A Novel Way to Document Therapeutic Phlebotomies in the Blood Bank Computer System

Therapeutic phlebotomies TP, like regular whole blood donation WBD, both require collection of whole blood into a blood bag set.  In whole blood donation, we ask two questions during the process:

  • Is it safe for the donor to donate?
  • Is it safe for the collected unit or its processed components to be given to recipients?

For TP, we only have to consider the first question so the process must ensure the patient/donor’s safety.  We do not have to concern ourselves with the use of the collected product—it will be discarded.

Since the donor collection processes of both TP and WBD are similar, why couldn’t we use the blood bank computer software to document the TP procedures?  The process is a subset of normal WB donation.  On this basis, I make suggestions on using the donor module to document the TP process.  It is basically a truncated version of blood donation process in the Medinfo Hematos IIG system:

  • Registration
  • Donor Safety
  • Vital Signs
  • Hemoglobin Determination
  • Blood Collection Data
  • Adverse Effect Reporting
  • Discard of Unit
  • Documentation of Physician’s Order and Transfusion Medicine Physicians Acceptance

Registration:  Positive patient identification can be made through the donor registration process;  force selection of an inexpensive bag type (not the Reveos set) for this purpose.

Donor Safety:  Perform a modified, shortened donor questionnaire covering the medical history and medications is used.  Confirm that the patient has had food and drink before donating.  Require a waiting period of 24 hours before the next procedure.

Vital Signs and Weight:  Measure weight plus BP, pulse, temperature, and respiratory rate as well as inspect the arm for scarring before procedure.  Allow repeat vital signs monitoring after the procedure if requested by the transfusion medicine physician.

Hemoglobin Determination:  Allow acceptable Hgb >= 11 g/dl or >33% hematocrit

Blood Collection:  Use the same process for the mixer-shakers but the amount collected can range up to 500 ml with amounts <405 ml acceptable for small patients

Adverse Effect Reporting:  The complications of TP collection are the same as WBD.  Use the same system as for WBD.

Discard of the Unit:  Print discard label and quarantine of the ISBT unit number in system (so that it cannot be used for transfusion).

Documentation of Order:  Create separate fields for the ordering physician and for the approving transfusion medicine physician.  Capture scan of paper orders and incorporate into the TP computer encounter.

Other Considerations:  In high-risk cases, e.g. with pre-existing cardiovascular, pulmonary, or cerebrovascular disease, one could consider using a remote monitoring device such as the Umana T1 device to record vital signs, EKG, and oxygen saturation that can continuously record these parameters and trigger user-definable alarms during the process and afterwards if desired.  The data can be incorporated into the blood bank computer encounter.

Antibody Titration

My practice across the globe has exposed me different rationales to performing antibody titration.  In my American training and practice (and also at international institutions following the American version of AABB accreditation), I only routinely performed titration of anti-D for Rh(D) hemolytic disease of the newborn and anti-A/anti-B for ABO-incompatible stem cell transplants AND ABO-incompatible renal transplants.

I have had heated arguments with some physicians who insisted they wanted titers for other antibodies.  The AABB Standards do not require this but leave it to the discretion of the Transfusion Service Medical Director.

In my entire career, I never worked in a blood bank or blood center which had optimal staffing or resources.  I focused on what was medically/technically necessary and even then still had shortages.  If performing a test does not change the clinical treatment, why perform it unless you are doing a research project!

Titration is a time-consuming, and until recently, a tedious manual task.  Recently some of the automated immunohematology analyzers offer a titration program.  We used the Ortho Vision Max which could perform both IgG and IgM titers within one hour—walk away!!  However, during that time, the titration procedure monopolized the analyzer.

Nowadays, low-anti-B-titer group A universal plasma and low-titer (anti-A and anti-B) group O whole blood may be offered as components.  At HMC Qatar, a preliminary study showed about 50% of units could be classified as low-titer (defined as a saline titer <1:128).  The amount of titration will require an automated analyzer.

The ABO-incompatible renal transplant program at HMC Qatar was modelled after Sweden’s Karolinska Institute.  However the latter site performed manual IgG and IgM titrations using Biorad/Diamed gels.

I did not have sufficient resources to commit staff to manual titration at HMC so I did a comparison study between the Ortho Max and the Biorad manual gel methods.  We were able to get good correlation and used the automated method for the transplant.

