CLINICAL OBSTETRICS AND GYNECOLOGY
Volume 57, Number 4, 791–796
Obstetric
Hemorrhage:
Recent Advances
ANTONIO SAAD, MD, and MAGED M. COSTANTINE, MD
Department of Obstetrics and Gynecology, Division of Maternal
Fetal Medicine, The University of Texas Medical Branch,
Galveston, Texas
Abstract: Hemorrhage is the most common cause of
maternal mortality worldwide, and represents the
third most common obstetrical cause of maternal
death in the United States. Although uterine atony
was previously a major cause of peripartum hemor-
rhage, more recently, it appears that abnormal pla-
centation is the leading etiology and the main
indication of peripartum hysterectomy. Early identi-
fication and aggressive management of obstetrical
hemorrhage is of utmost importance to prevent ma-
ternal morbidities and mortality.
Key words: obstetrical hemorrhage, massive trans-
fusion, placenta accreta
Introduction
According to the Centers for Disease
Control, about 650 women die each year
in the United States as a result of preg-
nancy-related complications, with obstet-
ric hemorrhage being a top tier leading
etiology of maternal mortality.1 World-
wide, hemorrhage remains the #1 cause of
Correspondence: Maged M. Costantine, MD, Depart-
ment of Obstetrics and Gynecology, Division of Mater-
nal Fetal Medicine, The University of Texas Medical
Branch, 301 University Blvd, Galveston, TX. E-mail:
mmcostan@utmb.edu
The authors declare that they have nothing to disclose.
CLINICAL OBSTETRICS AND GYNECOLOGY
r 2014, Lippincott Williams & Wilkins
maternal mortality and the most common
form of shock in obstetrical practice.1
Traditionally, uterine atony had been
the major cause for peripartum hysterec-
tomy; however, recently abnormal pla-
centation has surpassed it in the
developed world.2,3 This may be because
of the current trends in obstetrical pa-
tients and practice including advanced
maternal age at time of conception, higher
obesity rates, and increasing cesarean de-
livery rates. These may have resulted in
increased prevalence of placental abnor-
malities including placenta previa and
placental accretism (accreta, increta, or
percreta). It is estimated that placental
accretism complicates 1 in 533 pregnan-
cies; a rate that represents a sharp increase
from 1 in 4027 pregnancies in the 1970s.4
In recent years, novel pathways
thought to play crucial role in the patho-
genesis of hemorrhage have been identi-
fied. In addition, the standard transfusion
guidelines currently in place have been
questioned, with a push to make hemo-
static resuscitation (early aggressive
blood product replacement) and massive
transfusion protocols essential elements
/ VOLUME 57 / NUMBER 4 / DECEMBER 2014
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792 Saad and Costantine
in these guidelines.3 In this paper, we will
review the diagnosis and management of
placental accretism, as well as, discuss
advances in the medical management of
obstetrical hemorrhage. These topics
have been recently the subject of many
extensive reviews by Pacheco and
colleagues.5–7
DIAGNOSIS OF PLACENTA ACCRETA
In the majority of cases, an ultrasound
performed by an experienced and trained
sonographer has good sensitivity and spe-
cificity to diagnose placental accretism
(sensitivity of 77% to 87%, specificity of
96% to 98%, and negative predictive
value of 98%).8,9 Traditional sonographic
clues suggestive of placental accretism
include loss of the normal retroplacental
hypoechoic space, increased vascularity
with uterine wall vessel invasion on color
Doppler, and the presence of placental
lacunae giving a ‘‘moth-eaten or Swiss
cheese’’ appearance, which is the most
predictive sonographic sign with sensitiv-
ity of 79% and positive predictive value of
92%.
Although an ultrasound may be
enough in the majority of patients, mag-
netic resonance imaging (MRI) may be
useful in patients suspected of having
placental accretism to evaluate the depth
of invasion, especially for posterior pla-
centas, as well as to better discriminate the
involvement of adjacent organs when a
placenta percreta is suspected.10 Bulging
of the lower uterine segment, the presence
of a heterogeneous placenta, and dark
intraplacental linear bands on T2-
weighed MRI images are suggestive of
placental accretism.11 In general, the ac-
curacy of ultrasound and MRI in diag-
nosing placenta accretism is similar.5,12 Of
note, although the use of paramagnetic
contrast media (gadolinium) would likely
improve the diagnostic performance of
MRI by enhancing the outer placental
surface relative to the myometrium; how-
ever, the agent readily crosses the placenta
www.clinicalobgyn.com
and its effects on the fetus remains un-
certain. Therefore, use of paramagnetic
contrast media during pregnancy may be
undertaken only after evaluating the risk
benefit ratio of such approach, and if the
improved accuracy of the study is ex-
pected to significantly improve patient
care and guide essential therapeutic
interventions.
ANTEPARTUM CARE AND TIMING OF
DELIVERY
To ensure optimal care, it is recom-
mended that patients with suspected pla-
cental accretism or at risk for peripartum
hemorrhage should be referred to a ter-
tiary center and managed by a multidisci-
plinary team including specialists in
maternal fetal medicine, urology, vascu-
lar surgery, interventional radiology,
blood bank, and neonatology. Such an
approach has been shown to decrease
maternal morbidity.5,13
The use of serial ultrasound examina-
tions to monitor fetal growth is not rec-
ommended in patients with isolated
placenta previa without accretism, as the
latter was not found to be associated with
fetal growth restriction.14 However, when
placental accretism is suspected or
present, serial sonographic follow-up
every 3 to 4 weeks is recommended to
assess fetal growth, and the depth of
placental invasion.
Patients with suspected placental ac-
cretism or at risk for peripartum hemor-
rhage need to have their hemoglobin
levels optimized before delivery. It is com-
mon to start these patients on iron and/or
folic acid supplements, and occasionally,
intravenous iron and/or recombinant er-
ythropoietin may be needed as adjuvant
therapy. Preoperative autologous blood
donation may be considered in select pa-
tients, such as those with rare blood types
and/or alloimmunization to rare antibod-
ies. Patients [with hemoglobin >10 g/dL,
and within 42 d of surgery, the maximum
accepted time to maintain packed red

