practice placccc .pdf

À propos / Télécharger Aperçu
Nom original: practice placccc.pdf
Titre: Placental Thrombi and Other Vascular Lesions: Classification, Morphology, and Clinical Correlations
Auteur: S.C. Rayne

Ce document au format PDF 1.7 a été généré par Elsevier / , et a été envoyé sur le 14/01/2015 à 12:23, depuis l'adresse IP 41.142.x.x. La présente page de téléchargement du fichier a été vue 785 fois.
Taille du document: 8.5 Mo (16 pages).
Confidentialité: fichier public

Aperçu du document

Path. Res. Pract. 189,2-17 (1993)

Diagnostic Seminar

Placental Thrombi and Other Vascular Lesions
Classification, Morphology, and Clinical Correlations

s. C.

Rayne and F. T. Kraus

Department of Pathology, St. John's Mercy Medical Center, St. Louis, Missouri, USA

Vascular lesions, most often mediated by thrombi, are second only to infections as a cause
of fetal injury in the later weeks of pregnancy. In our experience many pathologists who
examine placentas fail to conduct a proper search for vascular lesions and some even fail to
recognize those exposed by their examination.
This review is intended to define the typical clinical background or circumstances that
suggest the presence of siginificant vascular problems, to define techniques calculated to
display them well, and to identify criteria for diagnosis. Further research is needed to
evaluate the prevalence of maternal and fetal hypercoagulable states and thrombi as a
cause fetal injury.


The developing fetus depends wholly upon the placenta
for growth and survival. Apart from genetically determined diseases, many problems that interfere with growth
and survival of the fetus do so by injuring the placenta or
membranes first. The two major categories of placental
injury are inflammation, mostly due to infections, and
vascular problems, mostly mediated by thrombi and
disorders of development. This review is concerned with
the problem of recognizing placental vascular lesions that
cause fetal injury or death.
The search for significant placental lesions begins with a
consideration of clinical information about the fetus.
While genetically determined problems are usually made
apparent in the first trimester by absence of a fetus,
deformities of the fetus, or the presence of hydropic
placental villi, both infectious and many vascular lesions
are usually made apparent by symptoms in the mother,
often in the third trimester.
We believe that an informative placental examination
requires prior knowledge of any medical problems identified during the course of the pregnancy. Fever may suggest
an infectious etiology; circulatory problems are implicated
by the occurrence (in a prior pregnancy) of fetal death in

utero, small size of placenta for gestational age, intrauterine growth retardation (IUGR), thrombotic events suggestive of maternal coagulopathy, and pregnancy-induced
hypertension (toxemia of pregnancy) with or without
If the clinical features do not suggest specific causes, the
gross examination and histologic sampling of the placenta
should be directed in a systematic way so that important
lesions are not overlooked.
Gross Examination
The state of maternal as well as fetal vascular components must be evaluated specifically. The spiral arteries
which reflect the final stage in the maternal vascular supply
to the placenta are often directly involved in placental
ischemic processes13, 16. Fetal vessels are easily identified
and any placental section will include them. The intervillous space, an extension of the maternal vascular system, is
also invariably sampled by any section of placenta. The
spiral arteries which supply the placenta itself are less
easily identified and are almost never included in a random
section. Finding spiral arteries can be difficult. This
difficulty is compounded in those cases of pre-eclampsia in
© 1993 by Gustav Fischer Verlag, Stuttgart

Placental Thrombi and Other Vascular Lesions· 3

which these vessels are often abnormally small or narrowed by organized thrombus. A conscientious pathologist, frustrated by the time consumed in his search, easily
concludes that their numbers are reduced in toxemia and
other conditions causing ischemia. Wigglesworth 66 prescribes squeezing the placenta to fill these spiral arteries by
retrograde filling, a method which does not work consistently in our hands. Plastoid injections 26 display these
relationships beautifully, but this approach is not practical
for routine pathological study.
We advocate a technique which is facilitated by letting
the placenta fix in 10% neutral formalin overnight after
the placenta has been examined, trimmed, and sliced. On
the maternal surface, the spiral arteries appear as small
dimples which tend to be located toward the center of the
cotyledon (lobule). The region occupied by a normal spiral
artery is evident on cut section of the decidual surface
where several small flattened channels 0.5 to 1 mm in

diameter appear in a small clusters (Figs. 1 and 2). If they
have been recently thrombosed, a distinctly abnormal
finding, they may stand out as small, red, dome-shaped
lesions, which on cut section appear as small thrombosed
vessels. A more tedious but consistently successful technique is to slice the decidual layer overlying the fixed
maternal surface near the center of a cotyledon with a
scalpel at 2 mm intervals until a small vascular space or
cluster of spaces is found.
Placental Thrombotic Lesions in Specific Pathologic
Maternal Circulation

Thromboembolic disease is a major complication when
it occurs in pregnancy; this risk is increased in pregnant
and postpartum women with deficiencies of protein

Table 1. Clinical and pathological findings in placentas associated with maternal coagulopathies


Placental pathology

Gestational age Treatment

Obstetrical history

Medical history

No 1,

Protein C

Hemorrhagic endovasculitis
Hypoplasia - 180 gm
Mural thrombi - spiral artery

31 weeks


Fetal demise

Severe headaches during

Organizing mural spiral artery

37 weeks

Heparin and

Healthy infant

Central retinal artery

G02Pl; Intrauterine growth

History of thrombophlebitis; other baby has cerebral palsy

No 2,

Protein C

Maternal floor infarct

36 weeks


No 3,

Protein C

Spiral artery thrombi - multiple

37 weeks

Heparin Aspirin Previous spontaneous abortions
(low dose)

