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Prehospital Emergency Care

ISSN: 1090-3127 (Print) 1545-0066 (Online) Journal homepage: https://www.tandfonline.com/loi/ipec20

Prehospital Transfusion of Low-Titer O + WholeBlood for Severe Maternal Hemorrhage: A CaseReport

Ryan Newberry, C.J. Winckler, Ryan Luellwitz, Leslie Greebon, Elly Xenakis,William Bullock, Michael Stringfellow & Julian Mapp

To cite this article: Ryan Newberry, C.J. Winckler, Ryan Luellwitz, Leslie Greebon, Elly Xenakis,William Bullock, Michael Stringfellow & Julian Mapp (2019): Prehospital Transfusion of Low-TiterO + Whole Blood for Severe Maternal Hemorrhage: A Case Report, Prehospital Emergency Care,DOI: 10.1080/10903127.2019.1671562

To link to this article: https://doi.org/10.1080/10903127.2019.1671562

Accepted author version posted online: 24Sep 2019.

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LTO+WB Transfusion for Maternal Hemorrhage

Prehospital Transfusion of Low-Titer O+ Whole Blood for Severe Maternal Hemorrhage:

A Case Report

Ryan Newberry, DO MPHa,b,*, C.J. Winckler, MD LP

b, Ryan Luellwitz, DOc, Leslie Greebon,

MDd, Elly Xenakis, MD

e, William Bullock, EMT-Pf, Michael Stringfellow, EMT-P

f, Julian

Mapp, MD MBA MPHa,b

aUS Army Institute of Surgical Research, JBSA Fort Sam Houston, TX 78234, USA

bDepartment of Emergency Health Sciences, University of Texas Health Science Center at San

Antonio, San Antonio TX 78229, USA cDepartment of Obstetrics & Gynecology, Dean Medical Group/SSM Health, Madison WI

53715, USA dDepartment of Pathology, University of Texas Health Science Center at San Antonio, San

Antonio TX 78229, USA eDepartment of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of

Texas Health Science Center at San Antonio, San Antonio TX 78229, USA fSan Antonio Fire Department, San Antonio, TX 78207, USA

*Corresponding Author Ryan Newberry ryan.k.newberry@gmail.com

Abstract

Beginning in 2017, multiple stakeholders within the Southwest Texas Regional Advisory

Council for Trauma collaborated to incorporate cold-stored low-titer O RhD-positive whole

blood (LTO+WB) into all phases of their trauma system, including the prehospital phase of care.

Although the program was initially focused on trauma resuscitation, it was expanded to included

non-traumatic hemorrhagic shock patients that may benefit from whole blood resuscitation. We

report the case of a patient with severe maternal hemorrhage secondary to placenta accreta who

received a prehospital transfusion of LTO+WB. We believe this to be the first reported case of

post-partum hemorrhage resuscitated out of hospital with whole blood. This case highlights the

potential benefits of a prehospital whole blood program as well as the controversy surrounding a

LTO+WB program that includes females of childbearing age.

Keywords: whole blood transfusion, maternal hemorrhage, post-partum hemorrhage, low-titer

O+ whole blood transfusion

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Introduction

Beginning in 2017, the San Antonio Medical Foundation, South Texas Blood and Tissue Center

(STBTC), UT Health San Antonio, University Health System, San Antonio Military Medical

Center, US Army Institute of Surgical Research and Southwest Texas Regional Advisory

Council for Trauma (STRAC) collaborated to incorporate cold-stored low-titer O RhD-positive

whole blood (LTO+WB) into all phases of their trauma system, including San Antonio Fire

Department (SAFD) ground ambulances in late 2018. In this program, LTO+WB is utilized due

to the limited O RhD-negative donor population needed to sustain an adequate O RhD-negative

blood inventory. Based on the demographics of south Texas, the stakeholders in this program

predicted that there would not be a sufficient population of type O RhD-negative donors to

sustain the necessary quantities of whole blood.1,2

Although the program was initially focused on

trauma resuscitation, the relevant stakeholders realized that non-traumatic hemorrhagic shock

patients, including pregnant women, may benefit from this program.

