Placenta
The placenta feeds the developing baby, breathes for it and disposes of its waste.
Clinical
Examination of the placenta
- Most placentas are not examined by a pathologist.
Indications for exam by a pathologist:
- Abnormalities in the:
- Fetus:
- Bad fetal outcome.
- Suspected or known congenital abnormalities or chromosomal abnormalities.
- Mother:
- Infection/suspected infection.
- Pre-term labour.
- Maternal disease (e.g. SLE, coagulopathy).
- Complicated pregnancy (preclampsia, pregnancy induced hypertension, gestational diabetes).
- Placenta:
- Unusual gross characteristics.
- Fetus:
Bleeding in late pregnancy
DDx of bleeding in late pregnancy:
- Placental abruption (most common).
- Placenta previa.
- Vasa previa (fetus losing blood).
Clinical screening tests
- PAPP-A - low values seen in aneuploidy.[1]
Normal histology
Amnion
General:
- Next to fetus, surrounds amniotic fluid, avascular.
Characteristics:
- Characterized by a single layer of cells.[2]
- Cuboidal/squamoid shape.
- Eosinophilic cytoplasm.
- Central nucleus.
- Squamous metaplasia may be seen at cord insertion.
- Basement membrane.
- 'Compact layer'.[2]
- 'Fibroblastic layer'.[2]
Chorion
General:
- Surrounds amnion.
Characteristics:
- Layers:[3]
- 'Reticular layer' - cellular (inner aspect).
- 'Pseudo-basemement membrane'.
- 'Outer trophoblastic layer'.
- Has blood vessels.
- Opposed to "trophoblastic X cells" on side opposite of amnion.[2]
- Beneath of the "trophoblastic X cells" is decidua (mnemonic NEW = nucleus central, eosinophilic, well-defined cell border), which is maternal tissue.
Common terms
- Chorionic plate - fetal aspect of placenta.
- Basal plate - maternal aspect of placenta.
- Has extravillous trophoblast.
- Place to look for maternal vessels.
Grossing
This is often very quick. The gross is quite important, as some things cannot be diagnosed microscopically.
General
- Dimensions:
- Disc.
- Length of cord, diameter of cord.
- Mass (weight) -- should be done 'trimmed' (cord cut-off, membrane cut-off).
- Umbilical cord
- Attachment.
- Location: central, eccentric, marginal.
- Marginal attachment assoc. with hypertension[4]
- Membranous or velamentous (veil-like) insertion.
- Vessels separate/branch prior to reaching placental disc.
- Furcate insertion - vessel run on fetal surface (more exposed to trauma).
- Location: central, eccentric, marginal.
- Knots (false vs. true).
- False knots are nothing to worry about -- look like a knot but aren't really one.
- Twisting/coiling.
- Number of vessels.
- Normal: 2 arteries, 1 vein.
- Attachment.
- Membranes - shiny, thin, translucent
- Attachment: marginal (normal), circummarginate (inside edge), circumvallated (folding on self).
- Placental disc.
- Fetal surface - normal is shinny (dull in chorioamnionitis).
- Maternal surface - are the cotyledons intact?
Sections
- Cord two sections.
- Cord at insertion.
- Membranes (rolled).
- Placenta - full thickness (maternal and fetal surface).
Placental membranes
Appearance:[5]
- Normal - shiny.
- Choriomnionitis - opaque/dull.
- Meconium - green.
- Amnion nodosum.
Placental mass
Placental mass by gestational age:[8]
Gest. Age/Percentile | 25% | 50% | 75% |
32 weeks | 275 g | 318 g | 377 g |
36 weeks | 369 g | 440 g | 508 g |
40 weeks | 440 g | 501 g | 572 g |
Linear regression - placental mass-gestational age
Based on the table in the AFIP book[9] I generated the following regression lines:
50% | 10% | 90% | |
slope (g/week) | 21.58088235 | 19.70588235 | 25.40196078 |
y-intercept (g) | -357.4558824 | -397.2352941 | -366.7254902 |
Pearson (r) | 0.988670724 | 0.988268672 | 0.982206408 |
placental mass = slope x gestational age + intercept
What to remember...