No 4,

No 5,

Protein S

History of pelvic vein
thrombosis and pulmonaryembolism

Healthy infant
Organizing spiral artery thrombi

36 weeks


Fetal demise

Hypoplasia - 240 gm

Lupus Anticoagulant

Chorangiosis; villous edema;
mural spiral artery thombosis;
Hypoplasia - 250 gm

31 weeks

Infarcts - multiple; Acute

31 weeks



Spiral artery thrombosis extensive; Decidual necrosis

16 weeks


G4PIS2 with fetal demise at
26 + 31 weeks

Fetal distress with emergency


No 6,

Lupus Anticoagulant

Spiral artery thrombosis;
decidual necrosis; infarcts

24 weeks


Fetal demise

No 7,


Spiral artery thrombosis; multipie; Infarcts - Multiple Fetal
vessel thrombosis; Accelerated

22 weeks


Intrauterine growth retardation

Acute spiral artery thrombosis,
extensive; Infarcts - multiple,
Infarcts - multiple, acute

37 weeks


IUGR; Acute fetal distress with
Acute promyelocytic leudecreased utero - placental flow. kemia (in remission)
Emergency C-Section

+ VORl

(false +)
+ anticardiolipin antibody
No 8,



G02Pl = Gravida'O, Para 2, Abortions 1; G6POA5 = Gravida 6, Para 0, Abortions 5; GIPOABO = Gravida 1, Para 0, Abortions 0; HELLP = Hemolysis, Elevated
LIver enzymes, Low Platelet count; IUGR = Intrauterine growth retardation.

Placental Thrombi and Other Vascular Lesions · 5

C12, 18,19,60, ProteinS 17,19,47, antithrombin II114,18,21 or
with circulating antiphospholipid antibodies 34 . Recurrent
pregnancy loss is a well described complication of the
antiphospholipid antibody (lupus anticoagulant) syndrome 9, 11,20,23,59 but also occurs in other coagulation
disorders in our experience (see below). Although the
pathologic alterations involving the placenta in patients
with lupus anticoagulant have been described elsewhere in
the literature 8, 10, 15,22,57, no documented cases of placental
pathology have been recorded in patients with the other
defective clotting mechanisms listed above. Our experience with placentas from patients with various coagulopathies is summarized in Table 1. We have studied placentas
from 3 patients with Protein C deficiency, 1 with Protein S
deficiency, 2 with lupus anticoagulant, 1 with the HELLP
syndrome62 and 1 with intravascular coagulation associated with promyelocytic leukemia (in remission).
Lesions vary in appearance but common to all these
placentas were maternal spiral artery thrombi presumably
related to the underlying hypercoagulable state. Acutely
thrombosed spiral arteries (Figs. 3 and 4), organized spiral
artery thrombosis (Figs. 5 and 6), decidual necrosis, and
infarcts were common findings and were more extensive in
untreated patients. Hypoplasia (decreased weight for
gestational age) and accelerated maturation were present
in some cases, suggesting an abnormal, decreased uteroplacental blood flow.
Patients 3 and 5 each had multiple miscarriages with late
second and early third trimester fetal demise. This type of
clinical history is typical of patients with the lupus
anticoagulant8 but it seems clear that other coagulopathies
deserve consideration in this clinical situation. In fact, the
prominent placental thrombi accompanied by third trimester fetal demise prompted the laboratory studies that
established a diagnosis of Protein C and S deficiencies in
patients 1 and 4. Catastrophic thrombosis in the affected
newborn may involve large vessels, including aorta and
vena cava52 ,5S. Subsequent pregnancies have been managed successfully after treatment with low doses of aspirin
or heparin. Unexplained intrauterine growth retardation
that complicated several of the pregnancies probably
reflects maternal vascular compromise caused by thrombi.

Fetal Circulation: Fetal Stem Artery Thrombosis
The importance of detecting thrombosed fetal vessels in
the placenta lies in the potential for occurrence of thrombi
or emboli in the fetus. This becomes most significant in


Fig. 5. Multiple spiral artery thrombi and infarcts were present in
this placenta from a 37 week gestation. This pregnancy was
complicated by pre-eclampsia and protein C deficiency. The
woman had had 5 previous spontaneous abortions, but responded favorably this time to treatment with heparin and aspirin.
Depicted is an organizing spiral artery thrombus. The baby
survived without complications. H & E, 90 x.

babies with brain injury. Most of the standard texts and
references do not deal with the significance of this lesion in
relation to the fetal complications and coagulation disorders2S,32. Fox, for instance, minimizes the importance of
thrombi when they are focal because small lesions are not
likely to diminish the physiologic vascular reserve to a
significant degree when fetal artery thrombosis is not
extensive. However, as noted by Benirschke 8 and Gruen-

Fig. 1. A normal spiral artery. Both the muscular and elastic tissue of the vessel wall have been replaced by amorphous eosinophilic
material. The lumen is dilated and the endothelial lining has been replaced by intermediate trophoblasts. H & E, 45 x. - Fig. 2. Gross
photograph depicting a section taken perpendicular to and including the maternal surface of a normal term placenta. Arrow shows a
cross-section of a spiral artery (3 x). - Fig. 3. Acute spiral artery thrombus at 38 weeks in a patient with promyelocytic leukemia (FAB
classification: AML-M 3) in complete remission. These thrombosed vessels were easily visualized on gross examination. Normal
uterolplacental blood flow was documented by Doppler technique 48 hours before delivery, but a sudden decrease in fetal movements
and fetal blood flow prompted immediate delivery of an acidotic and hypoxic infant who survived. H & E, 40x. - Fig. 4. One of
several thrombosed spiral arteries (upper portion of this photograph) from a 16 year old woman with circulating lupus anticoagulant.
The fetus was stillborn. H & E, 33 x .

