The normal separation of the placenta during the third
stage of labor occurs within the decidua, the soft endometrial layer. In effect, the placenta does not separate from its firm
attachment to the endometrium, but the decidualized endometrium is shed and the placenta travels with it. If the placenta
separates before delivery of the infant, and blood cannot egress, then a hematoma may form in the decidual layer beneath the
placenta forming a retroplacental hematoma (RPH). If this premature separation causes clinical symptoms of uterine tenderness,
occult hemorrhage, fetal distress or maternal coagulopathy, then the clinical consequences of the premature separation are
designated placental abruption, or in older terminologies, abruptio placentae or accidental hemorrhage. This review will first
examine the mechanism of normal placental separation, then look at proposed mechanisms of premature separation, and then look
at some of the clinical consequences of placental abruption. The review is not exhaustive.
B. Incidence of placental abruption and related mortality
A study from
the 1960’s found a rate of fetal death of approximately 1.2 per 1000 births for
" Fetal death associated with antepartum bleeding or retro-placental blood clot, excluding placental previa" . In the same
institution in the 1980's, the rate fell to .7/1000 attributed to better care. A study in 1970, using clinical criteria as
well as pathological criteria of hematoma with depression or disruption found an incidence of 130 abruptions /26,743 deliveries
(0.5%). There was 30% fetal mortality which yields 1.4 deaths/ 1000 deliveries . There is disparity in the rates in these
studies, but a range of large or lethal retroplacental hematomas is most likely between 0.5 to 4 / 1000 deliveries. Smaller,
incidental hematomas are likely to be at least as frequent.
A major problem in all epidemiologic papers on abruption is the variable definitions
from different studies. A study of 189 abruptions over 5 years from a population of 8,000-9000 deliveries per year (approximately
0.4%) had 189 stillbirths and 21 neonatal deaths (55% perinatal death rate for abruptions). All cases had to have a retroplacental
clot or crater and the vaginal hemorrhage had to mixed or concealed. They did not accept any cases diagnosed as “revealed
accidental hemorrhage”. These cases occurred before electronic monitoring (1965-1969), but clearly the diagnostic criteria
were adequate to identify a clinically significant condition. Twenty nine patients had plasma fibrinogen levels below 200mg/100ml,
and there was one maternal death.
A later study (1967-1989) in Norway had a 0.6% incidence
of abruption with a 32% perinatal mortality. This study was based on physician reporting of 523,977 pregnancies. Compared
to the British population study, both reasonably large, the increased incidence of abruption was associated with a lower incidence
of perinatal mortality. One possible explanation is that more vaginal bleeding without premature placental separation was
included in the physician reported abruption cases. The Norwegian study also found an increased incidence of reported abruption
in a subsequent pregnancy following a pregnancy with abruption (odd ration 6.4).
There is no study of the incidence of retroplacental hemnorrhages/hematomas
of the placenta independent of clinical abruption.
C. Myometrial contraction/ decidual shearing mechanism
of placental separation
The contents of the uterus prevent shortening of the myometrial
muscle during contractions, at least while the cervix is closed. With expulsion of the contents, the myometrium contracts
and shortens markedly (from an average uterine diameter of 21 cm to 5 cm). The placenta cannot contract. The resulting
stress tears the decidua, and the placenta is expelled. The key role of the decidua
had been suspected since the early 18th century. Monro described his dissection of the pregnant uterus “I observed the
smooth tense chorion from which the fungous substance separated most easily, and it did likewise from the placenta. (Edin
Med 1734)”. This “fungous substance” would later be termed decidua. This fundamental mechanism of placental
separation occurs because contraction of the myometrium shears the decidua beneath the rigid placenta. The spiral arteries
and endometrial veins traverse the decidua and must be torn apart with placental separation. These vessels can hemorrhage
and a hematoma could form with normal separation if the process was focally delayed.
A study of frozen sagittal sections of rhesus monkeys in
labor demonstrated two observations relevant to placental separation. First, the thinning of the uterus is not uniform.
Second, the separation of the placenta begins in the second stage of labor. Interval radiographs of placental separation in
breech and anencephalic deliveries, demonstrated that 17 started at the lower (cervical side) edge of the placenta, and only
three commenced centrally . In 20 cases radio-opaque dye was injected into the umbilical artery or vein after cord clamping
in breech deliveries prior to delivery of the head. In two cases, the dye was injected in the prolapsed umbilical cord of
anencepahlic fetuses. This dye delineated at least the main placental vessels if the injection was venous, with more distal
detail by arterial injection. In 18 timed cases, placental separation was complete within 5 minutes of delivery of the infant,
and in 6 of those is was complete at the end of the second stage of labor. Some of the authors detailed observations follow:
“Study of the soft tissue outlines of the uterus emphasizes that retraction is a process which occurs in all planes,
affecting the circumference, width and depth of the uterus as well as its length. At any one time, however, one part of the
organ may be more affected than another, ... retraction in mainly one plane may
persist until complete expulsion of the fetus …ultimately uniform retraction takes place.” “There were 3
cases in which placental separation occurred before there was evidence of significant uterine retraction. In the remainder,
retraction appeared to precede separation.” A plausible hypothesis is that local contraction of the lower uterine segment
in the process of cervical dilatation and fetal descent shortens sufficiently to shear the overlying decidua.
Modern ultrasound technology can demonstrate the contraction
of the uterus and consequent separation of the placenta in the third stage of labor. A color Doppler flow study in 55 women
found that in the third stage of labor, blood flow stopped at a median of 2.5 (0-230) seconds after delivery with median latent
phase of 91 (2-367) seconds and detachment phase of 39 (15-250) seconds. The separation in the vast majority of cases starts
at the caudal pole of the placenta and detachment may occur in phases which prolongs that phase. Another ultrasound study
of 101 women confirmed that separation usually starts at one pole, most often the lower, and is usually multiphasic with separation
and thickening of the adjacent myometrium occurring together. In fundal placentas, the fundal portion usually separates
A different concept of placental separation was suggested
by in vitro study of the placenta. The author argued that the Bernoulli theorem implies that the intervillous blood flow
should reduce blood pressure in the intervillous space compared to the amniotic fluid. A model of in vitro perfusion is used
in which increasing the perfusion pressure is counteracted with increasing amniotic fluid pressure to maintain the position
of the placenta. The plots were not linear at 45 degrees. The difference between a given rise in perfusion pressure compared
to a given rise in amniotic pressure is considered due to flow via the Bernoulli effect. Decreased flow would then result
in a higher pressure lifting the placenta upward. This is a very simplified model and there is little evidence that pressure
differences can separate the placenta. The chorionic plate is tightly glued to the basal decidua, and the placental does not
actually separate, but the decidua cleaves releasing the placenta with superficial decidua still attached.
After rupture of the membranes at term, the infant’s
body and residual fluid must prevent significant myometrial shortening. Rupture of membranes with polyhydramnios could result
in sufficient myometrial shortening to separate the placenta. A similar degree of myometrial shortening could occur after
delivery of one twin, particularly with rupture of both sacs in early gestation [12, 13]. Sufficient myometrial shortening
to separate the placenta might occur with rupture of membranes in the second trimester because the amniotic fluid volume is
proportionately more than in later gestation. A correlation between preterm premature rupture of membranes (PROM) and abruption
has been reported [14-16]. Complications of placental separation are more common at younger gestation including the need for
manual removal and post partum hemorrhage. The basis for this resistance to removal is not known, but could account for
the higher incidence of apparent retroplacental hematoma if placental separation is partial and delayed. The hematomas could
occur before or after delivery of the infant.
In one study, eight of 143 women, who delivered between
24 and 34 weeks of gestation, following at least 24 hours after PROM and without signs of abruption on admission, developed
abruption compared two of 143 controls (P<.05). The clinical indicators of abruption had to be severe enough to warrant
delivery and “verified by gross placental examination after delivery”. Only one of the cases had a 5 minute Apgar
score of less than 5, and the estimated percentage of abruption was 50% or less in 6 cases. One case met clinical criteria
for chorioamnionitis. Except for vaginal bleeding at or after PROM (6 cases), there were no other differences between features,
including decreased amniotic fluid, between mothers with and without abruption,. Another study found 19 abruptions in 298
patients, 25 to 36 weeks of gestation with PROM managed expectantly (incidence of 6.3%) compared to an 2.2% incidence of abruption
without PROM . Abruption was defined as a retroplacental hematoma indenting the placental substance, and was found in
53 of 1946 deliveries (incidence 2.7%). “The diagnosis was confirmed by histologic examination in all cases.”
