Tag: Donor Marker Testing

Any or all test methodologies

Medinfo COVID Convalescent Plasma Workflow Revisited

drzeyd

It now has been over eight 8 months since I prepared the CCP workflow in Medinfo.  It was built on the framework of the manual CCP process including donor prescreening with an abbreviated donor questionnaire.  It was really quite simple and used the donor and patient modules to create quarantine areas for donor screening, collection, processing, and hospital patient blood bank release.

Here are my current comments on the process:

Donor Qualification:

I would still exclude malaria and HTLV from the donor questionnaire and would update to UDQ 2.1.  Since these donors have recovered from a potentially life-threatening illness, I would keep the Hgb threshold at 11 g/dl.

Donor Collection:

In the future, I would consider using one of the soon-to-be-released portable devices that continuously monitor vital signs with pO2 and EKG lead to rule out asymptomatic pulmonary or cardiac problems.

I would also consider using low-ABO-titer, group A, universally to meet the demand for group B and AB patients.

Donor Testing:

There is still no need to segregate and separately test CCP donor specimens from regular blood donor specimens.  I would perform SARS-CoV-2 antibody testing and set a threshold for qualifying donors—that threshold will be based on the manufacturer’s recommendations.  However, if the treating physician wanted to use a low-titer unit, I would permit this.

Donor Processing:

There is no need to change this from the current processes.  Keep the CCP processing separate from the regular operations.

CCP Plasma Release:

I would keep the quarantine release and restrict it to the locations used for treating COVID-19 patients

Medinfo Software Modifications:

I would record the IgG and IgM titers for SARS-CoV-2 antibodies in each donation record.  This would include testing and entering the results on donations prior to this testing.  ISBT labels should include this antibody titer.

Hospital Information Software Modifications:

Set up restricted CCP ordering for the actual treating physicians only.  Also provide the ISBT code and shortened descriptors to it if necessary (certain HIS vendors still cannot read ISBT codes natively).

The original CCP workflow is attached for reference.

Manual Collection of COVID-19 Convalescent Plasma

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:

  1. 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.
  2. Pre-Screening:
    1. Clinical staff will use the prescreening document to select donors for pre-donation screening.
  3. 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.
  4. 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
  5. 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.
  6. Processing:
    1. Aliquoting, pathogen-inactivation, and labelling may proceed if the pre-donation screening results are acceptable.
  7. 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
  8. 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
  9. 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.
  10. Information Technology:  Medinfo Hematos IIG customized software to be implemented as soon as possible for all processes
  11. Not covered:  Transfusion Medicine is NOT responsible for:
    1. Triage of request for convalescent plasma
    2. Pickup and transport of components

References:

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

COVID-19 Convalescent Plasma Donor Pre-Screening

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:

  1. Administrative:
    1. Donors must come with a valid Qatari identity card:  no ID means no screening
  2. Sex:
    1. Males only to minimize the risk for transfusion-associated lung injury TRALI
  3. Donor Feeling:
    1. If the donor does not feel well, he should not come for screening/collection.
  4. Food/Drink:
    1. Donor must have eaten/drunk fluids within 4 hours of arrival for screening/collection.
  5. 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
  6. 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
  7. 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.

Bacterial Risk Control Strategies for Platelets—USA

drzeyd

I am attaching the US Center for Biologics Evaluation and Research CBER Guidance for Industry revision dated December 2020 to replace the one issued in September 2019.

This is a very detailed document that will require US blood centers to comply with newer more stringent safeguards to minimize the risk of bacterial contamination of platelet components.

The easiest way to comply is to universally pathogen-inactivate all platelet components:  then the rest of the algorithm does not apply.  I am happy that for over 10 years I have used pathogen-inactivation (riboflavin-based Mirasol, Terumo BCT) and not experienced any bacterial sepsis from platelet or plasma components.

For those of us practicing outside the USA, please note:

The US still does not permit pooled, buffy coat platelets to have either a 5 or 7 day outdate.  For pooled components stored at 20-24 C, the FDA only allows a four-hour outdate, regardless what the rest of the world permits.  Thus, the USA mainly uses apheresis platelets.

If you have pathogen-inactivated platelets, you are so fortunate that you don’t have to follow these other recommendations to have a low risk of bacterial contamination.

Reference:

Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion, Guidance for Industry, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research, September 2019 updated December 2020

CBER Guidance for Bacterial Contamination Guidance, Revised December 2020 (PDF)

COVID-19 Convalescent Plasma CCP Series Introduction

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.

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

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.

Donor Unit Discrepancies

drzeyd

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.

The blood bank computer system will detect many errors;  however, if the donor unit or its samples are mislabeled in the beginning, these may not be detected.  Medinfo enforces checks on the final ISBT label and will compare current results to the historical record and will alert to any errors. Additionally, the use of ISBT specimen labels will obviate the risk of barcode reading errors.

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/variance 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 the Division 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 institution’s policies and regulations.

2/11/20

Blood Bank Software is Dynamic, NOT Static

drzeyd

I was recently talking with one of the hospital software system administrators from my previous site.  He had originally worked on building the Medinfo system, but was then reassigned to the laboratory modules of the hospital information system.

His alarming comment to me was that the Medinfo build was completed so there was no need to worry about it now—it was finished.  I guess he was looking from the perspective of the general laboratory software.  There is no need to make major changes to the build, just update interfaces and troubleshoot.