Prescreened LTO+WB is a safe and effective solution for emergency transfusion that has

recently been approved by the American Association of Blood Banks (AABB) based on the

recommendations of a joint Trauma Hemostasis and Oxygen Research (THOR)-AABB working

group.3-5

An alternative modality to the balanced ratio (1:1:1) of blood component-based

resuscitation, LTO+WB has proven benefits compared to component therapy and ABO group-

specific approaches.1-3

One of the main disadvantages of component therapy mitigated through

the use of whole blood is overcoming the dilute blood mixture largely attributed to necessary

addition of anticoagulants and additive solution. Previous research has also suggested that

resuscitation with whole blood overcomes the thrombocytopenia that typically accompanies

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transfusion with component therapy.3 The current literature suffers from a paucity of prospective

patient outcome data concerning whole blood transfusion. However, multiple studies based on

retrospective data have suggested improved 30-day survival after resuscitation with whole

blood.6 Several recent articles have also suggested that whole blood provides the optimal

physiologic replacement and that LTO+WB is likely the preferred product for prehospital and

emergency department resuscitation.1-3

The SAFD Emergency Medical Services (EMS) division is comprised of 35 full-time paramedic

ambulances and six paramedic officers responding annually to approximately 168,000 EMS

responses.7 The paramedic officers, known as medic officers (MOFs), are EMS lieutenants who

have the responsibility and oversight of the EMS paramedic ambulances in their geographic

sector. The MOFs are available 24-hours per day and are dispatched for operational and logistic

needs of their assigned crews.2,7

Currently one unit of LTO+WB is carried on each of two

special operations paramedic ambulances and six MOF response vehicles. The LTO+WB is

transported in Pelican BioThermal Credo Golden HourTM

Mobile Series 4 2L EMT coolers.

These transport coolers are a combination of a temperature controlled medical transport bag and

a removable thermal isolation chamber (TIC pack) that are rated to protect blood products at a

temperature range of 2-8 degrees Celsius for a period of 48-hours per the manufacturer.8 This

was independently validated by STBTC and STRAC prior to implementation of the prehospital

LTO+WB program.9

The LTO+WB is received by SAFD directly from STBTC for the 0-14 shelf-life days. Each

SAFD EMS unit with blood transfusion capability utilizes a two TIC pack rotation system for the

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transport of the LTO+WB. At the beginning of each 24-hour shift, unused LTO+WB is rotated

from its current Golden HourTM

cooler and placed into a conditioned cooler for the next 24-hour

shift. At shelf-life day number 14, an unused LTO+WB unit is exchanged at STBTC for a fresh

LTO+WB unit and subsequently taken to a Level I trauma center for immediate use in trauma

resuscitation.

SAFD EMS units utilize a physiologic-based criterion for the decision of when to transfuse

LTO+WB to patients experiencing hemorrhagic shock of either medical or trauma etiology

(Figure 1, Figure 2). SAFD deploys the QinFlowTM

Warrior lite IV fluid warmer and two

pressure systems to transfuse LTO+WB, the VentlabTM

disposable pressure infuser and the

Braun Y-type blood set with an inline handpump (Figure 3). Together, these pressure systems

consistently allow transfusions of 500 mL of whole blood warmed to 38 degrees Celsius to be

completed in approximately 5 minutes.10

In addition to the EMS patient care report that is

generated after each EMS response, a triplicate prehospital blood transfusion record is completed

by the paramedics with two copies being issued to the receiving emergency department (Figure

4). Subsequently, the prehospital blood transfusion forms are distributed to the patient’s

emergency department health record and the receiving hospital’s pathology laboratory.

Here we report the case of a patient with severe maternal hemorrhage secondary to placenta

accreta who received a prehospital transfusion of LTO+WB. This case highlights the potential

benefits of a prehospital whole blood program as well as the controversy surrounding a

LTO+WB program that includes females of childbearing age. The University of Texas Health

Science Center San Antonio Emergency Health Sciences Office of the Medical Director

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(UTHSCSA OMD) maintains a whole blood registry as part of their ongoing prehospital whole

blood QA/QI program. Our team utilized the CAse REport (CARE) guidelines to report this

case, and the patient provided her informed consent.11

Case Report

The San Antonio Fire Department was called to the home of a 27-year-old, gravida 4 para 3

pregnant female at 35-weeks gestation, for an “OBGYN” call at 0018 hours. Her pregnancy was

complicated by known placenta previa with possible abnormally adherent placenta accreta.

