Manual Collection of COVID-19 Convalescent Plasma

29th Dec 202021st Nov 2020 drzeyd

This process was originally done in the first phase of CCP collection. I have updated it to include SARS-CoV-2 antibody testing.

Principle:

Due to the pandemic, we will initially MANUALLY collect an experimental, investigational-use-only plasma product from apheresis donors and treat it with Mirasol. THIS IS A EMERGENCY INTERIM PROCESS UNTIL THE MEDINFO HEMATOS IIG PROCESSES ARE PREPARED AND VALIDATED.

Policy:

Good Manufacturing Practice applies:
1. Manufacturers’ recommended processes for equipment and materials usage applies.
1. All staff engaged in these processes must be competency assessed successfully.
Pre-Screening:
1. Clinical staff will use the prescreening document to select donors for pre-donation screening.
Quarantine:
1. All processes (day 0, day 1, day 2, and product modification and release) will be done in quarantine areas SEPARATE and DISTINCT from regular Transfusion Medicine activities. This includes:
  1. Separate space and equipment must be provided.
    1. Equipment for this project may NOT be used for regular, non-quarantine processes
2. Non-Transfusion Medicine staff will not be permitted in operational areas.
3. Prospective donors will not be permitted in the processing, testing, storage, or blood bank work areas.
Donation Process:
1. Day 0: Registration, check donor deferral database, questionnaire, physical exam including arm check, and specimen collection using ISBT specimen labels
2. Use latest manual donor questionnaire.
3. Day 1: Donor marker and immunohematology testing, review of results, accept or reject donor for actual plasmapheresis
4. Day 2: Collect manufacturer’s recommended volume of plasma (500 ml if < 80 kg, 600 ml if >= 80 kg), aliquot, pathogen-inactivate (Mirasol), freeze at minus 80C
Testing:
1. Testing will be performed with regular blood donor specimens using ISBT specimen labels
2. Testing must be done by donor-specific processes (not those for clinical patients)
  1. Exclude malaria and HTLV testing.
3. Testing must be directly interfaced to Medinfo Hematos IIG donor module
4. CCP COVID antibody testing:
  1. SARS-CoV-2 antibody testing to be performed to determine cut-off for donor eligibility for CCP collection.
  2. Use of donors with antibody levels below threshold is at the discretion of the treating clinician.
Processing:
1. Aliquoting, pathogen-inactivation, and labelling may proceed if the pre-donation screening results are acceptable.
Storage:
1. Long-term in minus 80C quarantine freezer
2. Short-term at 1-6 C just after thawing in quarantine refrigerator
3. Standard temperature monitoring and alarms apply
Labelling:
1. The backup manual labelling process applies
2. The ISBT specimen label will the donor unit number
  1. Outdate will be 6 years if the product is stored at -65C, 1 year if stored at -18C
Product Release:
1. Orders must be on the PAPER requisition (old Blood Bank Order Form) with a patient prescription and signed by a physician designated to treat COVID patients.
  1. No orders in Cerner
2. Thawing plasma at 37C upon receipt of order by Transfusion Medicine staff
3. Signing out component to clinical unit by Transfusion Medicine Staff to locations treating COVID-19 patients.
Information Technology: Medinfo Hematos IIG customized software to be implemented as soon as possible for all processes
Not covered: Transfusion Medicine is NOT responsible for:
1. Triage of request for convalescent plasma
2. Pickup and transport of components

References:

Level 1-4 documents for donation, testing, processing, and release of blood components
COVID-19 Plasma Donor Prescreening Document, 8/4/20

COVID-19 Convalescent Plasma Donor Pre-Screening

28th Dec 202021st Nov 2020 drzeyd

All blood components are considered medications and are subject to Good Manufacturing Practices as mandated by international accreditation standards. The whole process must be done reproducibly and precisely by specific personnel trained and documented to be competent. This includes collection of convalescent COVID-19 plasma.

Transfusion Medicine will provide staff who are deemed competent for the entire process of the collection, manufacture, and release of this unlicensed, emergency-contingency component.