No pathological criteria are given. Ten of 81 PROM patients with a maximal amniotic fluid < 1 cm had abruption compared
to 6 of 169 with a fluid pocket > 2 cm (P<0.01).
The mechanism of the association of preterm PROM with retroplacental
hematoma may be simply myometrial shortening and incomplete placental separation. Two other mechanisms have been proposed.
One is that the retroplacental hemorrhage is primary and causes the ruptured membranes. A study of cultured decidual cells
found that thrombin upregulates matrix metalloproteinase. Progesterone blunts the effect. The study used decidua scraped
from the membranes which is likely contaminated by chorionic epithelium. The authors postulate that abruption causes decidual
thrombin which via metalloproteinase weakens the membranes and leads to membrane rupture. The hypothesis does not attempt
to quantify or localize the in vitro regulation in the living organism, but merely presents a hypothesis. If indeed abruption
causes PROM, a more logical explanation is that the extension of a retroplacental separation beneath the membranes would both
stretch and devitalize that portion of the membrane causing rupture both by weakening and a focal increase in wall tension.
There is no direct evidence of this hypothesis.
The second mechanism proposes that chorioamnionitis causes
abruption and chorioamnionitis is associated with preterm PROM. A study using the data from the New Jersey-Placental Abruption
Study found a statistically significant correlation of histological chorioamnionitis and abruption (P<.05) that was stronger
with severe chorioamnionitis. This study postulates that acute inflammation causes “destabilization of the utero-placental
interface, culminating in placental abruption, premature rupture of membranes, and preterm labor.” They acknowledge
that their data cannot prove this hypothesis. The criteria for abruption in this study include a retroplacental clot or hematoma
on the placental surface. Retroplacental hematoma diagnosed by direct observation as Cesarean section should be reliable.
However following a vaginal delivery the hematoma could have formed after delivery of the infant. There were no histological
criteria for the hematoma. The study also did not utilize any measure of severity such as fetal measures of asphyxia, maternal
coagulation status, or size of the hematoma. In a table comparing the mean gestational age with PROM and abruption, there
were 17 abruptions in PROM patients with no chorioamnionitis compared to 11 with any grade of chorioamnionitis. This argues
against a consistent causative role for chorioamnionitis. (The percentages of PROM in each chorioamnionitis category did not
add up to 100%, so I may have misinterpreted the table.) This study cited a study of thrombin enhanced interleukin-8 expression
in term decidua as providing a potential mechanism for chorioamnionitis induced abruption. That study argued instead that
the abruption led to fibrin that caused decidual secretion of interleukin-8 that caused neutrophil migration into the decidua.
They did not argue that decidual neutrophils caused abruption.
Jersey-Placental Abruption Study also cited a study of
nitric oxide synthesis in chorioamnionitis and abruption. The study sampled placental villi and maternal serum from 10 patients
with clinical symptoms of chorioamnionitis, and 6 patients with clinical abruption and a retroplacental hematoma. The
chorioamnionitis patients had histological chorioamnionitis, but it is not clear whether the abruption cases also had histological
chorioamnionitis. Gestational age is not mentioned as a factor in sampling, but the results suggest that most of the patients
were very preterm. Quantification in placental histology is fraught with difficulty because the placetone flow of the intervillous
blood results in visible local differences in villous maturation related to local differences in oxygen and blood flow. Thus,
local blood flow changes would have to be accounted for by extensive random or intentional systematic sampling of the villi.
Part of the study results depend on the interpretation of immunoperoxidase staining intensity, a measure that is subjective
and not necessarily linear with concentration. The abruption samples were taken above the hematoma in areas that would have
experienced complete anoxia. All of this makes interpreting the results of the study difficult. Even if the study results
are true, they only demonstrate an up-regulation of nitric oxide production in Hofbrauer cells and syncytiotrophoblast from
placentas with chorioamnionitis and from devitalized villi over abruption. Conceptually this result does not translate into
a mechanism of abruption in the basal decidua.
A study of pathology in 90 placentas from second trimester
fetal loss found more acute inflammation and possibly (P=.05) more histological evidence of abruption than in controls (second
trimester induction for anomalies). The study excluded cases with fetal death or twins. While not surprising that spontaneous
preterm labor has more acute inflammation than induced, the finding of increased abruption might contradict the mechanical
hypothesis of second trimester abruption. There are two reasons to suspect the results. The first is that the timing of rupture
of membranes and loss of fluid may have been different between induced and spontaneous labor, many of whom would have had
premature rupture of membranes. Second, there are no validated histological criteria of abruption. Those suggested in the
paper “evidence of retroplacental hemorrhage and any associated villous ischemic changes including increased syncytial
knots, villous stromal hemorrhage, and villous infarction” tends to favor longer duration retroplacental hemorrhages.
The criteria have not been independently validated as evidence of placental separation. Increased syncytial knots might be
expected adjacent to an infarction over time, but are not usually a criteria of acute devitalization. This paper also lumps
chronic inflammation such as plasma cells in the basal decidua, and chronic inflammation at the chorio-decidual junction with
acute membrane inflammation, and there is no validated basis for doing this. They are likely the result of different pathogenesis.
A study of 30 severe, third trimester abruptions (defined as antepartum hemorrhage,
firm tender uterus, maternal shock, and fetal distress or death) found no significant difference in the incidence (23% v 28%)
nor in the severity of chorioamnionitis compared to 60 control placentas. The opposite conclusion was reached in a study
of 37 women, less than 36 weeks of gestation who had heavy vaginal bleeding, intact membranes, a live fetus, and histological
evaluation of the placenta compared to 51 controls with similar criteria. An adherent retroplacental clot with depression
of the maternal surface was present in all cases, and 27 had histologic evidence of abruption including “decidual necrosis,
villous crowding, and marginal and pervillous fibrin deposition”. There was no attempt to explain or validate these
histologic criteria. 14 abruption infants had a five minute Apgar score less than 7. Fifteen cases (41%) compared to 4 controls
of 51 controls had histological evidence of chorioamnionitis. The paper states that 4 of 51 is 4% (which it is not) and is statistically significant at P <.001. One difference in the study is the very low incidence of
chorioamnionitis in controls. One difference between these two studies is that the mean gestational age was 34 weeks in the
first study and 30 weeks in the second which would increase the expected number of chorioamnionitis cases. This could explain
the difference in the case incidences of chorioamnionitis 23% v 41%, but not the low control incidence of 4 (really 8%). The
most likely explanation is the skewed control population in the second study which included 36 hypertensive disorders, and
the rest with other serious medical complications Chorioamnionitis is associated with preterm labor. If these pregnancies
were delivered because of these complications at the same mean gestation as those delivered with preterm labor, even if with
suspected abruption, the controls would be expected to have a lower incidence of chorioamnionitis.
Chorioamnionitis does not involve the basal decidua (that
is decidua beneath the placenta). There is an association of chorioamnionitis with abruption in preterm infants but this is
because preterm labor is associated with chorioamnionitis. Chorioamnionitis does not cause basal plate inflammation, and is
unlikely to be a direct cause of placental separation.
A perhaps unique hypothesis about abruption related to
uterine shortening was the proposal that orgasm could initiate abruption. The Collaborative Perinatal Project found a highly
significant correlation of coitus since the last antenatal examination before delivery and the incidence of antenatal hemorrhage
“severe enough to raise the clinical possibility of premature placental separation. Hemorrhages with a retroplacental
hematoma were designated abruption, those without were “hemorrhage of unknown origin”. Both types of hemorrhage
correlated with coitus, and with significantly increased perinatal mortality. The only exception was the group with abruption
at 24-27 weeks of gestation, which is precisely the group that may have separation based on loss of uterine volume with membrane
rupture. The mechanism of the association is not known, but orgasm may cause uterine contraction which conceivably could cause
abruption by decidual shearing. The study has not been reproduced.