When calling 9-1-1, it was reported that the patient had been vaginally bleeding for about twenty

minutes. The SAFD EMS unit arrived to the residence of the caller at 0026 hours and noted a

trail of blood leading to a second-floor bathroom. They subsequently found the patient sitting in

a pool of blood inside a bathtub. The paramedics estimated the amount of blood loss to be greater

than 500 mL. The patient was conscious, “lethargic,” and not speaking to anyone. Their primary

assessment of the patient demonstrated normal work of breathing, pale cool skin, moderate

vaginal bleeding and the monitor displayed no quantified blood pressure on initial usage.

The patient was assisted to a stair chair and rapidly extricated to the ambulance, where

intravenous (IV) access was obtained with a 16 gauge IV catheter in her right antecubital vein.

Initial vital signs at 0037 hours were a pulse of 85 beats per minute (bpm), blood pressure of

68/45 mmHg, respiratory rate of 14 and shock index of 1.3. At the same time, transfusion of 500

mL of warmed LTO+WB was initiated. The patient was then emergently transported to the

nearest community hospital. While en route vital signs were a pulse of 86 bpm, blood pressure of

84/55 mmHg, respiratory rate of 16 and shock index of 1.0. Placement of a second IV catheter

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was attempted but unsuccessful. Electrocardiogram (ECG) was also obtained and demonstrated a

normal sinus rhythm.

The patient arrived at the community hospital’s emergency department at 0055 with ongoing

resuscitation with LTO+WB. Her vital signs at 0055 were a pulse of 97 bpm, blood pressure of

100/56 mmHg, respiratory rate of 18, oxygen saturation (O2) 99% and shock index of 1.0. Initial

serum labs revealed a hemoglobin of 9.5 g/dL and hematocrit of 28.0%. Her chemistry panel and

coagulation studies were within normal limits. Pelvic examination performed by the emergency

physician noted coagulated blood in the vaginal vault with minimal active bleeding. A fetal heart

rate was found to be 140 bpm. The remainder of her emergency department course included

administration of 1.5 grams of cefuroxime, 30 mL of citric acid/sodium citrate and 1000 mL of

Lactated Ringers solution. The patient was then transferred to the operating suite for emergent

cesarean section.

The patient had an emergent cesarean delivery followed by an immediate hysterectomy without

complications. During the operation, she received an additional two units of packed red blood

cells (PRBC). Blood loss was estimated to be 1000 mL. The mother was subsequently found to

be of the blood type A RhD-positive. A viable male infant of the blood type O RhD-positive

was delivered with 1- and 5-minute APGAR scores of 7 and 8, respectively. The infant was

admitted to the neonatal intensive care unit (NICU) immediately after delivery. The patient’s

postoperative course was remarkable for a serum hemoglobin 5.0 g/dL and hematocrit of 16%.

She was subsequently transfused an additional two units of PRBCs. The remainder of her

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hospital course was unremarkable. She was discharged from the hospital on postoperative day

three. The infant was discharged from the NICU approximately two weeks later.

Discussion

Maternal hemorrhage remains a leading cause of maternal morbidity and mortality worldwide,

accounting for 11.4% of maternal deaths in the United States between 2006-2010.12

To further

improve the quality of maternal hemorrhage management, the National Partnership for Maternal

Safety recommended that U.S. birthing facilities partner with local transfusion services to ensure

the rapid availability of blood products and published hospital protocols that indicated blood

component therapy as a critical aspect of postpartum hemorrhage management.12,13

Our

prehospital LTO+WB program is an extension of this intention to treat maternal hemorrhage

early and decisively. However, there are risks associated with exposing females of childbearing

age to LTO+WB. In particular is the risk of maternal RhD alloimmunization. RhD

alloimmunization occurs when a woman with RhD-negative (Rh-) blood is exposed to RhD-

positive (Rh+) blood cells, leading to the formation of antibodies against RhD. Women of

childbearing age can be exposed to Rh+ blood cells through fetal-maternal hemorrhage as well as

blood product administration, including LTO+WB.14

During the first seven months of the SAFD LTO+WB initiative, there were 95 transfusions of

LTO+WB. Females accounted for 28 cases, of which 16 were women less than 40 years old.