It will help greatly if all candidates are prescreened to exclude the following candidates:

Administrative:
1. Donors must come with a valid Qatari identity card: no ID means no screening
Sex:
1. Males only to minimize the risk for transfusion-associated lung injury TRALI
Donor Feeling:
1. If the donor does not feel well, he should not come for screening/collection.
Food/Drink:
1. Donor must have eaten/drunk fluids within 4 hours of arrival for screening/collection.
Medication exclusions:
1. Antibiotics within the past 14 days
2. ACE inhibitors in the past 48 hours
3. Beta blockers
4. Anticoagulants
5. Anti-anxiety or other psychotropic medications
6. Other medications on the attached list
Medical exclusions:
1. Stable vital signs
2. History of seizures
3. History of dementia or other chronic neurologic disorder
4. Family history of dementia or other chronic neurologic disorder
5. Significant cardiac arrhythmias
6. History of hepatitis B, hepatitis C, HIV, brucellosis, Ebola
Travel history:
1. 5 years cumulative residence in Europe including Ireland and France 1980-2001
2. 3 months cumulative residence in the UK (and/or all its territories) 1980-1996
3. Any visit(s) to West Africa

This is NOT a complete list of criteria. Transfusion Medicine personnel will screen according to the full donor criteria. Thus, donors passing the pre-screening may still be otherwise disqualified based on the detailed process.

COVID-19 Convalescent Plasma CCP Series Introduction

24th Dec 202023rd Dec 2020 drzeyd

I will be posting a detailed series about the manual and software-enhanced COVID-19 processes that I set up in Qatar at HMC Doha in March-April 2020.

In this series I will provide you with screen shots of my Medinfo Hematos IIG software design for each step in the process: collection, processing, testing, inter-depot transfer, and hospital transfusion service/blood bank release.

This GMP-compliant software-enhanced system is based on the manual system I set up in early March 2020 at HMC.

I want to thank Medinfo Hematos IIG for their rapid response to building this parallel system based on my standard processes in so short a time (two weeks) and my special thanks to the software engineering team at Vital Health Technologies, the agent for Medinfo in Qatar.

To start the series, I am providing the basic workflow for the system. As is normal in Medinfo software design, a full mapping of the processes are made. This workflow shows the new CCP ISBT codes and the quarantine collection and processing steps. The donor testing (marker and immunohematology) processes are similar to those for regular donor units.

This is basically the same process both manually and in the software. I always say:

A good software process is based on a good manual process!!

Please note the following workflow for our initial discussion.

Use of Universal Low-Titer Group A Plasma

22nd Dec 202012th Nov 2020 drzeyd

Principle:

Since group AB plasma is in short supply, use of group A plasma with low anti-B titers may be substituted based on inventory levels.

Policy:

If the AB inventory is low, we will test group A donors at the time of collection for anti-B titers.
1. The numbers to be tested will depend on the level of the shortage and the availability of equipment to perform titration.
Use the automated analyzer to perform saline anti-B.
1. If the saline titer is less than or equal to 1:64, the plasma may be used for recipients of any ABO blood group and will be labelled as group AU—A Universal.
Process the unit routinely and perform pathogen-inactivation.
Medinfo Hematos IIG will only label for universal use if the titer is below the cutoff.
1. The ISBT label must explicitly show group AU plasma and the actual anti-B titer.
Allocation rules for low-titer group A plasma will be identical to group AB except:
1. For neonates, preferentially use group AB.
2. For children < 20 kg, use ABO-compatible plasma (non-group AB) before selecting group AB or if not available, low-titer A in that order.
Donors must have a new anti-B titer performed each donor encounter.

References:

Technical Manual, Current Edition, Bethesda, MD, USA
Standards for Blood Banks and Transfusion Services Current Edition, AABB, Bethesda, MD, USA

Framework for Establishing the Use of Universal Low-Titer Group A Plasma

21st Dec 202012th Nov 2020 drzeyd

This post outlines a framework for establishing the use of low-titer group A plasma as a universal donor. Manual titering large number of donor specimens in my organization is not practical. Using an automated system will also increase the precision of the results.

Process:

Select a cut-off anti-B titer. This should be determined by the blood bank medical director.
1. I selected saline 1:64 based on recent THOR (Thrombosis Hemostasis Oxygenation Research) meetings
Perform a survey of the anti-B titers in your blood donor population.
1. At my sites, about 50% had titers less than or equal to 1:64.
2. Determine how stable the titer is:
  1. For serial donor plasmapheresis, how long could you accept the donor as low-titer?
  2. Does the titer change between whole blood donations?
Determine the target inventory level for universal plasma (group AB and low-titer A) based on current/past usage.
Assess availability of automated immunohematology analyzers for titration.
1. Titration may take up to 30 minutes per sample, during which time the machine cannot be used for any other purpose.
Add a new blood type AU (for group A universal) for plasma in your blood typing algorithm.
1. AU should be used interchangeably with group AB.
Software:
1. Set up new truth table in your blood bank computer system.
2. Validate the modification in your blood bank donor and patient modules.
3. Update ISBT code for this new product, verify your transfusion service module can read this.

