Summary of Accomplishments at Hamad Medical Corporation 2011-2020

2011

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

2011

Qatar is the first to adopt non-PCR-based NAT technology (Grifols/Novartis Tigress) and becomes world reference site for this

2011

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!

2011-2020:

I established 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.

2012-2013

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.

2013-2014

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

2015

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

2015-2019

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)

2019

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)

2020

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

Other:

I was awarded two HMC Star of Excellence Awards:

2013—Liver Transplantation Transfusion Support

2019—ABO-Incompatible Renal Transplantation Support

Updated Donor Questions for Ebola Virus Screening

The AABB just updated its Ebola Toolkit and made proposed changes to the Uniform Donor Questionnaire UDQ to reflect this.  Up to five (5) questions should be included in your questionnaire.  What question(s) to use depends on:

  • Are you in an area with NO widespread transmission?—1 question (#1)
  • Are you in an area with widespread transmission?—5 questions (#1-5)
  • Are you in an area post-widespread (> 4 weeks) transmission?—1 question (#1)
 YesNo
Ebola Question 1: Have you ever had Ebola virus disease or infection?qq
Ebola Question 2: In the past 8 weeks, have you lived in, or traveled to, a country with widespread transmission of Ebola virus disease or infection? (Review list of affected areas, as classified by CDC) *qq
Ebola Question 3: In the past 8 weeks, have you had sexual contact with a person who has EVER had Ebola virus disease or infection?qq
Ebola Question 4: In the past 8 weeks, have you had direct exposure to body fluids (blood, urine, stool, saliva, semen, vaginal fluids or vomit) from a person who may have Ebola virus disease or infection, including a person under investigation?qq
Ebola Question 5: In the past 8 weeks, have you been notified by a public health authority that you may have been exposed to a person with Ebola virus disease or infection?qq

If the response to question #1 is YES, then the donor is indefinitely deferred.

For questions 2-5, there is an 8-week deferral.

In areas with no widespread transmission, self-deferral of donors with a history of Ebola infection should be adequate, only question #1 is required.  If there is widespread transmission, questions #2-5 should be added.  Four (4) weeks after widespread transmission stops, revert back to using question #1 only.

These can be easily added to the donor questionnaire in Medinfo blood donor module.

References:

  1. AABB v2.1 DHQ and Flowcharts Modified for Ebola Risk, March 2021, AABB, Bethesda, MD, USA
  2. AABB Ebola Toolkit, Revised May 2020, Bethesda, MD, USA
  3. Recommendations for Assessment of Blood Donor Eligibility, Donor Deferral and Blood Product Management in Response to Ebola Virus, Guidance for Industry,  U.S. Department of Health and Human Services, Food and Drug Administration Center for Biologics Evaluation and Research, January 2017

Plasma Project Considerations for Middle East

This is an update of a previous post.

I have been involved with planning for several plasma fractionation projects in the Middle East.

Many clients expressed the interest in using local plasma to make plasma derivatives (e.g. factor concentrates, intravenous gamma globulin, albumin), feeling that local plasma was safer than using imported plasma.  Some of these are in short supply in the world market so the only way to ensure their uninterrupted availability is to consider to manufacture them for local consumption.

Still, the major issue today is that it is difficult for any country in the region to collect enough plasma to make such a project feasible.  When I first considered such planning, we were looking for as much as 250,000 raw liters of plasma annually.  Since then, there are newer technologies that allow much smaller batches to be cost-effective.  Alternatively, one could charge higher prices for using smaller batches from local plasma.

Still, it is likely that plasma must be imported to sustain a plant.  There are different regulations for plasma donor qualification country-to-country.  Many of these jurisdictions may do less screening and testing than is done for normal blood and apheresis donors.  Other countries use their blood donors with the same requirement for both commercial plasma and blood donations.

In this era of emerging infectious diseases, I personally favor using the stringent blood donor criteria—same as routine collections.  It is not what we know, but the unknown pathogens that are potentially the most dangerous.

In addition to building a fractionation plant, one must train staff for this highly technical operation.  This may require developing a special curriculum to prepare students for these jobs.

To export the plasma to certain regions, one may have to use plasma quarantine.  In this protocol, plasma is held or quarantined until the next donation is collected and passes screening.  This requires a robust blood bank production software such as Medinfo to track serial donations.

