Syphilis testing uses a screening test (we used an EIA methodology to detect cardiolipin) and a confirmatory test a syphilis linear immunoblot assay LIA.
I emphasize that any test methodologies and testing algorithms can be designed in Medinfo. This is what I selected during the time I was HMC Doha.
My algorithm specification was:
Syphilis Testing:
Syphilis Ab test positive or indeterminate: do InnoLIA-Syphilis test
InnoLIA-Syphilis test positive: permanent deferral, refer to Infectious Disease clinic
InnoLIA-Syphilis test borderline or negative: defer for 1 year, then repeat all syphilis testing.
Repeat Syphilis Testing after 1 Year:
Syphilis antibody testing negative, reenter into donor pool
Syphilis antibody positive or borderline: do InnoLIA-Syphilis test
InnoLIA-Syphilis test positive: permanent deferral, refer to Infectious Disease clinic
If InnoLIA-Syphilis borderline or negative: permanent deferral, syphilis not confirmed
This was translated into Medinfo processes as follows:
Hepatitis B donor screening consists of HBsAg and HBcAb for all donors, the latter to detect the window period. In the USA, a non-negative HBcAb result will trigger a deferral. In the Gulf area/KSA, there HBV was positive higher than in the West so there was a high rate of HBcAb positivity often from recovered HBV infection.
Here was my last algorithm before I left HMC Doha, which allowed use of donors with protective titers of HBsAb. Note that the WHO cut-off for this is 10 IU/L whereas we used 100 IU/L as our threshold:
Hepatitis B:
HBsAg non-negative, then:
HBsAg positive with HBsAg confirmatory positive, regardless of other results: permanent deferral, refer to Infectious Disease clinic
HBsAg positive with HBsAg confirmatory borderline or negative, repeat all HBV testing after 8 weeks
HBsAg borderline: repeat all HBV testing after 8 weeks
HBV-DNA positive confirmed, regardless of other results: permanent deferral, refer to Infectious Disease clinic
If HBcAb positive, repeat after 8 weeks
Repeat Hepatitis B Testing After 8 weeks:
HBsAg positive with HBsAg confirmatory positive: permanent deferral, refer to Infectious Disease clinic
HBsAg positive with HBsAg confirmatory borderline or negative: permanent deferral, refer to Infectious Disease clinic
HBsAg borderline, permanent deferral, refer to Infectious Disease clinic
HBV-DNA positive confirmed: permanent deferral, refer to Infectious Disease clinic
HBcAb positive or borderline with negative HBsAg and negative HBV-DNA: review HBsAb level:
If HBsAb level >= 100 mIU/mL (100 IU/L), donor may be reentered
If HBsAb level < 100, then recommend to donor to receive booster HBV vaccine
After HBV vaccine administration, retest after 30 days:
If HBsAb level >= 100, donor may be reentered
If HBsAb level < 100, donor is indefinitely deferred
HBsAg, HBcAb, HBsAb all negative: reenter into donor pool
Here is the HBcAb and HBsAb part of the algorithm:
Previously, we had we had disqualified any donor with a nonnegative HBcAb:
As I designed this in Medinfo, this is algorithm uses an HIV- /HIV-2 antibody EIA screening test, HIV p24 antigen test, and a confirmatory linear immunoblot assay LIA that can discriminate between type HIV-1 and type HIV-2. If there is an indeterminate result, a repeat test is ordered after 8 weeks. A reentry protocol is also included (1.6.3 below).
