343.3 🏥 內科專科考前版

343.3.1 Mechanistic Deep Dive

343.3.1.1 ADAMTS13

  • Cleaves vWF multimers
  • Antibody-mediated deficiency in acquired TTP
  • Genetic: Upshaw-Schulman syndrome (congenital)
  • Activity < 10% diagnostic

343.3.1.2 Complement Dysregulation in aHUS

  • CFH (Factor H), CFI (Factor I), MCP (CD46), C3, CFB
  • Genes encoding regulators
  • 50%+ have identifiable mutations
  • ↑ MAC formation → endothelial damage

343.3.1.3 Caplacizumab

  • Anti-vWF nanobody
  • Inhibits vWF-platelet interaction
  • ↓ Microthrombi formation
  • HERCULES trial

343.3.2 Recent Trials & Updates

343.3.2.1 CORAL (2014) — ARAS Stenting

  • N = 947
  • Stent + OMT vs OMT
  • No CV benefit overall
  • Subgroups still selected for stent

343.3.2.2 HERCULES (2019) — Caplacizumab in TTP

  • ↓ Recovery time + relapses
  • Adjunct to PEX + steroids
  • FDA approval 2019

343.3.2.3 PRAISE — Ravulizumab for aHUS

  • Long-acting alternative to eculizumab
  • FDA approval

343.3.2.4 Iptacopan in TMA

  • Factor B inhibitor
  • Emerging for selected TMA

343.3.3 High-Yield Specialist Points

343.3.3.1 Resistant HTN Workup

  • Confirm with ABPM
  • Adherence + lifestyle
  • Secondary causes (aldosteronism, RAS, OSA, pheo)
  • Drug-induced
  • Refer to specialist

343.3.3.2 Renal Denervation

  • For resistant HTN
  • 2024 FDA approval
  • SPYRAL HTN, RADIANCE-HTN trials

343.3.3.3 Renal Artery Stent Procedure

  • Indications selectively
  • Procedural risk (cholesterol embolism)
  • Variable long-term success

343.3.3.4 TTP Caplacizumab Use

  • Initial 10 mg IV
  • 10 mg SC daily
  • Continue 30 days after PEX
  • Reduces relapses

343.3.3.5 eculizumab Pre-Vaccination

  • Meningococcal C/Y and B vaccines pre-treatment
  • 2 weeks before ideally
  • Strict prophylaxis if recent

343.3.3.6 Long-Term Outcomes Post-TMA

  • TTP relapses (in ~ 30% — esp ADAMTS13-deficient)
  • aHUS relapses with eculizumab discontinuation
  • Long-term surveillance

343.3.3.7 Drug-Induced TMA Specifics

  • Cyclosporine + tacrolimus: dose-related, switching helps
  • ICI-TMA: rare but increasing recognition; stop ICI + corticosteroids
  • VEGF inhibitors: HTN + proteinuria + TMA features; manage BP

343.3.3.8 Cholesterol Embolism Course

  • Months to develop
  • May plateau or progress
  • ~ 30-50% mortality first year
  • Statins may reduce inflammation

343.3.3.9 Hypertensive Emergency Drug Choices

  • Labetalol: most uses
  • Nicardipine: stroke, encephalopathy
  • Clevidipine: ICU titratable
  • Nitroprusside: short-term; cyanide toxicity caution
  • Hydralazine: pregnancy

343.3.3.10 Pregnancy + Antihypertensives

  • Labetalol, nifedipine, methyldopa
  • Avoid ACE/ARB (teratogenic)
  • Hydralazine for emergencies

343.3.3.11 Scleroderma + Pregnancy

  • Renal crisis risk
  • ACE inhibitor pre-pregnancy if existing nephropathy
  • Multidisciplinary

343.3.4 Pearls

  • ARAS: CORAL → OMT first-line
  • FMD: young women; balloon angioplasty
  • TTP: ADAMTS13 < 10%; PEX + caplacizumab + steroids + rituximab
  • aHUS: complement; eculizumab / ravulizumab
  • STEC HUS: supportive; avoid antibiotics
  • Cholesterol embolism: post-procedure; supportive
  • Scleroderma renal crisis: ACE inhibitor lifesaving
  • Malignant HTN: IV antihypertensives + careful Cr management
  • Renal denervation: 2024 FDA for resistant HTN