120.3 🩺 內科專科考前版

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120.3.0.1 📌 一頁重點

• 22E 重大進展:
  • Caplacizumab (Cablivi) approved 2019 for aTTP — anti-vWF A1 nanobody → ↓ TPE 次數 + ↓ exacerbation + ↓ death (HERCULES, TITAN)
  • Recombinant ADAMTS13 (TAK-755 / apadamtase) for congenital TTP approved 2024
  • TPO-RA (eltrombopag, romiplostim, avatrombopag) 第一線 2nd line for ITP：取代 splenectomy
  • Fostamatinib (Tavalisse) SYK inhibitor approved 2018 for chronic ITP
  • Rilzabrutinib (BTK i) + efgartigimod (FcRn antagonist) ITP trials
  • Eculizumab + ravulizumab for aHUS standard
  • HIT in DOAC era: rivaroxaban + apixaban approved alternative (RE-COVER, AMPLIFY data)
  • HHT: bevacizumab (anti-VEGF) IV for severe epistaxis + GI AVM bleeding
• Taiwan: TPE 健保條件給付 for TTP；caplacizumab 自費；eculizumab 健保 aHUS / PNH 條件給付；TPO-RA 健保條件給付 chronic ITP；fostamatinib 自費；HIT alternative AC (argatroban, fondaparinux) 健保條件

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120.3.0.2 🌟 Pearls (10)

1. TTP HERCULES trial: caplacizumab 加 standard care → ↓ time to plt > 150 + ↓ exacerbation 67% + ↓ TTP-related death
2. ADAMTS13 testing: ELISA + chromogenic assay；< 10% diagnostic for TTP；anti-ADAMTS13 Ab confirm autoimmune
3. PLASMIC score: 7-item score for predicting TTP probability before ADAMTS13 result（age, MCV, INR, creatinine, plt, hemolysis, malignancy/transplant）；high score → empiric TPE
4. Atypical HUS triggers: 妊娠, infection, surgery, autoimmune, drug → underlying complement mutation 表 phenotype
5. HIT post-cardiac surgery: very common (anti-PF4 Ab seroprevalence 高 but clinical HIT 較低)；timing typical 5-14 d；4Ts more reliable than ELISA alone
6. HIT in heparin-induced bridge to warfarin: warfarin 啟動 → protein C 急下降 → 臨界 procoagulant + thrombosis 風險 → wait plt > 150
7. Refractory ITP definition: failure of ≥ 2 lines including TPO-RA, rituximab, splenectomy
8. Splenectomy for ITP: response 60-70%, durable in 60% at 5 yr；vaccinate H. influenzae + meningococcal + pneumococcal pre-op + life-long encapsulated organism prophy
9. HHT diagnosis (Curaçao criteria): 3/4 = definite (epistaxis recurrent + telangiectasia + visceral lesion + family hist)；ENG/ACVRL1 mutations
10. Pregnancy + thrombocytopenia DDx: gestational vs ITP vs HELLP vs TTP；TTP 急性 → TPE; HELLP → deliver；ITP 1st/2nd trimester multidisciplinary care

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120.3.0.3 📍 Taiwan + 健保

120.3.0.3.1 治療

• TPE (Plasmapheresis) for TTP / atypical HUS / refractory ITP / GBS / MG: 健保條件給付
• Caplacizumab: 自費（每療程 NT$ 數百萬）
• Recombinant ADAMTS13: 自費 / clinical trial
• TPO-RA (eltrombopag, romiplostim, avatrombopag): 健保條件給付 chronic ITP failed first-line
• Rituximab: 健保條件給付 for autoimmune hematologic disorders
• Fostamatinib: 自費
• Eculizumab / Ravulizumab: 健保條件給付 for aHUS / PNH
• Argatroban: 健保條件給付 for HIT
• Fondaparinux: 健保條件給付
• Bivalirudin: 健保條件給付 for HIT during PCI
• DOAC (rivaroxaban, apixaban) for HIT: off-label 但醫院多接受
• DDAVP for vWD / uremia: 健保條件給付
• Splenectomy for ITP: 健保條件給付
• Bevacizumab for HHT: off-label 自費