D. Uterine venous occlusion as a mechanism of placental separation
Vena cava occlusion can lead to abruption, a mechanism
observed by direct compression in humans . The study was based on experimental
production of abruption in the dog by occlusion of the inferior vena cava and the left ovarian vein. The first patient had
direct compression of the vena cava, but not the ovarian veins, for 5.5 minutes and then delivery of the infant by Cesarean
section. The uterus was seen to become congested externally. Immediately after delivery of the infant, the placenta was palpated
and found to be almost completely separated. A second patient had 5 minutes of direct vena caval occlusion and developed a
central keyhole separation of the placenta involving ¼ to ½ of the placenta. Both patients had immediate systemic hypotension
with caval compression. The second patient had vena caval pressure measurements that started below 30 cm of water and with
direct pressure rose to above 40 cm of water. This mechanism of abruption was proposed as one of the complications of the
“supine hypotensive syndrome’, although as pointed out by Harris, in most cases of hypotension there is no abruption[27,
28].Only a minority of women experience hypotension in the supine position, and it is possible that the two cases studied
were susceptible. A study of inferior vena caval pressure with a transducer inserted in the femoral vein at the time of Cesarean
section in 8 gravid women demonstrated that the abdominal vena caval pressures were as high as those seen with manual compression
of the vena cava in non-gravid . Thoracic caval pressures were normal and the abdominal caval pressure dropped to normal
after removal of the infant. Most interestingly after the section, manual compression of the vena cava elevated pressure as
it would in a nongravid patient, but unlike the nongravid patient there was not a sharp fall in systolic blood pressure. This
was interpreted logically as evidence that the mothers had developed sufficient collaterals to be able to bypass the inferior
vena cava. They did not compress the vena cava prior to delivery, but the hemodynamics in the women studied make it unlikely
that this maneuver would have elevated uterine venous pressure. A ninth woman with polyhydramios was studied who had even
higher vena caval pressures (35 mm Hg compared to 18-24 Hg in the others). Normal pressures in the vena cava in the study
appeared to be < 5 mm Hg. A report of two pregnant woman requiring vena caval ligation just below the renal veins to prevent
pulmonary embolism had no complications from the occlusion. Kerr suggests that in the human experimental cases, lifting
the uterus to get to the vena cava may have directly obstructed uterine veins as the mechanism of abruption. In a follow
up paper to the two experimental cases, the authors report that in five subsequent women, compression did not lead to abruption.The
authors then discuss their observations of the distention of uterine veins over the placental insertion with different manipulations
of the uterus. The discussion states “In all these investigations no mother or infant was injured. Nevertheless, we
plan in the near future to continue the investigation in pregnant rhesus monkeys.” I could not find such studies published.
In experimental vena caval occlusion, there was prompt development of a Couvelaire uterus, that is extensive hemorrhage into
the myometrium. This implies that the elevated venous pressure in the capillary-venule bed of the uterus ruptures vessels
in more than the basal decidua. Elevated uterine venous pressure should also distend the intervillous space and parietal decidual
veins. There is no published evidence that these features can be used to diagnose this mechanism of abruption. The pathology
of two cases of Couvelaire uterus demonstrated extensive hemorrhage between myometrial fibers, and “in the walls of
many (veins) free haemorrhage had occurred, just beneath the endothelium and communicated freely with the hemorrhagic effuisoins
between the muscle fibers.” Intimal plaques were described in the arteries, which from the illustration, I think
are common in gravid uteri.
A review of the published reports on supine hypotensive
syndrome from 1922 to 1993 found several case reports of abruption associated with the syndrome. Two cases had serious
confounding factors respectively pre-eclampsia and obesity. The other three reports were of cases that delivered prior to
1960. I found no new English language reports of the association. A report from 1956 occurred when a near-term pregnant woman
fainted for 5 minutes following 25 minutes supine on the examining table. Two hours later she became symptomatic with
pain and and a tender uterus. An eventual Cesarean section revealed that the placenta was approximately one third separated
from the uterine wall by a dark hematoma. A single case can show a plausible temporal sequence, but alone can not prove causation.
I autopsied an 18 week gestation mother with lethal cerebral
hemorrhage following an abruption related to a day at the amusement park. The forces from the roller coasters may have pressed
the uterus against the vena cava. I also autopsied an infant with massive placental separation from a mother with a positive
toxicology screen for benzodiazepines, but not cocaine. There was no definite history of a decreased mental status, but had
she been asleep at the onset of abruption. The history is at least compatible with vena caval pressure or displacement of
the uterus causing abruption. Thus, a compression of the vena cava or local compression of uterine veins has not been disproved
as a cause of premature placental separation.
Another potential cause of uterine venous occlusion is
thrombus. Ovarian vein thrombus is usually a post partum complication of delivery, but with some forms of maternal thrombophilia,
the high turbulent flow in these veins might lead to prepartum occlusive thrombus. Thrombosis
of smaller veins in the basal decidua seems unlikely to lead to abruption, since the back pressure into the intervillous space
would be dissipated by drainage through all the remaining veins. Local decidual venous occlusion has been proposed as the
mechanism of subchorionic thrombo-hematoma. Perhaps there are veins large enough and without anastomosis in the uterus that
could lead to decidual hemorrhage. The evidence of an association of thrombophilia with abruption is more likely due to a
venous than arterial occlusion. Arterial thrombi would likely simply lead to infarction of the placenta supplied by that artery.
There are cases of an association of thrombophilia with
abruption, such as with Protein C or S deficiency, and hyperhomocysteinemia [36, 37] . A study of 27 cases of clinical
abruption found a Leiden Factor V mutation in 8 patients (5 heterozygotes, 3 homozygotes) compared to one heterozygote in
controls. Abruption was defined as profuse vaginal bleeding in the third trimester and “clinical observation of
the placenta after its expulsion or its extraction during a cesarean delivery”. Leiden mutation of exon 10 of the Factor
V gene in another study was not associated with abruption, but an allelic polymorphism, M385T, in exon 8 of the gene is negatively
associated with abruption . The criteria for abruption in this study required a clinical diagnosis and pathological confirmation
of a hematoma or histological confirmation, and one of three clinical criteria: 1) vaginal bleeding in late pregnancy, 2)
increased uterine tone 3) fetal distress of death. There was no detail on the features that histologically confirmed abruption.
An early study of activated protein C ratio in 29 patients with abruption found a level ≤ 2.5 in 17 of 27 patients compared
to 5 in 29 controls (P=.00125). 15 patients with low protein C ratios were tested for the Leiden mutation and 3 were homozygous,
and 5 heterozygous. The criteria for abruption were third trimester bleeding, not from placenta previa, and examination of
the placenta after expulsion or at Cesarean section. Eleven patients suffered fetal death.
The New Jersey Placental Abruption study compared placental
pathology in woman with an abruption between those with and without thrombophila based on a panel that included Factor V Leiden
mutation, prothrombin gene mutation, lupus anticoagulant, and anticardiolipin (IgG and IgM). Of 135 woman in the study,
85 had a thromobphilia. That seems very high given that all eligible women were recruited for the study. Not surprisingly
the study found an association of old placental infarction with the thrombophilia group, as infarction would be a consequence
of thrombosis in a spiral artery. They cite other studies confirming the association of thrombophilia with placental infarction.
As in their previous study it is not clear if the diagnosis of acute deciduitis and of recent infarction includes findings
directly related to a recent RPH.
A study of hereditary thrombophilias and obstetrical complications evaluated
20 woman with grade 2-3 abruptions and found 5 with the Leiden mutation (odds ratio 4.9 (1.4-17.4)), 3 with MTHF mutation
(2.0 (0.5-8.1)) and 5 with a prothrombin mutation (9.9 (1.8-43.6)). A study of 110 women with a history of either, preeclampsia,
abruption, or stillbirth found no predictive value of thrombophilia testing on subsequent complications. This study is
too small to directly disprove an association of any given thrombophilia with abruption, as only 17 cases had abruption to
begin with and only 5 reoccurred, and few of any one type of thrombophilia. All mothers also received aspirin therapy in the
subsequent pregnancy. The authors do not present the information on individual cases. The definition of abruption was clinical
“with histologic analysis of the placenta to confirm the disease”. A study based on genotyping newborn screening
cards found no association of antepartum bleeding with any Factor V, MTHFR or prothrombin mutations. The type of bleeding
was for any cause after 20 weeks gestation. The study did not specifically look at abruption.
