Keywords
umbilical artery - thrombosis - twin gestation - female fetus - histopathology
Introduction
Thrombosis of the umbilical cord vessels is rare. The incidence is ~1 for every 1300
deliveries, every 1000 perinatal autopsies, and 250 high-risk gestations. Male fetuses
are affected more commonly than females, the ratio being 1.6:1.[1] Venous thrombosis accounts for most cases (70%), followed by combined arterial and
venous thrombosis (20%). Arterial thrombosis alone is rare and accounts for 10% of
cases.[2] It can be associated with maternal conditions such as diabetes, protein S deficiency
of factor V Leiden mutation, and cord abnormalities such as long or short cord, hypercoiling,
true knots, marginal or velamentous insertion, loops around the body or cervical region,
and thin cord with less amount of Wharton’s jelly.[3] Intrauterine growth retardation (IUGR) is usually the presenting feature. During
the second trimester, the absence of flow signals during color Doppler performed at
the fetal bladder level can help detect umbilical artery thrombosis.[4] This condition calls for early delivery by cesarean section.[3] Gross and histopathological examinations are essential for the diagnosis of fibrin
clot within the lumen. They are associated with complications that are common in arterial
thrombosis than venous thrombosis.[5] The prognosis of umbilical artery thrombosis is poor, attributing to 80% of stillbirths
in babies with cord thrombosis.[1]
Herein, we present a case of thrombosis of both the umbilical arteries identified
during pathological examination of umbilical cord following the fetal demise in one
of the female fetuses of a 20-year-old primigravida, delivered at 35 weeks of gestation.
Case Report
A 20-year-old primigravida with twin gestation, at 35 weeks, and 5 days of gestation,
came for a routine antenatal check-up. Ultrasound scan of the abdomen and pelvis showed
that one of the twins had no cardiac activity, in breech presentation with overlapping
of skull bones with pleural effusion and ascites suggestive of intrauterine death.
In contrast, the other had a good cardiac activity with a cephalic presentation. The
mother had no history of hyperemesis gravidarum, bleeding per vaginum, or exposure
to radiation or teratogenic drugs and was neither hypertensive nor diabetic. She was
diagnosed with thyrotoxicosis and managed with propylthiouracil during the first 18
weeks of pregnancy and was currently euthyroid. She had complaints of pain abdomen
at 31 weeks, for which she was admitted with clinical suspicion of threatened preterm
and managed with tocolytics and steroids. The ultrasound abdomen was normal. She improved
symptomatically but was advised for a few more days of hospital stay for which the
patient refused. All the previous obstetric scans were unremarkable.
The emergency lower segment cesarean section was performed. The first amniotic sac
was ruptured from which straw-colored fluid was drained, and a dead female fetus was
delivered by breech extraction weighing 2 kg. The baby was macerated with peeled skin
and showed a positive Spalding sign. There were no external anomalies. Cord blood
could not be obtained. The second amniotic sac was ruptured from which clear and adequate
liquor was delivered. A live baby girl was delivered, weighing 2.32 kg. APGAR score
at first and fifth minutes was 9/10. Placenta and membranes were delivered in toto
and found to be dichorionic and diamniotic with a placental weight of 920 g. Placenta
with attached two umbilical cords was submitted for histopathological examination.
The specimen of the placenta measured 21 × 20.5 cx 6 cm, weighing 920 g with attached
two umbilical cords ([Fig. 1]). The umbilical cord, which belonged to the dead fetus, measured 29 cm in length
and 1.8 cm in diameter, with central insertion located at a distance of 6.5 cm from
the placental disc margin. No knots or pseudoknots were noted. The outer surface was
congested, dark brown, edematous, and hypocoiled. The umbilical cord cut surface showed
three vessels with the lumen of both arteries occluded by thrombus for a distance
of 7 cm at the proximal end ([Fig. 2A
]
[
B
]). Histopathology of the proximal end of larger and longer umbilical cord showed
an attached thrombus in both the umbilical arteries ([Fig. 3A]), with the tunica media showing scattered neutrophils ([Fig. 3B]). Mesenchymal tissue was edematous. The umbilical vein was unremarkable ([Fig. 3C]). Sections studied from dividing membranes showed focal fibrinoid necrosis, neutrophils
with denuded amnion, and chorionic epithelium with calcification ([Fig. 4]). Fetal surface of the placental disc belonging to stillborn fetus showed coagulation
necrosis, extensive intravillous fibrin with calcification, and crowding of villi
with increased syncytial knots ([Fig. 5]). The maternal surface showed focal areas showing calcification of decidual plate
with intravillous fibrin. Features were suggestive of thrombosis of both the umbilical
arteries with chronic maternovascular malperfusion and funisitis.
Fig. 1 Gross specimen of the placenta with attached two umbilical cords, one which is dark
brown, congested, and edematous (blue arrow) and other normal umbilical cord (red
arrow).
Fig. 2 (A) Cut surface of umbilical cord showing three vessels with the lumen of both arteries
occluded by a thrombus (arrow). (B) Closer view of the same, showing the thrombus (arrow).
Fig. 3 (A) Microscopy showing an attached thrombus in both umbilical arteries (arrows); (B) microscopy showing neutrophils in the vessel wall (arrow); (C) microscopy of the normal umbilical vein. Hematoxylin and eosin, 10x.
Fig. 4 Microscopy of membranes showing denuded epithelium with fibrinoid necrosis (arrow),
hematoxylin and eosin, 10x.
Fig. 5 Microscopy of the fetal surface of the placental disc of the dead baby showing extensive
intravillous fibrin (blue arrow) and calcification (red arrow), hematoxylin and eosin,
10x.
