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Case Report

Subinvolution of the Placental Site

Ivan Petrovitch, MD, R. Brooke Jeffrey, MD,

Amy Heerema-McKenney, MD

S
ubinvolution of the placental site is characterized by the abnormal persistence of
low-resistance widely dilated uteroplacental arteries in the absence of substantial
amounts of retained products of conception. It is an important cause of sec-
ondary postpartum hemorrhage (PPH) that can result in considerable morbidity
and mortality. Sonographically, subinvolution of the placental site manifests as
increased vascularity within the myometrium in the location of the prior placental
implantation site with increased low-resistance flow. Methods for treating patients
with subinvolution of the placental site include conservative medical therapy, hys-
terectomy, and fertility-sparing percutaneous embolotherapy.

Case Report

A 36-year-old woman, gravida 1, para 1002, came to the

emergency department with vaginal bleeding, chills, and
light-headedness 10 days after cesarean delivery of twins
from an uneventful pregnancy. On the day of admission,
the patient reported severe intermittent abdominal pain
with 2 episodes of profuse vaginal bleeding in addition to
soaking 10 to 12 pads over a 12-hour period.
Abbreviations On physical examination in the emergency depart-
PPH, postpartum hemorrhage; PSV, peak systolic velocity ment, the abdomen was tender and firm, and there was
bloody vaginal discharge. The patient was tachycardic
with a blood pressure of 100/67 mm Hg and was afebrile.
Initial blood work revealed leukocytosis with a white
blood cell count of 16,900/µL and a hemoglobin level of
Received April 1, 2009, from the Departments of 11.4 g/dL. The patient was resuscitated with fluids and
Radiology (I.P., R.B.J.) and Pathology (A.H.-M.), given 2 U of packed red blood cells.
Stanford University Medical Center, Stanford,
California USA. Revision requested April 18, 2009. Sonography was performed with an Acuson Sequoia 512
Revised manuscript accepted for publication April system (Siemens Medical Solutions, Mountain View, CA)
21, 2009.
Address correspondence to Ivan Petrovitch, MD, and showed a heterogeneous mass measuring 14.6 × 9.2 ×
Department of Radiology, Stanford University 10.4 cm distending the endometrial cavity (Figure 1A).
Medical Center, 300 Pasteur Dr, H-1307, Stanford,
CA 94305-5105 USA.
There was no vascularity present within the echogenic
E-mail: [email protected] mass. There was substantial vascularity along the anterior

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Subinvolution of the Placental Site

Figure 1. A, Transabdominal sagittal image of the uterus show- endometrium with a prominent myometrial ves-
ing diffuse expansion of the endometrial cavity with a hetero- sel along the left anterior myometrium (Figure
geneous echogenic thrombus. An anechoic tubular structure
is shown along the anterior endometrial surface. B,
1B). On the anterior endometrial surface, a large
Transabdominal transverse image of the uterus showing a anechoic tubular vessel was present. Pulsed wave
prominent myometrial vessel extending to the endometrial sur- sonography of this structure showed a low-
face and supplying the venous varix along the endometrial
velocity monophasic waveform with a “yin-yang”
surface. C, Transabdominal sagittal spectral Doppler image of
the uterus showing both the yin-yang appearance present with- appearance within its lumen (Figure 1C). This
in the varix and sustained low-resistance increased flow through constellation of findings suggested subinvolution
the vessel. of the placental site with formation of a venous
varix, although retained products of conception
A
could not be excluded.
The patient was initially treated conservatively
in the emergency department with a trial of rec-
tal misoprostol because there was continued
vaginal bleeding. Another hemoglobin sample
was drawn, and the level had decreased to 8.2
g/dL. The patient remained tachycardic with a
blood pressure of 81/40 mm Hg. She was taken to
the operating room for emergent dilation and
curettage. In the operating room, a vaginal
speculum examination revealed vaginal bleed-
ing. Despite curettage of the endometrium and
placement of a Bakri balloon (Cook Medical Inc,
Bloomington, IN) clinically, it was decided that
B the patient had disseminated intravascular coag-
ulopathy. Percutaneous embolotherapy was con-
sidered; however, the patient was deemed
clinically unstable, and an emergent hysterecto-
my was performed. During the hysterectomy,
laboratory results confirmed that the patient had
disseminated intravascular coagulopathy with a
fibrinogen level of 84 mg/dL, a prothrombin time
of 22.4 seconds, a partial thromboplastin time of
46.2 seconds, an international normalized ratio
of 2.0, and a hemoglobin level of 6.7 g/dL. During
the procedure, the patient underwent aggressive
life-saving resuscitation, and a total of 6 U of
C packed red blood cells, 4 U of fresh frozen plas-
ma, and 2 U of packed platelets were adminis-
tered, in addition to 4 L of normal saline.
Pathologic gross evaluation of the uterus iden-
tified a large thrombus in the endometrial cavity
and large ectactic-appearing vessels within the
anterior myometrium. Microcsopic examination
of the myometrium beneath the placental
implantation site showed persistently patent
uteroplacental arteries with varying degrees of
thrombosis adjacent to normally involuted ves-
sels (Figure 2, A and B). The large-caliber vessels
showed scattered trophoblasts within the walls