6 . S. C. Rayne and F. T. Kraus

wald 29 , the clinical significance of these lesions, even when
they are small, lies in their potential importance as
indicators of thrombi as the possible cause of lesions
elsewhere in the symptomatic fetus or neonate. Their very
existence establishes that a thrombotic event has occurred
in the fetal circulation, and in this setting other thrombi
may be reasonably proposed as a potential explanation for
important clinical problems. At the very least, thrombi in
fetal placental vessels confirm the occurrence of thrombi in

the fetal circulation as a presumptive cause for such
clinically evident lesions in the newborn as brain injury
which could be related to infarction. When possible, the
basis for a possible hypercoagulable state in the fetus
should be investigated by appropriate coagulation tests on
neonatal blood.
Fetal artery thromboses may affect vessels at any level of
the vascular tree from the umbilical cord to the villous
capillaries 8 • Large vessel thrombi, including those in the

Fig. 6. Organizing spiral
artery thrombus, one of several in this placenta from a
patient with untreated Protein S deficiency at 36
weeks. The placental weight
was well below the tenth
percentile for this gestational age. Fetal demise occurred 2 days prior to delivery.

Fig. 7. Placental villi affected by fetal stem artery
thrombosis. Fibrotic avascular villi (right side) contrast sharply with the well
vascularized villi (left side)
in a term infant. Decreased
fetal activity was noted for 2
days before delivery. The
infant was acidotic with
Apgars of 3 and 7 at birth.
Seizures developed shortly
after birth. This finding often indicates fetal stem artery
thrombosis several days or
weeks prior to delivery in
our experience (See Fig. 8).
H &E, 122x.

Placental Thrombi and Other Vascular Lesions· 7

cord or surface vessels, may be recognized grossly and are
most easily detected when the vessel is enlarged and
distended. Thrombi in umbilical vessels are known to
occur in velamentous insertions, severe inflammatory
reactions, varices and with mechanical compression (e.g.
umbilical cord knots, amniotic bands, etc.). In our experience fetal stem artery thrombi have been associated with
disseminated intravascular coagulation, cerebral palsy and
fetal demise.
Small vessel thrombi involving the stem vessels and their
distal vascular tree may accompany or occur independently of large vessel disease. These are microscopic lesions that
are typically manifested by discrete clusters of fibrotic,
avascular villi reflecting proximal vessel occlusion (Fig. 7).
In our experience a corresponding proximal stem artery
occlusion is often evident (Figs. 8 and 9), but may not
appear in the same histologic section depending on the
plane of section. Mural thrombi may produce a so-called
endothelial "cushion", when partly organized3 (Fig. 10).
Vascular changes caused by thrombi are similar to and
must be distinguished from, the regressive vascular alterations associated with intrauterine fetal demise. In general,

Fig. 9. Recanalized fetal stem vessel thrombosis from placenta of
the liveborn infant described in Fig. 7.

Fig. 8. Proximal fetal stem vessel thrombosis in the placenta
described in Fig. 6. Note multiple recanalized lumina signifying
an organizing process probably occurring several days prior to
delivery. H & E, lS0x.

intrauterine fetal death results in a generalized, progressive
fibromuscular sclerosis in response to the cessation of fetal
blood flow through all placental vessels 24,28,65. Ultimately
the vessels become totally fibrotic and disappear. All
vessels of comparable size are likely to be affected in a
similar manner. The smaller vessels are altered earlier, and
are the first to disappear. The sharp contrast between
well-vascularized villi in the functioning placenta and
adjacent clustered avascular villi resulting from a localized
stem artery thrombus should be easily distinguished from
the diffuse regressive changes in a placenta following
intrauterine fetal death. In our opinion the presence of
multiple channels of recanalization in an organizing
thrombus implies that the thrombus occurred while the
fetus was alive, and suggests that abnormal coagulation
should be considered as a potential etiologic factor even
when fetal death has occurred in utero.
Chronic villitis may also produce fibrotic, avascular villi
but chronic inflammatory changes are consistently present
in the background and the affected villi are usually
adherent to each other. Healed foci of chronic villitis will
also produce a cluster of fibrotic avascular villi, in some
cases as a result of focal lesions caused by cytomegalic
inclusion disease. The inclusions are no longer evident in
this chronic state.

8 . S. C. Rayne and F. T. Kraus

Fig. 10. The presence of an
intimal fibrin "cushion" lesion indicates an organizing
mural thrombus in a fetal
H & E,
x 122.

Vessel thromboses are significant regardless of their
etiology. We have seen them in association with fetal
septicemia with disseminated intravascular coagulation,
chorioamnionitis, vascular malformations and in mothers
with coagulation disorders (e.g. positive anticardiolopin
antibodies, HELLP syndrome and Protein C deficiency). In
many instances a specific etiology has not been identified.

Nevertheless, the consequences may be severe, resulting in
brain damage or death.

"Hemorrhagic Endovasculitis"
As originally defined by Sander in 1980 49 ,50 this lesion in
chorionic villi is characterized by obliteration of the villous

Fig. 11. Pattern of hemorrhagic endovasculitis produced by fetal stem vessel
thrombosis. H & E, 90x.
Inset: Same placenta showing typical villous histology
of hemorrhagic endovasculitis. Most of the terminal
villi have stromal hemorrhage with extravsated red
cell fragments and nuclear
debris. H & E, 120 x.

