SCF ENCYCLOPEDIA ENTRY

HEREDITARY HEMORRHAGIC TELANGIECTASIA (HHT)

SCF VASCULAR MORPHOGENESIS FAILURE & ANGIOGENIC SYNCHRONIZATION COLLAPSE DOSSIER

I. OFFICIAL DISEASE CLASSIFICATION

Hereditary Hemorrhagic Telangiectasia belongs to SCF Clinical Domains C11 (Vascular Biology), C12 (Hematology), C1 (Genomic Medicine), C3 (Hepatology), C4 (Pulmonology), and C7 (Neurology).

II. CLINICAL DEFINITION

Hereditary Hemorrhagic Telangiectasia is an inherited vascular disorder characterized by:

• Recurrent epistaxis
• Telangiectasias
• Arteriovenous malformations
• Chronic bleeding
• Iron deficiency anemia
• Multisystem vascular abnormalities

Primary affected systems:

• Microvasculature
• Pulmonary circulation
• Cerebral circulation
• Hepatic vasculature
• Gastrointestinal vasculature
• Mucocutaneous blood vessels

Associated conditions:

• Arteriovenous malformation
• Iron deficiency anemia

III. MAJOR CLASSIFICATIONS

A. HHT Type 1

B. HHT Type 2

C. SMAD4-Associated HHT

Associated condition:

• Juvenile Polyposis Syndrome

D. Rare HHT Variants

Genes include:

• GDF2
• BMP9 pathway abnormalities
• Other angiogenesis-regulating genes

IV. CORE SCF ETIOPATHOGENIC THESIS

Within the Synergistic Compatibility Framework (SCF), HHT represents a systems-level collapse of:

• Angiogenic harmonics
• Vascular morphogenesis fidelity
• Endothelial communication networks
• Tissue-perfusion architecture
• Hemodynamic synchronization systems

SCF interprets HHT as a decentralized vascular construction disorder in which blood-vessel patterning intelligence fails, resulting in structurally unstable vascular networks.

V. ANGIOGENIC FOUNDATION

Normal Vascular Development

Healthy angiogenesis requires:

1. Endothelial signaling
2. TGF-β/BMP pathway regulation
3. Vessel maturation
4. Capillary formation
5. Arterial–venous separation
6. Hemodynamic stabilization

Core Pathophysiologic Mechanisms

VI. MAJOR GENETIC CAUSES

Principal Genes

Genetic Characteristics

Associated condition:

• Autosomal dominant disorder

VII. SCF FAULT ARCHITECTURE

VIII. MULTI-OMICS PATHOGENESIS

A. Genomics

Affected pathways:

• Angiogenesis
• Endothelial signaling
• TGF-β signaling
• BMP signaling

B. Transcriptomics

Dysregulated pathways:

• Vascular remodeling
• Endothelial proliferation
• Vessel maturation
• Tissue repair responses

C. Proteomics

Observed abnormalities:

• Endoglin deficiency
• ALK1 signaling disruption
• BMP pathway dysregulation
• Angiogenic factor imbalance

D. Metabolomics

Key dysfunction:

• Chronic blood loss
• Iron depletion
• Tissue hypoxia
• Oxidative stress

E. Angiomics (SCF)

Observed abnormalities:

• Vascular routing errors
• Endothelial signaling disruption
• Perfusion instability
• Structural vessel fragility

IX. SCF PATHOGENESIS FLOW

Stage 1 — Genetic Mutation

Angiogenic signaling becomes abnormal.

Stage 2 — Vessel Maturation Failure

Capillary development becomes defective.

Stage 3 — AVM Formation

Direct arterial–venous connections emerge.

Stage 4 — Hemodynamic Stress

Fragile vessels experience abnormal flow.

Stage 5 — Hemorrhage

Bleeding episodes develop.

Stage 6 — Organ Dysfunction

Chronic vascular abnormalities impair tissue function.

X. SYSTEMIC CONSEQUENCES

Associated conditions:

• Epistaxis
• Stroke
• Pulmonary arteriovenous malformation

XI. RHENOVA INTERPRETATION

Project RHENOVA interprets HHT as an angiogenic-routing destabilization syndrome.

RHENOVA Dynamics

• Vascular-routing errors
• Flow-distribution abnormalities
• Endothelial instability loops
• Hemorrhage amplification cycles
• Angiogenic synchronization collapse

RHENOVA Biomarkers

XII. DBI INTERPRETATION

The SCF Decentralized Biological Intelligence framework interprets vascular networks as biological transportation systems coordinating:

• Oxygen delivery
• Nutrient distribution
• Waste removal
• Tissue communication
• Perfusion regulation

DBI Failure Features

• Routing errors
• Distribution inefficiency
• Structural instability
• Network bypass formation

This transforms a highly optimized vascular distribution system into a fragile and inefficient circulation network.