Thrombophilic assays of 101 women with a history of abruption or placental infarction sampled a mean of 48 months after
pregnancy demonstrated significant risk if more than one factor was in combination compared to 92 control women. The homocysteine
levels were distributed with a larger tail in the study group, and the combination of high homocysteine and decreased factor
C or S increased the risk compared to controls 3-4 times. The patients had no vitamin supplementation for at least 3 months.
Because this study combines infarctions which would be expected with maternal thrombophilia, with abruption in which the association
with thrombophilia is at least moot, and does not separately analyze the data, it can not prove an association of abruption
per se with thrombophilia.
The New Jersey Placental Abruption study interviewed 212
mothers with abruption and 206 controls after delivery about thrombotic disease (deep vein thrombosis, pulmonary embolism,
stroke, heart attack and other) in first degree relatives. There was a significant increase in disease in maternal (32 (7%)
versus 13 (3%)) but not paternal relatives (7% for both). There is no simple explanation for this discrepancy between
male and female relatives which may reflect chance.
There is an older literature suggesting that folate deficiency might be a factor
in abruption [47, 48]. These studies from the 1960’s used hematologic parameters and FIGLU assay of urine as an indirect
measure of serum folate. The first study found 23 abruptions in 407 women with megablastic anemia and increased FIGLU excretion.
The author then studied in Singapore 11 women with abruption compared to women with other causes of antepartum hemorrhage
and found similar results. The association was not found in a later study of random administration of folic acid in 2949 singleton
pregnancies, but folate supplementation may have reduced the incidence of abruption . This study reviewed other less conclusive
studies that also failed to show an association. One objection to the studies
is their use of a complex bioassay for folate, but this objection does not apply to a study that failed to find macrocytic
red cell changes in abruption cases . An association of abruption was found with hyperhomocysteinemia . A biologically
plausible role for folic acid is in the prevention of the hypercoagulation in hyperhomocysteinemia. Previous studies of folate
supplementation may not have had the power to uncover this effect on a subpopulation. A study using the Norwegian birth registry
did find a reduced risk in for clinical abruption including retroplacental hematoma, in woman who had folate and or vitamin
A symposium lecture by Eskes relates the complex relationship
of folate, a cofactor for the 5,10 methylenetetrahydrofolate reductase (MTHFR) in its role in remethylation of homocysteine
to methionine and control of blood levels of homocysteine. The C677T mutation of MTHFR can result in elevated serum homocysteine,
but is still sensitive to folate levels. Another study of 18 women with a history of abruption found no correlation with the
C677T MTHFR mutation alone, but did find an association with the A1298C mutation, both heterozygous and homozygous combined
with the C677T mutation. The A1298C mutation does not elevate homocysteine levels. The definition of abruption was “diagnosed
clinically and subsequently confirmed when more than 15% of the placental surface was covered with blood clots”.
A study of serum homocysteine levels in 84 women with a
history of abruption or placental infarction found increased homocysteinemia in that group compared to controls. The inclusion
criteria are very mixed: “The diagnosis of placental abruption was based on either the combined presence of tender,
hypertonic uterus and disseminated intravascular coagulation, and/or the histologic observation of a retroplacental hematoma
with or without signs of infarction. Placental infarction was diagnosed if the placental was characterized by circumscribed
areas of villous necrosis combined with a stillborn fetus or a severe growth retarded child,” This may not be a homogenous
group. The published scatter plot of fasting plasma homocysteine levels shows in the study group compared to controls 8 patients
who have values higher than the highest level in the control group (N=46). Since only a percentage of abruption or placental
infarctions are likely related to hyperhomocyteinemia, this would be good evidence of the existence of such a subgroup, with
many more cases than would be suspected.
Investigations of an association of abruption with polymorphisms
in the methylenetetrahydrofolate reductase (MTHR) gene have been inconsistent. This enzyme is needed to convert homocysteine
to methionine. A study by the New Jersey –Placenta Abruption Study found no association of abruption with MTHR polymorphisms 677C to T or 1298A to C mutations. The study uses broad criteria to define abruption
and does not stratify by gestation or fetal outcome. There were no cases or controls with double homozygous mutations, nor
any homozygous for the 1298 mutation with a heterozygous mutation at 677. There were no significant differences between cases
and controls for plasma folate or homocysteine. This same group did find an association with a homozygous mutation (742G T)
in the Betaine-homocysteine S-methyltransferase gene with abruption (25 cases of 196 abruptions compared to 17 of 191 controls,
adjusted odd ratio 2.82 (1.84-4.97). Decreased function of this enzyme could lead to elevated homocysteine. The abruptions
were not related to the homocysteine levels, but the assays were obtained without relation to dietary intake or folate supplementation.
As in all the studies by the New Jersey Abruption Study, the inclusion criteria did not require evidence of a fetal distress
or proof of significant predelivery placental separation, and did include very preterm infants.
Studies of the role of methionine/homocysteine metabolism
on abruption are complicated by the effects of nutrition particularly folate and B6, by smoking and alcohol use, and by a
possible interaction of multiple polymorphisms of the MTHFR gene on homocysteine levels and possibly on other aspects of disease.
In all of the studies there are confounding factors of the intrinsic severity of thrombophilia, the role of therapy, and the
inclusion of other common associations of abruption such as prematurity and preeclampsia that likely have non-thrombophilic
mechanisms of abruption. That some studies have found the association, and since there is a plausible biologic mechanism in
thromobsis of uterine veins, thrombophilia can not be dismissed as a risk factor for abruption.
E. Arterial hemorrhage as a mechanism of placental separation
An arterial hemorrhage as a mechanism of placental separation
implies that blood from a ruptured artery can dissect the basal decidua producing a hematoma. The blood in the trophoblast
canalized arteries is at relatively low pressure and high flow, but a hematoma produced by these vessels would expand until
it reached systemic blood pressure. A histological study of 462 preterm placentas found an association of basal hemosiderin
(but not membrane hemosiderin) with several histological lesions that may be related to decidual arteriopathy in infants delivered
between 22 and 32 weeks of gestation. A history of clinical bleeding more than 72 hours prior to delivery was significantly
associated with hemosiderin in both basal and membrane decidua (but looking at the data the basal hemosiderin had only negligible
differences with the no hemosiderin rates). A table that showed significance levels but did not specify for which variables
appeared to show an association of non-hypertensive abruption with a clinical history of bleeding in the first and second
trimester. The authors conclude that their study suggests that abruption could be due to a long standing arteriopathy. I would
interpret the results differently in that it appears that membrane hemosiderin is associated with vaginal bleeding which suggests
that some abruptions are associated with hemorrhage beneath the membranes prior to clinical abruption. The evidence that basal
decidual hemosiderin is a marker for potential abruption is weak.
Case reports of Doppler studies in patients with abruption
suggest that there is elevated resistance in the uterine arteries. In one case, a mother with a history of five recurrent
abruptions with 4 fetal losses was studied hours prior to an ultrasound documented abruption and stillbirth. Her uterine
arteries demonstrated a “very high” pulsatility index and a pronounced notch in the Doppler velocity waveform.
The umbilical vessels and fetal carotids were normal. The placenta showed some small infarctions. A second case was studied
during an abruption seen on ultrasound. The uterine arteries had a systolic/diastolic ratio of 6 (normal <2.6). The
umbilical artery had a dicrotic notch and a S/D ratio of 8 (normal <3.7). No placental examination was described. The evidence
of elevated uteroplacental resistance in both cases could have been due to mild preeclampsia in both mothers with poor trophoblastic
invasion and widening of spiral arteries although arterial spasm can not be excluded. The explanation of increased umbilical
resistance is more difficult to understand as the typical pathological picture is one of villous congestion with acute RPH.
I had assumed such congestion was due to fetal vascular ischemia and dilatation since the dilatation also occurs with infarction,
but perhaps the mechanism involves a chorionic venous constriction. Both the histological and the Doppler studies support
a possible arterial disease mechanism in premature placental separation.
