Placenta
Nonneoplastic placental conditions and abnormalities
Placental findings in specific conditions
Toxemia of pregnancy (preeclampsia and eclampsia)
Author: Khaldoon Aljerian, M.D., M.H.Sc.
Editorial Board Member: Ricardo R. Lastra, M.D.
Deputy Editors-in-Chief: Jennifer A. Bennett, M.D., Gulisa Turashvili, M.D., Ph.D.
Last author update: 7 February 2023
Last staff update: 19 January 2024
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: Toxemia of pregnancy / preeclampsia eclampsia
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2 | Board review style question #3 | Board review style answer #3Cite this page: Aljerian K, Turashvili G. Toxemia of pregnancy (preeclampsia and eclampsia). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/placentatoxemia.html. Accessed April 19th, 2024.
Definition / general
- Preeclampsia is a pregnancy specific hypertensive disorder diagnosed by the presence of 3 main signs: hypertension, proteinuria and edema
- Diagnosed after 20 weeks gestational age (GA) (usually begins at 32 weeks but may present earlier in patients with pre-existing kidney disease, hypertension or hydatidiform moles) (SAGE Open Med 2019;7:2050312119843700)
- Current view of the clinical picture of preeclampsia and its convulsive form, eclampsia, deviates from using proteinuria as the sole indicator; other than the maternal hypertension (160/110 mmHg) at bed rest and proteinuria that are consistently detected in preeclampsia, hepatic functions could be impaired and manifest serologically as hepatic marker values that are twice normal (SAGE Open Med 2019;7:2050312119843700)
- May lead to HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count) (SAGE Open Med 2019;7:2050312119843700)
- This syndrome may cause cerebral hemorrhage and consequently maternal and fetal demise
Essential features
- Thrombocytopenia, recalcitrant epigastric pain, progressive renal dysfunction, pulmonary edema; some cerebral and ophthalmic manifestations could be evident (SAGE Open Med 2019;7:2050312119843700)
- Pregnancy toxemia is scaled into (SAGE Open Med 2019;7:2050312119843700)
- Nonsevere hypertension / mild: systolic blood pressure (SBP) of 140 - 149/90 - 99 mmHg
- Nonsevere hypertension / moderate: systolic blood pressure of 150 - 159/100 - 109 mmHg
- Severe: systolic blood pressure of ≥ 160 mmHg
- Categorized into the following, depending on the gestational age that hypertension is discovered (SAGE Open Med 2019;7:2050312119843700):
- Chronic / pre-existing hypertension: before 20/52 gestational age
- Gestational hypertension: later than 20/52 gestational age and disappears postpartum
- Preeclampsia / eclampsia: later than 20/52 gestational age + at least 1 of the following:
- Proteinuria
- Maternal organ dysfunction (such as increased creatinine, increased liver enzymes, neurological complications, hematological complications)
- Uteroplacental dysfunction (such as intrauterine growth restriction [IUGR] or stillbirth)
- Chronic / pre-existing hypertension with superimposed preeclampsia / eclampsia: before 20/52 gestational age + preeclampsia or eclampsia
Terminology
- Toxemia of pregnancy (preeclampsia and eclampsia)
- Preeclampsia: pregnancy + hypertension, proteinuria and edema
- Eclampsia: preeclampsia + convulsions
- HELLP syndrome: hemolysis, elevated liver enzymes and low platelet count
ICD coding
- ICD-10:
- O14 - preeclampsia
- O11 - pre-existing hypertension with preeclampsia
- O11.1 - pre-existing hypertension with preeclampsia, first trimester
- O11.2 - pre-existing hypertension with preeclampsia, second trimester
- O11.3 - pre-existing hypertension with preeclampsia, third trimester
- O11.4 - pre-existing hypertension with preeclampsia, complicating childbirth
- O11.5 - pre-existing hypertension with preeclampsia, complicating the puerperium
- O11.9 - pre-existing hypertension with preeclampsia, unspecified trimester
- O15 - eclampsia
- ICD-11:
Epidemiology
- Prevalent within young pregnant women with a tendency to develop hypertension (SAGE Open Med 2019;7:2050312119843700)
Sites
- Placenta, brain, vascular system
Pathophysiology
- Exact pathogenesis of preeclampsia is not fully explored yet (SAGE Open Med 2019;7:2050312119843700)
- It seems that it has several predisposing factors, which could be seen to some extent in thrombotic microangiopathy, atypical hemolytic uremic syndrome and antiphospholipid antibody syndrome (SAGE Open Med 2019;7:2050312119843700)