Placental Thrombi and Other Vascular Lesions . 9

capillaries, thrombosis, and variable degrees of extravasation of erythrocytes into the villous stroma (Fig. 11).
Larger vessels may be similarly affected by thrombi with
diapedesis of red cells. Because there is no inflammation or
direct evidence of infection or other injurious agent, the
term "endovasculitis" may have been unfortunate. Since
the same changes are believed to occur in fetal vessels as a
regressive phenomenon after fetal death in utero, regardless of the cause, HEV is currently regarded by many as a
non-specific alteration8. As a focal lesion in the placenta of
a liveborn infant it strongly suggests the presence of a
thrombus in fetal vessels proximal to the domain of the
affected villi. In these circumstances it is not triviaPl,51,54
and should stimulate a search for thrombi in the placental
vascular tree and a careful evaluation of the infant.
As a diffuse, generalized alteration in the vasculature of
the placenta of a dead-born infant, hemorrhagic endovasculitis is most likely a nonspecific regressive change. In any
case the possibility of some form of hypercoagulable state
deserves thoughtful consideration and should be the basis
for an evaluation of the mother or both parents for
coagulopathy (presumably inherited homozygously by the
fetus) if no other explanation can be found for intrauterine
fetal death.
The Placenta in Pregnancy-induced Hypertension
(PIH): Toxemia, Eclampsia, Infarcts, and Hematomas
In current clinical parlance the term Pregnancy-Induced
Hypertension (PIH) has supplanted Toxemia of Pregnancy
and Eclampsia; the meanings are identical. The principal
lesions as found on placental examination have been very
well described8, 39, 43. These include distinctive changes in
the maternal vascular component of the placenta: spiral
artery "atherosis", narrowing, necrosis, and thrombosis 45 ,46; infarcts, old and recent39 , 64 abruption 7 ; and more
acute potentially reversible ischemic reactive changes such
as villous congestion and trophoblastic "knots" as originally described by Tenney and Parker58 .
In our experience pathologists have no difficulty recognizing spiral artery lesions when they see them; the
problem is that they are usually not demonstrated in the
typical "standard" placental examination, first because
the pathologist has no patient historical data anfl therefore
does not look for spiral arteries, and second because spiral
arteries are not easy to find and most pathologists do not
know how to look for them. Our goal in this review is to
correct this latter problem by describing how and where to
look and by showing what a pathologist can find when the
examination is conducted properly.
Our basic approach to finding spiral arteries has been
described above under "Gross examination". A clinical
history of low birth weight or hypertension should be the
basis for initiating the search, especially when the hypertension is very severe or is associated with convulsions
(eclampsia). Promising gross findings include a tiny cluster
of congested vessels within the decidua, usually impacted
with clotted blood. However, narrow spiral arteries with
adherent mural thrombi, mural necrosis, and scattered

Fig. 12. Acute atherosis in a patient with severe pregnancyinduced hypertension, thrombocytopenia, and intrauterine
growth retardation. Both the infant and the placenta were small
for gestational age. The spiral artery wall (at top) has undergone
extensive fibrinoid necrosis and contains foam cells. Gestational
age was 36 weeks; the small size of the villi suggests a mature or
hypermature pattern called "accelerated maturation" (see text).

H& E, 40x.

foamy cells (acute atherosis) are just as important, but are
virtually invisible to the unaided eye. In these circumstances we have found it necessary to increase the number
of random blocks cut from the maternal surface of the
placenta. If the process has been chronic the placental
weight may be low, less than the 10th percentile as judged
by comparison with standard growth curves made by
plotting the weight against gestational age 41 ,42. In histologic sections the villi of a premature placenta may look
inordinately mature because they are very small and
narrow with reduced branching of stem villi, a feature that
has been called "accelerated maturation" 48. This pattern
may occur normally in areas near the chorionic plate, but
has greater significance when it is seen near the maternal
floor 8 or 10 weeks prior to term (Fig. 12).
Vasculopathy of spiral arteries appears to have a
significant relationship to low birth weight with or without
hypertension. The lesions typically resemble the acute

10 . S. C. Rayne and F. T. Kraus

Fig. 13. Organizing spiral
artery thrombosis in a patient with HELLP syndrome
(Hemolysis, Elevated Liver
count) 62. H & E, 26x.

atherosis of toxemia, with variable degrees of inflammation 1•
Extensive thrombosis in a spiral artery may be very
prominent, both grossly and microscopically (Fig. 13);
reactive ischemic changes (trophoblastic knots) and
infarcts both old and recent are commonly found in the
overlying placenta. There seems to be a clear relationship
between PIH and infarcts 13 .
Early infarcts are most easily identified after fixation;
although similar in appearance to the surrounding parenchyma they are distinguished by their slightly indurated
texture, and may be slightly darker than the surrounding
tissues due to local congestion of villous capillaries. Older
lesions become pale. Well-established infarcts are firm
with a creamy yellow color. Important features to note are
the size, location, and extent of involvement35 , 42. Small
peripheral infarcts are common and if confined to the
placental margins, have less clinical significance. Infarcts
consistently have a granular cut surface reflecting the
presence of villi, while hematomas appear glossy and
smooth. Intraplacental hematomas usually have a laminated appearance which can be appreciated on gross
inspection. Like infarcts they are red if recent and become
yellow when they are older.
Infarcts are well described in many texts and need not be
illustrated here. Intraplacental thrombi often start at the
basal plate area, apparently by propagation from a
thrombus in a decidual vessel which may be either a vein or
spiral artery; frequently the vessel wall is so disrupted that
distinction between vein and artery is not possible.
Small intra placental hematomas are common and seem
to have little clinical significance. Large ones do occur
(so-called Breus' mole or "massive subchorial thrombohe-

matoma") with catastrophic results 53 . The basic etiology
remains unexplained.
Abruption begins as hemorrhage into the decidua. The
resulting hematoma results in partial or less frequently,
extensive or complete separation of the placenta from the
uterine wall. Localized decidual hematomas compress the
overlying placenta very obviously, but they can easily be
overlooked if closely spaced (no more than 1 em) crosssections of the placenta are not examined carefully.

