Platelet Yield Index PYI was calculated as a relative measure of the platelet yield.  To reach a goal of 2.4E11 platelets, the PYI indices for the individual platelet bags were added so that the total exceeded 240.

When combined with the Mirasol system, the component volumes for the plasma and platelets needed to be within specified ranges.  Both systems could easily meet these requirements.

When we switched from Atreus to Reveos, our platelet yields increased.  The transition period was only two weeks.   When we adopted platelet additive solution PAS at the same time, the Reveos had a special program to make “dry” platelets with less volume so that the PAS could be added and still stay within the acceptable range for pathogen-inactivation.

Throughout these years, Terumo sent us special engineers to handle the Atreus then Reveos, Mirasol, and PAS processing.  All staff were trained by Terumo initially before we finalized their competency assessments. 

We had excellent local service:  we never had downtimes due to equipment failures.  During the COVID pandemic, all materials (kits, filters, Mirasol solution, and PAS) have been provided without interruption.

We went live with Medinfo Hematos IIG software for the entire blood donor center and hospital blood banks in 2013.  From the first day 30/6/13 we had bidirectional interfaces first to the Atreus and later to the Reveos—the world’s first.  Likewise, the Mirasol and PAS processing were fully integrated with Medinfo when they were activated.

The residual buffy coat was not used for patient care.  However, it has proven invaluable as a quality control material for the stem cell laboratory.  In addition, many researchers have used it to establish cell lines for investigational use.

Proper handling the collected whole blood units is critical to success:

  1. Maintain the temperature below 25C.
  2. Carefully stack the whole blood units in the blood containers—do not play “ring toss” and just throw them into the container.

In summary, I am very pleased with using this system for over 10 years.  In a few weeks, the production laboratory was fully GMP compliant using a diverse group of staff with varying technical backgrounds.

The following are some pictures of the Reveos and its prepared blood components.

Reveos Machine has 4 chambers to process the 4 whole blood units.
Reveos takes up little space: this crowded corner processed all whole blood for Qatar.
Buffy-coat platelets processed by the Reveos
Close-up of Reveos buffy coat platelets: notice there are NO streaks of RBCs.

International Perspective

When I first moved overseas from the United States, I brought the perspective of my American training and experience.  I saw everything in my new blood bank through those eyes.

Yet, most of my staff were not American or even North American.  Few were even native in English, and most of those  were not American.  They had different qualifications, many of which would not have been accepted by the American schemes.  Still, they functioned well.

I also worked with the US military technologist staff during Gulf War One.  Some did not even have a Bachelor’s degree;  yet, they performed the work well.

I used many technologies that were not yet (or never) US FDA approved such as gel or glass bead typings and pooled buffy coat platelet production.  There were rare reagents I could buy off the shelf (e.g. anti-Tja/PP1Pk).

Later, I adopted pathogen-reduction technology (Mirasol), automated component production (Atreus then Reveos), and platelet additive solution.  I achieve a level of good manufacturing practice that would have been difficult to achieve by the FDA-approved methods.

My perspective had changed.  In the Middle East, I studied many frameworks and came to the conclusion that the best approach was to customize them to our local needs.  My particular experience was to start with one framework, i.e. Council of Europe CE, and then localize it.

To do this, I could not use an American turnkey blood bank software for either the donor or patient operations.  I needed a flexible system that could be customized to my needs.  Again, I chose a CE-marked system, Medinfo Hematos IIG that had already been adapted to many frameworks.

It is much easier to work solely within one system such as FDA.  However, if I had done that, I would have lost so much flexibility and not had a system optimized for local conditions.  I would not have used Mirasol, Reveos, Diamed, and many other reagents.

One big disappointment at such international meetings is the perspective by one country’s regulatory agency that they feel its regulations and framework will work well overseas.  I would wager that those people were not well acquainted with international conditions.

Another frustration was attending another international meeting in which the presenters apologized for the source of information since it came from a foreign country (France) and not their own (United States).

No country has a monopoly on what is best for everyone.  To share our experiences and compare is so valuable.  No one assume his way is the best.  In my career, I have had the richest experiences studying other perspectives and my organizations have benefited greatly from the exchange.  We can all learn from each other.  We are citizens of the world.

Reposted: Granulocyte Concentrates Prepared from Reveos Buffy Coats

The Reveos buffy coat is not approved for clinical use.  In my laboratory, I have offered this discard product to the stem cell laboratory and researchers as a quality control QC and a substrate to extract CD34+ cells for expansion and modification.

In this article (abstract attached) from Transfusion and Apheresis Science 59 (2020) 102682, the authors study pools of ABO-identical Reveos buffy coats for their granulocyte functionality and as a possible emergency replacement for granulocyte concentrates when the latter are not available.

I want to thank Terumo BCT (Brussels, Belgium) for referring me to this article and to the authors for a very interesting paper.