Etiology
- Idiopathic
Diagrams / tables
Clinical features
- Hypertension
- Proteinuria
- Creatinine: ≥ 90 μmol/L
- Increased alanine transaminase (ALT) or aspartate transaminase (AST): > 40 IU/L
- Pain, abdominal: right upper quadrant / epigastric
- Seizures (eclampsia)
- Altered visual / mental status
- Intrauterine growth restriction
- Stillbirth
- HELLP syndrome: hemolysis, elevated liver enzymes and low platelet count (< 150,000/μL) (SAGE Open Med 2019;7:2050312119843700)
- Abruptio placenta with prolonged seizures, 20 - 50% (Fetal Matern Med Rev 2011;22:91)
Diagnosis
- ~40% of women with eclampsia do not demonstrate conspicuous preceding symptoms before convulsions start (Fetal Matern Med Rev 2011;22:91)
- Preeclampsia: pregnancy + hypertension, proteinuria and edema (SAGE Open Med 2019;7:2050312119843700)
- Eclampsia: preeclampsia + convulsions (SAGE Open Med 2019;7:2050312119843700)
- Close follow up of vitals is mandatory (SAGE Open Med 2019;7:2050312119843700)
- Future diagnostic factors:
- There is increased soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sENG) (Pregnancy Hypertens 2017;10:18)
- sFlt1 / sEGFR and sFlt1 / PLGF were positively correlated with the severity (Pregnancy Hypertens 2018;13:127)
Laboratory
- Creatinine: ≥ 90 μmol/L (SAGE Open Med 2019;7:2050312119843700)
- Increased ALT or AST: > 40 IU/L (SAGE Open Med 2019;7:2050312119843700)
- Low platelet count: < 150,000/μL (SAGE Open Med 2019;7:2050312119843700)
- sEGFR was significantly lower (Pregnancy Hypertens 2018;13:127)
- sFlt1 was significantly higher (Pregnancy Hypertens 2018;13:127)
Case reports
- 27 year old woman who presented with abducens nerve palsy immediately after the delivery with severe preeclampsia (Tunis Med 2018;96:76)
- 28 year old, 33 + 4 weeks pregnant woman presented with severe preeclampsia and severe HELLP syndrome (BMC Nephrol 2020;21:204)
- 30 year old Bangladeshi - Bengali woman in her 28th week of pregnancy presented with severe systemic hypertension, biventricular heart failure and preeclampsia (BMC Res Notes 2014;7:814)
- 31 year old pregnant woman with a history of 2 pregnancy losses presented with preeclampsia and HELLP syndrome (BMC Pregnancy Childbirth 2018;18:191)
Treatment
- Delivery of baby and placenta (most effective)
- Corticosteroids (promote lung maturation of baby)
- Antihypertensives (treat hypertension)
- Anticonvulsants (magnesium sulfate, treat convulsions)
- Reference: SAGE Open Med 2019;7:2050312119843700
Gross description
- Placental hypoplasia:
- Placental weight: < 10th percentile of gestational age
- Thin umbilical cord (width: < 10th percentile for gestational age or < 8 mm at term)
- Placental infarction:
- Requires histologic confirmation / sampling
- Location: central or marginal (away from periphery is more significant)
- Also describe shape, color, consistency, size and percentage of infarcted parenchyma (significant percentage: any percentage preterm, > 5% at term)
- Compared to normal parenchyma, the lesions are:
- Demarcated slightly (new) to well (old)
- Red (new) to tan (old)
- Firmer consistency temporally
- Shape is rectangular, polygonal, wedge or triangular with base at maternal surface
- Rounded lesions represent intraparenchymal infarction hematomas / intraplacental abruption
- Retroplacental hemorrhage / abruption
- Reference: APMIS 2018;126:551
Gross images
Images hosted on other servers:
Focal placental infarction
Extensive placental infarction
Placental infarction, hematoma
Microscopic (histologic) description
- Placental findings can be variable ranging from no pathologic features to three main categories of lesions: lesions consistent with maternal vascular malperfusion, lesions consistent with fetal vascular thrombo-occlusive disease, lesions consistent with amniotic fluid infection (Placenta 2005;26:S114)
- Lesions consistent with maternal vascular malperfusion (Placenta 2014;35:696)
- Altered villous morphology (accelerated villous maturation):
- Small, thin, elongated villi with increased syncytial knots
- Should only be diagnosed based on examination of the villi adjacent to the maternal surface
- Morphology is identical to the normal appearance of the subchorionic zone which serves as an internal control