Structural Abnormalities of Fetal Blood Vessels

Intramembranous vessels: Velamentous Insertion of
Cord; Succenturiate Lobe
Intravelamentous vessels lack the cushioning effect of
Wharton's jelly and are therefore more easily compressed,
especially when situated low in the pelvis, resulting in stasis
and injury.
They therefore ultimately may have a greater predilection for stasis and injury resulting in thrombosis. The usual
membrane roll can easily be oriented to include cross
sections of intramembranous vessels. The intramembranous vessels of the placenta in Fig. 14 contained mural
thrombi which were highly significant because the infant
had severe central nervous system injury apparently
related to cerebrovascular thrombi and infarcts. Clusters
of avascular villi were prominent in multiple areas of this
placenta (Fig. 15) indicating multiple thromboembolic
events in the fetal circulation. In this situation, it is possible
to substantiate the notion that management of the delivery

Placental Thrombi and Other Vascular Lesions . 11

Fig. 14. Organizing fetal vessel thrombosis in the membranous
vessels supplying a succenturiate lobe. This infant survived, with
severe brain injury most likely secondary to thromboembolic
complications, resulting in multiple cerebral infarcts. H & E,

was not a significant factor in the disability of the
Occasionally large anomalous vessels may extend from
the cord all the way to the placental margin and then
continue parallel to the placental margin for some distance. Such a vessel in a low-lying placenta may be
vulnerable to compression and to various common obstetric manipulations, such as amniotomy. The anomalous
fetal artery in Fig. 16 was sliced longitudinally in the
process of an amniotomy, resulting in rapid exsanguination and death of the fetus.

Fig. 15. Clustered, avascular villi from same case indicating
proximal fetal artery thrombosis. H & E, 90 x.
Fig. 16. Gross photograph of a placenta in which an anomalous
fetal artery was lacerated during amniotomy. Arrows depict the
course of the fetal artery as it emerges from the umbilical cord and
passes to the site of vessel laceration, located circumfertially at the
placental margin. Note recent hemorrhage into adjacent tissues.


12 . S. C. Rayne and F. T. Kraus

~hor~ngi~sis2, 8, 25 .a proliferative abnormality of villous
capIllanes, IS assoCiated with increased frequency of
neonatal death and major congenital malformations2, 8, 25.
Some investigators have found this lesion to be characteristic of placentas from cases of maternal diabetes
mellitus, pre-eclampsia, and materno-fetal rhesus incompatibility25. The strict definition of chorangiosis specifies
that on~ must identify "with a lOx objective ... ten villi,
each wIth 10 or more vascular channels in 10 or more
non-infarcted and non-ischemic zones of at least 3 different placental areas" 3 (Fig. 17). It must be distinguished
from vascular congestion in which capillaries are distended
by erythrocyte~ but the vessels are less numerous, usually
from 5-7 per villous cross-section. In his study, Altschuler 3
found tha~ 74 of 1.350 placentas had chorangiosis (5.5%).
Of those mfants with chorangiosis, 39% of the infants
between 38-40 weeks of gestation died; another 27%
s~ffered .fr~m ,?ajor c~ngenital malformations. Significant
~Istologlc ~~Ich are associated with chorangiosis
mclude chromc vIlbtls of unknown etiology and placentomegaly. The pathogenesis of this lesion is unknown.

Vascular Malformations and Neoplasms
Certainly the most common vascular neoplasm of the
placenta is the chorioangioma (hemangioma). These
lesions are relatively common occurring in at least 1% of
all pregnancies 25 , 63. Numerous studies have documented a
variety of complications directly related to these vascular
lesions, including polyhydramnios, premature labor, toxemia, abruption, neonatal cardiac failure, thrombocytope-

nia, and microangiopathic hemolytic anemia 5,6,8,27,56,63.
These complications primarily occur with and relate to
sequestrati~n of blood elements in large chorangiomas,
and the eXlstance of a shunt by-passing the functional
placenta. There is evidence to suggest that in some cases
~horangi?mas may be the primary underlying cause of
mtrautenne growth retardation 30 , 36, 38, 61. In these
instances it appears that the relative size relationship
?etween the chorangioma, placenta, and baby may be as
Important as the size of the chorangioma alone 38 .
Oth~r types of vascular malformation of the placenta are
exceedmgly rare 33 • Two instances of extensive venous
varicosities in the placenta reported by Moscoso et al.37
~ere associated with marked alpha feto-protein elevations
m the maternal serum, and mesenchymal (connective
tissue) hyperpla~ia in the placental villi and septa. One
unusual, more diffuse vascular malformation in our recent
experience was complicated by extreme intrauterine
g:owth retardation. This term infant weighed only two
kilograms and had neurologic difficulties at birth. She had
to be treat~d for acute respiratory distress, persistent
hypoglycemIa, and thrombocytopenia. There was no
e.vld~nce. for an infectious etiology. Other significant
fmdmgs mcluded systemic perinatal hypoxia with cerebral
edema and seizure activity. The placenta weighed 400
grams and had light meconium staining.
Examination of the fetal surface revealed extensive
dilation and thrombosis of surface vessels. Both the
maternal surface and cut section were grossly unremarkable ..Histologically many stem vessels and villous capillary
lumma were greatly enlarged, many distended by recent
and organizing thrombi (Figs. 18-20). The umbilical cord
vessels were all unremarkable.

Fig. 17. Chorangiosis.
While normal terminal villi
contain approximately 5-6
capillaries, these abnormal
villi have more than 10
capillary vessels; in this case
from 10 to 20 capillaries per
villus can be counted.

Placental Thrombi and Other Vascular Lesions . 13
Fig. 18. Representative low power view of vascular malformation with markedly enlarged fetal stem vessels. Newborn with
severe intrauterine growth retardation was delivered at 36 weeks
with Apgars of 1 and 5. Post-delivery course was complicated by
respiratory distress, thrombocytopenia, and seizures. Infant is
currently alive and well but has residual neurologic deficit.