1. Epidemiologic risk factors and arterial disease
Most population surveys have found assoiciations of abruption
with maternal diseases that could be causing an arterial disease including chronic hypertension, pregnancy induced hypertension
and use of vasoactive drugs such as cocaine and cigarettes. A review of 415 cases of abruption from 36,875 unselected deliveries
at one hospital found significant associations with intrauterine growth retardation, histological chorioamnionitis, rupture
of membranes > 24 hours, preeclampsia, chronic hypertension, and cigarette smoking. Removal of growth retardation from
the regression model had little effect on the other associations. The definition of abruption were two or more criteria of
four : “1) antepartum hemorrhage after 20weeks of gestation, 2) uterine pain or tenderness, 3) fetal distress of death,
4) blood clot behind the placenta”. The findings were not related to gestational age.
A study using ICD-9 codes from the National Hospital Discharge
Survey (approximately 400 hospitals) from 1979 to 1987 found rates of reported abruption to be 0.8 to 1.2 % with higher numbers
in the most recent data. The total number of abruptions was approximately 286,000 and at a rate of 1%, the total deliveries
must have been near 28 million. The incidence of coagulopathy was 2.5% and of stillbirth 7.1% with abruption compared to 0.05%
and 1.2% in those without. The associated complications were twins, PROM, chorioamnionitis, chronic hypertension and preeclampsia.
A study of abruption in Peru using the criteria of the New Jersey Abruption study
group found that previous stillbirth was a significant risk factor for abruption., but there was no study of the prior stillbirths
to see their relationship to RPH or preeclampsia
There are many differences in the definition used for abruption
in epidemiologic studies. Abruption causing fetal distress or maternal defibrination may have different risks from those associated
with antepartum hemorrhage and a small adherent hematoma on the placenta. Stratifying the analysis of preterm infants from
term might aid separation of different mechanisms of abruption. Some of the epidemiologic abruption studies use, often with
modification, the classification of Page, King and Merrill:
“Grade 0. These are clinically unrecognized before delivery (diagnosis
based upon examination of the placenta).
Grade 1. These show external bleeding only, or mild uterine tetany, but no
evidence of maternal shock.
Grade 2. In this group there is uterine tetany, ordinarily with uterine tenderness,
possibly external bleeding, fetal distress (or death), but no evidence of maternal shock.
Grade 3. Here there is evidence of maternal shock or coagulation defect, uterine
tetany, and intrauterine death of fetus.”
The authors emphasize that Grade 1 did not progress to Grade 2 or 3, and fetal
mortality was related to the tendency for this grade to occur in premature infants, and not directly to abruption. Grade 2
often progressed to Grade 3 with time, and complications were related directly to the abruption. The authors excluded Grade
0 from their analysis. They also did not include preeclampsia/ eclampsia in the classification system because this disease
had a contribution separate from the abuption to the maternal and fetal complications.
2. Possible mechanisms of decidual arterial hemorrhage
a) Arterial spasm
The decidual spiral arteries supplying the placenta have
lost their media, but there must be a junction with arteries with a media capable of contraction. A persistent vasospasm of
this media could cause necrosis and subsequent rupture of the distal vessel or even rupture from constriction of the muscular
artery at the junction with the transformed spiral artery, leading to a deep arterial hemorrhage dissecting into the decidua.
Possibly patients with abruption, analogous to Berger syndrome, may be unusually susceptible to the vasoconstrictive effects
of the drugs or possibly a sudden rise in blood pressure may physically disrupt the artery.
Such spasm could
underlie the association of abruption with cigarette smoking or cocaine usage [63, 64]   [66, 67]. The abruption
following cocaine use anecdotally has occurred minutes to hours following snorting the drug[68, 69]. A study of 29 maternal
cocaine users that evaluated placental pathology did not find an increased incidence of retroplacental hemorrhage (1 case)
compared to controls, although 4 had a clinical history of abruption. Five had chorionic villous hemorrhage. The control
patients, all randomly selected, also had a high incidence of chorionic villous hemorrhage (3 of 20) which seems improbable
in my experience. Such intravillous hemorrhage is associated with premature placental separation.
Histological studies have not shown a consistent lesion
associated with abruption and cigarette smoking. A study of women with abruption found a statistical increase of intervillous
thrombus in the 20 smokers versus 169 non-smokers. The study did not define criteria for gross sampling of lesions, and
intervillous thrombi may not be consistently sampled as a lesion. More importantly there is no evidence that intervillous
thrombus is an indicator of placental hypoxia. Based on immunostaining of fetal hemoglobin, the lesion is the result of fetal
hemorrhage into the intervillous space with thrombosis of fetal and maternal blood. The same study found, at P = .04, a reduction
in placental infarctions in smokers. This suggests increased decidual arterial thrombi in the non-smokers.
b) Arterial hemorrhage into an infarction
An infarction in the brain, although initially bland, may
secondarily develop an expanding hemorrhage. Neuropathologists designate such a lesion as a red infarction. The infarcted brain, like the decidua, is a tissue with little firm structure to restrain a hemorrhage.
Infarctions of the placenta occur from occlusion of spiral arteries in the base of the placenta. Diseases that cause such
infarctions such as pre-eclampsia or maternal thrombophila are also associated with retroplacental hemorrhage. Decidual vessels in an infarction are connected to deeper and to collateral arteries at systemic pressure
that could produce an expanding retroplacental hemorrhage in the decidua equivalent to a red infarction of the brain.
Many studies have found an association of pre-eclampsia
with abruption. A study of 170 women with abruption from 22,905 deliveries over a decade at one Finnish hospital found a significant
correlation with pre-eclampsia. The authors point out that pre-eclampsia was a poor guide to risk since only 2.8% of pre-eclamptic
patients developed abruption and only 13% of abruptions were associated with pre-eclampsia. This study, as do most epidemiologic
studies of abruption, has an arbitrary but typical definition of abruption: “At least two of the following criteria
was required for diagnosis: 1) vaginal bleeding in late pregnancy 2) uterine tenderness with increased baseline uterine tone
monitored externally 3) fetal distress or death, and 4) blood clot behind the placenta.” By having 2 criteria perhaps
some cases of marginal or retromembrane bleeding are eliminated, but if 1 and 2 are the criteria used, not all may be selected.
If 3 and 4 used, many preterm infants will be selected without evidence that the retroplacental clot was a cause of distress
nor occurred prior to delivery of the infant, or at the least was not secondary to rupture of membranes in a very premature
infant. This particular study accepted all cases over 20 weeks of gestation. They did not stratify for gestational age, but
59% of cases were preterm birth (which would have included many of the pre-eclampsia cases) compared to 6% of controls. Of the cases 41% had one minute Apgar scores less than 7 and 26% had five minute scores
less than 7. This data shows that some of the cases had fetal distress. Severe
fetal distress was rare with only 5 cases having a fetal venous pH < 7.15.
Pathological criteria and their limitations will be discussed below.
c) Arteriopathy and arterial rupture
Hemorrhage may occur when a disease process weakens the
wall of an artery under systemic pressure. This is a familiar mechanism in hypertensive hemorrhages in the brain. A common
arteriopathy in pregnancy is acute atherosis which demonstrates microaneurysm formation, and fibrinoid necrosis of the media
often with accumulation of lipid foam cells. This lesion is associated with pregnancy induced hypertension, but occurs only
sporadically in that disease. The lesion is restricted to spiral arteries not canalized by trophoblast in both the basal and
parietal decidua. In a study of 445 consecutive women with severe preeclampsia/ eclampsia, abruption was not associated with
measures of clinical severity of the preeclampsia . In my experience, acute atherosis also does not appear related to
severity of preeclampsia. An older study that included the pathologist who first
described acute atherosis found the lesion only 7 times in 174 cases of premature placental separation associated with toxemia.
The study found in the same patient group an increased incidence of infarction but they did not compare to toxemic cases without
infarction, and in the discussion it is clear that they also included infarction above the retroplacental hematoma. This study
also proposed a classification of abruption that included the percentage of retroplacental hematoma , <1/6, 1/6 to 2/3,
and almost to complete which were associated with progressive clinical severity. A reasonable hypothesis is that pre-eclampsia
could cause retroplacental hemorrhage either through infarction or through necrosis of arterioles, that is acute atherosis.