- Altered villous architecture (distal villous hypoplasia) (Pediatr Dev Pathol 2016;19:31):
- Paucity of villi in relation to the surrounding stem villi (increased space around the villi), leading to prominent large stem vessels all the way to the maternal surface at low power examination
- Easier to recognize before 32 weeks of gestation
- In second trimester, loss of the normal gradient of larger immature villi to small mature villi at scanning magnification from midplacenta to maternal surface
- May be graded as:
- 0: none
- 1: mild to moderate (decreased density and sparseness of some distal villi, thinning of intermediate villi)
- 2: severe (significantly decreased density and sparseness of distal villi, thinning of intermediate villi); best identified at x4 objective
- Syncytiotrophoblastic knots (also known as Tenney-Parker change) (Pediatr Dev Pathol 2010;13:305):
- Increased nuclear clumping and basophilia of the multinucleated cells on the terminal villi
- Only reported when identified in every 40x field (30% of the villi) or when prominent under 36 weeks
- Decidual vasculopathy (Placenta 2016;42:37):
- Hypertrophic arteriopathy:
- Small arteries with wall thickening, swelling and detachment of endothelial cells and a sparse perivascular lymphocytic infiltrate
- Severe arteriopathy:
- Fibrinoid necrosis of vascular walls (amorphous eosinophilic vessel wall)
- Hypertrophic arteriopathy:
- Placental infarction (APMIS 2018;126:551):
- Groups of villi (at least 5) with ischemic necrosis (pyknotic nuclei, followed by karyorrhectic nuclei and loss of nuclear staining of the villous trophoblast and then villous stromal cells) and collapse of the intervillous space
- Infarcted areas are well circumscribed / clearly demarcated from the surrounding parenchyma
- Most infarcted areas are triangular and involve the maternal floor
- Infarction hematoma is a rounded (spherical) hemorrhage surrounded by infarcted villi
- Acute atherosis:
- Intimal foamy cells, usually seen in placental arteries but may extend into the decidual arteries
- May be associated with uteroplacental thrombosis, infarction, abruption
- Other features:
- Laminar necrosis of basal plate or membranes
- Diffuse decidual leukocytoclastic necrosis
- Islands of fibrin with extravillous trophoblasts
- Increase in intervillous fibrin
- > 3% of villi with fibrinoid necrosis
- Extravillous trophoblast cysts
- Membrane chorionic microcysts
- Proliferation of basal extravillous cytotrophoblasts and villous cytotrophoblasts
- Increased multinucleate trophoblasts in decidua basalis
- Intraluminal endovascular trophoblast in third trimester
- Presence of fetal nucleated red blood cells in villous vessels
- Thickened trophoblast basement membrane (highlighted by PAS stain)
- Placental mesenchymal dysplasia
- Chorangioma / localized or multifocal chorangiomatosis
- Calcifications
- Unconverted placental bed spiral arteries
- Meconium effects
- Altered villous morphology (accelerated villous maturation):
- Lesions consistent with fetal vascular thrombo-occlusive disease:
- Villous changes:
- Early: villous stromal-vascular karyorrhexis
- Late: hyalinized avascular villi
- Severe: fetal thrombotic vasculopathy (average of > 15 affected villi/slide)
- Vascular changes:
- Thrombi and intimal fibrin cushions in large fetal vessels
- Fibromuscular sclerosis in intermediate sized fetal vessels
- Basal intervillous thrombi (Benirschke: Pathology of the Human Placenta, 5th Edition, 2006)
- Associated with secondary changes such as loss of vascularity and fibrosis
- Inflammatory lesions:
- Chronic villitis of unknown etiology with obliterative fetal vasculopathy
- Villous changes:
- Lesions consistent with amniotic fluid infection:
- Chorioamnionitis, maternal response:
- Stage 1 early: acute subchorionitis / chorionitis
- Stage 2 intermediate: acute chorioamnionitis
- Stage 3 late: necrotizing or subacute chorioamnionitis
- Severe: subchorionic microabscesses
- Chorioamnionitis, fetal response:
- Stage 1 early: umbilical phlebitis / chorionic vasculitis
- Stage 2 intermediate: umbilical arteritis
- Stage 3 late: concentric umbilical perivasculitis (necrotizing funisitis)
- Severe: intense chorionic vasculitis with recent nonocclusive chorionic vessel thrombi
- Chorioamnionitis, maternal response:
Microscopic (histologic) images
Contributed by Khaldoon Aljerian, M.D., M.H.Sc.