Fig. 20. There were extensive, acute, and organizing fetal vessel
thromboses in the vascular malformation illustrated in Figs. 14
and 15. H & E, 135x.

Fig. 19. Abnormal, dilated villous capillaries from the vascular
formation illustrated in Fig. 15. H & E, 90x.

14 .

s. C. Rayne and F. T. Kraus

It appears that this vascular malformation of placental
fetal vessels caused this infant's intrauterine growth retardation and complicated the perinatal course by reducing
the amount of functional placenta and by shunting fetal
blood away from functional villi. The infant is now one
year of age and has residual neurologic deficits, presumably related to cerebral infarcts caused by thromboembolism from the placenta. Attention should be drawn to
the fact that unlike some previously reported vascular
malformations 33 gross examination alone would not have
revealed the extensive, dramatic nature of this clinically
significant lesion.

Maternal Floor Infarct
Maternal floor infarct is easier to describe and identify
than to define or explain. The maternal surface of the
placenta is firm, wrinkled or convoluted like the gyri of the
brain, and has a lighter pale tan color (Fig. 21). On
cross-section the layer of induration is usually only 2 or
3 mm thick (Fig. 22); similar strands of induration may

Fig. 22. Cross sectional view of maternal floor infarct illustrating
the variable 2-6 mm rind of fibrin deposition above the decidua
basalis (arrow). 3 x.

Fig. 21. Gross appearance of a maternal floor infarct involving
approximately 2/3 of the maternal surface area. The fibrotic,
cerebriform configuration of the maternal surface is characteristic
of this lesion.

extend into the placenta along placental septum. Often,
but not always, there is a considerable or even extensive
perivillous fibrin deposition. The placenta is usually small
for gestational age, and associated fetal growth retardation
is common4,44. Most significantly, maternal floor infarcts
are often fatal to the fetus, and they may recur in
subsequent pregnancies4 ,4o. They are uncommon, occurring in .09-0.5% of deliveries.
The basic lesion seems to relate to obliteration of villi
near the basal plate by a localized accumulation of
perivillous fibrin-like material. In histologic sections, the
villi nearest the decidual plate become incased in fibrin;
there is usually no significant inflammatory component
(Fig. 23). Plasma cells are uncommon. Infarcts of the usual
sort do not, in general, occur elsewhere in the placenta.
Spiral artery changes as seen in toxemia or eclampsia do
not generally occur. Occasionally, however, instances of
chronic villitis in the same basal plate location may
produce a very similar gross appearance. In such cases
decidual inflammation may be prominent and spiral
arteries may be occluded by thrombus.
Previous history of stillbirth is common and between
17%-40% of fetuses are stillborn4,40. Attention to future

Placental Thrombi and Other Vascular Lesions . 15

pregnancies may lead to salvage if attention is paid to fetal
distress so that delivery is expeditious when problems are
recognized near term.
The etiology is unknown. The relationship to villitis is
inconstant and uncertain 8 • It seems likely that more than
one disease entity is responsible.

Clinical Correlations
Placental vascular lesions associated with thrombi in the
maternal circulation should prompt an investigation of
possible maternal coagulopathy; the same considerations
apply to the newborn. Similarly, thrombi in the fetal
circulation of the placenta should prompt a consideration
of possible thrombotic events in the fetus, especially if
there is a fetal or neonatal neurologic deficit. Hemangiomas and other vascular malformations may be a source of
emboli and cause growth retardation if they are large
enough in proportion to total placental size to shunt or
segregate a significant amount of fetal blood. Intramembranous vessels are easily traumatized and may become the
basis for more generalized thrombi or emboli. Lesions that
narrow or occlude spiral arteries may cause placental
ischemia which is reflected by growth retardation, hypertension, or both.
"Hemorrhagic endovasculitis" represents local or generalized intravascular coagulation which may be a nonspecific diffuse regressive change after fetal death from any
cause or may represent a localized thrombotic event,
especially in a liveborn infant. Infarcts are the non-specific
result of placental ischemia which have little significance if

Fig. 23. Microscopic appearance of a maternal floor
infarct in which there is a
heavy fibrin deposition surrounding fibrotic, avascular
villi. H & E, 129x.

they are few, located at the margin, and small; infarcts
probably indicate a significant ischemic process when they
are numerous, large, and more centrally located.

Studies to identify Protein C and Protein S were performed by
H. Joist, M.D., St. Louis University School of Medicine. The
photomicrographs were prepared by Walter Clermont, Dept. of
Medicine, Washington University School of Medicine. Placenta:
We thank Oliver Culver for permitting the dissection and
photographs of spiral arteries of his normal placenta. We wish to
thank Susie Oberlander for preparation of the manuscript.

1 Althabe 0, Labarrere C, Telenta M (1985) Maternal vascular
lesions in placentae of small-for-gestationalage infants. Placenta
2 Altshuler G (1984) Chorangiosis. An important placental
sign of neonatal morbidity and mortality. Arch Pathol Lab Med
108: 71-74
3 Altshuler G (1991) The placenta. Chapter 2. In: Sternberg SS,
Mills SE (Eds.) Surgical Pathology of the Female Reproductive
System and Peritoneum. New York, Raven Press, page 31
4 Andres RL, Kuyper W, Resnik R, Piacquadio KM,
Benirschke K (1990) The association of maternal floor infarction
of the placenta with adverse perinatal outcome. Am J Obstet
Gynecol163: 935-938
5 Asadourian LA, Taylor HB (1968) Clinical Significance of
Placental Hemangioma. Obstet Gynec 31: 551-555