Abruption is also associated with chronic hypertension
  [16, 75]. This may in part relate an increased risk of preeclampsia, but arteriolar lesions from hypertension alone
may be significant. No correlation of retinal hypertensive arteriopathy and abruption is reported. If the common element of
elevated blood pressure in weakened vessels contributes to the risk of retroplacental hematoma in chronic hypertension and
in pregnancy related hypertension, then abruption should be related to the pressure at onset.
A retrospective chart review of 265 pregnancies more than 20 weeks gestation
with the clinical diagnosis of abruption (275 infants with twins) found a 24% (13/55) incidence of abruption in eclampsia,
10% (29/290) in chronic hypertension, and 2% (54/2320) in preeclampsia from 24,258 deliveries. Patients were counted more
than once if they had overlapping diagnoses, e.g. chronic hypertension with superimposed preeclampsia. Abruption required
“documentation of a retroplacental clot with depression or disruption of the underlying cotyledons”. The chronic
hypertensives, even excluding those that developed eclampsia, still had twice the incidence of abruption. They also had a
significantly higher incidence of previous abruption (24%) and of perinatal mortality with the current abruption (60%). The
degree of hypertension did not correlate with fetal mortality in the chronic hypertensive patients, but did in the preeclamptic
patients. These findings suggest that more than the pressure, rather the underlying vascular changes from chronic hypertension
may be the significant etiologic factor. Note that distal spiral arteries are lost with each menstrual cycle and would not
have chronic hypertensive change. No detailed study of the retinal vessels, etiology
or duration of the chronic hypertension was provided. As expected, maternal age was higher in the chronic hypertensive patients
(28 years) than in those with just preeclampsia (20 years).
A review of birth certificate data that links mother and
child found an inverse “dose response” curve of risk of abruption with percentile of birth weight that was parallel
for chronic hypertension alone and for superimposed pregnancy hypertension and fetal growth retardation. The risk of abruption
was also highest with superimposed pregnancy induced hypertension. With chronic hypertension alone, the relative risk of abruption
was increased after 32 weeks of gestation with a 1.8 times risk after 37 weeks of gestation. At the same gestation chronic
hypertension with only PIH had a relative risk of 3.7 and of 4.8 with only growth retardation. Chronic hypertension with a
large infant had no increased risk of abruption, unless there was also PIH with had a relative risk of 13. The study had 30,189,949 births with 126,648 abruptions. The study admitted that the results could be skewed
by various interventions, but I am equally concerned about the lack of a definition of abruption. Whatever the flaws, with
such huge numbers, the correlation of at least clinically perceived abruption with maternal vascular disease and intrauterine
ischemia appears well established.
The comparison of abruption in mothers with chronic hypertension
or preeclampsia compared to not having those diseases found a significantly lower umbilical cord pH in the study group.
The grade of abruption was higher, but not significantly, and the mortality rate was similar. They used a simplified grading
system: “1” is maternal bleeding, “2” is fetal distress, and “3” is fetal death.
Direct observation of a ruptured artery in abruption in
has been attempted with placental bed biopsies. A ruptured decidual artery in continuity with a small basal decidual hemorrhage
was identified using serial sections in a placenta with a larger 25 % placental separation from a woman with eclampsia .
Placental bed biopsy beneath abruption has demonstrated abnormal vessels . This study did not have controls and failed
to find vessels in 6 of 18 cases. The biopsies demonstrated intramyometrial hemorrhage. Four cases demonstrated a vessel with
subintimal thickening, no elastica, and fibrin thrombus. The authors interpreted these vessels as possible arterio-venous
malformation and as the possible site of hemorrhage. Subintimal thickening may be a biopsy artifact . Placental bed biopsy
studies have shown that acute atherosis can be found beneath the placenta in preeclampsia and in chronic hypertension with
preeclmapsia. This lends support to the concept that arteriolar lesions in preeclampsia could be the basis of retroplacental
hematoma. These biopsy studies have not proven (nor disproven) that the complex remodeling of arteries by trophoblast could
on occasion produce an abnormal vessel capable of initiating a hemorrhage and retroplacental hematoma.
F. Hemorrhagic diathesis as
a mechanism of placental separation
Hemorrhages associated with a bleeding diathesis may be
occurring at the capillary level, but the effect is that of arterial bleeding since the concept of such bleeding is that a
lower resistance pathway for arterial blood entering the decidua causes decreased and lower pressure in the intervillous space,
and accumulation of blood until the intrauterine pressure equals arterial pressure and tamponade occurs.
There is a report of a mother with congenital hypofibrinoginemia
who had only easy bruisability between pregnancies but had two fetal losses from abruption. The obstetrical history was only that of severe
pain and hemorrhage with no other details except that the second pregnancy was by Cesarean section and both infants were stillborn.
No placental pathology was provided. A 32 week gestation woman with disseminated intravascular coagulation (DIC) and renal
failure following a snake bite demonstrated a 75% placental separation seen at Cesarean section. There was fetal death, and it was not possible clinically to be certain that abruption did not occur first,
but DIC and renal failure were known complications of her Bothrops jararaca bite. No pathology was reported. A case of a needle
induced laceration of the margin of the placenta during percutaneous umbilical blood sampling produced a marginal abruption
A study of thrombectomy in pregnant women had 5 perinatal deaths (with one set of twins) attributed to abruption that the
authors attributed as likely due to anti-coagulation. No details on the patients are given but some in the series had
a family history of deep vein thrombosis or a known genetic thrombophilia. More than 90% of patients also had an arterio-venous
fistula created in the groin. Could this procedure increase uterine venous pressure?
G. External forces causing placental separation
Abruption from the physical shearing of the placenta from
the uterus occurs with motor vehicle accidents. External deceleration moves the placenta in relation to the uterine wall.
Not surprisingly, the more severe the maternal trauma, the more likely abruption will occur  . There have also been
reports of delayed fetal death from abruption in less severe motor vehicle trauma   . A peculiar variant of trauma
would be direct trauma from the fetus who may be able to jar or lift the margin of the placenta. Such fetal kicking was observed
by ultrasound in two cases of mild antepartum hemorrhage. Traumatic placental separation would be expected to involve
Obstetrical management of trauma patients includes looking
for a Kleihauer-Bedtke or other test of fetal to maternal hemorrhage. Placental separation occurs in the decidua, and should
not cause fetal hemorrhage. However, trauma could cause tearing of villi that are fixed in the chorionic plate and lead to
fetal hemorrhage into the maternal intervillous blood, and may be another piece of evidence correlating with traumatic placental
H. The clinical consequences of premature placental separation
1. Fetal asphyxia/ acidosis from devitalized placenta
Whether the abruption is clinically evident or silent, if a sufficient area
of placenta is suddenly devitalized, the infant may die from asphyxia due to decreased gas exchange with the maternal circulation.
If the fetus is rescued by delivery, the neonate may still suffer the consequences including hypoxic ischemic encephalopathy
with a risk of persistent neurologic deficit.
Particularly in automobile accidents, a delay of hours has often been noted between the trauma, the time of presumed
onset of the abruption, and the fetal death. In partial placental separation, the mechanism of fetal injury may be more complicated
than just the loss of a portion of placental exchange function. Examination of the placenta in these cases demonstrates that
the devitalized placenta is much deeper red than the uninvolved segments. Microscopically, this is associated with marked
vascular congestion, and sometimes intravillous hemorrhage . ( A note on this cited study: Histological examination of
placentas with either a >10% retroplacental hematoma or a description of separation at Cesarean section demonstrated intravillous
hemorrhage usually adjacent to the RPH, and more frequently in younger gestation but present at any gestation. The authors
conclude based on published papers of the association of RPH and positive Kleihauer Bedtke tests that fetal hemorrhage must
proceed RPH since there is no maternal circulation to carry away fetal blood after the RPH. They also postulate intervillous
hemorrhage as evidence of hyperfetal circulation and the source of fetal hemorrhage that must precede and therefore may be
a cause of abruption. The logic is tenuous.) To the extent that this congested
devitalized placenta is being fetally perfused, the fetus will be shunting blood away from areas of gas exchange, and into
dying tissue that would be expected to add a lactic acid load to the blood returning to the fetus. A small marginal abruption
produced by needling the margin of the placenta during percutaneous umbilical blood sampling caused persistent fetal bradycardia
that led to Cesarean section although the umbilical vein blood gas after delivery was not acidotic. The child had a seizure
in the nursery but was discharged without neurological deficit.
