Placental Diseases

Placental hematomas, as their name indicates, are localized collections of hematic material generated by a vascular lesion. They are generally self-limited and of variable location with respect to the placenta.

There is no standard ultrasound definition of placental hematoma. 15 Sonographically, their appearance varies according to their evolution over time. A hyperechoic or isoechoic appearance represents an acute form, whereas a hypoechoic appearance suggests a chronic form. Placental hematomas will never demonstrate a signal on color Doppler evaluation, which is helpful in distinguishing them from other pathologies on the differential diagnosis. 1

According to their location, we can further classify them into:

- Sub-amniotic hematoma

- Sub-chorionic hematoma

- Retrochorial hematoma

Sub-Amnionitc Hematoma

The sub-amniotic hematoma is located pre-placentally, between the amniotic membrane and the chorionic plate. This finding is quite infrequent and usually incidental. It is generally asymptomatic and typically diagnosed in the third trimester. Sub-amniotic hematomas may be caused by traction on the umbilical cord, either by fetal movements, external pressure, or an area of ​​weakness in the vascular wall, which ends up causing a vascular lesion. 2 When they present earlier, they usually evolve due to the formation of an organized clot.

Due to its location, it is usually seen as a rounded hypo or anechoic shape covered by a thin membrane (amnion), which protrudes from the fetal surface of the placenta towards the cavity. The base can be sessile or pedunculated. Their size are variable, as they can reach up to 5 to 9 cm in diameter according to certain reports. They can be associated with fetoplacental hemorrhage, fetal anemia, and fetal growth restriction.

The main differential diagnoses are placental cysts, cord cysts, chorioangioma, sub-chorionic hematoma as well as vanishing twin. Unlike sub-amnniotic hematomas, chorioangiomas are well vascularized. We must emphasize that the presence of placental cysts has not been associated with adverse perinatal outcomes, and their content is not bloody but a gelatinous material. 3

Clinical management should be individualized according to each situation. Due to the low association with complications, premature delivery is not recommended.

Sub-Chorionic Hematoma

A sub-chorionic hematoma can also be referred to as subchorionic intervillous thrombus, or occasionally, subchorionic fibrin deposition. 15 Some authors advocate for the preferred term ‘subchorionic thrombus’ given differing definitions of ‘subchorionic hematoma’ in the obstetrical and radiologic literature. 15 For example in early pregnancy, subchorionic hematoma has been used to describe retroplacental or retromembranous hematomas. 15

Sub-chorionic hematomas in turn can be found either pre-placentally (between the chorionic plate and leafy chorion), intraplacentally, or extra-placentally (between chorionic plate and parietal decidua).

Sub-chorionic hematomas are the most frequent placental hematoma. They are also the most frequent cause of bleeding in the first half of pregnancy. In other cases, they can be asymptomatic.

Sub-chorionic hematomas are throught to be due to the rupture of low-pressure maternal vessels in the thickness of the placental mass.

On ultrasound imaging there is no movement of blood seen inside the hematomas on directional color imaging or power Doppler ultrasound. 15 Slow blood movement can be seen on tissue color Doppler. 15

The differential diagnosis of sub-chorionic hematoma includes; massive subchorionic thrombohematoma or mole of Breus, placental lacunae, and chorioangioma.

Management is similar to sub-amniotic hematomas.

Retrochorial Hematoma     

Retrochorial hematomas are located between the decidua basalis and the leafy chorion. They are thought to be the result of rupture of maternal spiral arteries, which generates high-pressure bleeding.

Ultrasonographically, retrochorial hematomas appear as a well-circumscribed anechoic or hypoechoic area located between the placental mass and the myometrium. Using negative Doppler signal, retrochorial hematomas can be found separating the placenta from the myometrium. The “edge configuration” is when this separation occurs in relation to one of the placental edges.

With retrochorial hematomas, there is an increased risk of miscarriage, fetal death, premature delivery, and premature abruption of a normally inserted placenta - the latter being the most worrisome.

In the event that premature abruption occurs, the diagnosis would be clinical, and ultrasound imaging would be categorical. We must however, bear in mind that even though we may not be able to see this image on ultrasound, we could still be in the presence of a possible fatal outcome. ¹

Massive Perivillous Fibrin Deposition (MPFD) is a placental pathology of variable severity. It is characterized by inadequate deposit and excessive fibrinoid material. In this process, more than 25% of the intervillous spaces are occupied by fibrin.