Extrapolated from the linear regression (see above):
- 50% at term = 500 grams.
- 50% at 26 weeks = 200 grams.
- The change in mass/week is approximately linear and equal to 300 grams / 14 weeks ~ 20 grams/week.
- The spread in mass between 10% and 90%, crudely estimated, is 200 grams (for GA=26-40).
Overview of placental pathology
Approach
The pathology of the placenta is diverse and is not easy to group.
It terms of remembering things. It is probably easiest to take a combined anatomical, etiologic and morphologic approach.
Anatomical basis:
- Cord.
- Membranes.
- Disc.
Etiologic:
- Congential.
- Infectious.
- Neoplastic.
- Endocrine.
- Trauma.
- Vascular.
- Degenerative.
- Autoimmune.
- Toxic.
- Idiopathic.
Compartmental:
- Vasculature.
- Membranes.
- Parenchyma:
- Maternal part (decidua).
- Fetal part (villi, cord).
Common entities/diagnoses
- Normal.
- Chorioamnionitis.
- Placental abruption.
- Meconium.
- Hypertensive changes.
Sign-out
What should be commented on...
- Placenta:
- Maturity of villi (2nd or 3rd trimester).
- Infarction?
- Subchorionic less important than maternal aspect.
- Peripheral aspect of placental disc less important than central region of disc.
- Blood vessels.
- Maternal.
- Fetal.
- Membranes.
- Membranitis?
- Chorioamnionitis?
- Cord:
- 3 vessel?
- Vasculitis/inflammation?
Mnemonic: chorio, cord, vessels, villi (maturity, infarction).
Cord pathology
- Two vessel cord.
- Hypercoiling.
- Abnormal insertion.
- Cord knots (true vs. false).
- Strictures.
- Hematoma.
Two vessel cord
- AKA single umbilical artery.
- Associated with congenital abnormalities, esp. cardiac - key point.[10]
- Thought to be an acquired defect (as prevalence is lower in early in gestation).
- May be seen in association of other cord abnormalities (e.g. marginal insertion, velamentous insertion).
Image:
Insertion
Marginal insertion
Definition:
- The umbilical cord is attached to the placental disc at its margin.
Prevalence:
- Approximately 12% of placentas.[10]
Relevance:
- None according to WMSP.[10]
- In theory, the cord, dependent on its relation to the internal os, is at greater risk of injury (leading to vasa previa) and compression (fetal hypoxia). A retrospective study found cord position in relation to the internal os is predictive for vasa previa.[12]
Velamentous insertion
Definition:
- The umbilical cord inserts into the fetal membranes.[10]
- The vessels are not protected by Wharton's jelly.
- Wharton's jelly = the connective tissue surrounding the vessels in the cord.
- The vessels are not protected by Wharton's jelly.
Details:[10]
- 3/4 of the time the vessel also branch; in the remaining 1/4 the vessels stay together.
Relevance:
- Increased risk of vasa previa.[12]
Knots
General
Gross
Work-up:[14]
- Diameter measures and colour on both sides of the knot.
- Knot should be untied to assess for deformation of Wharton's jelly.
- Sections from both sides of the knot - to look for thrombi.
Note:
- False knots (large diameter - focally) are common - they cannot be untied.
Microscopic
Features:
- +/-Thrombi.
- Fibrin deposition.
- +/-Lines of Zahn.
Images:
Coiling
- There is little uniformity in how coiling is assessed in the medical literature - though 10% and 90% are considered the cut-points for normal.[15]
- What are the 10% and 90% cut-points? They are not given in WMSP. UT access to a journal article[16] that might have it is screwed-up.
- Hypo- and hypercoiling are both considered problematic.[10]
- Associated with cord stricture, which is usu. at the fetal end of the cord.[17]
Cord hematoma
Features:[17]
- Rare ~ 1/5500.