There are other processes to consider:  how to develop a transport network to keep plasma frozen at minus 80C viable in a region that reaches very high ambient temperatures.

I would recommend a graded approach to develop such an industry.  First I would negotiate a plasma self-sufficiency arrangement.  We would collect local plasma in the country and export it to a manufacturing plant in another country and the derivatives would be returned to us.  This may require inspection by the accreditation agency of the processing country to allow importation of the raw plasma for manufacture.

Since it is unlikely any one country has enough plasma for manufacture, recruiting neighboring countries to participate in a manufacturing plant is important.  Technology for such a plant is complex so establishing a joint venture with one of the plasma industry companies is essential.  Some manufacturers are very keen to develop extra capacity since there is a world-wide shortage of plasma fractionation and are even willing to help obtain external plasma sources for such a plant.

Such a plant is an excellent way to develop local talent to run such a plant, including training of local staff to be the industrial engineers in the plasma fractionation process.  It would take approximately two years of training to prepare engineers on-site at a plasma fractionation site if they have studied the necessary science and mathematics subjects.

Such a program would take several years of planning and development.  Some of the major steps needed include:

  1. Acquiring software for a blood center with plasma brokering capabilities.
  2. Passing accreditations such as international AABB and CE for transfusion medicine to allow export of our plasma to the external manufacturing site in the initial plasma self-sufficiency phase
  3. Identifying extended sources of plasma to feed a manufacturing plant.
  4. Preparing a curriculum suitable for training as staff for the plant.
  5. Establishing a joint venture to share technology with a major plasma company to design, build, and operate a plasma fractionation plant.

Overextending Oneself—Two Case Studies in the Blood Bank

One has to learn when enough is enough.  There are times when there are staff shortages but the conscientious staff wants to be the Super-Tech and handle all the work, whether or not there are sufficient resources.  This is a big gamble, and there may be serious consequences for the over-achiever and for the patient.

Anecdote #1:  Chicago Blizzard of 1979 (13-14 January):

When I was in my residency training in Chicago, I was in the blood bank during the blizzard of January, 1979.  The following tragedy occurred.

Suse was one of the best blood bank technologists that I have ever known, extremely conscientious and very meticulous—and very fast at doing things.  She was a workaholic.  Suse’s whole life centered on her job at our academic medical center—so much so that she had an apartment near the hospital complex.  In mid-January, a snow storm was predicted with an estimated snowfall of about 5 cm. total.  Actually, that night a blizzard developed and around a meter of snow fell with white-out conditions and zero visibility.  Preoperative patients had been admitted the night before based on the low snowfall prediction.

The next day was chaos.  Essentially only staff who lived near the hospital complex could report to work.  Suse came in and saw all the pending preoperative blood requests.  She decided to “double-up” and work on two cases at one time.  In the rush, she mixed up test tubes and issued ABO-incompatible blood for a surgical case.  The surgeon noted the abnormal oozing of blood at the operative site and stopped the transfusion.  Hematuria developed, but the patient survived.

Suse was suspended pending investigation.  Based on her excellent work record, she was offered to return to work.  Unfortunately, she became very depressed and was afraid to return since she feared she would make another mistake.  She never worked in the blood bank again.

Anecdote #2:  Shortage of Blood at Major Hospital:

1991 in another country, a large hospital complex was suffering a shortage of blood.  A large number of donors were called and the available staff were overwhelmed with work.  One donor phlebotomist decided to collect whole blood from two different donors simultaneously and in the confusion, mixed up the sample tubes for donor marker testing.

Unfortunately, one of those donors was HBsAg positive, but with the specimen mix-up was marked as negative.  The unit of blood was transfused, and the recipient developed fulminant hepatitis B and died.

Analysis:

In both these systems, there were processes in effect not to work on two patient specimens or collect two donors at one time, but the staff took short-cuts.

No one is super-human.  Don’t try to cut corners and handle more than one patient at a time.  Your intention may be good, but you will be judged by the consequences.  No one will care about the extenuating circumstances.  You will be blamed.  I tell my staff that if they cannot handle the workload, they should contact me as the Division Head, Transfusion Medicine, to triage the cases for them.  My role is to bring these events to the higher authorities to get the resources we need to do the work properly and safely.

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

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

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.

CCP COLLECTION AND EXPOSURE TO COVID VACCINES

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

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