HIV Testing:
HIV-RNA positive confirmed, regardless of other HIV results: permanent deferral and do HIV-InnoLIA, refer to Infectious Disease clinic
HIV-RNA borderline: do HIV-InnoLIA
HIV-InnoLIA positive, regardless of other HIV results: permanent deferral and refer to Infectious Disease clinic
HIV-InnoLIA indeterminate: repeat all HIV testing after 8 weeks
HIV Ab positive with negative HIV-RNA and/or borderline/negative HIV-InnoLIA: repeat testing after 8 weeks
Repeat HIV Testing After 8 Weeks:
HIV RNA positive and/or HIV-InnoLIA positive, regardless of other HIV results: refer to Infectious Disease clinic
HIV-InnoLIA and/or HIV antibodies indeterminate: permanent deferral, HIV infection not confirmed
HIV Ab negative and HIV-RNA negative and HIV-InnoLIA negative: reenter into donor pool
This algorithm is represented in Medinfo as follows:
HMC Doha 2011-2020: Set-up of both donor and patient modules including inter-depot transfer:
Donor:
Implemented COVID-19 convalescent plasma CCP production at HMC Doha over two-week period, February-March, 2020 including full integration with software
Donor collection, donor marker testing, donor immunohematology testing, inter-depot transfer between production site and hospitals and hospital-hospital transfers, ISBT labelling and specimen
Collection Interface (read-only) with Qatar Ministry of Interior to obtain both English and Arabic demographic information from donors
Establishing world’s first interfaces (bidirectional as required) with Terumo BCT Atreus and Reveos automated blood processing equipment, Mirasol pathogen-inactivation/platelet additive solution, Terumo Trima Accel donor apheresis machine, Terumo mixer-shaker donor collection device
Patient:
Implemented a CCP quarantine patient blood bank separate from regular hospital blood banks) for thawing and releasing of CCP plasma
Patient module including all compatibility testing, ABO/D typing, extended antigen typings, direct and indirect antiglobulin testing (antibody screens), antibody identifications, eluate, component modifications (thawing, pooling, aliquoting), interfacing of Diamed automated gel testing
Establishing algorithms for emergency release, electronic crossmatching, automated patient specimen titration with Ortho Vision MAX, prophylactic antigen matching, ensuring irradiation of blood components or use of pathogen-inactivation as required, allocation rules by algorithm, required and optional antigen matching in presence of antibodies
Development of bidirectional interface between Medinfo patient module and Cerner Millennium laboratory module (permitting order of transfusion tests and blood component orders in Cerner, transmission to Medinfo patient module for testing and allocation of components, and then sending test results and component status back to Cerner)
Common:
Developing current and future states to develop the workflows to prepare software processes
NGHA Riyadh 2009-2010: Set up of both donor and patient modules including inter-depot transfer:
Donor:
Collection, marker testing, immunohematology testing, component production, inter-depot transfer between production site and hospitals and hospital-hospital transfers, ISBT labelling and specimens
Patient:
Patient module including all compatibility testing, ABO/D typing, extended antigen typings, direct and indirect antiglobulin testing (antibody screens), antibody identifications, eluate, component modifications (thawing, pooling, aliquoting), interfacing of Diamed automated gel testing
Please refer to my website https://drzeydbloodbank.com for specific posts on Medinfo software process building. On the right hand side from the bottom TAGS menu, pick Medinfo Hematos IIG to see those articles.
As I designed in Medinfo, this is a much simpler algorithm than HCV and uses an HTLV-1/HTLV-2 screening test and a confirmatory linear immunoblot assay LIA that can discriminate between type 1 and type 2. If there is an indeterminate result, a repeat test is ordered after 6 months:
HTLV 1/2 Testing:
HTLV Antibodies positive, then do HTLV-InnoLIA:
HTLV InnoLIA positive for HTLV-1 and/or HTLV-2: refer to Infectious Disease clinic
HTLV InnoLIA indeterminate or negative, repeat HTLV Ab and HTLV InnoLIA testing after 6 months
Repeat HTLV Testing After 6 Months:
HTLV 1/2 antibodies positive, permanent deferral and do HTLV InnoLIA
HTLV 1/2 antibodies indeterminate, permanent deferral and do HTLV InnoLIA
HTLV InnoLIA positive for HTLV-1 or HTLV-2: refer to Infectious Disease clinic
The testing algorithms may trigger additional testing, repeat of current testing at some future date, or permanent deferral. One of the most complex processes is for HCV testing. The following criteria are based on US FDA CBER guidelines, but are modified for the availability of test methodologies not licensed in the USA.
For HCV, we use the following testing in all donors:
HCV antibody EIA
HCV NAT
If any of the tests are non-negative, then we do the HCV LIA immunoblot assay.
HCV LIA is more sensitive than RIBA-3 (now no longer performed in the USA) but is not available in the USA. This test has been incorporated into the testing algorithm from CBER:
Hepatitis C:
HCV-RNA positive confirmed, regardless of other HCV results: permanent deferral, refer to Infectious Disease clinic
HCV-RNA borderline: repeat all HCV testing after 6 months
HCV-InnoLIA positive, regardless of other HCV results: permanent deferral, refer to Infectious Disease clinic
HCV-InnoLIA indeterminate: repeat all HCV testing after 6 months
HCV-Ab positive, HCV-RNA negative, do HCV-InnoLIA:
If HCV-InnoLIA positive, permanent deferral, refer to Infectious Disease clinic
If HCV-InnoLIA indeterminate or negative, repeat all HCV testing after 6 months
Repeat Hepatitis C Testing After 6 months:
HCV-RNA or HCV-InnoLIA positive: permanent deferral, refer to Infectious Disease clinic
HCV-RNA or HCV-InnoLIA borderline: permanent deferral, HCV infection not confirmed
HCV-Ab positive or borderline without positive HCV-RNA or positive HCV-InnoLIA: permanent deferral, HCV infection not confirmed
HCV-Ab negative, HCV-RNA negative, HCV-InnoLIA negative: reenter donor into donor pool
Note that indeterminate HCV results may be carried forward repeatedly by CBER rules but I decided to permanently defer the donor after 2 cycles of indeterminate results. The donor must wait SIX MONTHS before the next round of testing. Should he/she return before that time, those results may not be used for determining donor eligibility (unless the results have become clearly positive).