A study following mothers with first trimester retroplacental or subchorionic (beneath the membranes) hematomas found
significant correlations with multiple obstetrical complications later in gestation. The largest relative risks of the
hematoma (retroplacental and subchorionic combined) were for abruption or preclampsia. Retroplacental hematoma specifically
was associated with perhaps related outcomes of preeclampsia, preterm delivery and fetal growth retardation. The study did
not try to correlate the ultrasound finding with a pathological correlate in the delivered placenta. The hematoma was retroplacental
in 68 of 159 pregnancies and large (greater than 50% of the size of the gestational sac) in 26 cases. The number of retroplacental
hemorrhages that were large was not provided.
A monkey fetus delivered with a presumption of stillbirth still had severe bradycardia at the time of autopsy.
The placenta showed two partial retroplacental hematomas, one older than the other. The brain showed severe cystic encephalomalacia
including the spinal cord. The author did not estimate the percentage of the placenta devitalized by the separations, but
they were relatively large judging from the illustration. The mother monkey had been asymptomatic although fetal movement
had been absent for at least two weeks prior to delivery which were post dates.
Logically, the larger the area of placenta separated from the uterus the more likely that stillbirth will result. A
study based on obstetricians reported estimate of the abruption did show a correlation of percentage size of the separation
and the logarithmic risk of stillbirth. The curve begins to inflect upward after 40-50% separation. There was no validation
of the obstetricians estimate to pathologic findings or to other clinical measures of severity of abruption such a fetal distress
or maternal coagulopathy. The same study found an association of abruption with risk of intrauterine growth retardation that
was adjusted for cofounding variables such as preeclampsia. The use of risk in this study does not imply causation, since
an increased risk of small separations with prematurity could as easily be explained if small adherent hematomas with vaginal
delivery were a consequence of preterm delivery. The definition of abruption in this study was the gross clinical examination
of the placenta.
The perinatal collaborative study, from the 1960's, found
abruption to account for 3.96 perinatal deaths / 1,000 births . Abruption
was defined as "an adherent retroplacental clot with depression or disruption of the underlying placental tissue or when there
were otherwise classical clinical findings including external or occult bleeding, increased firmness of the uterus and death
between 20 weks of gestation and the twenty eighth post natal day…” There were 138 stillbirths and 74 postnatal
deaths in 53,518 pregnancies, and the rate of perinatal deaths for abruption was the second highest cause of death in the
study. The study finds associations with many factors in a somewhat confusing mix, but does support the association with preeclampsia
(intrapartum hypertension, fibrinoid necrosis of spiral arteries, and placental infarctions)
and with maternal cigarette smoking (P<0.06). There are many histological correlations but the relationship of the
findings to the location or size of the retroplacental hematoma is not described, nor is the size of the hematoma. The study
demonstrated two peak gestational incidences, the first from 20-29 weeks of gestation and the second after 38 weeks of gestation.
If the first peak refers to the small marginal RPH seen in mid gestation, many of these were likely incidental to the infant’s
death. The author’s also suggest their data supports a role for maternal undernutrition, but the data is unclear and
weight gain over 37 weeks had only a P<0.1 which is not significant.
A review of abruption so severe as to the kill the fetus
found a reduction from 1 in 420 (1956 to1969) to 1 in 830 (1974-1989, 207 cases
in total deliveries 171,787) attributed in a change in racial distribution from a high risk black population (1 in 830) to
a low risk Latin American population (1 in 1473). Sickle cell trait was not a risk factor for abruption. Preeclampsia
was a risk factor for abruption, but could not account for the racial differences. Abruption recurred in 12% of subsequent
pregnancies and was fatal in 7%. The recurrent cases were presented in individual detail and a striking observation is that
almost all the cases first and second abruption were associated with low birth weight or less than term gestation.
2. Coagulopathy in the mother
It is an axiom of the management of abruption that defibrination
or disseminated coagulation is a potential complication of abruption. The mechanism is less clear. Early experimental studies
had demonstrated that a cold saline rinse of placenta injected into pregnant animals caused consumption of fibrin and often
pulmonary thromboemboli and less frequently cerebral thrombi . Placental trauma in experimental animals produced the same
results [95, 96] A reasonable hypothesis was that abruption would mimic these experimental results in that the margins of
the retroplacental hematoma would wash placental or decidual thromboplastin into the maternal blood stream. More recent work
suggests that the effects of placental separation on coagulation may be more complex, but that the underlying abnormality
is initiated from the intravascular injection of thromboplastin. This study correlated peripheral blood coagulation parameters,
especially fibrinolytic, with the severity of the abruption by clinical criteria (which also correlated with their estimate
of the observable extent of placental separation) in 19 patients presenting with abruption. In nine, they documented improvement
after uterine evacuation, for example the mean FDP fell from 150.6 to 10.6 microg/ml following delivery.
One problem of normal separation is how the utero-placental
blood flow is stemmed. A reasonable consensus is that myometrial contraction and elevated coagulation factors in pregnancy
and local tissue injury lead to mural thrombi in the uterine vessels that had supplied the placental bed. The local elevation
of clotting factors in the uterus has been measured directly in uterine vein blood following placental separation during Cesarean
section in 12 patients. Most striking was the elevation of whole blood clotting in the uterine vein compared to the pre-separation
umbilical vein blood and to the peripheral blood drawn simultaneously. Factor VII activity was also increased in this 1970
study. Decreased flow in the uterus has been visualized directly with MR scan showing marked decrease of fundal perfusion
at 5 hrs post partum. With retroplacental hematoma, blood flow is not stopped and local thrombotic factors in the decidua
may be elevated. If there is still venous return beneath the retroplacental hematomas, perhaps these decidual factors are
distributed systemically adding to risk of disseminated intravascular coagulation.
An ultrasound report of a mother whose history is suggestive
of HELLP syndrome with a dropping hematocrit, but no mention of hemolysis, had both diffuse intravascular coagulation and
a 4 x2 cm retroplacental hematoma documented at 18 weeks of gestation. The last sentence of the placental description
makes no anatomic sense “Breaks in the basal plate resulting in contact of necrotic decidua with maternal blood, were
not demonstrated.” A retroplacental hematoma is always in the decidua, there is no need to rupture the basal chorionic
plate for maternal blood to contact decidua. The case found infarcted villi above
the hematoma, and intervillous maternal blood would have been in contact with them.
The review of clinical abruption cases in which Page et.
al. presented their classification system reviews the literature up until that time on the evidence that abruption results
in defibrination in the mother from the intravascular injection of thromboplastin. Defibrination occurred only in the
severe cases. They provided some evidence that renal cortical necrosis associated with abruption was not directly related
to the shock and defibrination. The authors even recommended rupturing membranes to lower intrauterine pressure to decrease
injection of the thromboplastin. I have not found studies that chemically identify the thromoboplastin nor determine whether
it can be of decidual origin since decidual procoagulants appear to be necessary for normal postpartum coagulation of the
placental bed (i.e. bleeding with placental accrete). Normal separation does not produce defibrination which could be due
to rapid removal of the placenta from intervillous circulation. The early experimental
studies used a placental extract. I did not find studies confirming subclinical coagulation defects in small retroplacental
A preliminary study of 10 patients with abruption found
a significantly elevated level of CA-125 in maternal serum. Three had stillborn infants and the other 7 were classed
as grade 2 on a system by Sher. Abruption criteria were those of Hurd, and “The diagnosis of abruption placentae was
confirmed at delivery in each case with either gross examination of the placenta revealing a firmly adherent retroplacental
clot wit disruption of the underlying tissue, pathologic diagnosis, or both”. Of the 10 cases, only 5 had values clearly
above the controls, and only 2 were greatly higher. While no overall correlation with gestation or grade of abruption was
found, the individual values for each patient with the clinical history might have given some insight. The postpartum controls
were all elevated. The time course of CA-125 elevations in abruption and in normal separation would have been useful to evaluate
the level as a test for abruption. The authors postulate that the CA-125 was being released from decidua. A rapid marker of
placental infarction might better be able to separate retroplacetnal from retromembrane hemorrhage.