I still don not perform against performing titrations for antibodies other than anti-D.  I always ask, ‘Does the titration correlate with clinical severity?’  Unlike anti-D, antibodies such as anti-Kell and anti-c may be low titer but cause death.  Can anyone show me a definitive study that titers are useful except for transplants and Rh(D) hemolytic disease of the fetus/newborn?

Since the method was working well on the Ortho equipment, I next established an interface to Medinfo.  The test was performed separately for IgG and IgM antibodies.  Medinfo recorded the reactions in all the wells.  The last well showing a 1+ reaction was interpreted as the titer (e.g. if 1:64 were the last 1+ reaction, then the titer was 64 in Medinfo).

The Medinfo process is shown below.

My Opinion: Use of Enzyme Panels

This is an updated version of a previous post.

Working for many years in the Middle East/Gulf, I have encountered significant antibodies that can only be detected at enzyme phase.  This is especially true of Rh system antibodies, particularly anti-c in an R1R1 patient.  I have attached an example.

The reasons I strongly recommend this practice are:

  1. Weak Rh system antibodies (as above)
  2. Confirmation of enzyme-labile antibodies, especially if there may be combinations of enzyme-labile and enzyme-resistant antibodies (e.g. anti-Fya and anti-c).

It is also important to consider which enzyme to use:  bromelin, ficin, or papain usually and sometimes trypsin or chymotrypsin.  They do not always attack at the same site.

In addition to most common MNSs and Duffy system antibodies, many Kell antibodies (e.g. K or K1, Kpa) are labile with papain:  however, with ficin they may be partially labile, unaffected, or even enhanced.

Using enzymes is a double-edged sword since they may enhance cold antibodies and thus cause nonspecific reactions.  Thus, I know many of you may not routinely include them in your workups.

It is essential to follow the manufacturer’s recommendations for their use.  If you make your own enzyme-treated cells and prolong the incubation, you may get false positivity.  You should also be careful about using potentiators with enzyme-treated cells—normally I run them in saline.

Since anti-c may cause severe hemolysis and severe hemolytic disease of the newborn, I am especially vigilant in my R1R1 patients, particularly females of child-bearing age and all chronically transfused patients.  I prophylactically match R1R1 patients with R1R1 RBCs in these categories, regardless if either anti-E or anti-c are expressed.  I have seen many examples where the anti-c is only detected at enzyme phase.

It is my practice to always include an enzyme panel.  I would be very interested to know your practices?  When do you use enzymes?

My Opinion: Issues in Transfusion Medicine Software and Component Production

I anticipate that there are several innovations coming or in the process of coming to mainstream blood component production and software.  Some of these I have already addressed in some of my previous posts:

Pathogen inactivation:  We have had this for over a decade.  However, with new emerging pathogens, this will become more important so I expect it will be adopted in many centers where it is not currently being used.  I expect we will close the loop and pathogen-inactivated RBCs will be available so all components will be treated.  Still, the first-generation pathogen-inactivated RBCs may have reduced shelf life compared to regular, untreated units.

Automated component production:  Although this is expensive, it does provide excellent GMP production.  It is fast and may provide higher yields, especially for platelets.  I expect more centers will adopt this technology, especially in combination with pathogen inactivation.

Blood bank computer software:  This software must be considered as dynamically changing, and considerable resources are needed to keep in compliance with ever-changing international regulations and the latest epidemiologic data.  Production rules can be strictly and mercilessly enforced by a dedicated blood bank computer software.  It can also ensure that the final ISBT label is not applied unless all the production rules (registration, collection, processing, and testing) are met.  Manual processing is extremely risky nowadays with all the parameters to be monitored.

Patient Blood Management:  Current blood bank software does not adequately address the need for prospective review of component orders.  I expect that collaboration will occur between laboratory and blood bank software vendors to fill this gap.

Refrigerated platelets:  The pendulum swings back to this component which was used over 40 years ago.  Refrigerated platelets suspended in additive solution may be effective up to 14 days for hemostasis in the trauma setting.  These platelets are activated so standard 20-24C stored platelets may be preferred for prophylactic transfusions.

Low-titer group A universal plasma:  This is already available, but its use will increase because of the low numbers of group AB units available and increased demand.  This includes its production for COVID convalescent plasma.  Your transfusion medical director must decide what “low titer” means.  Also you need a robust way of performing anti-B titers, this may require use of an immunohematology analyzer with titration built-in.