- Mortality ~50% is severe.
Image: Hematoma (flylib.com).[18]
Membranes
- Squamous metaplasia.
- Chorioamnionitis - see infection section.
Passage of meconium
General
- Associated with fetal distress.
Gross
- Green/green discolourization.
Microscopy
Features:[19]
- Macrophages with brown fine granular pigment.
- Columnar morphology (normally cuboidal).
- "Drop-out" of individual cell -- the loss of individual cells.
Level of staining and time:[20]
- <1 h - no staining of membranes.
- 1-3 h - amnion is stained.
- >3 h - chorion is stained.
DDx:
- Hemosiderin-laden macrophages.
Images:
Special stains
- Hemosiderin +ve in hemosiderin-laden macrophages.
- PAS +ve in meconium-laden macrophages.[21]
Useful to differentiate hemosiderin-laden macrophages and meconium laden macrophages:
- Hemosiderin stain -- +ve for old blood.
- Prussian-blue stain = hemosiderin stain.[22]
- PAS-D -- +ve in chorioamnionitis???
Note:
- Meconium contains bile.[23]
Squamous metaplasia
- Benign common finding - no clinical significance.[24]
Image:
Twin placentas
These are often submitted... even if they are normal.
General
No membrane between fetuses.
- Split at approx. 7th day.
Diamnionic-monochorionic (DiMo)
- No interposed chorion.[26]
- Always monozygotic.
- Highest risk of TTTS (twin-to-twin transfusion syndrome).
Diamnionic-dichorionic (DiDi)
- Most dizygotic (70%), may be monozygotic (30%).
- If monozygotic -- split before 3 days.
Twin-to-twin transfusion syndrome
General
- Abbreviated as TTTS.
Definition:
- Monozygotic twins that share a placental disc, have vessels which cross-over between the twins that lead to a blood imbalance between the two twins.
- Only seen in monozygotic twins.
- Vascular connection may be vein-to-vein, artery-to-vein, artery-to-artery (uncommon).[27]
Prevalence:
- Seen in ~15% of monozygotic twins.[27]
Clinical:
- Donor:
- Twin: hypovolemic, oliguric, oligohydramnic, +/- anemia, +/-hypoglycemia, +/- small pale organs.
- Placental disc: large, pale.
- Recipient:
- Twin: hypervolemia, polyuria, polyhydramnios, +/- hydrops fetalis, +/- CHF, hemolytic janundice, +/- large congested organs.
- Placental disc: small, firm, congested.
Gross
- Large vessels that connect the two umbilical cords.
Microscopic
Features:[28]
- Artery-to-vein anatomosis - where artery and vein are associated with different umbilical cords.
- Donor twin side of placenta:
- Edematous villi.
- Increased nucleated RBCs.
- Recipient twin side of placenta:
- Congested.
Diseases of the placental attachment
Placenta acreta/percreta/increta
Placenta attaches to the uterus deeper than it should.
Placental abruption
General
Classic clinical manifestations:[29]
- Vaginal bleeding (~70%).
- Abdominal pain (~50%).
- Fetal heart rate abnormalities (~70%).
Pathologic findings
Features:
- Gross pathology: depression on maternal side, large blood clot.
- Central haemorrhage is the most worrisome.
Note:
- There are no good microscopic findings for placental abruption.
Infection
General[30]
- Infection usually ascending, i.e. from vagina up through cervix.
- Assoc. with intercourse.
- Hematogenous rare - manifest as villitis.
- Think TORCH infections (toxoplasmosis, others (syphilis, TB, listeriosis), rubella, cytomegalovirus, herpes simplex virus).
- Funisitis usually follows chorioamnionitis.
- Inflammatory cells in umbilical cord are fetal (trivia).
Types (by site)[30]
- Fetal membranes: chorioamnionitis, membranitis.[31]
- Umbilical cord: funisitis.
- Placenta: placentitis, villitis.
Grading infection (chorioamnionitis, membranitis, funisitis)
Membranitis:[31]
- PMNs - decidua only.