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Petrovitch et al

with only minimal intimal proliferation (Figure ucts of conception, trauma to the lower genital
2C). Interestingly, ectasia of the uterine veins was tract, and congenital or acquired coagulopathy.
also present. A rare microscopic intravascular Primary PPH, especially due to uterine atony, is
collection of obliterated fibrous chorionic villi much more common and therefore is well
was identified; however, this was not extensive described. Secondary PPH occurs in only 1% of
enough to explain the hemorrhage. There was no pregnancies, and its causes include retained
evidence of placenta accreta or appreciable products of conception, endometritis, dehis-
chronic inflammation of the decidua. cence of a cesarean scar, subinvolution of the
placental implantation site, fibroids, and, less
Discussion commonly, malignancy such as choriocarcino-
ma.1–4 Subinvolution of the placental site is an
Postpartum hemorrhage is a major cause of important entity to consider in patients with
maternal mortality. It is commonly divided into PPH because it can be associated with life-
primary and secondary subtypes. Primary PPH is threatening hemorrhage.
defined as hemorrhage occurring within the first The diagnosis of subinvolution of the placental
24 hours postpartum, whereas secondary PPH is site is under-recognized, partly because of the
defined as hemorrhage occurring from 24 hours fact that a pathologic specimen is required to
to up to 6 weeks postpartum. The causes of pri- confirm the diagnosis. The diagnosis is con-
mary PPH include uterine atony, retained prod- firmed histologically when large uteroplacental

Figure 2. A, Subinvolution of uteroplacental arteries in the pla-

A
cental site myometrium. This low-power image of the anterior
myometrium deep to the placental bed displays an abnormally
ectactic vein (white arrow), normally involuted uteroplacental
arteries (black arrow), and a persistently patent uteroplacental
artery (arrowhead) (hematoxylin-eosin, original magnification
×10). B, Subinvolution of uteroplacental arteries and architectural
disruption of the vascular wall. The uteroplacental artery under-
goes physiologic remodeling during pregnancy by invasive extra-
villous cytotrophoblasts. In this persistently patent vessel, disrup-
tion of the internal elastic lamina is shown, with variable intimal
proliferation (elastin von Giesson, original magnification ×40). C,
Subinvolution of uteroplacental arteries and persistence of associ-
ated cytotrophoblasts. An immunohistochemical stain for cytok-
eratin identifies numerous trophoblasts both within the intima
and in the modified vessel wall (anticytokeratin antibody mixture
[AE1/AE3, Dako, Carpinteria, CA; and cell adhesion molecule 5.2,
Becton-Dickinson, Burlingame, NC], original magnification ×400).

B C

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Subinvolution of the Placental Site

arteries that were modified for pregnancy by the will confirm the vascular characteristics of an
extravillous trophoblasts remain patent past the increased peak systolic velocity (PSV) with a low-
immediate postpartum period, failing to under- resistance waveform. Correlation has also
go the normal process of involution. The inci- shown that these increased areas of vascularity
dence of PPH from subinvolution is greatest in correlate with the placental implantation site
the second week postpartum.5 documented on second- or third-trimester
During normal pregnancy, the extravillous sonography.7 These lesions are not always easily
trophoblasts migrate in a retrograde fashion differentiated from either congenital or acquired
along the uteroplacental arteries, replacing the true arteriovenous malformations, although
endothelial layer and causing vascular remodel- arteriovenous malformations are described as
ing with destruction of the musculoelastic medi- high-flow uterine vascular malformations as
al tissues of the arteries and the deposition of opposed to subinvolution, which is described as
hyaline fibrinoid material.5,6 This results in a low-flow uterine vascular malformation.4,8
increased flow to meet the physiologic demands Additionally, retained products of conception
of the fetus. During the third trimester, there is re- may mimic these findings and should be includ-
endothelialization of the uteroplacental vessels ed in the differential diagnosis when echogenic
with a disappearance of the trophoblasts and tissue is present within the endometrial cavity.
regeneration of the elastic media. After delivery, In the normal postpartum uterus, it has been
there is necrosis and sloughing of the decidua observed that uterine vessels will have a PSV of
and superficial endometrium, which completes 0.22 m/s 3 days after delivery and will drop to
the normal involution of the uterus. In subinvo- 0.10 m/s after 6 weeks.4 There has been research
lution of the placental implantation site, the nor- to suggest that an elevated PSV within vascular
mal remodeling of the vessels during the third lesions of greater than 0.83 m/s poses a sub-
trimester is either delayed or inadequate, and the stantial threat of hemorrhage, whereas patients
uterus fails to revert to the nonpregnant state.6 with a PSV of less than 0.83 m/s remain at risk,
The result is the persistence of low-resistance and patients with a PSV of less than 0.39 m/s
dilated vessels with increased flow. may be safe for conservative management in the
Histologically, subinvoluted vessels are charac- absence of symptoms.9 However, other studies
terized as large dilated vessels often filled with red have shown that some lesions with elevated PSVs
blood cells and thrombi of varying chronicity. The may resolve spontaneously with conservative
walls of the vessels show deposition of hyaline management.10
replacing the elastic fibers and the media. The management of subinvolution of the pla-
Subinvoluted vessels are typically found adjacent cental site with bleeding in symptomatic patients
to one another within the placental bed of the remains controversial. Conservative manage-
myometrium and are commonly found adjacent ment with vaginal packing and uterotonic drugs
to normally involuted vessels. Periodic acid-Schiff may be attempted; however, more aggressive
and tissue elastin stains highlight the disrupted treatments such as ligation of the uterine vessels
vascular architecture of the persistently patent and hysterectomy are considered standard ther-
vessels.5 Immunohistochemical analysis with apies.4,11 There is a large body of literature that
antibodies to low-molecular-weight cytokeratin, supports the use of percutaneous embolothera-
inhibin α, melanoma cell adhesion molecule, and py of the uterine arteries to treat subinvolu-
human placental lactogen identifies residual tro- tion.4,12,13 Furthermore, fertility may be retained
phoblasts within the abnormal vessel walls.6 after selective arterial embolization.12 After per-
The sonographic diagnosis of subinvolution of cutaneous therapy has failed, hysterectomy
the placental site is made through visualizing the should be considered.
low-resistance vessels present along the inner Subinvolution of the placental bed is an impor-
third of the myometrium in the appropriate clin- tant diagnostic consideration in the female
ical setting. Grey scale imaging will typically patient with delayed PPH. The diagnosis should
show hypoechoic tortuous vessels within the be considered in patients with sonographic char-
myometrium. Pulsed wave Doppler sonography acteristics of increased myometrial vascularity

