Stem Cell Collection Logistics

Everyone is excited at the potential of using stem cells for research and therapy. Below is my presentation of the logistics necessary to get those stem collected in an orderly manner, especially in this time of the COVID-19 pandemic. It will also consider blood bank software logistics.

Policy: Selection of Components for ABO-Incompatible Renal Transplants

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

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

Sample Stem Cell Collection Apheresis Form

This is a sample of the stem cell therapeutic apheresis form that my apheresis team and I developed. It can be readily made into an electronic form. I want to thank Dr. Saloua Al Hmissi, Apheresis Consultant, and Ms. Mini Paul, Head Apheresis Nurse, for their efforts in making this form a success.

Preventing Graft vs. Host Hemolytic Anemia

Principle:

Donor lymphocytes in an organ transplant may make antibodies and cause a clinically significant hemolytic anemia, i.e. a graft vs. host hemolytic anemia GVHHA.  Optimal handling in these cases should include antibody screening/identification for all potential donors and recipients.  The transfusion medicine physician should review the results for possible issues of antibody/antigen incompatibilities to proactively select matched blood components and avoid GVHHA.

In the Medinfo blood bank computer system, we can make custom rules to ensure release of only antigen-matched units as needed.

Policy:

  1. Perform antibody screen and identification (if indicated) for all prospective organ donors and recipients.
  2. If the organ donor has clinically significant antibodies, check if the recipient has the corresponding antigens.  If so, select RBC units negative for the donor antibody specificities. 

Example:  Donor has anti-Kell (K1) and patient is K1-positive.  Use only K1-negative RBCs post-transplant.

  • Send the case to the transfusion medicine physician to review.  He will contact the clinicians as indicated.
  • Create a rule in Medinfo forcing the antigen matching.

References:

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

Liver Transplant Processes for the Transfusion Service

Principle:

Liver transplantation requires coordination of the Transfusion Service TS, Liver Transplant LTS , and the Blood Donor Center BDC to prepare blood components for this massive transfusion setting.

Policy:

  1. Whoever receives notification of a possible liver transplant should ensure that ALL of the following senior staff are also informed:
    1. Head, Transfusion Medicine
    2. Coordinator, Donor Recruitment
    3. Supervisor, Transfusion Service
  2. Transfusion Service Supervisor will arrange transfusion service staffing as needed to cover the surgery period and immediate post-operative period.
  3. The current, up-to-date inventory must be calculated.  The following minimum stock must be reserved:
    1. Twenty (20) packed RBCs
    2. Twenty (20) FFPs—-leukodepleted and pathogen-inactivated
    3. Three (3) platelet pools or apheresis doses (each ≥ 2E11 absolute number of platelets)—leukodepleted and pathogen-inactivated.
    4. The Medinfo Liver Transplant Protocol automatically orders all the above.
  4. Complex needs:
    1. If the patient has clinically significant antibodies, confirm the availability of the requested number of antigen-negative/compatible units.
    2. The Head, Transfusion Medicine, or the covering transfusion medicine consultant on-call will contact the liver transplant team to discuss the feasibility of proceeding after assessing the inventory of antigen-negative units.
    3. Only the transfusion medicine consultant can approve the use of antigen-incompatible RBCs in conjunction with the liver transplant team.
  5. Donor Center should increase recruitment/production to meet the anticipated usage as needed.
  6. When the procedure is confirmed:
    1. Crossmatch the RBCs by the appropriate technique according to our algorithms (i.e. computer/electronic, immediate-spin, or full AHG).
    2. Thaw the FFP:  the FFP is valid for FIVE days after thawing for use for the transplant patient or other patients with coagulopathy.
    3. If more than the above number of units is needed, HGH Transfusion Service must inform the Donor Center senior staff (Head, Donor Center; Administrative/Technical Director, and Coordinator, Donor Recruitment) to arrange for additional donations.

ABO Subgroup Testing for Organ Donors

Principle:

Organ donors with a history of RBC transfusion within the past three months must have ABO subgroup (weak A as detected by A2 cells and anti-A1 lectin) if the transfusion included group A RBCs.

Policy:

  1. Organ donors who are typed as A should be tested to distinguish group A1 from weak subgroups of A.
  2. Use anti-A1 lectin and A2 cells as indicated.

Reference:

Standards for Blood Banks and Transfusion Services, AABB, Current Edition, Bethesda, MD, USA

CMV Prophylaxis Policy

I developed this policy for HMC Doha where most of the local population are CMV-seropositive. Note that I used the CE definition of <1E6 instead of the American <5E6.

Principle:

Since most of the local population (>90%) are CMV-seropositive, it is impractical to rely on CMV-negative donors as our basis for CMV prophylaxis.  Instead, we perform universal leukodepletion and pathogen-inactivation to greatly reduce this risk:

  1. CMV transmission risk can be lowered to a level comparable to using CMV-seronegative components by universal leukodepletion to levels <1E6.
  2. Pathogen inactivation greatly reduces (at least 2 log10) the number of organisms with nucleic acid (DNA or RNA) and is used for all platelet (pools and apheresis) and plasma components.
  3. Platelet additive solution reduces the amount of original plasma to about 35 ml and further reduces donor exposure to foreign material.

Policy:

  1. All blood components (platelets, plasma, RBCs) are universally leukodepleted to residual levels below 1E6.
  2. All platelet and plasma components are pathogen-inactivated using the Mirasol system (riboflavin added and then exposed to ultraviolet light).
  3. All platelet components (pooled buffy coat and apheresis) are prepared in platelet additive solution PAS.

References:

  1. Technical Manual, AABB, Current Edition, Bethesda, Maryland, USA
  2. Standards for Blood Banks and Transfusion Services, Current Edition, AABB, Bethesda, Maryland, USA
  3. Guidelines to the Preparation, Use, and Quality Assurance of Blood Components, European Committee (Partial Agreement) on Blood Transfusion (CD-P-TS), Current Edition

Selection of Components for ABO-Incompatible Renal Transplants

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.

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