Category: Transfusion Medicine

Includes patient, donor, apheresis and related IT topics

Information to Collect Before Contacting the Transfusion Medicine Physician

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The Transfusion Medicine Physician needs certain minimal information to make a medical/clinical assessment and decide what action needs to be taken.

Policy:

  1. Before contacting the transfusion medicine physician, please obtain the following:
    1. Clinical diagnosis
    2. Transfusion history
    3. Medication history
  2. In the case of transfusion reactions, follow Interim Policy Transfusion Reaction Workup and be certain to include the following information before contacting:
    1. Vital signs (BP, pulse, temperature, respiratory rate) both pre- and post-transfusion
    2. Clinical symptoms (e.g. rash, urticaria, fever, respiratory distress, etc.)
    3. Pre-transfusion DAT if post-transfusion DAT is positive.
    4. Donor Unit DAT and eluate on the post-transfusion specimen if the post-transfusion DAT is positive and pre-transfusion negative.
    5. Eluate on the post-transfusion specimen if both the pre- and post-transfusion DAT are positive.

6/11/20

Rh Immune Globulin Candidacy Triage

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Principle:

All D-negative women without immune anti-D must be screened for the need to receive Rh immune globulin as soon as possible after birth.  If the mother is determined to be a candidate, then her specimen must either be screened for a large fetomaternal hemorrhage (FMH—e.g. by the E-rosette or similar technique) or directly quantitated for FMH by either the Kleihauer-Betke or flow cytometry.  The whole process must be completed so that the mother receives the entire dose of RhIG within 72 hours after delivery.

Pregnant women should have an ABO/D typing early in the pregnancy and an antenatal dose between 26-32 weeks.  Thus, at the time of birth, passive anti-D may be detected.  It is essential to know the history of RhIG administration.  In the following example, RhIG is dispensed by the Pharmacy.  If the RhIG is released by the blood bank, records should be easily obtained.

This procedure covers the hospital blood bank processes.  Close coordination between Transfusion Medicine and the obstetricians is essential for a successful Rh immunoprophylaxis program.

Abbreviations:

RhIG:  Rh immune globulin

FMH:  Fetomaternal hemorrhage

All plasma derivatives, including RhIG, are dispensed from Pharmacy.  It is the responsibility of the blood bank technologist to check the Pharmacy records for the history of RhIG administration.

For immunoprophylaxis after accidental Rh(D)-incompatible RBC transfusions, see the separate interim policy by that name.

Policy Details:

  1. Mothers with active (immune) anti-D are excluded from this procedure.  They do NOT need RhIG and to give them it is a waste of a valuable resource.
    1. If the D-negative patient has other RBC antibodies but no anti-D, then she remains a candidate for RhIG prophylaxis.
    2. RhIG has no effect for preventing alloimmunization to other RBC antigens.
  2. D-negative mothers with first-trimester abortions should be given at least 50 mcg IM RhIG dose.
    1. If clinically a large fetomaternal hemorrhage is suspected, then screen/quantitate for fetomaternal hemorrhage as detailed below.
  3. If the D-negative mother undergoes amniocentesis, version, or has had abdominal trauma, the obstetrician may request RhIG or if he suspects significant hemorrhage, fetomaternal hemorrhage quantitation and calculation of the RhIG dose as indicated below.
  4. Platelet transfusions from Rh(D) positive donors:
    1. Platelets derived from a Rh(D)-positive donor prepared by the buffy coat method or by apheresis, either suspended in plasma or PAS do not require RhIG administration.
    2. If a D-negative mother receives legacy, platelet-rich-plasma-derived platelets from a D-positive donor, it is at the discretion of the clinician to request one 300 mcg vial IM RhIG as potential immunoprophylaxis.  (Note:  PRP platelets are no longer prepared at HMC.)
  5. The cord blood of all infants from D-negative mothers without immune anti-D must be typed immediately for the D antigen upon receipt in the Blood Bank.
  6. If the D-negative mother received antenatal RhIG or if it is unclear if the anti-D detected in her blood is passive (i.e. antenatal) or active (immune), she must still be screened by this procedure.
  7. If the baby is D-negative, no further processing is necessary:  it is not necessary to give RhIG.
  8. If the baby is D-positive or if its D type is unknown, a maternal sample (EDTA-anticoagulated blood) must be screened for FMH (e.g. by the E-rosette technique).  This is done in Hematology Laboratory.
    1. The E-rosette test will detect a minimum of 10 ml of fetal RBCs.
  9. If the screen is not available, then direct FMH quantitation must be done (e.g. by either the Kleihauer-Betke staining or flow cytometry).  This is done in Hematology Laboratory.
  10. If the FMH screen is negative, then the mother should receive one 300 mcg. standard vial of IM-RhIG.
  11. If the FMH screen is positive, the dosage of RhIG must be determined by the amount of fetal bleed (expressed as “ml of fetal bleed”.)
  12. All FMH quantitation results must be calculated by a transfusion medicine physician or by the clinical service physician responsible for patient’s care and the dose of RhIG must be calculated as follows:
    1. Verify the type of RhIG available in Pharmacy:
      1. Type: IV or IM
      2. Dosage:  240/300 mcg and manufacturer’s suggested protection level:
        1. Each 240 mcg IM usually protects against 12 ml fetal bleed
        2. Each 300 mcg IM usually protects against 15 ml fetal bleed
        3. Note:  dosage depends on the origin of the pharmaceutical material.
    1. Calculate the number of vials as follows:
      1. Blood Volume in ml = (Weight in kg) X 70 ml/kg
      2. RBC Volume in ml = (Blood Volume in ml) X Hematocrit
      3. Fetal Bleed in ml = (%Fetal Bleed) X (RBC volume in ml)
      4. # Vials 300 mcg IM RhIG preparation = (Fetal Bleed in ml)/15
      5. # Vials RhIG 240 mcg IM = (Fetal Bleed in ml)/12
      6. Note:  some would add 1 additional vial to this calculation.
  13. If the calculation is performed by the Transfusion Medicine Physician, he should append a comment to the postpartum antibody screen ABID result of the mother using Medinfo Hematos IIG.
    1. If the calculation is performed by a designated individual outside Transfusion Medicine, he should document it in the patient’s medical record.
  14. The appropriate RhIG dose should be administered within 72 hours of delivery whenever possible.
    1. If greater than 72 hours post-delivery, still administer the dosage; however, the efficacy at preventing Rh(D) alloimmunization may be reduced.