XIII. CLINICAL MANIFESTATIONS

Mucocutaneous Manifestations

• Recurrent nosebleeds
• Oral telangiectasias
• Facial telangiectasias
• Skin vascular lesions

Associated condition:

• Telangiectasia

Pulmonary Manifestations

• Dyspnea
• Hypoxemia
• Pulmonary AVMs
• Hemoptysis

Associated condition:

• Hypoxemia

Neurologic Manifestations

• Stroke
• Brain abscess
• Seizures
• Cerebral AVMs

Associated condition:

• Brain abscess

Hepatic Manifestations

• Hepatic AVMs
• High-output heart failure
• Portal hypertension

Associated conditions:

• Portal hypertension
• High-output heart failure

XIV. DIAGNOSTICS

Diagnostic Hallmarks

Angiogenic principle:

ENG/ACVRL1\ Dysfunction \Rightarrow Abnormal\ Angiogenesis

Structural relationship:

Capillary\ Failure \Rightarrow AVM\ Formation

Clinical consequence:

Vascular\ Fragility \Rightarrow Hemorrhage\ +\ Organ\ Dysfunction

XV. SCF SYSTEMIC AXIS INVOLVEMENT

XVI. STANDARD OF CARE

Bleeding Management

Examples:

• Tranexamic acid
• Iron supplementation
• Blood transfusion when required

AVM Management

Procedures:

• Embolization of pulmonary AVMs
• Surgical intervention when indicated
• Endovascular treatment

Associated procedure:

• Embolization

Anti-Angiogenic Therapy

Examples under selected circumstances:

• Bevacizumab

XVII. SCF-PCR THERAPEUTIC ARCHITECTURE

A. Preventative (PCR-P)

Goals:

• Prevent hemorrhage
• Detect AVMs early
• Preserve organ function

B. Curative (PCR-C)

Goals:

• Restore angiogenic signaling
• Correct ENG/ACVRL1 dysfunction
• Normalize vascular architecture

C. Restorative (PCR-R)

Goals:

• Restore endothelial resilience
• Improve vascular stability
• Reduce chronic bleeding
• Rebuild angiogenic synchronization harmonics

XVIII. ETHNOBIOPROSPECTING TARGETS

Note: These are investigational supportive research targets and are not substitutes for evidence-based HHT management.

Traditional Chinese Medicine

• Astragalus membranaceus
• Salvia miltiorrhiza

Ayurveda

• Centella asiatica

Vietnamese Thuốc Nam

• Phyllanthus amarus

XIX. SCF API DISCOVERY TARGETS

High-Priority Molecular Targets

• ENG restoration technologies
• ALK1 signaling modulators
• Endothelial stabilization platforms
• AVM-remodeling therapeutics
• Anti-angiogenic precision therapies
• Iron-loss prevention systems
• Angiogenic synchronization restoration technologies

XX. SCF LAYMAN’S SUMMARY

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder that causes abnormal blood vessel formation throughout the body. Instead of developing normal capillary networks, some blood vessels connect arteries directly to veins, creating fragile structures called arteriovenous malformations (AVMs). These abnormalities can cause recurrent nosebleeds, anemia, gastrointestinal bleeding, lung complications, strokes, and liver problems. SCF interprets HHT as a disorder of vascular construction and communication in which the body’s blood-vessel development system loses its ability to build stable and properly synchronized circulation networks.

XXI. STRATEGIC RESEARCH PRIORITIES

1. ENG gene-restoration technologies
2. ALK1/BMP signaling correction platforms
3. Endothelial stabilization therapeutics
4. AI-driven AVM-risk forecasting systems
5. Precision anti-angiogenic therapies
6. Vascular remodeling technologies
7. Angiogenic synchronization restoration platforms

MASTER REGISTRY INDEX

SCF-HHT-0001 — Hereditary Hemorrhagic Telangiectasia Master Registry

SCF-HHT-ANGIO-0002 — Angiogenic Signaling Failure Layer

SCF-HHT-AVM-0003 — Arteriovenous Malformation Layer

SCF-HHT-RHENOVA-0004 — Vascular Routing Destabilization Layer

SCF-HHT-DBI-0005 — Endothelial Communication Failure Layer

SCF-HHT-PCR-0006 — Preventative–Curative–Restorative Layer