After extrapolating this data from our whole blood registry, our team projects that the SAFD will

transfuse a total of 23 female patients under age 40 per year over a 12-month period. This cohort

of 23 patients includes both Rh+ and Rh

- females. Using a 15% incidence of Rh

- individuals in

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the overall population, the SAFD ground ambulance whole blood initiative may expose

approximately four Rh- young females to LTO+WB annually. However, the demographics of the

greater San Antonio metropolitan area suggests that 15% is an overestimate of the prevalence of

Rh- blood types in our patient population. For example, one of our local trauma centers

conducted a 30-month review of their massive transfusion protocol (MTP) recipients and found

that only 6.3% of the female MTP recipients were Rh-.1

Exposure to Rh+ blood cells does not directly translate to alloimmunization. Recent studies of

hospitalized patients observed that the alloimmunization rate of exposed individuals is between

11.5% and 30.4%.15-18

This rate is considerably lower than the often cited 80 to 92%

alloimmunization rate derived from two small studies of healthy volunteers conducted in 1970

and 1981 respectively.19,20

Assuming a 30.4% conversion rate, the SAFD ground ambulance

program whole blood program would lead to one woman of childbearing age undergoing RhD

alloimmunization annually.

However, if we consider alloimmunization the endpoint when considering the adverse effects of

transfusing LTO+WB to a Rh- young woman, several assumptions have to be made. One, she

desires future pregnancies. Two, she will conceive with a male partner who has an Rh+ blood

type. Three, the prevention of alloimmunization via administration of Rh Immune globulin

(RhIg) or red blood cell exchange was unsuccessful or not plausible after exposure to the RhD

antigen. Four, the affected fetus will have severe hemolytic disease and fetal blood transfusions

will be ineffective.

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The development of anti-RhD antibodies in the Rh- female of childbearing age is a serious

adverse event that may lead to significant complications in future pregnancies. However, it must

be appropriately weighed against the dangers of withholding potentially life-saving early

resuscitation to patients in hemorrhagic shock. Therefore, an LTO+WB program may be the only

way to provide a balanced, blood-based, resuscitation to patients in the prehospital phase of care

that are in hemorrhagic shock.

RhD alloimmunization has been successfully prevented with the administration of Rho(D)

immune globulin, also known as RhoGAM (RhIg). A standard pre-natal or post-natal dose of

RhIg consists of a single 300 microgram (ug) vial and is administered intravenously or

intramuscularly, depending on the manufacturer. Each 300 ug vial effectively prevents

alloimmunization after exposure to 15 mL of Rh+ PRBCs or 30 mLs of Rh+ whole blood.

Typically, Rh- women receive anti-D immunoglobulin within 72 hours after suspected fetal-

maternal hemorrhage, miscarriage, ectopic pregnancy and delivery to prevent the formation of

antibodies against RhD.21-23

Maternal RhD alloimmunization can have significant implications in

subsequent pregnancies, including hemolytic disease of the fetus.14

With the risk of maternal

RhD alloimmunization, it is prudent to evaluate if women of childbearing age should receive

LTO+WB.

For women who receive LTO+WB that are subsequently found to be Rh-, it is recommended that

the trauma services within receiving hospitals create a protocol to determine RhIg candidacy. At

one of our local trauma centers, a protocol has been devised where the trauma service consults

pathology and obstetrics services within 24 hours of LTO+WB transfusion to enable counseling

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of the patient on potential alloimmunization and possible candidacy of RhIg administration.1