It is important to consider that scant deposit of fibrinoid material in the marginal and subchorionic zone may be physiologic. This is why it is necessary to assess not only the amount of material deposited but also its location. The amount of physiologic fibrin storage increases progressively in the third trimester. 4

Although MPFD was first described in the literature by Benirschke and Driscoll in 1967 and Maternal Floor Infarction (MFI) by Fox in 1976, its etiology still remains unknown. Many hypotheses have been formulated such as establishment of autoimmunity, infections and cytotoxicity, caused by the proliferation of extravillous trophoblasts. The presence of anti-HLA I antibodies, CD4 deposits in the umbilical vein endothelium, complement activation and plasma cell deciduitis were found more frequently in patients with this condition, which supports the theory of autoimmunity in relation to the inflammatory state. 5. Likewise, patients who present with this condition usually have a personal and family history of autoimmune pathologies, such as antiphospholipid antibody syndrome.

It is hypothesized that the pathophysiology is based on an imbalance between anti-angiogenic and angiogenic factors, in favor of anti-angiogenesis, due to the increase in soluble forms of vascular growth factor (VEGFs) and endoglin (sEng) and the decrease in factor placental growth factor (PlGF). 6

The reported incidence of MPFD in all pregnant women is 0.09% in recent studies. The reported prevalence is 0.028 to 0.5%, although some more recent studies show a lower prevalence than what is published. We must bear in mind that this estimate varies according to gestational age, as it is found more frequently in abortions that occurred during the first trimester (2.7%). 7

Although the presumptive diagnosis can be uncovered prenatally through imaging studies, the definitive diagnosis will ultimately be made by the pathologist. Ultrasound findings suggestive of MPFD include cystic hypoechoic areas surrounded by echogenic tissue with very low blood flow and an enlarged placenta. 15 The hyperechogenic regions represent villi compressed by laminated fibrin and erythrocytes. 15

Macroscopically, MPFD can be distinguished in the placenta as yellowish-white plaques with irregular edges and variable size, or more diffusely as a yellowish parenchyma. Histologically, dense fibrinoid material is observed occupying the intervillous spaces and surrounding the chorionic villi. This is accompanied by proliferation of extravillous trophoblasts. The fibrin deposited in the intervillous space interferes with normal maternal blood flow, generating placental insufficiency, which is closely related to the complications that derive from this condition. 8

This pathology has been associated with high morbidity and mortality, as well as an increase in fetal growth restriction (54%), premature birth (58%), fetal death (40%) and recurrent miscarriages. 9 It is also associated with pre-eclampsia. 15 In turn, it poses a recurrence risk of approximately 30% in in subsequent pregnancies.

To date, there are no validated methods to assess the risk of perinatal complications or to predict the risk of recurrence in future pregnancies. To date, there have been no effective forms of prevention found.

Regarding treatment, the most widely used drugs, as a single or combination therapy, have been aspirin, low-molecular-weight heparin (alone or combined with low-dose aspirin) and immune-suppressors (eg. IV immunoglobulin). 6

Placental blood supply is dependent on maternal blood supply. Therefore, compromised placental blood supply leads to placental infarction and necrosis which may compromise the basal plate. Placental infarcts can be of various sizes and are not visible sonographically.

Although the etiology and pathogenesis of placental infarcts are not yet fully understood, they are thought to be related to narrowing or occlusion of the spiral arteries by a thrombus. 15 Susceptibility of maternal vessels to obstruction is likely to be secondary to defective transformation of maternal arterioles in the first trimester. 15

Often placental infarcts are asymptomatic and found in approximately 25% of placentas in the postpartum period. They are strongly associated with preeclampsia 10. They are also associated with fetal conditions such as growth restriction and lesions at the level of the neonatal CNS. These vascular alterations are observed more frequently in late-onset fetal growth restriction than in pregnancies without growth restriction pathology and, in turn, have a higher incidence in early-type IUGR. 12 In one study, 72% of fetuses with absent or reversed end-diastolic flow in the umbilical artery had placental imaging showing hypoechogenic areas highly suggestive of placental infarcts. 15

Sonographically, placental infarcts are defined as hyperechoic or echolucent avascular areas within the placenta without blood flow. 15

A series of 142 singleton placentas born more than 34 weeks with normal umbilical artery (AU) Doppler velocimetry found that 54.2% had placental weights <3rd percentile (compared with 9.9% of 142 placentas found in infants of normal growth, P < 0.001). Only 21.8% (31/142) of the placentas were free of histological abnormalities, while 74.6% (106/142) were in the normal growth group (p < 0.001). 11,13

In another retrospective population study (CHAMPS study) conducted in Canada among 75,380 women with placental syndromes such as placental infarction, preeclampsia, etc. demonstrated a higher incidence of premature cerebral-vascular disease in this population (HR 2.0, CI 1.7–2.2). ), with increased risk in the combined presence of maternal placental syndrome and fetal growth restriction (HR 3.1, CI 2.2–4.5) or intrauterine fetal death (HR 4.4, CI 2.4–7.9) 14 In conclusion, we could determine an association between placental infarction and adverse obstetrical conditions such as preeclampsia, IUGR, CNS lesions of the newborn, and perinatal death. 14

Although placental infarcts cannot be clearly seen by ultrasound, we can find them in the placental pathology reports of mothers with preeclampsia or hypertensive-disorders or fetuses diagnosed with growth restriction or other poor perinatal outcome.