Note:

  1. RhIG will only protect against forming anti-D antibodies, not any other clinically significant antibodies.
  2. If the patient is D-negative but has other clinically significant antibodies, still administer the RhIG as per the protocol above.

References:

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

Opinion: Understanding Each Step of the Process

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During an AABB inspection many years ago, I observed the Lead Assessor interacting with a medical technologist at the bench.  As expected, the Assessor asked in detail about the test and where the documentation and any teaching aids were located.  Most importantly, the tech was asked to explain the procedure step-by-step and if they knew WHY each step was done and how the various outcomes affected the test.

In my opinion, the WHY is the most important issue.  In our testing and processing, we are not baking a cake.  We do not need a mindless automaton to perform the steps without knowing what they are doing.  To get it right, the technologist must understand why he/she does each and everything—and what are the consequences for not following the procedure precisely.  If the staff member knows this, he/she has respect for the process and is more likely to adhere to the proper method.

In my interactions with my staff, I want to engage them in the importance of their testing to the patient’s care.  If they know that the result may affect the care, they may become more respectful of their work since they are part of the patient care team.

I want them to understand what each of the various results will mean to the patient, i.e. how he will be handled.  I give them updates about the patient’s condition.  A caring technologist is more likely to follow the steps properly.  They understand that a deviation from the process may adversely affect the patient.

To this day, I often go to the technologists and quiz them about what they are doing, e.g. why do they add a particular reagent, why the incubation time is 15 minutes versus 60 minutes.  I encourage them to check and recheck what they are doing if they have any doubts.  Working the bench is not a quiz or examination.  If they are uncertain, I want them to seek out the information, ask questions.  In fact, I tell them there is no shame in saying, “I don’t know”—but be certain to add, “I will find out what to do.”

Blood bank can be fatal to those who guess.  Each of us must know our individual limitations and seek the necessary knowledge.  In fact, many of my assessments are open-book.  They can use any resource in the blood bank or references on-line.  This is real life:  I discourage them from relying on memory if they are understand.  Our end point is the correct action.

13/12/20

Pre- and Post-Exposure Antiretroviral HIV Prophylaxis

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Principle:

Use of anti-retroviral therapy as prophylaxis for pre- or post-exposure (PrP or PEP) HIV prophylaxis may lower the viral load below detectable levels.

Policy:

  1. Defer any donor taking PrP or PEP anti-retroviral ART medications for three (3) months since the last dose.
  2. Donors taking ART drugs as treatment for HIV infection are still indefinitely deferred.
  3. Donor information pamphlets should be updated to include this new deferral.