I was surprised.  He had no idea of how many times we have to update the structure for new rules and regulations, and changes in blood bank practice—let alone emerging pathogens such as ZIKA, dengue, Chikungunya, and most recently, COVID-19.

My daily morning routine was to survey several blood bank websites with changes to blood donor criteria including US FDA CBER, read the transfusion journals (Transfusion, Vox Sanguis, etc.), AABB, and ASFA.  If there were any changes pertinent to our organization, I had to make interim policies and procedures, and finally prepare specifications for changes in the Medinfo software.

The Medinfo engineers would prepare flow charts of the proposed changes and implement them in a test environment for the Super-Users to test.  I had to prepare validation protocols for the testing, and then review the validation results and finally approve the adoption of the changes.

I cannot remember even a month going by without some revision in the donor protocols.  When COVID-19 came, I had to prepare a parallel, but separate, processing and allocation/release system.

This was a never-ending story that kept the Super Users and the local Medinfo engineers busy.  I always reminded the hospital information system staff that playing with blood bank software was like playing with fire:  there is a good chance you will get burned if you do not set it up properly.

31/10/20

Look-Back of Patients and Donors

drzeyd

Principle:

Using the Medinfo Hematos IIG program, it is easy to perform look-back for patients who have developed an infectious disease that might have been transmitted by a blood component.  Likewise, if a donor develops an infectious disease that is transmissible to patients, we can check which patient(s) received blood components from the incriminated donor.  The time interval for checking will vary according to local regulations.

Policy:

  1. If a patient is reported to have developed an infectious disease which might have been transmitted by a blood component transfusion:
    1. Review the patient’s infectious marker testing data.
    2. Review the patient’s transfusion history, especially for any transfusions at outside institutions or any other body fluid exposures.
    3. Look up the transfusion history in Medinfo HIIG.
    4. Determine which transfusions occurred during the deferral period for that disease.  Examples:
      1. HBV—6 months
      2. HCV—6 months
      3. HIV—2 months
      4. Malaria—6 months
      5. HTLV—6 months
      6. Syphilis—12 months
    5. Look up the donors for each donation during the specified interval.
    6. Check each donor’s donation records for:
      1. Infectious disease marker testing
      2. Questionnaires—any irregularities noted?
    7. Call donors back for repeat testing (only on advice of the investigating transfusion medicine physician)
    8. Collate all results and prepare an interpretative report.
    9. Interpretative report must be reviewed/released by the Head, Transfusion Medicine.
    10. Submit the report to Infectious Disease and the patient’s most responsible physician
    11. If any irregularities are found, assess processes to make any improvements in an attempt to minimize future risk.
    12. Prepare an OVA according to HMC procedures.
  2. If donor develops an infectious disease:
    1. Review the donor’s infectious marker testing results.
    2. Check if the donor had any body fluid exposures.
    3. Obtain new specimen from the donor.
    4. Look up all components made from that donor.
    5. Determine which transfusions occurred during the incubation period for that disease.  Examples:
      1. HBV—6 months
      2. HCV—6 months
      3. HIV—2 months
      4. Malaria—6 months
      5. HTLV—6 months
      6. Syphilis—12 months
    6. Recheck the complete donor history including infectious disease marker testing and questionnaire
    7. If samples are available from the interval, repeat donor marker testing on it.
    8. Look up the patient/recipients for each donation during the specified interval
    9. Check each patient’s records for infectious disease marker testing results
    10. Call patients back for repeat testing (only on advice of the investigating transfusion medicine physician in conjunction with the Infectious Disease department.)
    11. Collate all results and prepare an interpretative report.
    12. Interpretative report must be reviewed/released by the Head, Transfusion Medicine.
    13. Submit the report to Infectious Disease and the patient’s most responsible physician
    14. If any irregularities are found, assess processes to make any improvements in an attempt to minimize future risk.
    15. Prepare an OVA according to HMC procedures.

Reference:

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

Policy: ISBT Specimen Labelling Audit

drzeyd

Principle:

ISBT specimen labels have a check-digit to reduce the risk of misreading the label.  They are generated by the blood bank computer system Medinfo.  Normally one group of labels is printed for all needs (donor unit, marker testing, donor immunohematology, and donor processing.  Reprinting the same number is restricted to minimize the risk of using the wrong label on a specimen or unit.  These labels are NOT used for patient testing.

ISBT specimen labels are only printed at the time of donor registration.  We must securitize them so that they are not used for other, potentially malicious purposes.  Remember:  a labelling mistake may cause fatality in a patient receiving the wrong blood component.

Policy:

  1. ISBT specimen labels are only for blood donor specimens, initially labelling of donor collections, and intermediate processing of components.
  2. They must be applied to the primary specimens directly at the donor’s bedside.
  3. They must be applied to aliquots from the original ISBT-labelled tubes.
  4. They may NOT be applied to any other specimen (e.g. for routine laboratory testing outside Transfusion Medicine)
    1. If an ISBT label not corresponding to the correct donor is discovered, an OVA or event report must be generated and investigated immediately.
  5. If additional ISBT labels are needed, this must be documented on a specific audit sheet with signature of the person taking the extra labels and a second person to witness their removal.  It will also be noted in the Medinfo system for auditing purposes.
  6. The audit sheet must be kept in a secure place for future reference in Blood Donor Center.

14/10/20