Month: Dec 2020

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.

Donor History Medication Deferral List UDQ 2.1

drzeyd

This table and explanatory page shows the Uniform Donor Questionnaire latest version 2.1, which includes deferral for both pre- and post-exposure HIV prophylaxis.

I am showing 2 versions of this deferral list:

  1. My modification referring certain medications to the transfusion medicine physician for review that are otherwise permitted in the original 2.1 list.
  2. The original UDQ 2.1 list that permits patients taking anticoagulants and other medications.

I would prefer for the donor screening transfusion medicine physician to review the reasons for these anticoagulants and other medications before deciding whether to accept the donor.

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.

Policy: Selection of Components for ABO-Incompatible Renal Transplants

drzeyd

Principle:

Kidneys have strong expression of ABO type and must be matched the same way as RBC components.  In the case of ABO-incompatible renal transplants, we must not give significant amounts of plasma incompatible to the ABO type of the donor kidney.  Plasma must also be compatible with the patient’s ABO type for RBC transfusions.  The amount of residual plasma in PRBCs is limited since we use an additive solution SAGM.  Likewise, platelet components are suspended in platelet additive solution with only minimal residual plasma.  Cryoprecipitate has only minimal plasma and is given without regard to the patient’s ABO type.

All of the following rules can be built into the blood bank computer system Medinfo without hard coding.

Policy:

  1. RBC components:  Use ABO-compatible RBCs in SAGM.  DO NOT USE WHOLE BLOOD!!
  2. Platelet components in platelet additive solution PAS (normally available component):  Any ABO type may be given
  3. Platelet components in plasma:  Only group AB platelets may be used.
  4. Plasma (any type FFP, FP24, solvent-detergent treated, or thawed):  Only group AB plasma may be used
  5. Cryoprecipitate:  Any ABO type including mixed types may be used, mixed types are preferable to neutralize the minimal ABO-incompatible plasma.

References:

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

My Experience: Blood Bank Considerations for Setting Up ABO-Incompatible Renal Transplantation

drzeyd

Setting up ABO-incompatible renal transplants is a major undertaking and requires close coordination between Transfusion Medicine and the clinical team.  This post addresses my experience in setting up this program in 2019 at HMC in Qatar.

Like any process involving titration, it is best to automate it to minimize inter-technologist variability.  Unfortunately, doing both IgG and IgM titers takes up to 1 hour per machine and totally monopolizes the machine during that interval.  I did not have sufficient staff to even consider doing the titrations manually.  Performing automated titers disrupted my workflow so I encouraged the clinicians to send the specimens for off-peak processing.

Titration:

  1. Obtain the full clinical protocol and especially note the thresholds for transplantation.
  2. Determine the methodologies used at the reference site.  Can you do this at your local site or do you have to use an alternative method?
  3. Do you have equipment to automatically titer?  Doing both IgG and IgM may monopolize an immunohematology analyzer for one hour?  How will this affect your other testing?
  4. Regardless if it is the same method, you must still correlate your titers with the protocol site, both IgG and IgM.
  5. If you are using multiple analyzers for titration, you must do a comparison study between them.  How much does the titer vary?

Columns:

  1. Determine column inventory and order the A, B, and AB columns.  You must order enough to finish the course of treatment.  It may take weeks to get additional columns, depending on your supply chain.  Each column costs thousands of euros.
  2. Where are you going to store the columns?  Ours needed 2-8C storage.  Can you keep them away from quarantined products and patient specimens?
  3. Are your columns single-use? 
  4. If multi-use, who is going to restore them after use?  How do you ensure that it is dedicated for the right patient?

Apheresis Equipment:

  1. How are you going to attach the column to the apheresis equipment?
  2. Will you use your therapeutic apheresis equipment like Terumo Optia directly or will you use a second machine (e.g. Medicap)?
  3. Do you have all the clamps, tubing, and holder for the column?

Staffing:

  1. Do you have sufficient apheresis nurses to perform the procedures?  You may be running the apheresis for up to 8 hours.  How does this impact your other procedures or donor center operations?  Our pool of apheresis nurses was very limited.  They also covered routine blood donation.  How will doing this process impact your regular donation and other apheresis operations—donor and therapeutic?
  2. Do you have sufficient supplies of ACD-A anticoagulant and calcium gluconate?

Specimen Collection:

  1. Perform titrations expeditiously:  Can you finish titration testing before the next scheduled procedure?  In our institution, we collected specimens at 0400 and had them directly brought to the blood bank for testing.  Results were ready at 0600 so the clinicians could decide early if another procedure was needed.

Table of Permissible ABO Types:

  1. Define acceptable blood products by blood type—take into consideration pathogen inactivation and platelet additive solution if used.  At our institution, all RBCs were in additive solution and all platelets were pathogen-inactivated in platelet additive solution PAS so residual ABO antibodies were minimal in the final components.  Since the platelets contain only minimal plasma, we did not concern ourselves with matching their ABO type with the donor kidney.  Otherwise, platelet types with plasma compatible to the donor kidney must be selected.

Software:

  1. Prepare a truth table for acceptable ABO component types based on #16 above.
  2. Include the titer cutoff for IgG and IgM antibodies in the organ transplant module.

Selection of blood component for ABO-incompatible renal transplantation is discussed in a separate post that will follow.

25/12/20

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.

Leukodepletion Apheresis Form

drzeyd

This form is the result of a collaborative effort between my therapeutic apheresis team and me. I want to thank Dr. Saloua Al Hmissi, Consultant, Transfusion Medicine, and Ms. Mini Paul, Head Apheresis Nurse for all their efforts.

This form can be readily converted into a computer data entry form–depending on your software’s capabilities.

Use of Universal Low-Titer Group A Plasma

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:

  1. 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.
  2. 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.
  3. Process the unit routinely and perform pathogen-inactivation.
  4. 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.
  5. 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.
  6. Donors must have a new anti-B titer performed each donor encounter.

References:

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