ACRETISMO Y HPP, JUNIO 2023.pdf

Placenta Accreta
Spectrum and
Postpartum
Hemorrhage
MAHMOUD ABDELWAHAB, MD,
and MICHAEL CACKOVIC, MD
Department of Obstetrics and Gynecology, The Ohio State
University College of Medicine, Columbus, Ohio
Abstract: Placenta accreta spectrum is a group of
disorders involving abnormal trophoblastic invasion
to the deep layers of endometrium and myometrium.
Placenta accrete spectrum is one of the major causes of
severe maternal morbidity, with increasing incidence
in the past decade mainly secondary to an increase in
cesarean deliveries. Severity varies depending on the
depth of invasion, with the most severe form, known
as percreta, invading uterine serosa or surrounding
pelvic organs. Diagnosis is usually achieved by ultra-
sound, and MRI is sometimes used to assess invasion.
Management usually involves a hysterectomy at the
time of delivery. Other strategies include delayed
hysterectomy or expectant management.
Key words: placenta accreta spectrum, cesarean hys-
terectomy, delayed hysterectomy
Introduction
Placenta accreta spectrum (PAS) is a
group of disorders involving abnormal
trophoblastic invasion to the deep layers
of endometrium and myometrium that
prevent normal completion of the third
stage of labor or manual delivery of the
placenta during cesarean delivery. PAS is
one of the major causes of severe maternal
morbidity.1,2
The incidence of PAS has been increas-
ing in modern obstetrics, mainly secon-
dary to an increase in rates of cesarean
deliveries and a decline in the rate of
operative deliveries throughout the
United States. The incidence was esti-
mated to be 1 in thousands in the 1970-
1980s, making it a rare encounter.3
A
national study estimated the incidence to
be 1 in 272 patients between 1998 and
2011, which is more than a 10-fold
increase, with potentially higher rates
present now.1,4
RISK FACTORS
The most important risk factors for PAS
are previous cesarean deliveries and pla-
centa previa. With one cesarean delivery,
The authors declare that they have nothing to disclose.
Correspondence: Mahmoud Abdelwahab, MD, Division
of Maternal-Fetal Medicine, Department of Obstetrics
and Gynecology, The Ohio State University College of
Medicine, Columbus, OH. E-mail: Mahmoud.
Abdelwahab@osumc.edu
CLINICAL OBSTETRICS AND GYNECOLOGY / VOLUME 66 / NUMBER 2 / JUNE 2023
www.clinicalobgyn.com | 399
CLINICAL OBSTETRICS AND GYNECOLOGY
Volume 66, Number 2, 399–407
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Copyright r 2023 Wolters Kluwer Health, Inc. All rights reserved.

the rate of PAS is estimated to be 0.3%
versus 6.7% with 5 or more cesarean
deliveries.1,5
Rate of PAS in patients with
placenta previa is estimated to be 3% in
the absence of previous cesarean deliv-
eries. A synergistic relationship exists
between previous cesarean deliveries and
placenta previa when it comes to the risk
of PAS. The absence of endometrial re-
epithelization following trauma by cesar-
ean delivery allows for deep trophoblastic
invasion when implantation happens
close to the scar.6
The clinical presenta-
tion of 1 previous cesarean delivery and
placenta previa, the risk of PAS is esti-
mated to be 11%. While risk is 40% with 2
previous cesarean deliveries, 60% with 3
previous cesarean deliveries, and 67% if
more than 3 previous cesarean deliveries.7
Double-layered uterine closure has been
suggested to reduce the risk of PAS.