Low titer group O whole blood:  Use of this product may reduce the need for components in massive transfusion settings but it requires performing anti-A and anti-B titers on large numbers of units.  Your transfusion medical director must decide what “low titer” means.  Also you need a robust way of performing anti-A and anti-B titers, this may require use of an immunohematology analyzer with titration built-in.  Also, you must decide whether to leukodeplete the whole blood units:  few whole blood filters are platelet-sparing.

Order of the Steps in Serologic Testing

This is a teaching document I give to new staff, medical technology students, pathology and residents.  Very often I get the question, “Why can’t I just do the antiglobulin phase crossmatch first and then phenotype the RBC unit?” Or:  “Why do I have to add reagents in a particular order?”

My practice has always been to select an antigen-negative RBC unit first, then do the antiglobulin-phase AHG crossmatch.  This way I know that the unit was definitely phenotyped before release.  Likewise, the blood bank computer now only offers antigen-negative units for allocation and then crossmatching if there is a clinically significant antibody.

In a manual setting without a blood bank computer system, performing the AHG crossmatch may yield a negative result, even if the unit is antigen-positive.  With storage, some antigenic expression is weakened so it may not be detected at the time of crossmatch.  Yet, there may still be enough antigen present to cause hemolysis.  Not detected does not necessarily mean not present!!

I expect that many inexperienced staff may be tempted to forego the antigen typing if the AHG crossmatch is negative.

This is an analogous logic to the question, “Do I add the cells or the antiserum/plasma/serum first for the reaction?”  If you add the cells first, you may forget to add the patient’s plasma/serum or a typing antiserum and you might not be able to detect the omission by looking at the tube or gel.  Actually, I once recommended to one vendor that it color the typing antiserum so it was conspicuously showing on the gel.

I was taught that this is a matter of discipline to ensure that all steps are performed.

However, for every practice, there has to be flexibility.  If there is no typing reagent or if it is very expensive or in short supply, one may have no choice but to do the AHG crossmatching first.  Often there is still another option:  one can often preliminarily screen units first before using a rare reagent—examples:

  • Check if patient is group O first and antibody screen panreactive in suspected anti-H.
  • Check P1 typing first if there is a suspected anti-PP1Pk.
  • Check the antibody screen for panreactivity first for antibodies of high-incidence or prevalence antigens.

ABO Incompatible Stem Cell Transplant: What ABO type of RBCs Should I Use?

In an ABO-incompatible stem cell transplant, both donor and recipient RBC types may be present.  Likewise, immune effector cells from both the donor and recipient may be present.

Using group O RBCs and AB plasma is an option but there are limited supplies of both.  Since we use RBCs in additive solution (SAGM), only minimal residual donor plasma is available and unlikely to be clinically significant.

Here is my approach:

  1. Use fresh specimen to perform forward and reverse type
  2. Check the reverse type:  does it show either anti-A and/or anti-?
    1. If anti-A detected, do not transfuse group A RBCs.
    2. If anti-B detected, do not transfuse group B RBCs.
    3. If both anti-A and anti-B detected, continue using only group O RBCs.

Massive Transfusion: When to Revert to the Original ABO Type

In a massive transfusion setting, the patient’s forward and reverse type will reflect the use of group O RBCs and the patient may even fully type as group O, depending on the number of units transfused.  Group O RBCs are very precious and in short supply so we need to switch the patient back to his/her own type as soon as feasible.  RBCs in additive solution (e.g. SAGM) have only minimal residual plasma so the load of anti-A,B from the O cells is minimal.  In my organization, we did not titer ABO hemolysins in blood donors.

Here is my approach:

  1. Use fresh specimen to perform forward and reverse type
  2. Check the reverse type:  does it show either anti-A and/or anti-B from the group O massive transfusion?
    1. If anti-A detected, do not give group A RBCs.
    2. If anti-B detected, do not give group B RBCs.
    3. If both anti-A and anti-B detected, continue using only group O RBCs.

Some people would recommend performing a full AHG crossmatch using the patient’s current plasma and RBCs of the original ABO type:

  1. If compatible, return to the original ABO type.
  2. Otherwise, continue using group O RBCs.

I did NOT do the full AHG crossmatch and had no hemolytic transfusion reactions if the RBCs were compatible with the current reverse type plasma.