The other umbilical cord measured 24 cm in length and 1 cm in diameter with marginal
insertion. Coiling appeared to be normal. No knots and pseudoknots were noted. The
outer surface was pale white. Cut surface showed three vessels with a patent lumen.
Membranes appeared translucent. The rupture of membranes was marginal. The dividing
membrane was thick and opaque. The fetal surface of the placental disc was unremarkable.
The maternal surface showed cotyledons with few pale white areas.
The postoperative period was uneventful. Blood parameters and coagulation profile
were within normal limits.
Discussion
The umbilical cord helps in exchanging nutrition and oxygen between the mother and
the baby. It has two arteries that carry deoxygenated blood from fetus and one umbilical
vein that carries oxygenated blood to the fetus. Hence, umbilical vein thrombosis
can be lethal to the fetus.[6] Some of the common conditions affecting the umbilical cord are a single umbilical
artery, cord prolapse, vasa previa, and umbilical cord knots. Umbilical vessel thrombosis
is a rare condition, which can cause fetal hypoxia and, eventually, fetal death. Umbilical
vessel thrombosis is around 1.6 times more common in male fetuses.[1] Thrombosis of the umbilical vein is more common than arterial thrombosis.[2] In the present case, thrombosis of both umbilical arteries was noted in a female
fetus. There has been an association of umbilical vessel thrombosis with maternal
conditions such as diabetes, thrombophilic disorders such as protein S deficiency
or factor V Leiden mutation, and cord abnormalities such as the presence of a long
cord (> 70 cm) or short cord (< 35 cm), excessive twisting (> 0.3 cm/loop), reduced
diameter (< 8.0 mm), anomalous placental insertions, and presence of true knots and
loops.[3] Etiopathogenesis of umbilical vessel thrombosis may be explained by the Virchow’s
triad, which includes hypercoagulability, endothelial injury, and blood stasis. Hypercoagulability
may be due to inherited or acquired maternal or fetal thrombophilia. Endothelial injury
may be due to funisitis or meconium-induced vascular necrosis. Stasis of blood may
be caused by mechanical or anatomical obstruction.[6] In the present case, there was evidence of endothelial damage, causing funisitis
of umbilical arteries. There was no history of diabetes mellitus or hypercoagulability
in the mother or evidence of umbilical cord anomalies. Symptoms are usually those
of IUGR, and umbilical vessels' thrombosis should be suspected if no other cause of
IUGR can be determined.
In the present case, the patient had an episode of pain abdomen at 31 weeks, which
was suspected to be threatened preterm and was managed accordingly. The ultrasound
abdomen was normal. However, to evaluate further, the patient refused advice on further
stay at the hospital.
Prenatal diagnosis of umbilical artery thrombosis remains a clinical challenge with
minimal literature on umbilical artery thrombosis cases being diagnosed by ultrasound
examination. When one of the umbilical arteries is thrombosed, it is usually misdiagnosed
to be a single umbilical artery. This can be avoided by comparing it with earlier
ultrasound scans.[7] On color Doppler, “orange grabbed sign” is the characteristic finding seen in umbilical
artery thrombosis. The occluded artery and the normal artery are surrounded by the
uterine vein, which appears like “an orange grabbed by a hand.” The highly curving
“C-shaped” vein, which surrounds the arteries, may indicate hypercoiling of the umbilical
cord. This can help in the prenatal diagnosis and help in perinatal fetal management.[8] 7 Intrauterine death of one of the twin fetuses was diagnosed on ultrasonography
when performed at 35 weeks, 5 days during her routine antenatal visit.
Cord thrombosis is associated with many complications such as intrauterine death,
respiratory distress, skull abnormalities, and low birth weight.[5] Inducing fetal lung maturation by giving steroids after 34 weeks of gestation, early
delivery by cesarean section, and monitoring APGAR score can help manage fetuses with
umbilical vessel thrombosis.[3]
Grossly, the umbilical cord may be swollen and edematous with identifiable thrombi
on the cut surface. Histologically, in contrast to umbilical vein thrombosis, thrombotic
umbilical cord arteries show partial necrosis of the vessel wall, with the inner layer
being more commonly affected. Since the umbilical arteries lack vasa vasorum, oxygen
supply to the intima is provided by the blood flow, and to the outer layer by amniotic
fluid, thrombi occluding the lumen can cause necrosis of the inner layer with sparing
of the outer layer.[2] Since umbilical vessels have no vasa vasorum, thrombi are not organized, which leads
to necrosis and calcification within the thrombi.[4] In the present case, thrombus in both the umbilical arteries was evident on the
gross and microscopic examination, which may have been due to undetected maternofetal
infection (funisitis and chorioamnionitis), causing endothelial injury, as seen by
the presence of neutrophilic infiltrate in the arterial wall. Also, there was twin
gestation in the present case, resulting in external compression of cord by the other
fetus, resulting in the stasis of blood and thrombosis.
Hyrtl’s anastomosis, which is the anastomosis of two umbilical arteries, can be seen
in 90% of placentas. This anastomosis can prevent placental hypoxia and infarctions
caused by umbilical artery thrombosis.[9] In the present case, no Hyrtl’s anastomosis was found on histological examination.
Fetal surface of placental disc belonging to dead fetus showed features of chronic
maternovascular malperfusion.
Conclusion
Umbilical artery thrombosis is a rare condition and has a poor prognosis causing perinatal
morbidity and mortality. Usually, it is associated with many predisposing maternal
and umbilical cord factors but sometimes remains idiopathic. Prenatal detection of
umbilical artery thrombosis by ultrasound scan remains a challenge to the radiologists,
although using color Doppler may help diagnose it. There are chances that thrombus
may rapidly occur between antenatal visits. Hence, the antenatal visits must be closely
monitored in the third trimester, and any abnormalities should be managed as early
as possible to avoid adverse pregnancy outcomes.