- PMNs - in subamniotic tissue.
- 1 or 2 + necrosis in decidua or chorion/subamniotic tissue.
Chorioamnionitis:[31]
- placental chorionic plate only.
- 1 + subamniotic tissue.
- 1 or 2 + necrosis or abscess.
Sternberg separates vasculitis and funisitis without really explaining the terms[31] -- I presume: vasculitis = inflammation of vessels in the umbilical cord. funisitis = inflammation of the cord (vessels and Wharton jelly).
Umbilical cord vasculitis:[31]
- +0.5 for each vessel.
- +0.5 for each vessel with severe involvement.
Umbilical funisitis:[31]
- focal inflammation.
- diffuse inflammation.
- necrosis - in vessels or Wharton jelly.
Note: There is no such thing as chorionitis.[32]
Villitis of unknown etiology
- Abbreviated VUE.
General
Features:[33]
- Usu. term placenta.
- Prevalence: 5% to 15% of all placentas.
- Associated with:
- Intrauterine growth restriction.
- Recurrent reproductive loss.
Microscopic
Features:[33]
- Maternal T-lymphocytes (mostly CD8-positive) in villous stroma.
- +/-Intervillositis (lymphocytes between villi).
Images:
- VUE (bmj.com).[34]
- VUE (flickr.com).[35] **CHECK**
Infarction
True infarcts
General
- Associated with retroplacental hematoma.
Gross
Features:[17]
- Early - red.
- Late - white/grey.
Images:
Microscopic
Features:
- Loss of intervillous space.[17]
- Villi appear to be crowded.[36]
- Prominent syncytial knots.
- Thickened trophoblastic basement membrance (below cytotrophoblasts).
- +/-Acute atherosis (vaguely like atherosclerosis).
- Fibrioid necrosis.
- Vessel wall lipid deposition.
Images:
- Recent infarct (pathweb.uchc.edu).
- Placental infarct (umpmc.edu).[37]
- Placental infarct - necrotic villi (mda-sy.com).
Significant infarcts
- > 3cm --or-- central location --or-- in 1st or 2nd trimester.
- Small foci are accepted in term placentae - typically at periphery.
Perivillous fibrin deposition
- Massive perivillous fibrin deposition is assoc. with anti-phospholipid antibody (APLA) syndrome.[38]
- APLA is assoc. with recurrent miscarriage - can be treated with heparin + ASA.[38]
- Thought to be an immunologic problem - resulting in platelet activation and fibrin deposition.[38]
Gross
- Pale (white).
- Firm.
- White fibrous sepatae.
Microscopy
- Acellular eosinophilic material around formed villi.
- Obliteration of intervillous space.
Fetal disease
Fetal thrombotic vasculopathy
General
- May cause IUGR.
- Associated with cerebral palsy and common in perinatal deaths.[39]
Microscopic
Features:
- Thrombus in the fetal vasculature +/- recanalization.
- Eosinophilic (light pink on H&E), moderately granular intravascular material (fibrin) with layering.
Images:
Maternal disease
Hypertensive changes
Features:[42]
- Enlarged endothelial cells - fetal capillaries.
- Atherosis of the spiral arteries - placental bed (maternal).
Associated changes:[42]
- Placental infarcts.
- Increased syncytial knots.
- Hypovascularity of the villi.
- Cytotrophoblastic proliferation.
- Thickening of the trophoblastic basement membrane.
Hypertrophic decidual vasculopathy
Features:[43]
- Mild or moderate:
- Perivascular inflammatory cells.
- +/-Vascular thrombosis.
- Smooth muscle hypertrophy.
- Endothelial hyperplasia.
- Above two lead to narrowing of the decidual spiral arteries[44] -- key feature.
- Severe:[43]
- Atherosis of maternal blood vessels.
- Foamy macrophages within vascular wall.
- Fibrinoid necrosis of vessel wall (amorphous eosinophilic material vessel wall).
- Atherosis of maternal blood vessels.
