Preparation and transfusion of blood for

Intrauterine Transfusion

Gwen Clarke MD

Faculty Disclosure

No Disclosures

I have no actual or potential conflict of interest in relation to this annual

meeting or this presentation.

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Objectives

• Why

• Indications and why this is different from neonatal or pediatric transfusion

• Pretransfusion testing & Hemoglobin assessment

• What: Component preparation

• ABO Rh and Phenotype

• Age of component

• CMV status, irradiation

• Component preparation (concentrated, leukoreduced)

• Where and How:

• Infusion sites

• Dose calculation

• Monitoring outcomes

• Linking patient files

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Sources

• Articles, Textbooks

• Wikipedia

• Operating procedures online

• SHOT (UK)

• local or regional programs

• Vox Sanguinis International forum participants

Vox Sanguinis International forum

• Sent to contacts from 16 countries

• 10 completed replies

• 23 questions in 6 categories

– Indications and numbers of

procedures

– Fetal Blood sample testing

– Blood product selection for

transfusion

– Blood component preparation

– Administration

– Monitoring and traceability 4

Clarke G, Bodnar M, Lozano M, Nadarajan VS, Lee C, Baud D, Canellini G, Gleich-Nagel T, Torres OW, Rey PL, Bub CB, Kutner JM, Castilho L, Saifee NH, Delaney M, Nester T, Wikman A, Tiblad E, Pierelli L, Matteocci A, Maresca M, Maisonneuve E, Cortey A, Jouannic JM, Fornells J, Albersen A, de Haas M, Oepkes D, Lieberman L. Vox Sanguinis International forum on the selection and preparation of blood components for intrauterine transfusion. Vox Sang. 2020 Nov;115(8):e18-e38. doi: 10.1111/vox.12902. Epub 2020 May 12. PMID: 32400066.

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Why is IUT different from other transfusion?

• Fetus is a unique transfusion recipient

(a child not a small adult; a fetus not small neonate)

– Very small blood volume

– Relatively immunosuppressed recipient

– Inaccessible for transfusion without an invasive procedure

(with small but measurable) potential for harm (~1%risk of

fetal loss)

• Minimize the need for repeat transfusions if possible

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Why do we need to do IUT? (Indications for IUT)

• fetal anemia

• most for maternal alloimmunization • anti D the most common antibody

• Many other indications including• viral infection with anemia or pancytopenia (Parvovirus and

CMV)• Fetal Maternal Hemorrhage (FMH) • twin twin transfusion (or Twin Anemia Polycythemia

Sequence - TAPS) • inherited/genetic causes for anemia• Intrauterine cardiac surgery

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How many?

• Programs serving individual hospital or small communities have very low volumes ( 0 or 1 to 8 per year)

• Those serving large regions or whole countries had up to 72 per year.

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Approach

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• Cord vessel

• Transplacental/intrahepatic

• Intraperitoneal

• combination

https://en.wikipedia.org/wiki/Percutaneous_umbilical_cord_blood_sampling

percutaneous blood sampling

Courtesy of Dr. David Somerset; University of Calgary & Foothills Medical Centerhttps://www.mayoclinic.org/tests-procedures/percutaneous-umbilical-blood-

sampling/multimedia/cordocentesis/img-20006443

Blood Sampling and testing

• Variable

• Some – minimal tests ( a pre and post transfusion point of care hemoglobin) assessment to determine volume to transfuse

• Others – complete battery of hematology biochemistry and BB tests for diagnosis and full evaluation

• Most: Hb, ABO, Rh & antigen corresponding to maternal antibody +/- DAT

• Crossmatch with maternal plasma and donor red cells

• post testing for hemoglobin and percentage of fetal hemoglobin

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Fetal blood Sampling

• Fetal blood is drawn into 1ml heparinized syringes.

• Draw can be slow and clots can form: need to

check for clots when reporting Hemoglobin and

Platelet counts

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How Much?

Calculated based on a formula• Based on fetal – placental

blood volume & degree of anemia

• Takes into account initial hematocrit which allows determination of transfusion volume required

• Include small enough change in hemoglobin concentration to avoid hemodynamic instability in the fetus

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http://perinatology.com/protocols/rhc

How often? (in an alloimmunized pregnancy)

• Only safe to double initial fetal Hb

• Assume fetus can lose all remaining fetal Hb in one week

• second transfusion typically 3-10 days later depending on final Hb and % fetal Hb remaining

• Once no fetal Hb remaining, assume loss of 1% Hct(0.3g/L Hb) / day

• Thus third and subsequent IUT done when fetal Hb estimated to be =/< 80 g/L

• MCA Doppler still useful, but less accurate once significant adult Hb on board

• Typically transfuse q2-3 weeks until 36 weeks

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Product selection (what do we give)

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• Most use allogeneic blood except where mother has a very rare phenotype

• For rare pheno some report use of maternal blood others use frozen rare inventory or frozen maternal red cells.

• Many use additive collected red cell components that have the additive removed +/- AB plasma or saline reconstitution to predetermined hematocrit

• One reporting site collects fresh whole blood for the IUT (same day on pre- screened donor) with addition of AB plasma for hemagglutinin titers >1:50

Product selection continued

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• CMV antibody testing of donors

• Quite variable. All use leukoreduced, most also choose CMV seronegative donor but not all

• (depends on CMV seroprevalence)

• HbS testing to exclude donors with Sickle cell trait

• Depend on frequency of Hb S in the population

• One site reports testing for Parvovirus B19 antibodies in donors

• Selection of donors with antibodies/immunity

Component preparation

• Concentrate and/or wash to remove

additive solution followed by adjustment

with normal saline to a hct between .70

and .85

• In some cases AB plasma is used to

reconstitute to the appropriate hct (but

not many)

• Most use a manual centrifugation

• Two reported using an automated

process with a cell washer

Component selection and preparation

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• Units may be freshly collected (whole blood, same day, or within 3, 5, or 7days post collection; or frozen/deglycerolized)

• Irradiation is performed just before issue of units or just before transfer from supplier to hospital (<6 hours - < 24 hours pre transfusion)

• Phenotype selection always includes Rh(D) and negative for the cognate antigen in cases with maternal alloimmunization

• May include Cc Ee match with maternal phenotype

• May include Kell negative

• Rarely includes Kidd Duffy and Ss match with maternal phenotype

Component

preparation

• 1 site reported a

requirement for

isohemagglutinin titres

<1:50 (this site used fresh

whole blood).