Single-layer closure with the incorpora-
tion of endometrium in the myometrial
closure or strangulation of tissue by lock-
ing sutures has been associated with
weaker scars in some reports.8
However,
studies have failed to prove the superior-
ity of double-layer closure over single-
layer closure to reduce the chance of
PAS.9
Interestingly the presence of a
low-lying placenta within 2 cm from the
cervix was not found to be associated with
increased risk for PAS in the presence of
previous cesarean deliveries.10
Other uterine surgeries have been asso-
ciated with an increased risk of PAS,
including myomectomy, dilation and cur-
ettage, and endometrial ablation.11
PAS
rate was reported to be 23% following
endometrial ablation.12
PAS has been
described in the absence of uterine sur-
geries as well. Some nonsurgical risk
factors include previous endometritis, ute-
rine anomalies, adenomyosis, submucous
fibroids, and assisted reproductive
techniques.11
The rate of PAS has been
estimated to increase by 13-fold following
in vitro fertilization (IVF) procedures,
making it an important contributing risk
factor given the increasing rates of IVF.13
Pregnancy following uterine artery embo-
lization may also be associated with an
increased risk for PAS.14
PATHOGENESIS
The exact mechanism of abnormal
trophoblastic invasion leading to PAS is
poorly understood. A previous insult to
the endometrial-myometrial interface,
which fails to limit trophoblastic invasion,
is the most accepted hypothesis.1,6
This
theory stems from the fact that multiple
uterine surgeries are one of the major risk
factors for PAS. However, PAS can rarely
happen in the absence of uterine surgeries,
which contradicts the simplicity of this
hypothesis.
Differential gene expression has been
reported in the literature in PAS patients.
DOC4, a gene involved in some cancer
progression, is 3 times more expressed in
invasive placentas compared with normal
placentas. Higher expression of the B2M
gene has also been demonstrated, which is
involved in the function of the MHC 1
complex, with potential immune modu-
lating function.15
That can be one of the
explanations for the exaggerated immune
tolerance to the invasive placenta. Differ-
ent genes have been reported to be either
up or downregulated in PAS patients,
with many of the upregulated genes being
associated with cellular proliferation and
tissue invasion, including COL17A1,
MMP12, and FSTL3.16
The mechanism
by which the expression of those genes is
altered is unknown.
GRADING
Traditionally PAS was graded into 3
categories, placenta accreta, increta, and
percreta. Increta refers to placenta
extending to deep myometrial tissue and
percreta refers to an extension to or
beyond uterine serosa. In 2019, a more
descriptive grading system was published
by FIGO, similar to oncologic gradings,
in an attempt to standardize how PAS is
400 Abdelwahab and Cackovic
www.clinicalobgyn.com

described and reported across different
centers. (Table 1).
Grade 1 is described as abnormal
invasion to deep decidual layers and
superficial myometrial layers without
deep myometrial invasion. Clinically, it
presents with failure to deliver the placen-
ta without obvious macroscopic features
of PAS at the time of laparotomy. Grade
2 is equivalent to the term increta, where
the placenta extends to deep myometrial
tissue but not to uterine serosa. Grade 3
involves an extension to the uterine serosa
(3a), urinary bladder (3b), or other pelvic
organs (3c).17
A recently published study supports
that the use of the FIGO classification
system at the time of laparotomy corre-
lates accurately with histopathological
examination.18
Supporting the use of
FIGO as a standard grading system
for PAS.
DIAGNOSIS OF PAS
Antenatal diagnosis of PAS is crucial to
optimize the management and reduce
maternal morbidity and mortality. How-
ever, the diagnosis remains challenging,
one-third to one-half of PAS patients are
not diagnosed antenatal, even in special-
ized obstetric imaging units.19–21
Two-dimensional ultrasonography
remains the primary tool for antenatal
detection of PAS. The sensitivity of
ultrasonography is reported as 90.7% in
the literature, with a specificity of
96.9%.22
There are several key ultrasound
findings that are suggestive of PAS, but
one specific sign/finding has not been
identified as diagnostic. The presence of
risk factors is one of the most important
indicators to diagnose PAS antenatally.