Special notes:

At my last location, we had only 3 analyzers capable of doing the titration. Thus, we could only do 6 titrations per hour at the expense of stopping all other testing. You will have to coordinate the titration with your other immunohematology testing. Also, verify if all these equipment interface to your production software. In my system, any test (including titration) could be performed at any location and its results be used for production purposes.
Donor ABO antibody titers may fluctuate. I would not use previous results to qualify a donor to be AU. I would repeat the anti-B titer each donor encounter. If I collect donor plasmapheresis, I would determine for how long the titer can be used (see 2.2.1 above).

References:

Technical Manual, Current Edition, Bethesda, MD, USA
Standards for Blood Banks and Transfusion Services Current Edition, AABB, Bethesda, MD, USA
Medinfo Hematos IIG Donor Production Module

Data Entry Verification: Updated Version

19th Dec 202011th Nov 2020 drzeyd

This is an update from the previous version posted to include low-titer group A FFP/FP24 and low ABO-titer group O whole blood.

Principle:

This policy outlines steps taken to minimize the risk of data entry errors and is based on a dualistic approach: review of results by a senior technologist and/or supervisor and various computer safeguards built into the Medinfo Hematos IIG blood bank computer HIIG system. This policy also discusses the verification (here called authorization) and purge processes of HIIG.

Policy:

Review by senior technical, supervisory, or transfusion medical staff:
1. Designated test procedures require review by a second technologist before authorization.
2. Complex immunohematology testing and specimens showing aberrant results (e.g. ABO/D discrepancies) are reviewed by the supervisors or designates and ultimately a transfusion medicine physician before authorization.
Computer system HIIG rules:
1. Privileges:
  1. System restricts which staff can perform specific tests
2. Patient/donor identity:
  1. System asks end-users to verify patient/donor identity before starting any access to the patient/donor record.
  2. System performs historical database checking and flags any inconsistencies (e.g. historical ABO/D typing differences, etc.)
3. Testing:
  1. Only selected staff have privileges to authorize or purge.
  2. ABO/D testing algorithms require entry of reactions, not interpretation of results and are compared to a truth table.
    1. Aberrant results require special review before ABO/D typing results can be authorized/purged.
    2. D-controls must be negative to allow D typing results to be authorized for liquid D-typing reagents.
  3. DAT results require appropriate controls to meet truth-table criteria.
  4. Eluates require last wash to be negative before authorization
4. Blood components:
  1. Selection of RBC or plasma units requires two independent sample determinations within 72 hours of each other.
  2. ABO-incompatible RBC or FFP/FP24 transfusions are not allowed.
  3. Titer-based ABO blood group selection:
    1. Low titer group A FFP may be used as universal plasma like group AB.
    2. Group O whole blood with low anti-A and anti-B titers may be used for all ABO types.
    3. Acceptable titer threshold is specifically defined as parameters in Medinfo.
  4. Donors with any detectable clinically significant antibodies are permanently deferred.
  5. Depending on the patient’s antibody history, release of RBC units may require antigen-matched units. Examples:
    1. Mandatory matching (only antigen negative matched units allowed—no antigen positive or antigen-untyped units): Antibodies against H, D, c, K, k, Kpa, Kpb, Jsa, Jsb, Jka, Jkb antigens, anti-PP1Pk
    2. Priority matching (incompatible or untested can be approved by a transfusion medicine physician): C,E, e, Fya, Fyb, M, S, s
    3. Antigen matching not required: Lea, Leb, N
  6. Least-incompatible crossmatch require special authorization to release
  7. Protocols to force irradiation or other modified components can be setup in HIIG.
5. Donors:
  1. Donor tests have same criteria as the same test used in patient testing for controls, etc.
  2. Donor demographics are read directly from the Ministry of Interior database—no manual entry (bar code only used).