1. Guía clínica: Hematomas placentarios. Desprendimiento prematuro de placenta. Hospital Universitario Clinic de Barcelona. Yasmina Barral, Teresa Cobo, Marta López, Edurne Mazarico. 2011
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3. Deans A, Jauniaux E. Prenatal diagnosis and outcome of subamniotic hematomas. Ultrasound Obstet Gynecol. 1998 May;11(5):319-23. doi: 10.1046/j.1469-0705.1998.11050319.x. PMID: 9644769.
4. Lampi K, Papadogiannakis N, Sirotkina M, Pettersson K, Ajne G. Massive perivillous fibrin deposition of the placenta and pregnancy outcome: A retrospective observational study. Placenta. 2022 Jan;117:213-218. doi: 10.1016/j.placenta.2021.12.013. Epub 2021 Dec 16. PMID: 34959167.
5. Romero R, Whitten A, Korzeniewski SJ, Than NG, Chaemsaithong P, Miranda J, Dong Z, Hassan SS, Chaiworapongsa T. Maternal floor infarction/massive perivillous fibrin deposition: a manifestation of maternal antifetal rejection? Am J Reprod Immunol. 2013 Oct;70(4):285-98. doi: 10.1111/aji.12143. Epub 2013 Aug 1. PMID: 23905710; PMCID: PMC4122226
6. Chaiworapongsa T, Romero R, Korzeniewski SJ, Chaemsaithong P, Hernandez-Andrade E, Segars JH, DeCherney AH, McCoy MC, Kim CJ, Yeo L, Hassan SS. Pravastatin to prevent recurrent fetal death in massive perivillous fibrin deposition of the placenta (MPFD). J Matern Fetal Neonatal Med. 2016 Mar;29(6):855-62. doi: 10.3109/14767058.2015.1022864. Epub 2015 Apr 20. PMID: 25893545; PMCID: PMC4710361.
7. Kim EN, Lee JY, Shim JY, Hwang D, Kim KC, Kim SR, Kim CJ. Clinicopathological characteristics of miscarriages featuring placental massive perivillous fibrin deposition. Placenta. 2019 Oct;86:45-51. doi: 10.1016/j.placenta.2019.07.006. Epub 2019 Jul 12. PMID: 31326089.
8. He M, Migliori A, Maari NS, Mehta ND. Follow-up and management of recurrent pregnancy losses due to massive perivillous fibrinoid deposition. Obstet Med. 2018 Mar;11(1):17-22. doi: 10.1177/1753495X17710129. Epub 2017 Aug 4. PMID: 29636809; PMCID: PMC5888839.
9. Andres RL, Kuyper W, Resnik R, Piacquadio KM, Benirschke K. The association of maternal floor infarction of the placenta with adverse perinatal outcome. Am J Obstet Gynecol. 1990 Sep;163(3):935-8. doi: 10.1016/0002-9378(90)91100-q. PMID: 2403172.
10. Asim kurjak, Frank A. Chevernak. Ecografia en obstetricia y ginecología. 2da edición. 2009. // E. Gratacos, R. Gomez, K. Nicolaides, R. Romero, L.Cabero. Medicina Fetal. 2007.
11. Apel-Sarid L, Levy A, Holcberg G, Sheiner E. Term and preterm (<34 and <37 weeks gestation) placental pathologies associated with fetal growth restriction. Arch Gynecol Obstet. 2010 Nov;282(5):487-92. doi: 10.1007/s00404-009-1255-1. Epub 2009 Oct 24. PMID: 19855989.
12. Adams-Chapman I, Vaucher YE, Bejar RF, Benirschke K, Baergen RN, Moore TR. Maternal floor infarction of the placenta: association with central nervous system injury and adverse neurodevelopmental outcome. J Perinatol. 2002 Apr-May;22(3):236-41. doi: 10.1038/sj.jp.7210685. PMID: 11948388.
13. Figueras F, Caradeux J, Crispi F, Eixarch E, Peguero A, Gratacos E. Diagnosis and surveillance of late-onset fetal growth restriction. Am J Obstet Gynecol. 2018 Feb;218(2S):S790-S802.e1. doi: 10.1016/j.ajog.2017.12.003. PMID: 29422212.
14. Ray JG, Vermeulen MJ, Schull MJ, Redelmeier DA. Salud cardiovascular después de los síndromes maternos placentarios (CHAMPS): estudio de cohorte retrospectivo basado en la población. Lanceta. 2005;366:1797–803.
15. Hernandez-Andrade E, Huntley ES, Bartal MF, et al. Doppler evaluation of normal and abnormal placenta. Ultrasound Obstet Gynecol. 2022;60(1):28-41. doi:10.1002/uog.24816

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