However, PAS can happen in the absence
of risk factors, and caution should be
taken for delivery planning once risk
factors have been identified. Despite
ultrasonography being the standard of
care for diagnosing PAS, considerable
interobserver variation in the inter-
pretation of the ultrasound images has
been reported.23
A standardized reporting
system has been suggested in the literature
to reduce interobserver variability.24
(Table 2).
Some of the ultrasound findings
include: Greyscale suggestive findings
include the loss of clear zone underneath
the placental bed, myometrial thinning
<1 mm, and abnormal placental lacunae
that are large or irregular. Findings
suggestive of extrauterine spread can
be seen too, including interruption of
the bladder wall and placental bulge into
surrounding organs (Fig. 1). Color Dop-
pler is also helpful in the diagnosis,
uterovesical hypervascularity, subpla-
cental hypervascularity, bridging vessels
with vessels running perpendicular in the
myometrium towards bladder or other
organs is very suggestive. (Fig. 2).1,24
The rail sign has been described in the
literature as a sign of deep villous
invasion. It is defined as 2 parallel neo-
vascularization over the uterovesical
junction connected by perpendicular
vessels.25
TABLE 1. PAS FIGO Grading
PAS Grade Histopathologic findings
Grade 1 Decidua absent between villi and myometrium with placental villi attached to the superficial
myometrium, without invasion of deep myometrium
Grade 2 Villi reaching deep myometrial tissue, occasionally reaching the lumen of deep uterine
vascular
Grade 3a Villi reaching to or extending beyond uterine serosa
Grade 3b Villi reaching the bladder wall or urothelium
Grade 3c Villi invading any other pelvic organ
Placenta Accreta Spectrum and Postpartum Hemorrhage 401

Three-D power Doppler might have a
role in the diagnosis of PAS as well and
has been reported in the literature to
improve the positive predictive value of
ultrasonography.26
It has been suggested
as a complementary technique to further
examine the placental bladder interface.
Two views have been suggested to eval-
uate the placental bladder interface,
including a lateral view and a basal view.
Signs that might help differentiate
between placenta previa and PAS on
those views include extreme hypervascu-
larity with chaotic branching with coher-
ent vessels fused into large vascular com-
plexes.27
Further studies are needed to
better understand the role of 3D power
Doppler to assist with diagnosis.
With the advancement of ultra-
sonography and the increased rate of
first-trimester anatomy, ultrasounds have
been performed. The role of first-trimester
ultrasonography in the detection of PAS is
increasing. The advantage of diagnosing
PAS in the first trimester is that it adds the
option of pregnancy termination to man-
agement options in patients who do not
desire to continue with pregnancy due to
increased risk of hysterectomy and mater-
nal morbidity and mortality. In women
with risk factors for PAS, suggestive ultra-
sound findings might be demonstrated as
early as the first trimester. Signs include
low implantation pregnancy, placental
lacunae, lower uterine segment hypervas-
cularity, myometrial thinning, and loss of
retroplacental clear zone.28,29
The role of MRI remains controversial
when it comes to the diagnosis of PAS.
Some experts recommend MRI whenever
extrauterine involvement is suspected on
ultrasound or in the event of unequivocal
findings rather than routine.30
Substantial
interobserver variability in reading signs
of PAS has been reported on MRI, with
overall lower sensitivity and specificity
than ultrasonography.31
Furthermore, a
study evaluated the utility of MRI as an
additional tool for patients with sugges-
tive ultrasound findings in PAS, and
found that infrequently MRI falsely
TABLE 2. Ultrasound Findings Suggestive
of PAS
Ultrasound findings suggestive of PAS
Loss of retroplacental translucent zone
Myometrial thinning <1 mm
Large irregular placental lacunae
Bladder wall interruption
Placental bulge
Uterovesical hypervascularity
Bridging perpendicular vessels travelling toward
the bladder
FIGURE 1. Interruption of the bladder wall with a placental bulge.