Decidual vasculopathy
Decidual vasculopathy thrombus
Retroplacental hemorrhage thrombus
Positive stains
- CD34: particulate / granular (starburst) pattern in and around the vessel wall (Placenta 2016;42:37)
Negative stains
- Desmin: loss or fragmentation of staining in hypertrophic decidual arteriopathy (Placenta 2016;42:37)
Molecular / cytogenetics description
- Dysregulation FLT1
- ACVR2A and ERAP2 genetic variants
- Reference: Am J Obstet Gynecol 2018;218:211
Videos
Categories of placental pathology
by Dr. Drucilla Roberts
Sample pathology report
- Placenta and membranes, spontaneous vaginal delivery:
- Maternal vascular malperfusion; consistent with toxemia of pregnancy (see comment)
- Comment: Singleton placenta. Placental weight: < 5th percentile for gestational age. Evidence of maternal vascular malperfusion with villous changes: increased intervillous fibrinoid with calcifications, multifocal placental / villous infarction (40%). Implantation site shows evidence of maternal vascular malperfusion: increased placental site giant cells / immature intermediate trophoblasts, decidual arteriopathy. Retroplacental hematoma with intraplacental extension (abruptio placenta) with acute and chronic hemorrhage with hemosiderin laden macrophages. The retroplacental hemorrhage with villous infarction and maternal vascular malperfusion may be consistent with gestational hypertension and may have resulted in the low placental weight; this is consistent with toxemia of pregnancy. Clinical correlation required.
Differential diagnosis
- Disc edge infarction:
- Groups of villi confined to the (term) placental edge showing ischemic necrosis and villous agglutination
- Infarction of < 5%, full term disc:
- Less than 5% of the placental disc shows villi with ischemic necrosis and villous agglutination
- Increased perivillous fibrin:
- Abundant perivillous fibrin that obliterates the intervillous space with loss of the syncytiotrophoblast
- Requires at least 1 area of full thickness involvement / entrapment of at least half of the villi on a single slide
- Normal muscular decidual arteries:
- Thick muscular walls
- Lack endothelial disruption and perivascular lymphocytes
- Highlighted with desmin
- Features mimicking accelerated maturation:
- Small, widely spaced, elongated villi with increased syncytial knots (normally seen under the fetal plate and in a patchy distribution near the maternal surface in the region of venous drainage)
Board review style question #1
Which disease is included in the definition of preeclampsia?
- Elevated liver function tests
- Hemolysis
- Hypertension
- Hypovolemic shock
- Low platelets
Board review style answer #1
Board review style question #2
Which diagnosis is related to toxemia of pregnancy and may lead to death by cerebral hemorrhage?
- Convulsions
- Disseminated intravascular coagulation
- HELLP syndrome
- High platelets
- Hypovolemic shock
Board review style answer #2
Board review style question #3
A 30 year old gravida 2 para 1 with gestational hypertension, edema and proteinuria with intrauterine growth restriction presents at term for spontaneous vaginal delivery (SVD). The placenta is small for the gestational age. Histological examination of the placental disc section reveals the above changes in the decidual arteries. Which complication should we be aware of?
- Convulsions
- Depression
- Diabetes
- High platelets
- Hypovolemic shock
Board review style answer #3