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Petrovitch et al

showing low resistance. Alternatives that should 13. American College of Obstetricians and Gynecologists.
ACOG Practice Bulletin. Clinical management guidelines
also be included in the differential diagnosis
for obstetrician-gynecologists number 76, October 2006:
include retained products of conception and the postpartum hemorrhage. Obstet Gynecol 2006; 108:
more rare uterine arteriovenous malformations. 1039–1047.
Treatment with percutaneous embolotherapy
may be useful in providing hemostasis while
retaining future fertility.

References

1. Biko DM, Spanier JF, Nagamine M, Dwyer-Joyce L, Ball DS.

Persistent secondary postpartum hemorrhage after uterine
artery embolization. J Vasc Interv Radiol 2008; 20:
279–281.

2. Khong TY, Khong TK. Delayed postpartum hemorrhage: a

morphologic study of causes and their relation to other
pregnancy disorders. Obstet Gynecol 1993; 82:17–22.

3. Lausman AY, Ellis CA, Beecroft JR, Simons M, Shapiro JL. A

rare etiology of delayed postpartum hemorrhage. J Obstet
Gynaecol Can 2008; 30:239–243.

4. Maleux G, Timmerman D, Heye S, Wilms G. Acquired uter-

ine vascular malformations: radiological and clinical out-
come after transcatheter embolotherapy. Eur Radiol 2006;
16:299–306.

5. Andrew AC, Bulmer JN, Wells M, Morrison L, Buckley CH.

Subinvolution of the uteroplacental arteries in the human
placental bed. Histopathology 1989; 15:395–405.

6. Weydert JA, Benda JA. Subinvolution of the placental site

as an anatomic cause of postpartum uterine bleeding: a
review. Arch Pathol Lab Med 2006; 130:1538–1542.

7. Van Schoubroeck D, Van den Bosch T, Scharpe K, Lu C,

Van Huffel S, Timmerman D. Prospective evaluation of
blood flow in the myometrium and uterine arteries in the
puerperium. Ultrasound Obstet Gynecol 2004; 23:378–
381.

8. Timmerman D, Van den Bosch T, Peeraer K, et al. Vascular

malformations in the uterus: ultrasonographic diagnosis
and conservative management. Eur J Obstet Gynecol
Reprod Biol 2000; 92:171–178.

9. Timmerman D, Wauters J, Van Calenbergh S, et al. Color

Doppler imaging is a valuable tool for the diagnosis and
management of uterine vascular malformations.
Ultrasound Obstet Gynecol 2003; 21:570–577.

10. Dar P, Karmin I, Einstein MH. Arteriovenous malformations

of the uterus: long-term follow-up. Gynecol Obstet Invest
2008; 66:157–161.

11. Cheng YY, Hwang JI, Hung SW, et al. Angiographic

embolization for emergent and prophylactic management
of obstetric hemorrhage: a four-year experience. J Chin
Med Assoc 2003; 66:727–734.

12. Chauleur C, Fanget C, Tourne G, Levy R, Larchez C, Seffert

P. Serious primary post-partum hemorrhage, arterial
embolization and future fertility: a retrospective study of
46 cases. Hum Reprod 2008; 23:1553–1559.

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