Definition/General
Introduction:
Fetal thrombotic vasculopathy (FTV) is characterized by fetal vascular malperfusion due to thrombotic occlusion
It involves fetal stem villous vessels and chorionic plate vessels
It represents upstream obstruction of fetal circulation
It results in avascular villi and villous stromal-vascular karyorrhexis.
Origin:
Results from thrombotic occlusion of fetal vessels in placenta
May originate from umbilical cord abnormalities
Fetal thrombophilia or coagulation disorders
Mechanical obstruction of fetal vessels
Inflammatory damage to fetal endothelium
Leads to downstream avascular change.
Classification:
Classified based on extent and severity
Focal FTV: Limited to few cotyledons
Multifocal FTV: Multiple cotyledons involved
Diffuse FTV: Extensive involvement
Graded as Grade 1 (mild) to Grade 3 (severe).
Epidemiology:
Incidence approximately 3-5% of all pregnancies
More common in pregnancies with fetal compromise
Associated with stillbirth in 15-20%
Risk increases with maternal thrombophilia
More frequent in pregnancies with intrauterine growth restriction.
Clinical Features
Presentation:
Fetal growth restriction (IUGR)
Oligohydramnios
Non-reassuring fetal heart rate patterns
Stillbirth (may be presenting feature)
Decreased fetal movements
Abnormal Doppler studies (increased resistance)
Preterm delivery.
Symptoms:
Maternal awareness of decreased fetal movement
Measuring small for gestational age
Oligohydramnios on ultrasound
Abnormal fetal heart rate monitoring
Signs of fetal distress during labor
No specific maternal symptoms.
Risk Factors:
Maternal thrombophilia (Factor V Leiden, Prothrombin mutation)
Antiphospholipid syndrome
Maternal diabetes mellitus
Chronic hypertension
Smoking during pregnancy
Previous pregnancy with FTV
Umbilical cord abnormalities.
Screening:
Fetal growth assessment by ultrasound
Doppler studies of umbilical and middle cerebral arteries
Amniotic fluid volume assessment
Non-stress testing
Biophysical profile
Thrombophilia workup if indicated.
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Gross Description
Appearance:
Pale, firm areas in placental parenchyma corresponding to infarcted regions
Sharply demarcated areas of pallor
May show hemorrhagic margins
Affected areas feel firm and granular
Multiple pale patches of varying sizes.
Characteristics:
Placental surface shows pale, depressed areas
Cut surface reveals firm, pale tissue
Areas of infarction well-demarcated
Geographic distribution pattern
May involve entire cotyledons
Chorionic vessels may appear thickened.
Size Location:
Variable size from few millimeters to several centimeters
May involve single or multiple cotyledons
Can affect peripheral or central placental areas
Random distribution pattern
Total affected area correlates with severity.
Multifocality:
Often shows multifocal distribution
Multiple discrete areas of involvement
Skip lesions with normal intervening tissue
May have confluent areas in severe cases
Bilateral involvement possible.
Microscopic Description
Histological Features:
Avascular villi with loss of fetal capillaries
Villous stromal-vascular karyorrhexis (nuclear debris)
Stem villous vessel thrombosis with organization
Villous stromal fibrosis
Mineralization may be present
Chronic villous changes.
Cellular Characteristics:
Villous stroma shows fibroblastic proliferation
Karyorrhectic debris (nuclear fragments)
Absence of fetal capillaries in affected villi
Stromal calcification in chronic cases
Trophoblast may show reactive changes.
Architectural Patterns:
Loss of villous vascularity
Stem villous vessels show thrombosis and recanalization
Terminal villi become sclerotic and avascular
May show villous agglutination
Chorionic plate vessels may show similar changes.
Grading Criteria:
Grade 1: Focal avascular villi (<5% of terminal villi)
Grade 2: Moderate involvement (5-15% of terminal villi)
Grade 3: Extensive involvement (>15% of terminal villi)
Based on percentage of affected villi.