blood cells (RBC) in the blood bank] may
donate their own blood units during preg-
nancy, and these will be later used intra-
operatively if needed. Disadvantages of
such approach is that it has not been
shown to be cost-effective, is not well
studied in pregnancy, and may not be
acceptable by Jehovah’s Witnesses
patients.15
Regarding timing of delivery, the Soci-
ety of Maternal Fetal Medicine recom-
mends that patients with placenta previa
should be delivered at 36 to 37 weeks, and
those with suspected placental accretism
at 34 to 35 weeks.16 Testing for fetal lung
maturity before delivery is not thought to
not provide any additional benefit, and
thus is not recommended.17 The decision
to deliver a pregnant woman with sus-
pected accretism between 34 and 37 weeks
should be individualized depending on
the patient obstetrical history, pregnancy
complications, and risk of preterm labor
and/or vaginal bleeding.5,18
PERIOPERATIVE INTERVENTIONS
Although a complete sympathectomy (eg,
spinal anesthesia) may impair the pa-
tient’s ability to vasoconstrict and in-
crease systemic vascular resistances and
thus may put the patient at risk from the
hypovolemia associated with acute blood
loss; a continuous epidural technique is
safe and may be appropriate for patients
with placental accretism.19,20 However, in
emergent situations of massive bleeding,
general anesthesia may be more appro-
priate. In contrast, permissive hypoten-
sion (with systolic blood pressure of 80 to
100 mm Hg) may be discussed with the
anesthesia team and considered in pa-
tients with postpartum hemorrhage. No
data are available on its safety before
delivery of the fetus as it may compromise
uterine perfusion.5,6
Although acute normovolemic hemo-
dilution may be considered in certain
patients (those with hemoglobin level
>10 g/dL and no history of
Systolic Blood Pressure 793
cardiovascular disease), there is minimal
evidence that it alone reduces significantly
the need for transfusion. This technique
involves collecting 500 to 1000 mL of
blood from the patient and replacing it
with either colloid (1:1 ratio) or crystal-
loid (3:1 ratio) fluids to maintain hemo-
dynamics.15 After surgical bleeding is
controlled, the patient is transfused the
previously collected blood. This techni-
que is acceptable for some Jehovah’s Wit-
nesses as long as the collection bag is
connected to the central venous line at
all times, without any ‘‘circuit’’
disconnections.15
Another safe and effective technique
that may be accepted by Jehovah’s Wit-
nesses patients is intraoperative cell sal-
vage.5,6 After collecting and filtering
aspirated blood from the surgical field,
sterile filters will separate tissue factor, a-
fetoprotein, platelets, and circulating pro-
coagulants.21 The collected blood is then
reinfused to the patient after its reaches a
hematocrit concentration >55%. A Klei-
hauer-Betke stain and appropriate ad-
ministration of anti-D immunoglobulin
is required for prevention of alloimmuni-
zation in Rh-negative blood type pa-
tients.15 Moreover, there is no evidence
of increased risk of amniotic fluid embo-
lism with the use of this technique in the
400 plus cases described in the obstetric
literature.22
Another therapy that is being more
frequently used in obstetric hemorrhage
is recombinant factor VII a (rFVIIa).
Traditionally, this therapy has been ap-
proved for patients with hemophilia and
inhibitory alloantibodies.23 However, it
has been used off-label in various clinical
scenarios including trauma, cardiovascu-
lar surgery, and obstetrical hemorrhage;
and is being added to many massive trans-
fusion protocols. The agent has a short
half-life (2 to 6 h), requires multiple ad-
ministrations, and its use is associated
with increased risk of arterial throm-
boembolism. rFVIIa is not the first line
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794 Saad and Costantine