16 . S. C. Rayne and F. T. Kraus
6 Bauer CR, Fojaco RM, Bancalari E, Fernandez-Rocha L
(1978) Microangiopathic hemolytic anemia and thrombocytopenia in a neonate associated with a large placental chorioangioma.
Pediatrics 62: 574-577
7 Benirschke K, Gille] (1977) Placental pathology and asphyxia. In: Intrauterine Asphyxia and the Developing Fetal Brain,
Gluck L (Ed) Yearbook Medical Publishers, Chicago
8 Benirschke K, Kaufman P (1990) Pathology of the Human
Placenta, 2nd ed., Springer-Verlag, New York
9 Branch DW, Scott ]R, Kochenour NK, Hershgold E (1985)
Obstetric complications associated with the Lupus anticoagulant.
New Eng] Med 313: 1322-1326
10 Branch DW, Andres R, Digre KB, Rote NS, Scott]R (1989)
The association of antiphospholipid antibodies with severe
preeclampsia. Obstet Gyncol 73 (4): 541-545
11 Branch DW (1990) Autoimmunity and pregnancy loss.
]AMA 264 (11): 1453-1454
12 Brenner B, Shapira A, Bahari C, Haimovich L, Seligsohn U
(1987) Hereditary protein C deficiency during pregnancy. Am]
Obstet 157: 1160-1161
13 Brosens I, Renaer M (1972) On the pathogenesis of
placental infarcts in preeclampsia. J. Obstet Gynaec Brit Cwlth
79: 794-799
14 Caldwell DC, Williamson RA, Goldsmith]C (1985) Hereditary coagulopathies in pregnancy. Clin Obstet Gynecol 28:
15 Carreras LO, Vermylen ] (1981) "Lupus" anticoagulant
and inhibition of prostacyclin formation in patients with repeated
abortion, intrauterine growth retardation and intrauterine death.
Brit] Obstet and Gynaec 88: 890-894
16 Carter ]E, Vellios F, Huber CP (1963) Circulatory factors
governing the viability of the human placenta, based on a
morphologic study. Am] Clin Pathol 40 (4): 363-373
17 Comp PC, Esmon CT (1984) Recurrent venous thromboembolism in patients with a partial deficiency of protein S. New Eng]
Med 311: 1525-1528
18 Conard], Horellou MH, Van Dreden P, Samama M (1987)
Pregnancy and congenital deficiency in antithrombin III or
Protein C. Thromb Haemostas 58 (Abstract 143)
19 Conard ], Horellou MH, Van Dreden P, Lecompte T,
Samama M (1990) Thrombosis and pregnancy in congenital
deficiencies in AT III, Protein C or Protein S: Study of 78 women.
Thromb Haemostas 63: 319-320
20 Cowchock S, Smith ]B, Gocial B (1986) Antibodies to
phospholipids and nuclear antigens in patients with repeated
abortions. Am] Obstet Gynecol155: 1002-1010
21 De Stefano V, Leone G, De Carolis S, Ferrelli R, Di
Donfrancesco A, Moneta E, Bizzi B (1988) Management of
pregnancy in women with antithrombin III congenital defect:
Report of four cases. Thromb and Haemostas 59: 193-196
22 De Wolf F, Carreras LO, Moerman P, Vermylen ], Van
Assche A, Renaer M (1982) Decidual vasculopathy and extensive
placental infarction in a patient with repeated thromboembolic
accidents, recurrent fetal loss, and a lupus anticoagulant. Am ]
Obstet Gynecol142: 829-834
23 Feinstein DI (1985) Lupus anticoagulant, thrombosis, and
fetal loss. New Eng] Med 313: 1348-1350
24 Fox H (1967) Abnormalities of the foetal stem arteries in the
human placenta. ] Obstet Gynaec Brit Cwlth 74: 734-738
25 Fox H (1978) Pathology of the Placenta: Major Problems in
Pathology. Vol. 7, W.B. Saunders, Philadelphia
26 Freese UE, Maciolek B] (1969) Plastoid injection studies of
the uteroplacental vascular relationship in the human. Obstet
Gyn 33: 160-169
27 Froehlich LA, Fujikura T, Fisher P (1971) Chorangiomas
and their clinical implications. Obstet Gynecol37: 51-59