Determination of RhIg administration candidacy is based on the patient’s desire of future

pregnancy, clinical condition, prognosis and the volume of transfused LTO+WB.14

RhIg

administration may be considered in a patient who has received less than 20% of their total blood

volume (TBV) during transfusion of LTO+WB. If the volume of LTO+WB transfused is less

than 20% TBV with other favorable clinical characteristics, then RhIg is dosed at 18-20 ug per

mL of transfused red cells to prevent isoimmunization. A standard whole blood unit will contain

approximately 250 mL of red blood cells. Therefore, due to this large volume of exposure,

dosing to cover the mLs of RBCs transfused results in large doses of RhIg and thus should be

divided and administered over several days via intravenous infusion only. If the volume of

transfusion exceeds 20% TBV of the patient, RhIg administration is not usually pursued since

there is considerable risk of inducing splenic sequestration and extravascular hemolysis. In larger

volume transfusion events (greater than 20% TBV), red blood cell exchange(s) may be

considered to remove antigenic stimulus. In addition, it is recommended for follow-up testing at

three, six and twelve months to determine if alloimmunization occurred.1,21-23

Conclusion

We present the case of a 27-year-old female with severe hemorrhage that was successfully

treated with prehospital low-titer O Rh-positive whole blood. The development of anti-RhD

antibodies in the RhD-negative female of childbearing age is a serious adverse event that may

lead to significant complications in future pregnancies, and it must be appropriately weighed

against the dangers of withholding potentially life-saving early resuscitation to patients in

hemorrhagic shock. We conclude that due to the low risk of maternal RhD alloimmunization

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EMS systems should consider including females of childbearing age into protocols where only O

Rh-positive blood products are available.

Prior Presentations

none

Funding/Conflict of Interests

none

Author contributions

RN, RL, and JM drafted the original manuscript. All authors critically reviewed, contributed and

edited the case report. RN takes responsibility for the paper as a whole.

Disclaimer

The views expressed in this article are those of the author(s) and do not reflect the official policy

or position of the city of San Antonio, the U.S. Army Medical Department, Department of the

Army, Department of Defense, or the U.S. Government.

References

1. McGinity AC, Zhu CS, Greebon L, et al. Prehospital low-titer cold-stored whole blood: Philosophy for ubiquitous utilization of O-positive product for emergency use in hemorrhage due to injury. J Trauma Acute Care Surg 2018;84:S115-S9. 2. Zhu CS, Pokorny DM, Eastridge BJ, Nicholson SE, et al. Give the trauma patient what they bleed, when and where they need it: establishing a comprehensive regional system of resuscitation based on patient need utilizing cold-stored, low-titer O+ whole blood. Transfusion 2019;59:1429-1438. 3. Weymouth W, Long B, Koyfman A, Winckler C. Whole blood in trauma: a review for emergency clinicians. J Emerg Med 2019;56(5):491-498. 4. Press release: emergency release low titer O whole blood is now permitted by AABB standards. In: The trauma hemostasis and oxygen research (THOR) network; 2018. https://rdcr.org/press-release-emergency-release-low-titer-group-o-whole-blood-now-permitted-aabb-standards/. 5. American Association of Blood Banks (AABB). Standards for blood banks and transfusion services. Bethesda, MD: AABB; 2018. 6. Fisher AD, Miles EA, Cap AP, Strandenes G, et al. Tactical damage control resuscitation. Mil Med 2015;180:869-75. 7. San Antonio Fire Department. City of San Antonio Fire Department Annual Report 2018. San Antonio, TX, 2018. [cited 04Aug2019]. Available from: http//www.sanantonio.gov 8. Pelican BioThermal. Golden HourTM Medic Series 4. Plymouth, MN. [cited 12Aug2019]. Available from www.pelicanbiothermal.com 9. Kumar, S. Project to qualify Level I helicopter blood transport box operational qualification report. MaxQ Research LLC. MaxQ Project No TV1101007. Project end date 30Nov2017. Document not reproducible with the written authorization of MaxQ Research LLC.

