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:
This is an updated job description of what I used at NGHA Riyadh for a Systems Administrator for laboratory software. Such a person will have software privileges as agreed by the hospital information systems department. In our system there, there was a separate laboratory information systems section LIS:
Basic Function:
To analyze laboratory databases and prepare reports to optimize laboratory utilization and management
Principal Duties:
Maintains and secures the laboratory information server (to be distinguished from the LIS hardware) and its associated databases
Uses downloaded database files from laboratory computer system to prepare reports as deemed necessary by and as prioritized by the Pathology Chairman, Laboratory Operations Administrator, and/or Portfolio Head, LIS, which may include but is not limited to:
Cost containment (implementation of CEO directives)
Internal laboratory and external hospital committees (as requested by them)
OVA statistical analysis
Specimen referrals to outside laboratories
Specimen referrals from other hospitals or hospital systems
ER Stat Laboratory utilization reports
Laboratory Utilization Committee, including STAT turn-around-time and critical values
Quality Improvement-Accreditation Portfolio
Test utilization metrics
Any other reports requested/approved by the Portfolio, LIS, Laboratory Operations Administrator, and/or Chairman
Assists in the management of the document control program for the laboratory
Assists in the management of the intellectual property control program for the laboratory
Performs any other assignments as directed by the Pathology Chairman, Laboratory Operation Administrator, and/or Portfolio Head, LIS
Essential & Preferred Education & Experience:
B.S. degree or higher in computer science including coursework in networking, database structure, and management
Experience (at least two years) in operating enterprise-level (e.g. Oracle, IBM DB2), business-level (Postgresql, MySQL, Microsoft SQL Server) databases as well as Microsoft Access® desirable
Fluency in English (high-level) essential, fluency in Arabic desirable
Experience (at least one year) in working with databases in a variety of operating systems (Win32/64, Linux, UNIX) desirable
Experience (at least one year) in working in a hospital laboratory environment desirable, not necessarily as a laboratory technologistLa
Must be self-reliant and disciplined to operate independently and have excellent organizational and interpersonal skills to relate to a wide variety of laboratory and hospital personnel
Degree of Responsibility:
This is a middle-level management position within the Department of Pathology and Laboratory Medicine. The analyst must be self-reliant and disciplined to operate independently, have excellent organizational and interpersonal skills to relate to a wide variety of laboratory and hospital personnel.
In my long career, there have been cycles in transfusion practice. Today’s dogma becomes yesterday’s heresy and then later again the dogma. Just consider the selection of blood components before the introduction of cyclosporine for intended renal transplant recipients.
In training, I was told NEVER, NEVER use the intended donor’s blood for the renal recipient. This would immunize him against the donor tissue antigens and cause the transplant to fail.
Several years later after cyclosporine, we were doing a booming business of directed RBC transfusions from the donor to his/her recipient.
Just a few years ago, I used blood component therapy for all, especially trauma patients. Give the victim what he lacks: for oxygen-carrying capacity, RBCs; for volume crystalloid; for low protein albumin; for coagulopathy FFP, factor concentrates, cryoprecipitate; for thrombocytopenia, platelets.
Most recent studies now mention the danger of giving too much crystalloid, etc. It talks about using fresh whole blood to provide all of the above in less volume. Results from trauma and military studies are encouraging and may be better than individual component therapy.
There are special considerations for whole blood:
21-day outdate for the RBCs
Platelet functionality limited after 7 days
Use of group O, low-ABO-titer
Pathogen-inactivation of whole blood is CE-approved by riboflavin (Mirasol). Terumo BCT is developing an exciting technology to first use Mirasol and then make components using the Reveos automated component system—RBCs, plasma, and platelets. This is an ongoing project so for now the only CE-approved project is use as whole blood. Such Mirasol-treated whole blood has been shown to prevent malaria transmission in Ghana.
From my review of the literature, these are my specifications as of this date 18/8/20:
Use/ordering restricted to trauma and selected ICU/surgery suites
Only male donors
7 day outdate
Group O, Anti-A and anti-B IgM titers, both <= 1/256
Leukodepleted < 1E6 residual WBCs
What level of anti-A and anti-B titers is acceptable? The titer was set as low as 1:32 but at recent THOR meeting 1:256 has been used. In Qatar in a pilot study, I found that about 50% of our donors had titers < 1:256. The issue is that each time the donor presents himself/herself, we must repeat the titer—it is not stable.
Of course, performing even just a saline-titer is time consuming. The only practical way for us in Doha would have been to use an automated titration option on an immunohematology analyzer—in our case, the Ortho Vision MAX, which could perform 1 titration run in about 30 minutes, and the instrument cannot be used for any other testing during the process.
I personally would perform leukodepletion to conform to CE, but you need a special whole blood filter that removes WBCs butspares the platelets. Terumo BCT has such a filter that achieves <1E6 residual WBCs. Never use a standard RBC leukodepletion filter since it will remove BOTH platelets and WBCs—this would defeat the purpose of using whole blood.
At HMC Doha, female donors were only used for packed RBC production—all plasma and platelets were discarded. Some centers do HLA antibody screens and allow negative females to donate.
Finally, many groups do not leukodeplete at all. I am concerned about the risk of adverse reactions and TRALI so I would conform to CE and do it.
Whichever conditions you stipulate, it is easy to create the process in Medinfo. The most important thing is to know what you want to specify.
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 following protocol is the one I made for National Guard Health Affairs in Riyadh and has been updated to include the use of a blood bank computer system.
Medinfo has an emergency mode that facilitates release of blood components even if all the usual testing is not available
If Medinfo software is used, one can write a protocol based on the diagnosis of placenta previa to automatically allocate the blood and keep it on hold at all times.
Ward Responsibilities:
As soon as a patient with high-risk placenta previa is identified, order type and crossmatch for 4 units PRBCs.
Immediately forward the specimen and its requisition to the blood bank for expedited processing. BE CERTAIN TO INDICATE ON THE FORM AND/OR IN THE COMPUTER SYSTEM THAT THIS IS A PLACENTA PREVIA CASE!!
Send a new specimen for crossmatching every 3 days until delivery.
Phone the blood bank immediately when blood is needed for the patient before coming to the Blood Bank. DO THIS BEFORE SENDING SOMEONE TO THE BLOOD BANK TO PICK UP THE BLOOD!
Blood Bank Responsibilities:
Check the order comments for placenta previa.
Handle all such requests as emergency or STAT.
Enter a comment in the computer that this is a placenta previa case.
Verify that the specimen has been properly collected and labelled.
If the specimen is not acceptable, request new specimen.
In emergencies, use emergency release/emergency mode in Medinfo.
If specimen valid:
Perform ABO/Rh typing and antibody screen if one is not available within the past 3 days.
Check for previous history of ABO/Rh typing and antibodies—performed by blood bank computer system.
Allocate 4 units, electronic crossmatch or full AHG as indicated by our rules.
Provide antigen-matched units accordingly.
When the ward calls that a placenta previa patient needs blood, immediately prepare the blood for release. This is an emergency request of the highest priority. VERBAL REQUESTS FOR BLOOD IN THESE CASES ARE ACCEPTABLE.
Use emergency mode/emergency release in Medinfo if all the testing is not done or current.
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.
Dr. Zeyd Merenkov 