References:

  1. AABB Association Bulletin #4, The Impact on Blood Safety of Effective Antiretroviral Medications for HIV Prevention and Treatment, 5/5/20
  2. DHQ Medical Deferral List, Version 2.1, AABB, Bethesda, MD, USA, June 2020

Patients Post-Stem-Cell Transplant

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Principle:

The patient’s blood type may change after receiving an ABO-incompatible stem cell (HPC-A stem cell or HPC-M marrow) transplant.  We must verify that the change detected is due to the transplant and NOT due to a mistake in identifying the correct patient at the time of the specimen collection.  Thus, the first time there is a specimen after transplant, we should treat the patient as if there is an ABO/Rh discrepancy, i.e. positively identify the patient again and redraw a new specimen and verify the type.

After transplant, both the original and new clones of RBCs may survive.  It is important to check for ABO discrepancies between the forward and reverse type.

Also note that the other RBC antigen phenotypes may have changed.  Particularly, note if the D type has changed.  The previous extended phenotype may no longer apply.

Policy:

  1. On the first encounter with a patient post-stem cell transplant, if the ABO/D type has changed, request a second (NEW) specimen:
    1. Repeat the ABO/D type, verify that both specimens from this admission agree.
    2. Perform the ABO/D type using a gel or glass bead methodology, check for mixed field reactions.
    3. Verify that that forward and reverse types agree (i.e. are there any discrepant reactions?)
  2. Contact the Division Head, Transfusion Medicine, and give the history (i.e. date of the transplant) and describe all the reactions (historical type, new type, ABO discrepancies).  He will tell you what blood groups of RBCs and plasma to use for transfusion.

Note:  In an emergency situation, use group O RBCs and AB plasma.  If the patient was previously D-positive and now post-transplant is D-negative, use D-negative RBCs if it is a female < 55 years old.

Platelet ABO/D Type Substitutions/Mitigations

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Principle:

Platelets have only weak ABO antigen expression but contain the naturally occurring antibodies of the original donor.

Policy:

  1. 20 kg or more:
    1. Platelets of any ABO/D type may be given to any patient
  2. Below 20 kg:
    1. First choice:  ABO identical
    2. Second choice:  Plasma compatible
    3. Third choice:  Platelet components in platelet additive solution PAS
    4. Fourth choice:  Contact transfusion medicine for use of plasma-incompatible type
  3. Do NOT volume reduce platelets:  this adversely affects platelet function and requires a prolonged recuperation period of several hours before the platelets can be transfused.  Platelets in additive solution have only minimal residual plasma (35 ml out of 200 ml volume).
  4. There is no need to chose platelet types from a D-compatible donor because we use methods that minimize RBC contamination (automated component processing to prepare buffy coats for pooling or apheresis).
    1. It is at the discretion of the ordering physician if he wants to consider Rh immunoprophylaxis if D-incompatible type is chosen.

References:

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

Opinion: Handling Incorrect Physician Orders

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Most of the non-transfusion-medicine physicians with whom I have worked have had only limited training in placing component or hospital blood bank orders.  In previous posts I have discussed this and suggested that all physicians who may possibly order blood bank tests or blood components should have a training and documented competence on a periodic basis.  Only a very few physicians, mainly hematologists and some organ transplant physicians, have placed reliable orders.

Before we had a blood bank computer system, we received orders on a manual paper requisition.  If there were errors, my technical staff and I corrected the order.  Any changes were made by me in my capacity as the blood bank medical director.  The ordering physicians and I had good relations and they had no problem with this—in fact, many were afraid of the blood bank and felt happy to be relieved of the responsibility.

In the current software era, what happens depends on how the order is placed.  Can the technical staff and I correct the order directly or must we each and every time contact the physician to revise his/her order?  Do my staff have to cancel each erroneous order and wait for the corrected order?  This could slow down the work process and prevent release of blood components in a timely manner.

Should the non-blood bank physician be allowed to order our complicated esoteric transfusion tests directly—e.g. ordering extended antigen typings or antibody identifications or elutions?   What if they order something unnecessary or inappropriate?

At a recent hospital position as Division Head of Transfusion Medicine, I discovered that the Hospital Information System HIS was very slow for all blood bank orders.  The physicians complained, I would allow them to bypass the HIS and use the manual backup system in critical situations.  If we had been forced to cancel the order and have the physician reorder, this would have greatly disrupted the work process.

We did not use the HIS at all in Transfusion Medicine.  We had patient and donor modules in the dedicated blood bank system Medinfo.  We had a limited ordering interface from the HIS to Medinfo for blood components and some basic testing (e.g. ABO/D typing, DAT, type and screen/group and save, cord blood testing, and transfusion reaction workups).  All work was done in the dedicated blood bank system.