• 2 sites reported use of a

waterbath to warm

components but most allow

aliquots and tubing to warm

to RT during prep without

active warming

Photo courtesy of Dr. David Somerset

Adverse events

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• Most survey respondents reported no immediate nor delayed adverse events

• 2 commented on fetal bradycardia which resolved with decreased infusion rate

• One commented on a transfusion reaction (with no details provided)

• 135 IUTs performed on 56 fetuses over 14 years, 121 (90%) of the procedures were uneventful.

• In 14 cases, (10%), mild adverse events occurred. The most common mild events were prolonged hemorrhage from the puncture site and uterine contractions.

• In two cases, these led to a severe adverse event: one emergency cesarean section within 24 hours after IUT and one preterm birth within 7 days after IUT.

• There were no fetal or neonatal deaths in the study population

Pasman, S.A.; Claes, L.; Lewi, L.; Van Schoubroeck, D.; Debeer, A.; Emonds, M.; Geuten, E.; De Catte, L.; Devlieger, R. (2015). "Intrauterine transfusion for fetal anemia due to red blood cell alloimmunization: 14 years experience in Leuven". Facts, Views & Vision in ObGyn. 7 (2): 129–136

SHOT reports (2012)https://www.shotuk.org/shot-reports/report-summary-and-supplement-2012-2

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One fatality following IUT due to TA-GVHD

• 15 mL maternal blood transfused to a fetus in an emergency due to severe anemia (non-leucodepleted, non-irradiated and related). The fetal Hb rose from 44 g/L to 100 g/L and initially the procedure was uneventful. However, the fetus subsequently developed a bradycardia with poor cardiac output so an emergency intracardiac transfusion with a further 18 mL maternal blood was given.

• The baby was pancytopenic at birth and required multiple blood and platelet transfusions.

SHOT reports (2012) continued…

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• A bone marrow aspirate at 2 months of age confirmed aplasia, and chimerism studies confirmed maternal engraftment.

• A diagnosis of TA-GvHD was made, and the baby underwent a stem cell transplant (maternal donor) but died of pneumonitis a week later.

https://www.shotuk.org/wp-content/uploads/myimages/SHOT-Annual-Report-20121.pdf pp 133

SHOT conclusions on irradiation – some contexthttps://www.shotuk.org/wp-content/uploads/myimages/SHOT-Report-2018_Web_Version-1.pdf pp17

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• Irradiation of cellular components (for a variety of indications, including IUT) was missed in 81 patients in 2018.

• In 64/81 (79.0%) cases the error was made in clinical areas and 17 in the laboratory.

• The cumulative number of reports of patients known to have missed irradiation is now 1478 since 1999. Patients were exposed to one or more components.

There have been no cases of TA-GvHD reported since 2001 in patients who received leucodepleted red cells.

SHOT Conclusions (2018)

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Case 23.2: Transfusion of red cells of the wrong group to a neonate due to a failure to communicate the previous intrauterine transfusions (IUT)

• A baby received three transfusions of group O D-negative red cells in utero. Following delivery, the baby’s group was reported as O D-negative, and group O D-negative plasma and platelets were issued and transfused. In view of the IUT the baby should have received group AB plasma components. This error occurred because the fetal and newborn case records had not been merged.

• Learning point • It is vital the history of in utero transfusions is communicated with the hospital transfusion laboratory staff. If this does not occur errors can be made in assigning the neonatal blood group to the group of the blood given for the intrauterine transfusion (IUT) – and irradiation requirement may be missed

https://www.shotuk.org/SHOT-Report-2018_Web_Version-1.pdf pp23

Documenting the IUT & Linkage to maternal and

neonatal records – International forum respondents

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All comment on documentation in

• Maternal chart

• +/- neonatal chart

• Most have a manual system relying on communication between Obs and Peds and /or BB

• National programs may have automatic updates to chart (2 reporting sites)

• Important because

• need for modifications to neonatal transfusion products, such as irradiation for subsequent top up transfusion

• traceability

• Also impacts on blood group (neonate will appear as group O) and may contribute to a delay in neonatal erythropoiesis with a prolonged reticulocytopenia and delayed nadir in hemoglobin concentration

Unique “automatic” documentation

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• One site indicated use of an “alias” for fetal record at the time of IUT, to be linked to neonatal record immediately post birth when neonatal number is available.

• A second site utilizes a fetal diagnostics test and result code for pre transfusion diagnostic test on blood drawn pre IUT as well as linking IUT to maternal record

• IUT information is appended to this file

• Link to maternal record is important for blood component traceability

• Link to neonatal file is important for ensuring appropriate product attributes, antigen status and blood group information as well as blood component modifications (irradiation)

Summary and Conclusions

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• Most providers for IUT provide similar blood components and for similar indications

• Fresh, group O red cells, concentrated to remove additive solution and hematocrit adjusted with saline are commonly used

• All irradiate prior to use

• Transfusion volume is calculated based on fetoplacental volume and the desired increase in fetal hematocrit using standard calculations

• Adverse events are rare