122.3 🩺 內科專科考前版

22E 重大進展:
- CARAVAGGIO (NEJM 2020): Apixaban ≥ dalteparin for cancer-associated VTE (most cancers)
- Hokusai-VTE Cancer: Edoxaban ≥ dalteparin
- SELECT-D: Rivaroxaban ≥ dalteparin
- TRAPS (NEJM 2018): Rivaroxaban worse than warfarin in triple-positive APS → DOAC contraindicated
- API-CAT: Apixaban for CAT 一年 ↑ outcome
- Factor XI inhibitors (abelacimab, milvexian, asundexian, fesomersen, osocimab): 抗血栓不增 bleed → 多 phase 3 (AZALEA-TIMI for AF; AXIOMATIC trials)
- Vorapaxar (PAR-1 antagonist) approved for secondary prevention 2014 (但限制使用 due 出血)
- Eculizumab + ravulizumab for PNH thrombosis 預防
Taiwan: 健保 DOAC for VTE / AF；LMWH for CAT；warfarin (INR target);全部 thrombophilia testing 條件給付；APS testing 條件給付；PNH testing 條件給付（流式）；eculizumab 健保 PNH/aHUS

Factor V Leiden mechanism: G1691A → R506Q substitution → resistance to APC cleavage → ↑ thrombin generation；homozygous 50-100x baseline VTE risk
APS pathophysiology: anti-β2-GPI Ab → endothelial activation + monocyte tissue factor + complement + neutrophil NET formation → multi-mechanism thrombosis
APS extra-criteria manifestations: Libman-Sacks endocarditis, livedo reticularis, thrombocytopenia, hemolytic anemia, nephropathy, cognitive dysfunction → multi-system disease
CARAVAGGIO subgroup: GI cancer 出血 rate 較高 with apixaban → LMWH 仍 preferred；Pancreas, biliary, lung 也 careful
Submassive PE 個別評估: PEITHO trial (tenecteplase) 顯著 ↓ hemodynamic decompensation 但 ↑ ICH；should be selected pts；catheter-directed thrombolysis (CDT) 同 efficacy 較少 bleeding
Distal DVT: 30% extend proximally；treat full vs serial US；多 prefer treatment if symptomatic / risk factors
Cerebral venous sinus thrombosis (CVST): thrombophilia + OCP + post-partum + dehydration；MRV 確診；anticoagulation 數月 → 多 recover
Splanchnic vein thrombosis: portal (cirrhosis), Budd-Chiari (MPN常)；workup MPN with JAK2; AC if active hemorrhage 可控
HIT 表現 thrombosis 占 50-80%: 不像 AC 弱，HIT 是 prothrombotic disorder；DOAC + argatroban 取代 AC
Catastrophic APS (CAPS): ≥ 3 organ thrombosis < 1 wk + 病理 confirm + APS lab+ → mortality 50%；治 high-dose steroid + plasmapheresis + IVIg + AC

Hereditary thrombophilia 評估邏輯 (when to test, off-AC, family screening)
APS 2023 ACR / EULAR criteria + extra-criteria + lab persistence ≥ 12 wk
APS triple-positive + DOAC 不效 (TRAPS) + 替代
CAT 22E: CARAVAGGIO + SELECT-D + Hokusai-Cancer + DOAC choice per cancer type
Submassive PE management dilemma: thrombolysis vs catheter-directed vs AC alone
Cerebral / splanchnic / portal vein thrombosis management
HIT 治療 + warfarin transition
Catastrophic APS (CAPS): 緊急 multidisciplinary
Factor XI inhibitors (22E new): mechanism + 試驗 + future
AC bridging perioperative + bleed risk assessment

Anti-β2-GPI Ab 結合 β2-glycoprotein-1 on endothelium
啟動 multiple pathways: complement, monocyte tissue factor, neutrophil NETosis, platelet activation
不限 vascular thrombosis：包括 placental thrombosis (妊娠失敗)

Active AC 病人 PC/PS/AT 檢查 → false low；要 off AC 至少 2 wk
Acute thrombotic episode 病人 thrombophilia 檢查 → low values；應 outside acute window
APS triple positive 用 DOAC → 風險高
Submassive PE 全部 thrombolysis → 個別 weighing bleed risk
CAT 全部 LMWH → DOAC 多 OK 除 GI/GU/brain mets
HIT 病人 LMWH instead of UFH → 仍可 trigger
HIT warfarin 直接 transition → limb gangrene
Distal DVT 不 follow → 30% 進展 proximal
CVST + APS 用 LMWH alone → 應 long-term warfarin
AC perioperative 不 bridge / bridge 過度 → 個別 risk-benefit

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