Enhance Antiphospholipid Syndrome

[cmungall]

Task

Review and enhance kb/disorders/Antiphospholipid_Syndrome.yaml

Current compliance: 89.8%

Checklist

• Review existing pathophysiology evidence
• Add missing phenotype evidence
• Add treatment evidence (anticoagulation, etc.)
• Validate with just qc

Key Features to Document

• Anti-phospholipid antibodies (aCL, anti-β2GPI, lupus anticoagulant)
• Thrombotic manifestations
• Pregnancy complications
• Catastrophic APS variant

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Part of Epic #216

[github-actions]

Summary

This issue tracks the enhancement of the Antiphospholipid Syndrome (APS) entry, which is currently at 89.8% compliance and represents the final remaining task in Epic #216 (Autoimmune Diseases Curation Project).

Current Status Analysis

The existing Antiphospholipid_Syndrome.yaml file is comprehensive with:

✅ Strong existing content:

• Well-documented subtypes (Primary APS, Secondary APS, Asymptomatic APS)
• Detailed pathophysiology (6 mechanisms with extensive evidence)
• Rich phenotype section (11 phenotypes across multiple categories)
• Comprehensive biochemical markers (5 antibody types)
• Genetic associations (HLA-DR7, HLA-DR4)
• Environmental factors (smoking, infection)

❌ Missing content (preventing 100% compliance):

• No treatments section - This is the primary gap
• Limited catastrophic APS variant documentation (mentioned in issue but not detailed in file)
• Some evidence quality issues (see lines 751-787 for NO_EVIDENCE tags on genetic markers)

Key Enhancement Priorities

1. Add Treatments Section (Critical for Compliance)

The file completely lacks a treatments: section. Standard APS treatments that should be documented:

Anticoagulation therapy:

• Warfarin (vitamin K antagonist) - standard of care for thrombotic APS
  • MAXO:0000058 (pharmacotherapy) + CHEBI:10033 (warfarin)
• Low-molecular-weight heparin (LMWH) - especially for pregnancy
  • MAXO:0000058 + CHEBI:6495 (heparin)
• Aspirin - for some patients, especially obstetric APS
  • MAXO:0000058 + CHEBI:15365 (aspirin)
• Direct oral anticoagulants (DOACs) - controversial, not recommended for triple-positive APS

Pregnancy management:

• LMWH + aspirin combination
• Close monitoring

Other interventions:

• Hydroxychloroquine - especially for SLE-associated APS
  • MAXO:0000058 + CHEBI:5801 (hydroxychloroquine)
• Immunosuppressants for refractory cases

2. Enhance Catastrophic APS Documentation

Consider adding a subtype for Catastrophic APS (CAPS):

• Rapid onset multi-organ failure
• Microvascular thrombosis
• High mortality (30-50%)
• Requires aggressive treatment (anticoagulation + corticosteroids + plasma exchange)

3. Review and Strengthen Evidence

Several genetic markers have NO_EVIDENCE or weak support:

• HLA-DR7 (lines 748-777) - all references marked NO_EVIDENCE
• HLA-DR4 (lines 778-793) - conflicting evidence

Consider either finding better evidence or removing these entries.

4. Add Clinical Trials (Optional Enhancement)

Per Issue #154, clinical trials are now supported in the schema. Consider adding relevant APS trials from ClinicalTrials.gov.

Relevant Schema Patterns

When adding treatments, follow the established pattern from other disorders (e.g., Wilson's Disease):

treatments:
  - name: Warfarin Anticoagulation
    description: Vitamin K antagonist for long-term thrombosis prevention in APS. Target INR typically 2-3.
    treatment_term:
      preferred_term: pharmacotherapy
      term:
        id: MAXO:0000058
        label: pharmacotherapy
      therapeutic_agent:
        - preferred_term: warfarin
          term:
            id: CHEBI:10033
            label: warfarin
    evidence:
      - reference: PMID:XXXXXXXX
        supports: SUPPORT
        snippet: "Exact quote from paper about warfarin efficacy in APS"
        explanation: Why this supports the treatment

Related Issues & Context

• Part of Epic Epic: Autoimmune Diseases Curation Project #216 - Autoimmune Diseases Curation Project (90% complete)
• Related to Issue Editorial: Add therapeutic_agent CHEBI qualifiers to pharmacotherapy treatments #155 - Treatment terms should use CHEBI qualifiers
• Related to Issue Define pattern for using the therapeutic_agent slot on TreatmentDescriptor #146 - Therapeutic agent slot pattern
• Related to Issue Editorial: Frequency qualifiers often lack direct evidence support #112 - Evidence quality for frequency qualifiers

Recommended Next Steps

1. Literature search for recent APS treatment guidelines (e.g., EULAR, ACR recommendations)
2. Add treatments section with at least 3-4 evidence-based treatments
3. Add catastrophic APS subtype if evidence supports it
4. Review genetic evidence - remove or strengthen HLA associations
5. Run validation: just qc kb/disorders/Antiphospholipid_Syndrome.yaml
6. Check compliance: Should reach ~95-100% after adding treatments

Useful PMIDs to Consider

Based on the existing references, these high-quality sources are already in the file and may have treatment information:

• PMID:26125104 - mentions "novel oral anticoagulants and eculizumab"
• PMID:26307097 - diagnostic guidelines (may reference treatment)
• PMID:20822807 - comprehensive APS overview

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Note: This is a high-priority enhancement task as it's the final blocker for completing the Autoimmune Diseases Epic. The main gap is the missing treatments section, which should be straightforward to add using existing literature.