Donor marker testing algorithms are very complex and serve multiple objectives:
Is the blood safe for the recipient, i.e. minimize likelihood of disease transmission?
How do we to counsel the affected donor? Does he need referral for treatment or follow-up?
Often the donor disposition is unclear based on a single encounter and a temporary deferral must be triggered so the current results may be compared to future ones, usually after 8 weeks, 6 months, or one year—depending on the pathogen in question.
Regretfully, the significance of reactions that do not meet the criteria for positivity may be unclear. It is very difficult to explain to the donor that he has abnormal results and cannot donate but we as physicians do not know what their significance is.
Thus, the testing algorithms may trigger current additional testing, temporary deferral with repeat of testing at some future date, or permanent deferral.
At my previous positions, I started with the AABB/FDA CBER Uniform Donor Questionnaire UDQ and then modified it to include some advanced methodologies not available in the USA.
In the next series of posts I will elaborate on the processes developed for this for each marker.
I started building this using the Uniform Donor Questionnaire UDQ from the AABB; however, I modified it to include coverage for Chikungunya, Zika, etc. and to include enhanced processes for malaria based on the Australian Red Cross.
For each screening question, I prepared the exact wording (usually the UDQ’s) and set the deferral to temporary (how many days) or permanent.
Some questions were more open-ended, and the interviewer manually entered a medication, surgical procedure, etc. The transfusion physician would review this and assign a temporary (specifying the interval) or permanent deferral.
The questionnaire was constantly being updated by changes. My role was to review different accreditation systems (AABB, CE, etc.) and the World Health Organization’s websites. I would then prepare an interim policy and pass the specifications for the changes to the Medinfo software engineer and when ready, finally to the Super Users for testing. If there was an urgent change, the whole process could be completed in less than one day including validation testing.
The following shows examples of the software processes:
Medications
Body fluid exposures
Vaccinations
Malaria
Ebola/Zika
I emphasize that all of these settings are user-definable (at least in jurisdictions that permit all open, non-turnkey software).
Medication Questions:
Vaccinations:
Blood and Body Fluid Exposures:
Malaria Example: DMAL refers to the malaria antibody test.
Building the Software Processes for the Donor Collection 5:Donor Physical Examination and Adverse Reaction Reporting
Donor Physical Examination and Adverse Reactions
Donor physical examination, along with the donor questionnaire, are important both for donor and patient safety. In general:
Is it safe for the donor to donate?
Is it safe for the patient to receive the blood even if it is safe for the donor to donate.
Any donor who does not feel well must not donate. This may be the single most important step in ensuring a safe blood supply.
The donor physical examination includes the vital signs (blood pressure, pulse, temperature, heart rate, and temperature). I have attached a sample set of criteria for review. All are user-definable. Note how the arm examination is also included (looking for scarring, skin lesions, etc.)
For all types of donations, there may be adverse reactions. These must be documented in the record along with the disposition of the donation. Will the donor need an extended deferral if the RBCs in the apheresis run are not returned? This can be built from the reaction documentation. Note the following sample table of reactions.
Donation can be whole blood or apheresis-based. The sex and age for each donation type is specified. At HMC, we did not accept females for platelet or plasma donations, so the starting age is listed as 99 years. Otherwise, in accordance with Qatari law, the starting age for donation is 18. All these parameters are user-definable, and a transfusion medicine physician can override the rules if necessary.
For each and every combination of donations, the deferral interval must be specified. Examples follow. The temporary deferral period is in days:
Previous donation whole blood, current donation whole blood: 56
Previous donor platelets, current donation whole blood: 2
Previous donation whole blood, current donation platelets: 56
Also note how for each possible combination there is an entry for male AND female. Females are restricted to whole blood donation and only RBCs will be made from the collection.
If there is a collection incident and the apheresis procedure is not completed, the interval will be set to 56 days. This will be covered in the post on donor adverse effect reporting.