upgrades or downgrades the severity of
PAS.32
MANAGEMENT
The standard management of PAS in
most centers is through a cesarean hys-
terectomy. The recommended timing of
delivery in otherwise stable patients is
between 34w0d to 35w6d.1,33
This range
is recommended to avoid the onset of
labor in these patients and the need for
emergent unscheduled hysterectomy.
Improved outcomes have been reported
in scheduled cases of PAS when they are
performed at centers, with adequate
PAS volume and experience, so avoid-
ance of emergent delivery and referral to
appropriate centers with experience is
important. Multidisciplinary care for
PAS patients has shown to improve out-
comes with prior planning and discus-
sions across different services, particularly
for complication patients with PAS grade
3b or 3c.34,35
The components of the
multidisciplinary team should include
maternal-fetal medicine (MFM), an exp-
erienced pelvic surgeon, an anesthesiolo-
gist, a critical care specialist, a urologist,
an interventional radiologist, and blood
bank specialist.34
The role of each special-
ist should be identified before the case; in
many centers’ delivery is performed by
MFM or general obstetrician, and the
hysterectomy part is performed by the
gynecologic oncologist. However, it
depends on the expertise and experiences
of the individuals in every team; the
specialty of the physician performing
the hysterectomy is not as important as
the personal experience with performing
these complex cases, given the unique
pelvic anatomy and vascularity of PAS
patients.
Different techniques have been
described to minimize blood loss in cases
of PAS. Most important is to position the
hysterotomy away from the placental
bed, to avoid disruption of the placenta.
In cases where clear signs of the invasive
placenta are seen on entering the abdo-
men, manual removal of the placenta
should not be attempted as it can lead to
catastrophic hemorrhage. One technique
that has been described in the literature
involves creating an avascular hysteroto-
my using diathermy and stapler. This
technique is associated with 500 to 800
mL less blood loss.36
Another technique
to limit blood loss is deliberately create a
cystotomy with excision of the bladder in
cases where bladder invasion is suspected,
rather than bladder dissection, which is
often unsuccessful and can lead to a
significant increase in blood loss.34
FIGURE 2. Perpendicular vessels running towards the bladder.

The placement of preoperative ureteric
stents has been a controversial topic when
it comes to PAS patients. Some experts
advocate for ureteric stents in compli-
cated cases, where bladder invasion is
highly suspected.37
The goal of ureteric
stents is to aid with ureteric identification
in the event of distortion of pelvic anat-
omy or in cases where massive bleeding is
anticipated, where careful visualization of
the ureter might be challenging. However,
data regarding ureteric stents are mixed.
A systematic review of almost 300
patients did show a significant reduction
in unintentional urologic injuries.38
Other
studies have shown no benefit of
placement.39
However, since the place-
ment of ureteric stents is a low-risk
intervention, consideration for placement
is reasonable in complicated cases, and
preoperative cystoscopy might offer the
additional benefit of evaluating bladder
invasion before delivery.40
Another controversial topic is preoper-
ative internal iliac artery balloons. Hypo-
thetically, since most of the uterine blood
supply comes from the uterine artery,
which branches from the anterior division
of the internal iliac, occluding the internal
iliac should help minimize blood loss.
However, prominent aorto-iliac collater-
als are present in the pelvic vasculature, as
well as anastomosis with external iliac,
and those collaterals are exaggerated in
pregnancy and particularly in PAS cases.
A randomized controlled trial compared
patients with and without internal iliac
artery balloon occlusion and found no
difference in blood loss or the number of
transfused units.41
On the contrary, the resuscitative endo-
vascular balloon occlusion of the aorta
(REBOA) might be more promising. A
systematic review evaluated the use of
REBOA in over 300 patients and found
a significant reduction in blood loss with-
out related vascular complications.42
However, numerous REBOA complica-
tions have been reported in non-obstetric
literature including aortic dissection, rup-
ture, perforation, air emboli, and periph-
eral ischemia.43
Furthermore, rapid
access to REBOA and trained personnel
are not available in all centers.