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10. QinFlow Incorporated. The warrior modular system. North American Headquarters, Plano, TX. [cited 12Aug2019]. Available from www.quinflow.com 11. Gagnier JJ, Kienle G, Altman DG, et al. The CARE guidelines: consensus-based clinical case report guideline development. J Clin Epidemiol 2014;67:46-51. 12. Butwick AJ, Goodnough LT. Transfusion and coagulation management in major obstetric hemorrhage. Curr Opin Anaesthesiol 2015;28:275-84. 13. Alexander JM, Sarode R, McIntire DD, Burner JD, Leveno KJ. Whole blood in the management of hypovolemia due to obstetric hemorrhage. Obstetrics and gynecology 2009;113:1320-6. 14. Prevention of Rh D alloimmunization. Practice Bulletin No. 181. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;130:e57–70. 15. Frohn C, Dumbgen L, Brand JM, Gorg S, Luhm J, Kirchner H. Probability of anti-D development in D- patients receiving D+ RBCs. Transfusion 2003;43:893-8. 16. Yazer MH, Triulzi DJ. Detection of anti-D in D- recipients transfused with D+ red blood cells. Transfusion 2007;47:2197-201. 17. Gonzalez-Porras JR, Graciani IF, Perez-Simon JA, et al. Prospective evaluation of a transfusion policy of D+ red blood cells into D- patients. Transfusion 2008;48:1318-24. 18. Tchakarov A, Hobbs R, Bai Y. Transfusion of D+ red blood cells to D- individuals in trauma situations. Immunohematology 2014;30:149-52. 19. Gunson HH, Stratton F, Cooper DG, Rawlinson VI. Primary immunization of Rh-negative volunteers. British medical journal 1970;1:593-5. 20. Urbaniak SJ, Robertson AE. A successful program of immunizing Rh-negative male volunteers for anti-D production using frozen/thawed blood. Transfusion 1981;21:64-9. 21. Nester T, Rumsey D, Howell C, Gilligan D, et al. Prevention of immunization to D+ red blood cells with red blood cell exchange and intravenous Rh immune globulin. Transfusion 2004;44(12):1720-3. 22. Anderson B, Shad A, Gootenberg J, Sandler S. Successful prevention of post-transfusion Rh alloimmunization by intravenous Rho (D) immune globulin (WinRho SD). Am J Hematol 1999;60(3):245-7. 23. Ayache S, Herman J. Prevention of D sensitization after mismatched transfusion of blood components: toward optimal use of RhIG. Transfusion 2008;48(9):1990-9. Table 1: Prehospital, Emergency Department Hospital Course vital signs, laboratory results and interventions

Time Intervention Heart Rate

Blood Pressure

Lab Fluid

00:18 Public Safety Answering Point

0:18 SAFD EMS Units Dispatched

00:26 SAFD Paramedic Ambulance On-Scene

00:28 Paramedic 85 Automated

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Primary Assessment

Cuff not able to detect

00:30 SAFD Ladder Company On-Scene

00:32 16 g IV Right AC

00:33 Patient extricated from residence with stair chair

00:35 SAFD Medic Officer On-Scene

LTO+WB Capable

00:37 Cardiac Monitor ECG: NSR 85 68/45

00:37 Decision to transfuse 1 U LTO+WB

1 U LTO+WB

00:40 Cardiac Monitor ECG: NSR 85

00:41 Cardiac Monitor 86 84/55

00:42 Transport to Emergency Department

Completed LTO+WB transfusion en route

00:50 Arrival at Emergency Department

00:55 Emergency Department

97 100/56

Emergency Department

Cefuroxime 1.5 gm Citric Acid 30 mL

LR 1000 mL

01:01 Emergency Department

CBC: Hgb 9.5, HCT 29.7, WBC 26.1, Plt 262 Chem: Na 137, K 3.9, Cl 104, CO2 20, BUN 9, Cr 0.5, Glu 124, Ca 1.01

01:07 Patient Cesarean 2 U O-

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discharged from ED to OR

delivery Hysterectomy

PRBC

Post-operative Course

Patient discharged on January 10 Male infant admitted to NICU, discharged after 14 day course

Range: 81-97

Range: 92-114 SBP

01/08 CBC: Hgb 5.9, HCT 17.9, WBC 9.7, PLT 148 01/09 CBC: Hgb 7.1, HCT 21.1, WBC 9.6, PLT 163

2 U O- PRBC

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Figure 1. San Antonio Fire Department Low Titer O+ Whole Blood Trauma Clinical Operating Guideline

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Figure 2. San Antonio Fire Department Low Titer O+ Whole Blood Medical Clinical Operating Guideline

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Figure 3. San Antonio Fire Department Medic Officer transfusing low titer O+ whole blood to a trauma patient.

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Figure 4. Southwest Texas Regional Advisory Council prehospital blood product transfusion record.

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