Immunohistochemistry
Positive Markers:
CD34 (highlights loss of fetal capillaries in affected areas)
Factor VIII (shows vascular compromise)
Smooth muscle actin (shows stem villous vessel changes)
Fibrin (demonstrates thrombosis)
Collagen IV (shows basement membrane changes).
Negative Markers:
CD34 negative in avascular villi (loss of endothelial cells)
Factor VIII negative in compromised vessels
Smooth muscle actin may be reduced in damaged vessels
Loss of vascular markers diagnostic.
Diagnostic Utility:
CD34 immunostaining essential for demonstrating avascularity
Quantifies extent of vascular compromise
Confirms diagnosis of fetal thrombotic vasculopathy
Helps distinguish from other causes of villous sclerosis
Aids in grading severity.
Molecular Subtypes:
Not applicable for routine classification
Thrombophilia genetic testing may be performed on fetal/maternal blood
Factor V Leiden mutation
Prothrombin G20210A mutation
MTHFR polymorphisms.
Molecular/Genetic
Genetic Mutations:
Fetal thrombophilia mutations may predispose
Factor V Leiden (most common)
Prothrombin G20210A mutation
Protein C deficiency
Protein S deficiency
Antithrombin deficiency
MTHFR C677T polymorphism.
Molecular Markers:
Coagulation studies in mother and fetus/neonate
D-dimer levels (may be elevated)
Fibrinogen levels
Platelet function studies
Antiphospholipid antibodies
Genetic testing for thrombophilia.
Prognostic Significance:
Correlates with fetal outcomes
Extensive FTV associated with stillbirth
Neurodevelopmental outcomes may be affected
Risk of recurrence in subsequent pregnancies
Severity grading predicts outcomes.
Therapeutic Targets:
Anticoagulation therapy in at-risk pregnancies
Low-dose aspirin prophylaxis
Heparin therapy for high-risk cases
Folic acid supplementation (MTHFR variants)
Enhanced fetal surveillance
Timing of delivery optimization.
Differential Diagnosis
Similar Entities:
Chronic villitis (inflammatory infiltrate present)
Maternal vascular malperfusion (different vascular pattern)
Post-term changes (gestational age-related)
Villous dysmaturity
Meconium-associated vascular necrosis.
Distinguishing Features:
FTV: Avascular villi without inflammation
FTV: Stromal-vascular karyorrhexis
Chronic villitis: Inflammatory infiltrate present
Maternal malperfusion: Different vascular pattern
Post-term: Gestational age >42 weeks
Meconium: Meconium-laden macrophages.
Diagnostic Challenges:
Distinguishing from other causes of villous avascularity
Recognition of early changes
Sampling adequacy for accurate grading
Correlation with clinical history
CD34 immunostaining essential for diagnosis.
Rare Variants:
Hemorrhagic endovasculitis (acute phase)
Organized thrombi in stem villous vessels
Calcific vasculopathy
Combined with maternal vascular malperfusion
Extensive chorionic plate involvement.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Placenta weighing [weight]g, showing pale firm areas involving [percentage]% of parenchyma
Diagnosis
Fetal Thrombotic Vasculopathy (Fetal Vascular Malperfusion)
Classification
Classification: Grade [1/2/3] FTV based on extent of involvement
Histological Features
Shows avascular villi with stromal-vascular karyorrhexis and loss of fetal capillaries
Immunohistochemistry
CD34: Loss of staining in [percentage]% of terminal villi, confirming avascularity
Severity Assessment
Severity: [Grade] FTV involving [percentage]% of terminal villi
Clinical Correlation
Findings consistent with fetal vascular compromise and correlate with [clinical findings]
Recommendations
Thrombophilia workup recommended. Enhanced surveillance in future pregnancies. Genetic counseling if indicated.
Final Diagnosis
Fetal Thrombotic Vasculopathy, Grade [1/2/3], with associated fetal vascular malperfusion