Therapeutic Apheresis Volume Calculations

You can get the values off the therapeutic apheresis machine, but in the middle of the night when you have to write orders, it is convenient to estimate the volumes (whole blood, plasma, RBCs).  These are the values from my lectures to hematology fellows while I was at HMC Doha:

Whole Blood:

Weight in kg X 70 ml/kg = whole (whole) blood volume adult

Weight in kg X 85 ml/kg =whole blood volume for child (prepubertal)

Weight in kg X 100 ml/kg = whole blood volume for neonates/premature

Example:  70 kg adult has 4900 ml blood volume (I round up to 5 liters)

Plasmacrit + hematocrit = 1.00 in fractions (100%), ignore buffy coat volume

Plasmacrit = 1- hematocrit

Plasma volume:

Plasma volume = whole blood volume x plasmacrit = whole blood volume X (1-hematocrit)

RBC volume:

RBC volume = whole blood volume x hematocrit

Estimates for blood components:

The volumes will depend on the original amount collected (e.g. 450 vs 500 ml),  original preservative solution used (e.g. CPD), use of automated component production such as Terumo Atreus or Reveos, use of RBC additive solution (e.g. SAGM), leukodepletion, platelet additive solution, pathogen inactivation.

At HMC Doha, the average values were:

300 ml for leukodepleted RBCs in SAGM prepared by Reveos

300 ml for platelet pools in Mirasol and platelet additive solution (residual WBC < 1E6)

300 ml for plateletpheresis concentrate (2.4E11) in Mirasol and platelet additive solution

250 ml for leukodepleted, pathogen inactivated plasma

Processes and Software Building 40: Reveos Detailed Settings

A major advantage in using a specific blood bank computer software is to enforce the Good Manufacturing Processes.  Medinfo is merciless:  there are no exceptions without authorization and that is restricted by the security policies.

The following tables show the values established at HMC Doha during my tenure.  These values were recommended by the Terumo BCT Reveos engineer after his direct, hands-on set-up of the equipment.

The minimum and maximum volumes for platelets are specifically designed to work for pooling the buffy coats before Mirasol pathogen inactivation.  There are different settings for platelets suspended in plasma versus those suspended in platelet additive solution PAS.

Similarly, there are specific volume ranges for plasma so that pathogen inactivation can be performed according to Terumo BCT recommendations.

To Be Continued:  4/9/20

Summary of Accomplishments at HMC 2011-2020

I resigned from HMC on 16/4/20.  Here are a set of my major accomplishments during that period. None of my work after this date has any relationship to HMC.


Established automated component production using Atreus technology, plasma and platelet pathogen inactivation (Mirasol)—made HMC component production Good Manufacturing System GMP compliant

Adopted non-PCR-based NAT technology (Grifols/Novartis Tigress) and Qatar becomes world reference site for this

Based on the above, Qatar can now completely process all whole blood into blood components (red cells, platelets, and plasma) in as little as 5 hours from collection!


Prepared policies and procedures for the hospital blood banks/transfusion services, blood donor center, therapeutic apheresis, and laboratory information systems to bring HMC in compliance with the Council of Europe, international AABB, and other standards.  I customized our own standards for our local needs based on them.


Implemented custom build of the multilingual blood bank computer system (Medinfo) for both patient and donor services, including development of interfaces to all production equipment including Atreus and Mirasol (world’s first) and a direct link to Ministry of the Interior to obtain patient demographics in English and Arabic—Qatar became the world’s first site to combine fully-interfaced, automated component production with pathogen inactivation:  Qatar becomes world reference site for this.


Built, validated, and implemented laboratory build of hospital information system, Cerner Millennium


Replaced and updated Atreus with Reveos automated component production to allow faster throughput and capacity with a full bidirectional interface (world’s first), introduced platelet-additive solution PAS with pathogen inactivation (Mirasol)—Medinfo interfaces updated to Reveos for all equipment:  this doubles the capacity to process whole blood into components using the same physical space


Updated dedicated blood bank software Medinfo Hematos IIG by several versions using Division Head, LIS, and internally trained Super Users—at great cost savings to HMC by not using outside consultants (e.g. Dell Consulting)


Established column absorption technology using Terumo Optia therapeutic apheresis machine for treatment of ABO-incompatible renal transplants:  I validated using the Ortho Vision MAX to perform ABO antibody titers for this system and correlated it with the reference method at Karolinska Institutet in Stockholm (manual gel) to bring rapid throughput and labor savings—Qatar being the first-site in the world to do this.  We saved money by using the same apheresis machine to use this column absorption technology (no need for second machine to use the columns)


Expedited setup (two weeks total) of COVID-19 convalescent plasma production, initially manual and then fully integrated into the Medinfo computer system as a customized module with separate quarantine collection, production, and transfusion service functions


I was awarded two HMC Star of Excellence Awards:

2013—Liver Transplantation Transfusion Support

2019—ABO-Incompatible Renal Transplantation Support