FIGURE 1. Massive transfusion protocol in obstetrics. Once activated, blood bank personnel
will continue preparing blood products until the protocol is inactivated by the surgical team.
After 2 sequences of rounds 1 to 3, if not inactivated, the protocol will start again from round 1.
*The utilized dose of recombinant activated factor VII is based on local expert opinion. ^If
bleeding is not controlled the sequence is repeated. FFP indicates fresh frozen plasma; pRBC,
packed red blood cells. Adapted from Pacheco et al.7

of treatment for massive hemorrhage and based on massive administration of crys-

should only be used after surgical bleed-
ing has been controlled, with a combina-
tion of various blood products, and
only after meeting multiple prerequisites
including platelet count >50,000/mm3,
fibrinogen >50 to 100 mg/dL, tempera-
ture >321C, pH>7.2, and normal ionized
calcium.24 Multiple, nonobstetric, rando-
mized controlled trials have been pub-
lished where rFVIIa has been used to
control bleeding, and none showed that
its use improves survival. However, 4 of 17
studies concluded that it reduced trans-
fusion requirements or blood loss.25 The
optimal dose of rFVIIa, especially in preg-
nancy, is unknown, but the majority of
reports in obstetrical hemorrhage have
used a dose of 40 to 90 mg/kg.6,7
Acute coagulopathy remains a major
complication in the setting of massive
hemorrhage, most commonly secondary
to ‘‘dilutional coagulopathy.’’ Tradition-
al resuscitative maneuvers are heavily
talloids, colloids and packed RBC, with
the use of fresh frozen plasma (FFP),
cryoprecipitates, and platelets limited to
low fibrinogen (<100 mg/dL), prolonged
prothrombin or activated partial throm-
boplastin times (usually >1.5  normal),
and thrombocytopenia (platelet count
<50,000/mm3).26 However, it is been
shown that massive early crystalloid re-
suscitation may worsen bleeding.27 This is
thought to be due to the increased intra-
vascular hydrostatic pressure, disruption
of fresh clot formation, and enhancement
of the fibrinolytic pathway.27,28 On the
basis of these mechanisms of early coa-
gulopathy, it is suggested that early
replacement of clotting factors, and con-
trol of the fibrinolytic state may be
beneficial.6,7
In addition to restriction of early ex-
cessive crystalloid and packed RBC ad-
ministration, recent data from the
nonobstetric literature also suggest

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transfusion of packed RBC concomi-
tantly with platelets and FFP at a ratio
as close to 1:1:1 as possible. This has been
shown in several retrospective studies in
military and civilian trauma settings to
reduce mortality by 15% to 62% com-
pared with higher ratios of FFP:PRBC.29
However, these studies are limited by
survival bias30,31 and they did not include
pregnant women.6
In an attempt to improve the response
to massive obstetrical hemorrhage, many
centers in the United States including our
labor and delivery unit have implemented
massive transfusion protocols that in-
clude early administration of high plate-
let:FFP:PRBC ratios and early use of
rFVIIa. An example of such protocol,
adapted from Pacheco et al7 is depicted
in Figure 1. This protocol is activated if
hemorrhage is expected to be massive
(anticipated need to replace Z50% of
blood volume within 2 h) or in patients
with ongoing bleeding after the transfu-
sion of 4 U of packed RBCs within a short
period of time (1 to 2 h).7
POSTOPERATIVE CARE
Patient recovering from a massive obstet-
rical hemorrhage are at increased risk for
thromboembolic events during the post-
partum period. This is secondary to endo-
thelial injury, inflammation, prolonged
surgery, immobilization, as well as the
thrombotic state of the postpartum peri-
od. Mechanical deep venous thrombosis
prophylaxis should be applied intraoper-
atively and continued thereafter; and
pharmacological prophylaxis should be
started as soon as the clinician feels it is
safe and the bleeding risk is minimal.6 In
addition, abdominal compartment syn-
drome (ACS) may occur secondary to
fluid third spacing after crystalloid and
colloid administration and endothelial in-
jury. This leads to increase intra-abdomi-
nal pressures, collapse of abdominal and
retroperitoneal vessels, leading to de-
crease cardiac preload, and ultimately
Systolic Blood Pressure 795
cardiac output and blood pressure.32
Clinically, ACS frequently presents as
oliguria and/or hypotension postopera-
tively which does not respond, and may
worsen, with administration of intrave-
nous fluids. If there is suspicion of in-
creased abdominal pressures, clinicians
should consider bladder pressure meas-
urement, which reflects the pressures in
the abdomen.32 The diagnosis of ACS
includes a bladder pressure of >20 mm
Hg and dysfunction of at least 1 organ,
and these patients are managed with fluid
restriction, enteral feeding, but most will
need surgical decompression.32
Summary
Obstetrical hemorrhage remains among
the major causes of maternal morbidity
and mortality, with placental accretism
representing the major cause and the most
common indication for a cesarean
hysterectomy in the developed world.
Early identification of placental accretism
and patient transfer to a tertiary care
center with multidisciplinary team ap-
proach, improves maternal and fetal out-
comes. Various strategies have been
identified that may assist in management
of these patients including, normovolemic
hemodilution, intraoperatively use of cell-
saver, hemostatic resuscitation, and the
use of massive transfusion protocols.
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