Month: Mar 2021

A Novel Way to Document Therapeutic Phlebotomies in the Blood Bank Computer System

drzeyd

Therapeutic phlebotomies TP, like regular whole blood donation WBD, both require collection of whole blood into a blood bag set.  In whole blood donation, we ask two questions during the process:

  • Is it safe for the donor to donate?
  • Is it safe for the collected unit or its processed components to be given to recipients?

For TP, we only have to consider the first question so the process must ensure the patient/donor’s safety.  We do not have to concern ourselves with the use of the collected product—it will be discarded.

Since the donor collection processes of both TP and WBD are similar, why couldn’t we use the blood bank computer software to document the TP procedures?  The process is a subset of normal WB donation.  On this basis, I make suggestions on using the donor module to document the TP process.  It is basically a truncated version of blood donation process in the Medinfo Hematos IIG system:

  • Registration
  • Donor Safety
  • Vital Signs
  • Hemoglobin Determination
  • Blood Collection Data
  • Adverse Effect Reporting
  • Discard of Unit
  • Documentation of Physician’s Order and Transfusion Medicine Physicians Acceptance

Registration:  Positive patient identification can be made through the donor registration process;  force selection of an inexpensive bag type (not the Reveos set) for this purpose.

Donor Safety:  Perform a modified, shortened donor questionnaire covering the medical history and medications is used.  Confirm that the patient has had food and drink before donating.  Require a waiting period of 24 hours before the next procedure.

Vital Signs and Weight:  Measure weight plus BP, pulse, temperature, and respiratory rate as well as inspect the arm for scarring before procedure.  Allow repeat vital signs monitoring after the procedure if requested by the transfusion medicine physician.

Hemoglobin Determination:  Allow acceptable Hgb >= 11 g/dl or >33% hematocrit

Blood Collection:  Use the same process for the mixer-shakers but the amount collected can range up to 500 ml with amounts <405 ml acceptable for small patients

Adverse Effect Reporting:  The complications of TP collection are the same as WBD.  Use the same system as for WBD.

Discard of the Unit:  Print discard label and quarantine of the ISBT unit number in system (so that it cannot be used for transfusion).

Documentation of Order:  Create separate fields for the ordering physician and for the approving transfusion medicine physician.  Capture scan of paper orders and incorporate into the TP computer encounter.

Other Considerations:  In high-risk cases, e.g. with pre-existing cardiovascular, pulmonary, or cerebrovascular disease, one could consider using a remote monitoring device such as the Umana T1 device to record vital signs, EKG, and oxygen saturation that can continuously record these parameters and trigger user-definable alarms during the process and afterwards if desired.  The data can be incorporated into the blood bank computer encounter.

Antibody Titration

drzeyd

My practice across the globe has exposed me different rationales to performing antibody titration.  In my American training and practice (and also at international institutions following the American version of AABB accreditation), I only routinely performed titration of anti-D for Rh(D) hemolytic disease of the newborn and anti-A/anti-B for ABO-incompatible stem cell transplants AND ABO-incompatible renal transplants.

I have had heated arguments with some physicians who insisted they wanted titers for other antibodies.  The AABB Standards do not require this but leave it to the discretion of the Transfusion Service Medical Director.

In my entire career, I never worked in a blood bank or blood center which had optimal staffing or resources.  I focused on what was medically/technically necessary and even then still had shortages.  If performing a test does not change the clinical treatment, why perform it unless you are doing a research project!

Titration is a time-consuming, and until recently, a tedious manual task.  Recently some of the automated immunohematology analyzers offer a titration program.  We used the Ortho Vision Max which could perform both IgG and IgM titers within one hour—walk away!!  However, during that time, the titration procedure monopolized the analyzer.

Nowadays, low-anti-B-titer group A universal plasma and low-titer (anti-A and anti-B) group O whole blood may be offered as components.  At HMC Qatar, a preliminary study showed about 50% of units could be classified as low-titer (defined as a saline titer <1:128).  The amount of titration will require an automated analyzer.