All components were leukodepleted to < 1E6, all platelet and plasma were Mirasol pathogen-inactivated, all platelets were in platelet additive solution PAS.

The doctors did not order the specific blood component, rather they indicated a preference, e.g.

  • Packed RBCs
  • Platelets (adult dose of 2.4 E11)
  • Plasma
  • Cryoprecipitate

The following appeared as an order comment in the blood bank system:

  • The specific number or amount of the each component type
  • Preferences for pooled vs. apheresis platelets, washed RBCs, irradiated RBCs.

The blood bank staff could review the doctor’s request and order in Medinfo as per our internal protocols under my responsibility.  In effect, I was modifying the orders when needed just as I had done under our manual system.  This included type, modification, and quantity.  Yet now, I did not have to change any orders since the doctors had only indicated preferences.

For blood bank testing orders, we had our own internal algorithms for the workups.  The doctors could not order antibody identifications, elutions, or any antigen typings other than ABO/D.  They latter were triggered by the screening test results.

This system allowed us to avoid cancellations due to physician errors.  I was very comfortable taking the responsibility to alter the orders for best patient care.  If a physician did not agree with our algorithms, they could discuss the issue with one of the transfusion physicians, or ultimately appeal to me.  I was fortunate that there were no legal issues with this approach where I practiced.

In summary, my recommendations are:

  1. Have the doctors order a preference for the type of blood component.  They still order the quantity and can request modifications such as washing or irradiating or apheresis-derived or buffy coat pool platelets.  The actual allocation is made by blood bank staff under my direction.
  2. Offer algorithmic based testing.  Doctors only order basic testing which triggers reflex algorithms.  Most of the test menu is not orderable directly by the physicians (example:  an antibody identification is triggered by a non-negative antibody screen.

9/12/20

Anti-CD47 Interference

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Background:

Anti-CD47 (Hu5F9-G4)interferes with all phases of pretransfusion testing, including ABO reverse typing.

Anti-CD47 (Hu5F9-G4) is a human monoclonal IgG4 antibody used to treat hematologic or solid malignancies.  CD47 is a glycoprotein expressed on all cells. 

All plasma samples reacted 3-4+ in all phases with RBCs, including immediate spin.  Stronger reactivity may occur in D-negative RBCs.  Plasma reacted with DTT, trypsin, papain, alpha-chymotrypsin or WARM (warm autoantibody removal medium—Immucor). 

DAT and autocontrol are negative or weak whereas eluates are 3+ reactive.  Reactivity is removed by multiple alloadsorptions with papain-treated cells or pooled platelets.  PEG absorption is invalid due to precipitation of the antibody.  Gamma heavy-chain specific AHG reagent (Gamma-clone IgG—Immucor) does not detect IgG4 antibodies.

Process:

  1. Always check medication history for anti-CD47 treatment.
  2. If positive, use gamma heavy-chain specific AHG reagent (Gamma-clone IgG) for IAT.

The following table summarizes anti-CD47 reactivity and compares it to anti-CD38—see reference below.

Reference:

Randall Velliquette et al, Anti-CD47 Interference in Red Cell and Platelet Testing, Transfusion 2019; 59, 730-737

Off-Line Donor Medinfo Transactions

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Principle:

When you cannot establish a direct link to the live Medinfo program, you must arrange for the local Medinfo engineers to create a local server that will have the current Medinfo donor database for use at outside campaigns where the internet connection cannot be used.  This can also be used if for some reason the Blood Donor Center link is down in order to register donors and check the donor deferral database.

Policy:

  1. For each outside campaign, there should be a pre-campaign visit to verify the availability of internet to connect to Medinfo.
    1. If the internet connection is working, use Medinfo using the 4G access points.  Otherwise:
    2. If none, inform the Medinfo engineers to prepare a local server on one of the laptops at least ONE DAY in advance of the campaign.
      1. Give Medinfo engineers the laptop to download the database and software.  This will be the offline server for the campaign.
      2. Link the offline server to the other portable computers for the campaign (see the corresponding Medinfo job aid).
      3. Use the local network (offline server and other portable computers) for registering donors.
      4. Upon return to the Blood Donor Center, upload the data.
      5. Continue the regular processes after uploading.

Note:  When the offline data is uploaded into Medinfo main database, it will be checked against the latest donor deferral database.  The latter will be applied for the donation.

Liver Transplant Processes for the Transfusion Service

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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.