General:
- Seen in intrauterine growth restriction (IUGR).
Images:
HELLP syndrome
General
- Diagnosed clinically.
- Pathologically not the same as severe preclampsia.[45]
Definition:
- H = hemolysis.
- EL = elevated liver enzymes.
- LP = low platelets.
Microscopic
Features:[46]
- Thrombotic microangiopathic vasculopathy.
- In essence: severe hypertrophic decidual vasculopathy. (???)
Tumours
Chorangioma
General
- Hamartoma-like growth in the placenta consisting of blood vessels.[47]
Epidemiology
- Often benign.
- May be association with:
- Fetal maternal haemorrhage.
- Hydrops.
- IUGR.
Microscopy
Features:
- Mass of capillaries.
Image:
See also
References
- ↑ URL: http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5069. Accessed on: 7 July 2010.
- ↑ 2.0 2.1 2.2 2.3 Sternberg, Stephen S. (1997). Histology for Pathologists (2nd ed.). Lippincott Williams & Wilkins. pp. 974. ISBN 978-0397517183.
- ↑ Sternberg, Stephen S. (1997). Histology for Pathologists (2nd ed.). Lippincott Williams & Wilkins. pp. 977. ISBN 978-0397517183.
- ↑ J Anat. Soc. India 49(2) 149-152 (2000). Available at: http://www.indmedica.com/anatomy/aindex1.cfm?anid=41. Accessed on: January 21, 2009.
- ↑ Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 461. ISBN 978-0443066450.
- ↑ URL: http://medical-dictionary.thefreedictionary.com/amnion+nodosum. Accessed on: 18 November 2010.
- ↑ http://library.med.utah.edu/WebPath/PLACHTML/PLAC042.html
- ↑ AFIP Placental pathol. ISBN: 1-881041-89-1. P.312
- ↑ AFIP Placental pathol. ISBN: 1-881041-89-1. P.312
- ↑ 10.0 10.1 10.2 10.3 10.4 10.5 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 464. ISBN 978-0781765275.
- ↑ URL: http://www.glowm.com/?p=glowm.cml/section_view&articleid=151. Accessed on: 8 January 2011.
- ↑ 12.0 12.1 Hasegawa J, Farina A, Nakamura M, et al. (December 2010). "Analysis of the ultrasonographic findings predictive of vasa previa". Prenat. Diagn. 30 (12-13): 1121–5. doi:10.1002/pd.2618. PMID 20872421.
- ↑ 13.0 13.1 Airas U, Heinonen S (April 2002). "Clinical significance of true umbilical knots: a population-based analysis". Am J Perinatol 19 (3): 127–32. doi:10.1055/s-2002-25311. PMID 12012287.
- ↑ 14.0 14.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 464. ISBN 978-0781765275.
- ↑ Khong TY (December 2010). "Evidence-based pathology: umbilical cord coiling". Pathology 42 (7): 618–22. doi:10.3109/00313025.2010.520309. PMID 21080869.
- ↑ PMID 16076615.
- ↑ 17.0 17.1 17.2 17.3 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 465. ISBN 978-0781765275.
- ↑ URL: http://flylib.com/books/en/2.953.1.49/1/. Accessed on: 10 January 2011.
- ↑ ALS. 6 Feb 2009.
- ↑ 3 Apr 2009.
- ↑ Povýsil C, Bennett R, Povýsilová V (January 2001). "CD 68 positivity of the so-called meconium corpuscles in human foetal intestine". Cesk Patol 37 (1): 7–9. PMID 11268705.
- ↑ Sienko A, Altshuler G (September 1999). "Meconium-induced umbilical vascular necrosis in abortuses and fetuses: a histopathologic study for cytokines". Obstet Gynecol 94 (3): 415?0. PMID 10472870.
- ↑ Sienko A, Altshuler G (September 1999). "Meconium-induced umbilical vascular necrosis in abortuses and fetuses: a histopathologic study for cytokines". Obstet Gynecol 94 (3): 415?0. PMID 10472870.
- ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 463. ISBN 978-0781765275.
- ↑ URL: http://flylib.com/books/en/2.953.1.49/1/. Accessed on: 10 January 2011.
- ↑ Sternberg, Stephen S. (1997). Histology for Pathologists (2nd ed.). Lippincott Williams & Wilkins. pp. 979. ISBN 978-0397517183.
- ↑ 27.0 27.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 469. ISBN 978-0781765275.
- ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 469-70. ISBN 978-0781765275.
- ↑ Tikkanen M, Nuutila M, Hiilesmaa V, Paavonen J, Ylikorkala O (2006). "Clinical presentation and risk factors of placental abruption". Acta Obstet Gynecol Scand 85 (6): 700–5. doi:10.1080/00016340500449915. PMID 16752262.
- ↑ 30.0 30.1 Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1106. ISBN 0-7216-0187-1.
- ↑ 31.0 31.1 31.2 31.3 31.4 31.5 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 2311. ISBN 978-0781740517.
- ↑ ALS. February 2009.
- ↑ 33.0 33.1 Redline RW (October 2007). "Villitis of unknown etiology: noninfectious chronic villitis in the placenta". Hum. Pathol. 38 (10): 1439–46. doi:10.1016/j.humpath.2007.05.025. PMID 17889674.
- ↑ URL: http://jcp.bmj.com/content/61/12/1254.abstract. Accessed on: 11 January 2011.
- ↑ URL: http://www.flickr.com/photos/jian-hua_qiao_md/3954021698/. Accessed on: 11 January 2011.
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1109. ISBN 0-7216-0187-1.
- ↑ URL: http://path.upmc.edu/cases/case75/micro.html. Accessed on: 6 January 2011.
- ↑ 38.0 38.1 38.2 Sebire NJ, Backos M, Goldin RD, Regan L (May 2002). "Placental massive perivillous fibrin deposition associated with antiphospholipid antibody syndrome". BJOG 109 (5): 570–3. PMID 12066949. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1470-0328&date=2002&volume=109&issue=5&spage=570.
- ↑ Kraus FT, Acheen VI (July 1999). "Fetal thrombotic vasculopathy in the placenta: cerebral thrombi and infarcts, coagulopathies, and cerebral palsy". Hum. Pathol. 30 (7): 759–69. PMID 10414494.
- ↑ URL: http://jcp.bmj.com/content/61/12/1254.abstract. Accessed on: 12 January 2011.
- ↑ URL: http://gut.bmj.com/content/41/3/354.full. Accessed on: 12 January 2011.
- ↑ 42.0 42.1 Soma H, Yoshida K, Mukaida T, Tabuchi Y (1982). "Morphologic changes in the hypertensive placenta". Contrib Gynecol Obstet 9: 58–75. PMID 6754249.
- ↑ 43.0 43.1 Roberts, DJ.; Post, MD. (Dec 2008). "The placenta in pre-eclampsia and intrauterine growth restriction.". J Clin Pathol 61 (12): 1254-60. doi:10.1136/jcp.2008.055236. PMID 18641412.
- ↑ AFIP - Placental Pathology. P.122. ISBN: 1-881041-89-1. 2004.
- ↑ Vinnars MT, Wijnaendts LC, Westgren M, Bolte AC, Papadogiannakis N, Nasiell J (May 2008). "Severe preeclampsia with and without HELLP differ with regard to placental pathology". Hypertension 51 (5): 1295–9. doi:10.1161/HYPERTENSIONAHA.107.104844. PMID 18362224.
- ↑ Ornstein MH, Rand JH (July 1994). "An association between refractory HELLP syndrome and antiphospholipid antibodies during pregnancy; a report of 2 cases". J. Rheumatol. 21 (7): 1360–4. PMID 7966086.
- ↑ Amer HZ, Heller DS (2010). "Chorangioma and related vascular lesions of the placenta--a review". Fetal Pediatr Pathol 29 (4): 199–206. doi:10.3109/15513815.2010.487009. PMID 20594143.