28 Fujikura T, Benson R (1964) Placentitis and fibrous occlusion of fetal vessels in the placentas of stillborn infants. Am] Obst
and Gynec 89: 225-229
29 Gruenwald P (1961) Abnormalities of placental vascularity
in relation to intrauterine depravation and retardation of fetal
growth: Significance of avascular chorionic villi. New York] Med
61: 1508-1513
30 King CR, Lourien EW (1978) Chorangioma of the placenta
and intrauterine growth failure. ] Pediatr 93: 1027-1028
31 Kinnane L, Sander CH, Ellicott LA, Tauscher ]W, Wright
LM (1985) Developmental abnormalities in live births with
hemorrhagic endovasculitis of the placenta: Follow-up at 5 years.
Lab Invest 52: 35A
32 Kurman R] (1987) Blaustein's Pathology of the Female
Genital Tract, 3rd edition, Springer Verlag, New York
33 Lee GK, Chi]G, Cha KS (1991) An unusual venous anomaly
of the placenta. Am] Clin Pathol 95: 48-51
34 Lubbe WF, Liggins GC (1985) Lupus anticoagulant and
pregnancy. Am] Obstet Gynecol153: 322-327
35 Macpherson T (1991) Fact and Fancy. What can we really
tell from the placenta? Arch Path Lab Med 115: 672-681
36 Mahmood K (1977) Small chorangiomas and small-forgestational age baby. Am] Obstet Gynecol127: 440-442
37 Moscoso G, ]auniaux E, Hustin] (1991) Placental vascular
anomaly with diffuse mesenchymal stem villous hyperplasia. Path
Res Pract 187: 324-328
38 Mucitelli DR, Charles EZ, Kraus FT (1990) Chorioangiomas of intermediate size and intrauterine growth retardation.
Path Res Pract 186: 455-458
39 Naeye RL (1977) Placental infarction leading to fetal or
neonatal death: A prospective study. Obstet Gynecol 50:
40 Naeye RL (1985) Maternal floor infarction. Human Pathol
16: 823-828
41 Naeye RL (1987) Do placental weights have clinical significance? Hum Pathol18: 387-391
42 Naeye RL (1987) Functionally important disorders of the
placenta, umbilical cord, and fetal membranes. Human Pathology
18 (7): 680-691
43 Naeye RL (1989) Pregnancy hypertension, placental evidences of low uteroplacental blood flow, and spontaneous
premature delivery. Human Pathol 20: 441-444
44 Nickel RE (1988) Maternal floor infarction: An unusual
cause of intrauterine growth retardation. Amer] Dis Child 142:
45 Robertson WB, Broseus I, Dixon HG (1967) The pathological response of the vessels of the placental bed in hypertensive
pregnancy. ] Path Bact 93: 581-592
46 Robertson WB, Khong TY, Broseus I, DeWolf F, Sheppard
BL, Bonnar] (1986) The placental bed biopsy: review from three
European centers. Am] Obstet Gyecol155: 401-412
47 Rose PG, Essig GF, Vaccaro PS, Brandt]T (1986) Protein S
deficiency in pregnancy. Am ] Obstet Gynecol 155 (1):
48 Rushton I (1984) Placenta as a reflection of maternal
disease. Chapter 3. In: Perrin E VDK (Ed) Pathology of the
Placenta. Churchill Livingstone, New York
49 Sander CH (1980) Hemorrhagicendovasculitis andhemorrhagic villitis of the placenta. Arch Pathol Lab Med 104:
50 Sander CH, Stevens NG (1984) Hemorrhagic endovasculitis
of the placenta: An indepth morphologic appraisal with initial
clinical and epidemiologic observations. In: Path Annual- Vol. I.
Appleton - Century, Norwalk, p. 37-79
51 Sander CH, Kinnane L, Stevens NG, Echt R (1986)
Haemorrhagic endovasculitis of the placenta: A review with
clinical correlation. Placenta 7: 551-574

Placental Thrombi and Other Vascular Lesions· 17
52 Seligsohn U, Berger A, Abend M, Rubin L, Attias D, Zivelin
A, Rapaport S (1984) Homozygous Protein C deficiency manifested by massive venous thrombosis in the newborn. New Eng J
Med 310: 559-562
53 Shanklin DR, ScottJS (1975) Massive subchorial thrombohematoma (Breus' mole). Br J Obstet Gynaecol 82: 476-487
54 Shen-Schwarz S, Macpherson T A, Mueller-Heubach E
(1988) The clinical significance of hemorrhagic endovasculitis of
the placenta. Am J Obstet Gynecol159: 48-51
55 Sheridan-Pereira M, Porreco RP, Hays T, Shannon Burke
MS (1988) Neonatal aortic thrombosis associated with the lupus
anticoagulant. Obstet Gynecol 71: 1016-1018
56 Sieraki JF, Parke TW, Harrat BL, Perrin EV, Nanda B
(1975) Chorangiomas. Obstet Gynecol46: 155-159
57 Silver MM (1988) Massive placental infarction due to the
lupus anticoagulant [AbstractJ. Modern Pathology 1: 85 A
58 Tenney B, Parker F (1940) The placenta in toxemia of
pregnancy. Am J Obstet Gynecol39: 1000-1005
59 Triplett DA (1989) Antiphospholipid antibodies and recurrent pregnancy loss. Am J Reprod Immunol 20: 52-67

60 Vogel J], de Moerloose PA, Bounameaux H (1989) Protein
C deficiency: A case report. Obstet Gynecol 73 (3) Pt. 2:
61 Wallenburg HCS (1971) Chorangioma of the placenta.
Obstet Gynecol Surv 26: 411-425
62 Weinstein L (1982) Syndrome of hemolysis, elevated liver
enzymes, and low platelet count: A severe consequence of
hypertension in pregnancy. Am J Obstet Gynecol 142:
63 Wentworth P (1965) The incidence and significance of
hemangioma aof the placenta. Br J Obstet Gynaecol 72:
64 Wentworth P (1967) Placental infarction and toxemia of
pregnancy. Am J Obstet Gyecol 99: 318-326
65 Wigglesworth JS (1969) Vascular anatomy of the human
placenta and its significance for placental pathology. J Obstet
Gynaec Brit Cwlth 76: 979-989
66 Wigglesworth JS (1984) Perinatal Pathology, Major Problems in Pathology. Vol 15. W.B. Saunders Company, Philadelphia

Received March 11, 1992 . Accepted March 11, 1992

Key words: Placenta - Coagulopathies - Vascular malformations - Maternal floor infarct
Frederick T. Kraus, M.D., Department of Pathology, St. John's Mercy Medical Center, 615 South New Ballas Road, St. Louis, Missouri
63141-8221, USA

Aperçu du document practice placccc.pdf - page 1/16

practice placccc.pdf - page 2/16
practice placccc.pdf - page 3/16
practice placccc.pdf - page 4/16
practice placccc.pdf - page 5/16
practice placccc.pdf - page 6/16

Télécharger le fichier (PDF)

Sur le même sujet..

Ce fichier a été mis en ligne par un utilisateur du site. Identifiant unique du document: 00293727.
⚠️  Signaler un contenu illicite
Pour plus d'informations sur notre politique de lutte contre la diffusion illicite de contenus protégés par droit d'auteur, consultez notre page dédiée.