120.3.0.3.2 在地分布

• TTP: 台灣 incidence ~ 3/百萬；多 acquired (autoimmune)
• aHUS: 罕見；NSCT (Newborn Screening for Complement Triggered) 不普及
• HIT: 心臟外科 + 加護病房 awareness 重要；4Ts score routine
• HHT: 台灣案例稀少；醫學中心 ENT + GI 共照
• 學會: 台灣血栓暨止血學會 共識

120.3.0.3.3 在地衛教

• ITP 病人 vaccination + 避免抗血小板藥物 + 月經量大 → tranexamic acid
• TTP 病人 long-term ADAMTS13 + 復發 monitoring (relapse rate ~30% 年)
• HIT 病人終生避免 heparin（含 catheter flush）+ 醫療警示牌
• HHT 病人 lung AVM screening (CT) + brain AVM (MRI) + paradoxical embolus 預防

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120.3.0.4 🎓 內專必懂 (10)

1. ITP 2nd line decision: TPO-RA vs rituximab vs splenectomy vs fostamatinib + 個別化選擇
2. TTP / TMA 鑑別: ADAMTS13 + complement testing + PLASMIC score
3. Caplacizumab 機制 + indication + 監測 (vWF Ag tracking)
4. HUS subclassification: STEC vs aHUS vs secondary (drug, transplant, malignancy)
5. HIT 4Ts + 治療 (含 DOAC alternative) + warfarin transition
6. Glanzmann + Bernard-Soulier + MYH9 + storage pool 鑑別
7. Pregnancy thrombocytopenia DDx
8. HELLP: 急救 + delivery
9. HHT diagnostic criteria (Curaçao) + screening (lung CT, brain MRI)
10. Refractory ITP + 新藥 (rilzabrutinib, efgartigimod) trials

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120.3.0.5 🔬 進階機轉

120.3.0.5.1 Caplacizumab Mechanism

• Bivalent humanized nanobody binding vWF A1 domain
• 阻止 vWF binding to platelet GP1b → 阻止 microthrombi formation
• 即時 effect (不需 ADAMTS13)
• TPE 同時 + 之後持續 30 day

120.3.0.5.2 ADAMTS13 Genetic Variants

• Upshaw-Schulman syndrome: 雙等位基因 ADAMTS13 mutations → congenital TTP
• 表現：新生兒 / 兒童 / 妊娠時 acute；多 hospitalization 觸發
• 治療：FFP infusion (含 ADAMTS13) regular；rADAMTS13 22E approval

120.3.0.5.3 aHUS Complement Mutations

• CFH (Complement Factor H) — 50%
• CFI (Complement Factor I)
• MCP (CD46)
• C3 gain-of-function
• THBD (thrombomodulin)
• 部分病人 anti-CFH antibody

120.3.0.5.4 HIT Pathophysiology

• Heparin + platelet PF4 → conformational change → 形成 antigen
• IgG anti-PF4-heparin Ab → bind FcγRIIA on platelet → activation + microparticles
• Microparticles + tissue factor → procoagulant state → thrombosis

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120.3.0.6 ⚠️ 內專易錯點

• TTP 不立即 TPE 等 ADAMTS13 結果 → mortality ↑↑
• TTP 給 platelet → fuels microthrombi + worse outcome
• PLASMIC score 高但等 ADAMTS13 → 應立即 empiric TPE
• HIT 給 platelet transfusion
• HIT warfarin 直接 transition → limb gangrene
• HIT subsequent surgery 用 heparin → re-trigger（要 alternative AC）
• aHUS 不查 complement panel + genetics → 漏 eculizumab indication
• STEC-HUS 給 antibiotic → 加重 toxin
• ITP refractory 不考慮 splenectomy 仍然 viable（TPO-RA 不一定取代）
• HHT 病人 atrial fibrillation 用 standard AC without 評估 lung/brain AVM → paradoxical embolus 風險
• Pregnancy thrombocytopenia 不分型 → 漏 TTP / HELLP 緊急性

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