Category: Donor

Includes registration, questionnaire, physical exam and arm check, collection, marker testing, component separation, donor immunohematology testing

Processes and Software Building 35: Donor Malaria Test Screening

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Processes and Software Building—Part 35:

Malaria Testing Donor Screening Process

Zeyd Merenkov, MD, FCAP, FASCP

Independent Consultant in Transfusion Medicine and Information Technology

The malaria screening varies considerably by country.  I chose for Qatar to follow a combination of WHO and Australian guidelines as per the attached criteria.  We used a malaria antibody screen and malaria antigen test.  There are many alternate approaches, including using a malaria NAT.  The actual specification was:

  1. Malaria Testing:
    1. Defer donor if he has been in malarial endemic zone within the past 3 months
    2. If travel to malarial zone > 3 months, do malarial antibody testing:
      1. Malaria antibody negative:  no deferral
      2. Malaria antibody positive, perform malarial antigen test:
        1. Malaria antigen test positive, refer to Infectious Disease clinic—defer until 3 years after cessation of treatment
        2. Malaria antigen test negative:
          1. Plasma may be collected
          2. RBCs and platelets must be destroyed.
        3. Repeat malarial antibodies after 3 years:
          1. If malarial antibody test positive, donor must not be used for RBC components but may be used for plasma production
          2. If malarial antibody test negative, reenter donor for all components
    3. Defer donor if he has received malarial treatment (not prophylaxis) for 3 years
      1. After 3 years, perform both malarial antibody and antigen testing:
        1. Defer based on section 5.2

The Medinfo testing algorithm follows:

To Be Continued:

22/8/20

Processes and Software Building 34: Donor Syphilis Testing

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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:

  1. Syphilis Testing:
    1. Syphilis Ab test positive or indeterminate:  do InnoLIA-Syphilis test
      1. InnoLIA-Syphilis test positive:  permanent deferral, refer to Infectious Disease clinic
    2. InnoLIA-Syphilis test borderline or negative:  defer for 1 year, then repeat all syphilis testing.
    3. Repeat Syphilis Testing after 1 Year:
      1. Syphilis antibody testing negative, reenter into donor pool
      2. Syphilis antibody positive or borderline:  do InnoLIA-Syphilis test
        1. InnoLIA-Syphilis test positive:  permanent deferral, refer to Infectious Disease clinic
        2. If InnoLIA-Syphilis borderline or negative:  permanent deferral, syphilis not confirmed

This was translated into Medinfo processes as follows:

To Be Continued:

21/8/20

Whole Blood

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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:

  1. 21-day outdate for the RBCs
  2. Platelet functionality limited after 7 days
  3. 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:

  1. Use/ordering restricted to trauma and selected ICU/surgery suites
  2. Only male donors
  3. 7 day outdate
  4. Group O, Anti-A and anti-B IgM titers, both <= 1/256
  5. 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 but spares 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.

19/8/20

Processes and Software Building 33: HBV Donor Testing

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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:

  1. Hepatitis B:
    1. HBsAg non-negative, then:
      1. HBsAg positive with HBsAg confirmatory positive, regardless of other results:  permanent deferral, refer to Infectious Disease clinic
      2. HBsAg positive with HBsAg confirmatory borderline or negative, repeat all HBV testing after 8 weeks
      3. HBsAg borderline:  repeat all HBV testing after 8 weeks
      4. HBV-DNA positive confirmed, regardless of other results:  permanent deferral, refer to Infectious Disease clinic
    2. If HBcAb positive, repeat after 8 weeks
    3. Repeat Hepatitis B Testing After 8 weeks:
      1. HBsAg positive with HBsAg confirmatory positive:  permanent deferral, refer to Infectious Disease clinic
      2. HBsAg positive with HBsAg confirmatory borderline or negative:  permanent deferral, refer to Infectious Disease clinic
      3. HBsAg borderline, permanent deferral, refer to Infectious Disease clinic
      4. HBV-DNA positive confirmed:  permanent deferral, refer to Infectious Disease clinic
      5. HBcAb positive or borderline with negative HBsAg and negative HBV-DNA:  review HBsAb level:
        1. If HBsAb level >= 100 mIU/mL (100 IU/L), donor may be reentered
        2. If HBsAb level < 100, then recommend to donor to receive booster HBV vaccine
          1. After HBV vaccine administration, retest after 30 days:
            1. If HBsAb level >= 100, donor may be reentered
            2. If HBsAb level < 100, donor is indefinitely deferred
      6. 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:

To Be Continued: 

18/8/20

Processes and Software Building 32: HIV-1/HIV-2 Donor Screening

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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).

  1. HIV Testing:
    1. HIV-RNA positive confirmed, regardless of other HIV results:  permanent deferral and do HIV-InnoLIA, refer to Infectious Disease clinic
    2. HIV-RNA borderline:  do HIV-InnoLIA
    3. HIV-InnoLIA positive, regardless of other HIV results:  permanent deferral and refer to Infectious Disease clinic
    4. HIV-InnoLIA indeterminate:  repeat all HIV testing after 8 weeks
    5. HIV Ab positive with negative HIV-RNA and/or borderline/negative HIV-InnoLIA:  repeat testing after 8 weeks
    6. Repeat HIV Testing After 8 Weeks:
      1. HIV RNA positive and/or HIV-InnoLIA positive, regardless of other HIV results:  refer to Infectious Disease clinic
      2. HIV-InnoLIA and/or HIV antibodies indeterminate:  permanent deferral, HIV infection not confirmed
      3. HIV Ab negative and HIV-RNA negative and HIV-InnoLIA negative:  reenter into donor pool

This algorithm is represented in Medinfo as follows:

To Be Continued:

17/8/20

Processes and Software Building 31: HTLV Donor Testing

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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:

  1. HTLV 1/2 Testing:
    1. HTLV Antibodies positive, then do HTLV-InnoLIA:
      1. HTLV InnoLIA positive for HTLV-1 and/or HTLV-2:  refer to Infectious Disease clinic
      2. HTLV InnoLIA indeterminate or negative, repeat HTLV Ab and HTLV InnoLIA testing after 6 months
    2. Repeat HTLV Testing After 6 Months:
      1. HTLV 1/2 antibodies positive, permanent deferral and do HTLV InnoLIA
      2. HTLV 1/2 antibodies indeterminate,  permanent deferral and do HTLV InnoLIA
      3. HTLV InnoLIA positive for HTLV-1 or HTLV-2: refer to Infectious Disease clinic
      4. HTLV InnoLIA indeterminate, donor permanently deferred.
        1. Issue letter HTLV-Not Confirmed
      5. HTLV 1/2 Ab negative and HTLV InnoLIA negative, reenter donor.

This is translated into the following Medinfo processes:

To Be Continued:

15/8/20

Processes and Software Building 30: Donor HCV Screening Tests

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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:

  1. HCV antibody EIA
  2. HCV NAT
  3. 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:

  1. Hepatitis C:
    1. HCV-RNA positive confirmed, regardless of other HCV results:  permanent deferral, refer to Infectious Disease clinic
    2. HCV-RNA borderline:  repeat all HCV testing after 6 months
    3. HCV-InnoLIA positive, regardless of other HCV results:  permanent deferral, refer to Infectious Disease clinic
    4. HCV-InnoLIA indeterminate:  repeat all HCV testing after 6 months
    5. HCV-Ab positive, HCV-RNA negative, do HCV-InnoLIA:
      1. If HCV-InnoLIA positive, permanent deferral, refer to Infectious Disease clinic
      2. If HCV-InnoLIA indeterminate or negative, repeat all HCV testing after 6 months
    6. Repeat Hepatitis C Testing After 6 months:
      1. HCV-RNA or HCV-InnoLIA positive:  permanent deferral, refer to Infectious Disease clinic
      2. HCV-RNA or HCV-InnoLIA borderline:  permanent deferral, HCV infection not confirmed
      3. HCV-Ab positive or borderline without positive HCV-RNA or positive HCV-InnoLIA:  permanent deferral, HCV infection not confirmed
      4. 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).

To Be Continued:

10/8/20

Processes and Software Building 29: Donor Marker Testing Overview

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Donor marker testing algorithms are very complex and serve multiple objectives:

  1. Is the blood safe for the recipient, i.e. minimize likelihood of disease transmission?
  2. 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.

To Be Continued

9/8/20

My Opinion: Separate Transfusion Medicine from the Laboratory

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Transfusion Medicine includes laboratory and non-laboratory functions.  The non-laboratory and purely clinical functions are unique and have no analogy within the general laboratory.

The transfusion service/hospital blood bank laboratory is the closest to a laboratory operation, but there is component modification and complex manual testing, especially for reference immunohematology testing.  The staff must make detailed manual decisions, the errors for which could be life-threatening for the patient.

The blood donor center manufactures a pharmaceutical, i.e. blood components with collection, donor qualification, donor abnormal results review, infectious disease marker testing, component production, and donor immunohematology testing—all subject to Good Manufacturing Practices.  Never forget:  Blood is a drug!!

No other laboratory section is directly responsible for treatment of critically ill patients.  Therapeutic apheresis is essential for organ and stem-cell transplants, nephrology, neurology, etc.  No other laboratory section is directly responsible for treatment of critically ill patients.  Transfusion Medicine physicians are functioning as intensivists.  There is no hiding in the laboratory from clinical medicine.

There may also be an industrial manufacturing plant to extract various blood derivatives (e.g. factor concentrates, albumin, Rh immune globulin, etc.)  This is pharmaceutical manufacturing on a large-scale basis.  There is medical, technical, and special administrative expertise.

Many functions may operate 24/7.  The transfusion medicine physician may be on-call for donor issues and review of complex immunohematology problems to acutely decide which blood component (and phenotype) should be given as well as review all adverse reactions to transfusion.

The unique blend of clinical skills is unlike anything else in the laboratory.  Also, those outside the blood bank rarely have the skills or judgments for the best course of action for transfusion medicine or for its operations.

The clinical transfusion medicine physician must make acute, life-threatening decisions unlike anyone else in the laboratory.  The blood bank technologist is at the cutting edge of the battle with his testing and interpretations.  No other area of the laboratory is at such risk for injuring or even killing the patient.  There is high stress and burn-out.

I have talked with many blood bankers and many seem to share the exasperation that the laboratory does not understand us.  The latter looks at blood bank testing like that coming off a hematology or chemistry analyzer—although patients rarely would have severe morbidity or mortality like the blood bank from errors in those analyzers.

No laboratory pathologist has the pressure of the blood bank physician on-call.  It really is 24/7 and requires a broad, clinical background to make the right decisions.  It is very stressful and does not permit a good night’s sleep.

Thus, I make my case to separate us from the laboratory.  We can form our own more effective administrative organization and optimize our own planning.  Regretfully, I have never worked in such an administrative structure.  I also am a realist that cost-containment nowadays makes it much less likely high administration would permit this change for a mere cost center.  This will probably never happen during my career.

Finally, Transfusion Medicine is an essential service.  Blood components are essential drugs.  The operations and staff must be free of political influences.  This is a service for the entire region or country like the fire department, civil defense, etc.

8/8/20

Processes and Software Building 28: Donor Questionnaire

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Donor Collection 6

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:

  1. Medications
  2. Body fluid exposures
  3. Vaccinations
  4. Malaria
  5. 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.


Ebola and Zika Examples:

7/8/20