The ABO-incompatible renal transplant program at HMC Qatar was modelled after Sweden’s Karolinska Institute.  However the latter site performed manual IgG and IgM titrations using Biorad/Diamed gels.

I did not have sufficient resources to commit staff to manual titration at HMC so I did a comparison study between the Ortho Max and the Biorad manual gel methods.  We were able to get good correlation and used the automated method for the transplant.

I still don not perform against performing titrations for antibodies other than anti-D.  I always ask, ‘Does the titration correlate with clinical severity?’  Unlike anti-D, antibodies such as anti-Kell and anti-c may be low titer but cause death.  Can anyone show me a definitive study that titers are useful except for transplants and Rh(D) hemolytic disease of the fetus/newborn?

Since the method was working well on the Ortho equipment, I next established an interface to Medinfo.  The test was performed separately for IgG and IgM antibodies.  Medinfo recorded the reactions in all the wells.  The last well showing a 1+ reaction was interpreted as the titer (e.g. if 1:64 were the last 1+ reaction, then the titer was 64 in Medinfo).

The Medinfo process is shown below.

Building Your Blood Bank Software—Initial Considerations

drzeyd

In a series of posts, I will elaborate on how I built the processes and settings for a blood bank computer system in conjunction with the vendor’s software engineers.  This also applies to other laboratory software.

If you don’t know exactly what you are doing, how can you improve it?  Regardless whether you currently have laboratory software, you still need to optimize processes, determine critical control points, and plan improvements based on that.  A good manual system is the foundation for a good software build.

I was never taught in medical school how to do this.  I learned on-the-job at a time when software was quite rudimentary and mainly to record results.

Staffing:

For our first system, we used medical technologists to make settings for and administrate.  We thought that only those with a technical background in the field could do this.  It was moderately successful.  There was some antagonism between the technologist computer staff and the hospital computer department.  The technologists did not have a background in databases and programming;  the IT staff did not know the laboratory and were frustrated in dealing with the laboratory staff.

Later, to help reconciliate the two when a new hospital system was installed, we tried a different approach.  We found a database professional who was a very good listener.  Although he had no blood bank technical background, he could listen and map out the processes.  He was well-liked by the technologists who saw that he just wanted to understand their work and help them.  He was very successful in this endeavor.  I strongly recommend a software engineer as the lead in the project, one who can work with technical and medical staff to map out processes.

Unifying Processes Across Multiple Sites;

If your organization covers multiple sites, it is best to unify your processes as much as possible.  We built our dedicated blood bank system AFTER we had done this so the processes (except for some equipment differences) were the same everywhere.   This allowed us to move work between institutions quickly and makes system administration easy.

At one organization, I worked at, they had not done this.  They built their system based on the processes at the first site to go live, which was a small hospital with less than 10% of the workload.  It was not designed for the high-volume sites, and this was major problem as the larger sites were implemented. 

Capturing the Current State:

Most importantly, I cannot emphasize enough the need to capture the current state.  Take the time to do this properly and thoroughly.  This will help you whether or not you are building a computer system or just optimizing your manual processes.

At one institution in a non-blood bank system build, the administrative decision was to rush and not wait to complete this task so the actual processes were not captured—I actually rejected the proposed current state but was overruled.  The institution did not unify their processes as much as possible across sites.  The result was a suboptimal system that many/most people do not like:  should you blame the build or the limitations of the underlying software?  In my opinion, you can’t fully blame the software itself, if you didn’t design your build properly.

My Opinion: Use of Enzyme Panels

drzeyd

This is an updated version of a previous post.

Working for many years in the Middle East/Gulf, I have encountered significant antibodies that can only be detected at enzyme phase.  This is especially true of Rh system antibodies, particularly anti-c in an R1R1 patient.  I have attached an example.