EXPECTANT MANAGEMENT
Expectant management of PAS awaiting
spontaneous resolution and delayed hys-
terectomy has been gaining popularity in
the obstetric community. Expectant man-
agement is defined as leaving the placenta
in place either completely or partially
after delivery, with close follow-up until
complete resolution. Studies reporting the
outcomes after expectant management
are understandably limited. Complica-
tions with expectant management include
bleeding, infection, sepsis, and, less com-
monly, uterovesical fistula. The success of
expectant management depends on the
degree of PAS, with less success reported
with percreta than accreta or increta. The
overall success rate reported varies from
14% to 78%.44–46
Most common causes
for failed expectant management requir-
ing hysterectomy include either bleeding
or infection. A few cases of maternal
mortality have been reported secondary
to sepsis or uncontrollable hemo-
rrhage,44–46
which makes the decision of
expectant management challenging and
requires very detailed counseling and
close patient follow-up. Patients who
desire future fertility should be counseled
about the rate of recurrence of PAS,
which is estimated to be ~28%.47
The use of additional tools to aid with
placental absorption has been suggested
including arterial embolization and
methotrexate. Arterial embolization has
not been fully evaluated in PAS patients
to help with resorption but has been
suggested for patients with mild persistent
bleeding.48
However, no evidence to sug-
gest routine pelvic devascularization is
useful.44
Methotrexate has been suggested
by some experts to aid with placental
resorption.49
Given that methotrexate

inhibits rapidly dividing cells and the
trophoblasts are no longer rapidly divid-
ing after delivery, the benefit from its use
is questionable. A case of maternal mor-
tality was reported following methotrex-
ate administration post-delivery for PAS,
secondary to maternal sepsis and acute
kidney injury.44
Methotrexate is currently
not recommended to have a role in
expectant management for PAS.1,50
DELAYED HYSTERECTOMY
Delayed hysterectomy is becoming the
primary recommendation for the man-
agement of PAS patients in several cen-
ters across the United States. This
technique involves planning delivery at
34 to 35 weeks, mapping the placenta
intraoperative, and placing the uterine
incision away from the placental bed,
and then the placenta is left in place after
delivery. Hysterotomy is then closed, and
the hysterectomy is performed 4 to 6
weeks later. The hypothesis is to allow
for regression of the congested pelvic
vessels and involution of the uterus, so
the hysterectomy is associated with less
blood loss and maternal morbidities.48
The protocol that has been suggested
for delayed hysterectomy involves hospi-
tal admission for 7 days, with 72 hours of
broad-spectrum antibiotics, and daily
CBCs. Patients are discharged home with
close follow-up after this observation
period if there is no bleeding, signs of
infection, or elevated white blood cell
count. Patients are only discharged if they
live close to the hospital and have reliable
transportation to attend outpatient fol-
low-up appointments. Patients then
receive weekly outpatient visits, with a
hysterectomy planned 4 to 6 weeks later
after preoperative MRI.48
Delayed hys-
terectomy has been shown to be associ-
ated with less operative time, less blood
loss, and less transfusion of blood
products.48
The rate of unscheduled hys-
terectomy secondary to bleeding or infec-
tion before the scheduled delayed
hysterectomy date was estimated to be
23%, which is similar to patients opting
for expectant management.51
The surgical approach for delayed hys-
terectomy has traditionally been a lapa-
rotomy. However, recently minimally
invasive delayed hysterectomy techniques
have been described with encouraging
outcomes including less blood loss and
faster recovery.52
Care for PAS patients should be indi-
vidualized based on the grade of PAS,
expertise of providers, and patient wishes
for future fertility or uterus preservation.
Hysterectomy at the time of cesarean
delivery remains the most widely used
approach for the management of PAS
in most centers. However, in patients
where immediate hysterectomy carries
significant risks secondary to extensive
invasion, the approach of delayed hyster-
ectomy should be considered. Detailed
counseling before delivery is advised
in cases where extensive accreta’s are
suspected.
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