References:

Workflows for Hematos IIG (1001 through 1005), 2013-2020
Standards for Blood Banks and Transfusion Services, Current Edition, AABB, Bethesda, MD, USA
Guidelines to the Preparation, Use, and Quality Assurance of Blood Components, European Committee (Partial Agreement) on Blood Transfusion (CD-P-TS), Current Edition

Pre- and Post-Exposure Antiretroviral HIV Prophylaxis

12th Dec 202030th Oct 2020 drzeyd

Principle:

Use of anti-retroviral therapy as prophylaxis for pre- or post-exposure (PrP or PEP) HIV prophylaxis may lower the viral load below detectable levels.

Policy:

Defer any donor taking PrP or PEP anti-retroviral ART medications for three (3) months since the last dose.
Donors taking ART drugs as treatment for HIV infection are still indefinitely deferred.
Donor information pamphlets should be updated to include this new deferral.

References:

AABB Association Bulletin #4, The Impact on Blood Safety of Effective Antiretroviral Medications for HIV Prevention and Treatment, 5/5/20
DHQ Medical Deferral List, Version 2.1, AABB, Bethesda, MD, USA, June 2020

Off-Line Donor Medinfo Transactions

7th Dec 202027th Oct 2020 drzeyd

Principle:

When you cannot establish a direct link to the live Medinfo program, you must arrange for the local Medinfo engineers to create a local server that will have the current Medinfo donor database for use at outside campaigns where the internet connection cannot be used. This can also be used if for some reason the Blood Donor Center link is down in order to register donors and check the donor deferral database.

Policy:

For each outside campaign, there should be a pre-campaign visit to verify the availability of internet to connect to Medinfo.
1. If the internet connection is working, use Medinfo using the 4G access points. Otherwise:
2. If none, inform the Medinfo engineers to prepare a local server on one of the laptops at least ONE DAY in advance of the campaign.
  1. Give Medinfo engineers the laptop to download the database and software. This will be the offline server for the campaign.
  2. Link the offline server to the other portable computers for the campaign (see the corresponding Medinfo job aid).
  3. Use the local network (offline server and other portable computers) for registering donors.
  4. Upon return to the Blood Donor Center, upload the data.
  5. Continue the regular processes after uploading.

Note: When the offline data is uploaded into Medinfo main database, it will be checked against the latest donor deferral database. The latter will be applied for the donation.

Processes and Software Building 56: Multi-Site Patient and Donor Considerations

25th Nov 202015th Oct 2020 drzeyd

As our hospital network expanded, there were many patients who moved between locations. They might first start in an emergency room and then be transferred to a specialty hospital. These locations might be served from different hospital blood banks/transfusion services. What happens if work is progress from one site when the new site receives the patient. Must the previous workup be repeated or could it be used for transfusion at the next site?

For example, the ABO typing could be performed at one site and the antibody screen at a second site, and the antibody identification at still another site. Could the results be used across the entire system?

I had multiple hospital blood banks and blood donor centers. The general and specialty laboratories had multiple sites. The hospital information system was set up so that the various tests could only be performed at specific designated sites. This posed problems as patients were moved around or if some site(s) became inoperative since the specimens then had to transported at great distances for testing. Only a few basic STAT tests were available at all sites.

It was my decision to allow all test categories at all sites, e.g. a DAT request from any site, any methodology, could be used to satisfy the order. Similarly, all donor processes were available at all donor centers (the processes could be completed at one or more sites). Different hospital blood banks had different equipment but all the test categories were the same across site—the methodologies might differ. We had at least four different DATs across our system.

The interface between the blood bank and hospital system worked as follows: In the hospital information system HIS, test orders pointed to a category of testing and any methodology for that category at any site could be used in the blood bank system for testing and reporting back to the HIS. Any test in a category from any site could be used to satisfy the test request. Blood bank staff would choose the particular test methodology to use. It was NOT specified by the HIS!

In summary, for blood banks and donor centers within our system, the work could be flexibly moved between sites. There was no need to repeat testing when a patient transferred to a new site. The only type the work was repeated if testing was done at an institution outside our system.

Sample Validation Change Protocol: Donor Hgb Levels

20th Nov 202011th Oct 2020 drzeyd

Changes to donor criteria can occur at any time. This example is the change in donor criteria for males to 13.0 g/dl based on AABB Bulletin #16-05.

I made a validation protocol, which was subsequently performed by a Donor Center Medinfo Super-User. The data was then sent to me for review and then accepted.

Note that females were included in the testing for regression purposes. Females were only permitted to donate RBCs—all other components were discarded in production. Contraindication information appears in RED.