The reasons I strongly recommend this practice are:

  1. Weak Rh system antibodies (as above)
  2. Confirmation of enzyme-labile antibodies, especially if there may be combinations of enzyme-labile and enzyme-resistant antibodies (e.g. anti-Fya and anti-c).

It is also important to consider which enzyme to use:  bromelin, ficin, or papain usually and sometimes trypsin or chymotrypsin.  They do not always attack at the same site.

In addition to most common MNSs and Duffy system antibodies, many Kell antibodies (e.g. K or K1, Kpa) are labile with papain:  however, with ficin they may be partially labile, unaffected, or even enhanced.

Using enzymes is a double-edged sword since they may enhance cold antibodies and thus cause nonspecific reactions.  Thus, I know many of you may not routinely include them in your workups.

It is essential to follow the manufacturer’s recommendations for their use.  If you make your own enzyme-treated cells and prolong the incubation, you may get false positivity.  You should also be careful about using potentiators with enzyme-treated cells—normally I run them in saline.

Since anti-c may cause severe hemolysis and severe hemolytic disease of the newborn, I am especially vigilant in my R1R1 patients, particularly females of child-bearing age and all chronically transfused patients.  I prophylactically match R1R1 patients with R1R1 RBCs in these categories, regardless if either anti-E or anti-c are expressed.  I have seen many examples where the anti-c is only detected at enzyme phase.

It is my practice to always include an enzyme panel.  I would be very interested to know your practices?  When do you use enzymes?

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.

Investigation of Donor Unit Mislabelling

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Principle:

All donor unit mislabeling is potentially life-threatening and must be stringently investigated as soon as possible after the discrepancy is detected.  Most importantly, if there is one error, there may be possibly ADDITIONAL donor unit errors (e.g. switch of donor tubes or units, etc.).  All donor units processed in the same batch must be also quarantined until the discrepancies are resolved.

Definitions:

Responsible blood bank physician:  specialist or consultant physician on-call at the time the discrepancy is detected

Policy Details:

The following steps MUST be performed as soon as possible:

  1. The Component Processing Supervisor or Senior Technologist must be IMMEDIATELY notified of any discrepancy.
  2. The Blood Bank Supervisor will inform the Division Head, Transfusion Medicine.  If the Head is not available, notify the Transfusion Medicine on-call.
  3. Quarantine ALL donor units collected and processed in the same batch.
  4. Obtain copies of all testing including photos of the gel/glass bead cards documenting the discrepancy.
  5. Obtain copies of all worksheets used in donor processing for the affected batch.
  6. Perform repeat ABO/D typing of ALL DONOR UNITS in the affected batch.  Any further discrepancies must be investigated and resolved.
  7. Identify all staff who were involved in handling the donor unit (phlebotomist, blood bank technicians processing and labelling the unit).  Identify those associated directly with the error.
  8. Submit all documents and photos to the Blood Bank Supervisor or designate.
  9. Prepare an occurrence/variation OVA report documenting all the data, findings, and interpretations.
  10. All investigations must be reviewed by the Supervisor, responsible blood bank physician, and one of the senior consultants.
  11. All such investigations must then be finally reviewed and approved by Head, Transfusion Medicine or his designate.  Only when the issue(s) are completely resolved and investigation is approved may the donor unit be properly relabeled and released into available stock.  Also, only at that time may the other units in the affected batch be released into available stock!!
  12. Photograph the correctly relabeled unit and attach it to the other documentation of the incident.
  13. If the discrepancy cannot be resolved, ALL units in the affected batch must be discarded.
  14.  The implicated staff’s personnel record should be reviewed for previous errors.   Appropriate disciplinary action should be taken and documented in the personnel record.  If a verbal warning is given, it should still be documented in the written record.
  15. If there is a systemic cause for the error, appropriate measures should be taken to minimize reoccurrence.
  16. All actions must be in accordance with the applicable regulations.

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

Reveos Interface to Medinfo Hematos IIG

drzeyd

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

drzeyd

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.