2. Marginal and retromembrane hematomas
Marginal hemorrhages may occur because of contraction of the lower uterine segment beneath the lower pole of the placenta.
This may lead to vaginal bleeding, but demonstrate no pathological lesion, no fetal compromise, and no association with maternal
disease. In other cases, the dissection of a retroplacental hematoma to the lower margin of the placenta may permit vaginal
bleeding to decompress a dissecting retroplacental hematoma, and perhaps prevent a more complete separation of the placenta.
In this later case, there should be a retroplacental hematoma as well as a marginal hemorrhage. A study of 24 patients with
ultrasound prior to a Cesarean section divided into three equal presurgical clinical diagnoses, A) typical severe abruption
B) suspected abruption confirmed by ultrasound, and C) threatened premature delivery with abruption diagnosed by ultrasound
separated ultrasound findings into either a central thickening or an edge hematoma. Seven of the patients in group A and 3
in group B fell into the central thickened group. Those with an edge hematoma
had smaller areas of placental abruption, less coagulation abnormality and higher Apgar scores . An alternative theory
of marginal hemorrhage is the rupture of the large veins at the periphery of the placenta in the decidua and myometrium) .
A retrospective study of patients with a clinical diagnosis of abruption found that up to 25% had retromembranous (N=6) or
retroplacental (N=6) hematomas on ultrasound. Most of these patients had low grade abruptions based on a system that
had grades 0 and 1 without significant complications, grade 2 with concealed hemorrhage, uterine tenderness, rare coagulopathy,
and fetal distress. Grade 3 had in addition maternal hypotension, fetal death, and often coagulopathy. The data were not clear
but most patients fall into the 0-1 group in which the only difference is that the group 0 is diagnosed after delivery by
finding a retroplacental clot. This group especially in the preterm group could have a prolonged period before delivery without
The incidence of intrauterine hematomas seen in threatened abortion is relatively high. An ultrasound study with an
incidence of 22% intrauterine hematomas in women with threatened abortion (hematoma volumes from <10 to >30ml, gestation
ages from 2-24 weeks) found an increased risk of eventual fetal loss (16.3% versus 5.5%; P<.05). While one image shows
the hematoma beneath the placenta, the study does not clearly differentiate the location of the hematoma, nor examine placental
pathology at birth.
A review of marginal separation
considers that the association with premature labor and premature rupture of membranes is possibly causative. Fragility
of the marginal attachment and underlying large veins was postulated as the primary cause of the placental separation with
consequent decidual injury producing prostaglandins and preterm labor. In part the review is based on the author’s pathological
study of 90 preterm placentas with exclusions designed to have an uncomplicated sample of premature labor from 20 to 37 weeks
of gestation compared to 45 term placentas. He did find more pathological lesions in the premature placentas including
more marginal hematomas, as well as marginal necrosis and fibrin. The study states “ At the placental margin, an adherent
clot is present. This clot is readily differentiable from the clot often seen after normal postpartum separation in that the
antepartum clot is adherent to the placenta and membranes and is removed only with difficulty. It is dark in color, frequently
contains fibrin, and may be laminated. Polymorphonuclear infiltration is often noted.”
Except that I am not sure what is meant by “contains fibrin”, this is a fair description of a common observation.
These observations do not prove that the hematoma precedes the onset of preterm labor. These finding might even occur in a
prolonged third stage of labor in preterm gestation. The paper states that it is only speculation that the marginal separation
causes preterm labor. The review also disposes of the concept of a marginal sinus of the placenta as being disproven by angiography
of monkey placentas by Ramsey. In reviewing one of the papers on marginal sinus, the observations are based on gross examination
of the delivered placenta. The paper refers to abscission windows believed formed by the necessary disruption of transdecidual
veins at the margin of the placenta. The observation of the marginal sinus itself
is likely an artifact of the separation of the decidua away from the junction of the membrane chorion and the basal plate
chorion. The concept of venous bleeding from the lower margin of the placenta being likely venous blood and of different significance
from abruption is reasonable. Likely venous return is obstructed by labor especially through collateral veins in the cervix
or lower uterine segment, and this back pressure could rupture the large thin walled veins in the marginal decidua.
An unusual complication of a retromembrane or marginal hematoma would be rupture into the amniotic cavity which has
been reported by ultrasound observation. The sometimes described “port wine” colored amniotic fluid with
abruption is likely diffusion of hemoglobin through the overlying membranes, rather than direct hemorrhage. Hematomas confined
to a retroplacental location can not color the amnion fluid, but those at the margin or under the membranes could. A role
of retromembrane hematomas in devitalizing fetal membranes and causing rupture of membranes is not established
3. The pathological identification of very acute abruption
When an abruption has a rapid and witnessed clinical onset,
an emergency Cesarean section will usually deliver a living infant. Typically, the placenta will show a retroplacental hematoma
in situ at Cesarean section. The pathologist often can not identify the retroplacental hematoma from the examination of the
placenta. In a brief interval, there would also be no anatomic evidence of villous necrosis. The existence of clinical abruption
without pathological retroplacental hematoma was noted by Gruenwald who also noted retroplacental hematomas without clinical
abruption. He reviewed the clinical chart and the pathology of 612 cases
with either a clinical abruption or a pathological diagnosis of placental separation. And found that the two designations
overlapped in less than half of either category alone. He did not define the pathological criteria for placental separation,
but did classify them as marginal if they extended over the placenta less than 5 cm from the margin, and major if they extended
over the central placenta for more than 5 cm from the margin. He did note that after 28 weeks of gestation having both diagnoses
had a higher rate of perinatal mortality.
A recent paper by the New Jersey Placental Abruption Study
also noted the poor correlation between the pathological and the clinical diagnosis of abruption with only 49 of 162 clinical
abruptions confirmed pathologically. This study also looked at a broader range of pathological correlations, but the
results can not be interpreted since the cases included 55% with gestation under 35 weeks (7% below 25 weeks) compared to
12% in the controls. The cases had 14% preeclampsia compared to 1% of controls. Some of the lesions studied are already correlated
with prematurity (lesions with acute inflammation) or preeclampsia (lesions such as infarction and villous changes of utero-placentla
ischemia). Some of the lesions are of unproven significance and reliability such as villous dymaturation or decidual vasculopathy
(which included muscular thickening, not just acute atherosis).
If a lack of findings can occur in the witnessed abruption,
could it not also occur in very acute partial abruptions that occur just prior to vaginal delivery? Adherence of the blood clot may not be a reliable criterion, since the conditions of post partum and immediately
prepartum separation may be similar. In very acute separation, the overlying villi may show vascular dilatation compared to
other areas. In some cases, this is associated with intravillous hemorrhage. The association with intravillous hemorrhage
was postulated as a cause of abruption in a paper describing the lesion. An equally plausible hypothesis is that a large
retroplacental hematoma could cause both ischemia of the endothelium in the overlying villi, and sufficient hypoxia/acidosis
to produce heart failure and elevated pressure in the right heart. An ischemic capillary or venule distended by increased
pressure might hemorrhage.
Abruption was produced in the rabbit by injection of a
pregnancy urine extract called antuitrin-S (Parke, Davis and Co.). The uterus developed marked intramural hemorrhage
in all layers associated with partial placental separation. Administration of daily subcutaneous doses of cocaine did produce
abruption in rats that occurred near the time of fetal maturity. There was no histological study.
The experimental production of placental abruption in dogs
was mentioned in reference to vena caval occlusion in humans. An industry study using this the vena caval occlusion in dogs,
found that giving a “ganglionic blocker”, trimethaphan camphorsulphonate, reduced the number of abruptions produced.
The drug was being tested for its ability to protect the kidney following abruption, and the results were unexpected. The
authors note that there is less increase in venous pressure in vena caval ligation when the drug is used. The same study was
able to produce abruption but of lesser frequency by subjecting the pregnant dogs to hypoxia (10% oxygen environment). The
authors speculate that the effect of vena caval ligation is to both elevate decidual venous pressure and produce tissue anoxia,
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