123.3 ๐Ÿฉบ ๅ…ง็ง‘ๅฐˆ็ง‘่€ƒๅ‰็‰ˆ

123.3.0.1 ๐Ÿ“Œ ไธ€้ ้‡้ปž

  • 22E ้‡ๅคง้€ฒๅฑ•:
    • Factor XI inhibitors: AZALEA-TIMI 71 (abelacimab vs rivaroxaban AF) โ†’ ้กฏ่‘— โ†“ bleed๏ผ›ๅ…ถไป– trial: AXIOMATIC (milvexian/asundexian); ้ ่จˆ 2025-2027 ๅคš approvals โ†’ ๆŠ—่ก€ๆ “ ไธๅขž bleed ้ฉๅ‘ฝ
    • Vorapaxar (PAR-1) ้™็”จ (TRA 2P-TIMI 50: 2nd prevention but ๅ‡บ่ก€ โ†‘)
    • DAPT shorter duration: TWILIGHT (3 mo + ticagrelor mono); SMART-CHOICE; STOPDAPT-2; SHORT-DAPT ๅ…จ้ƒจๆ”ฏๆŒ high-bleed pts shorter DAPT
    • DOAC for cancer-associated thrombosis: CARAVAGGIO + Hokusai-VTE Cancer + SELECT-D ๅทฒ paradigm shift
    • Andexanet alfa (Xa reversal): ANNEXA-4 + 22E ANNEXA-I (ICH on apixaban) approved + ๅปฃๆณ›
    • Tenecteplase ๅ–ไปฃ Alteplase: AcT trial 2022 (NEJM) showed tenecteplase non-inferior + easier dosing; 2024 ๅคš stroke center ๆŽก็”จ
    • Stroke thrombolysis 9 hr extended window (ECASS 4 / EXTEND)๏ผšๅ€‹ๅˆฅ imaging-guided
    • Mechanical thrombectomy for stroke up to 24 hr (DAWN, DEFUSE-3)๏ผšๅ–ไปฃ / ่ฃœ thrombolysis
  • Taiwan: ๅฅไฟ DOAC for AF + VTE ๆขไปถ็ตฆไป˜๏ผ›NOAC ๅญธๆœƒ + ๅฟƒ่‡Ÿๅญธๆœƒๅ…ฑ่ญ˜๏ผ›warfarin ๅฅไฟๆœ€ไพฟๅฎœ๏ผ›fondaparinux/argatroban for HIT ๅฅไฟๆขไปถ๏ผ›idarucizumab/andexanet ่‡ช่ฒป (็ทŠๆ€ฅๆ™‚) ๏ผ›alteplase + tenecteplase ๅฅไฟ stroke + STEMI

123.3.0.2 ๐ŸŒŸ Pearls (10)

  1. Ticagrelor pleiotropic effects: ไธๅช P2Y12 ้˜ป โ€” ้‚„ โ†‘ adenosine availability โ†’ coronary vasodilation + dyspnea (mechanism); brady (vagal) AE
  2. Clopidogrel CYP2C19 polymorphism: poor metabolizer (~30% Asian) โ†’ ไธ่ฝ‰ active form โ†’ ่—ฅๆ•ˆๅทฎ๏ผ›ๅฏ่€ƒๆ…ฎ prasugrel/ticagrelor or ๅขž dose๏ผ›test if recurrent ischemic event
  3. DAPT duration nuance: ACS 12 mo standard but PEGASUS ่ญ‰ ticagrelor + ASA ร— 3 yr ้ƒจๅˆ† high-risk pts๏ผ›DAPT score / PRECISE-DAPT score ๆŒ‡ๅฐŽ
  4. Warfarin pharmacogenetics: CYP2C9 2/3 + VKORC1 -1639 G>A โ†’ variable dose๏ผ›genotype-guided dosing trials ็ตๆžœ mixed (COAG no, GIFT yes)
  5. Heparin resistance: AT-deficient pt ๅฐ UFH ๅๆ‡‰ๅทฎ โ†’ AT concentrate / FFP supplement๏ผ›่ฆ anti-Xa monitoring not aPTT (false short)
  6. DOAC perioperative: low bleed risk procedure โ†’ continue or 24 hr hold๏ผ›high bleed risk โ†’ 48-72 hr hold๏ผ›renal failure ๅปถ้•ท๏ผ›spinal anesthesia โ†’ 48 hr+ hold
  7. DOAC drug interactions: P-gp + CYP3A4 inhibitor (azole, HIV PI, amiodarone) โ†’ โ†‘ DOAC level๏ผ›inducer (rifampin, phenytoin) โ†’ โ†“
  8. Andexanet reservations: half-life short (1 hr) need infusion๏ผ›rebound anti-Xa activity๏ผ›cost $30-50K per dose๏ผ›4F-PCC alternative cheaper
  9. tPA combined with mechanical thrombectomy for LVO stroke: bridging strategy (vs thrombectomy alone) โ€” DIRECT-MT, MR CLEAN-NO IV mixed results
  10. Fibrinolytic AE specific: tPA-induced angioedema (~ 1.3%, ACE inhibitor + tPA combined risk โ†’ laryngeal edema)๏ผ›orolingual edema ็ซ‹ๅณ stop tPA + steroid + epi

123.3.0.3 ๐Ÿ“ Taiwan + ๅฅไฟ

123.3.0.3.1 ๆŠ—่ก€ๅฐๆฟ
  • Aspirin (Bokey 100 mg): ๅฅไฟ
  • Clopidogrel (Plavix): ๅฅไฟๆขไปถ็ตฆไป˜ ACS / PCI / stroke / PAD
  • Prasugrel (Effient): ๅฅไฟๆขไปถ็ตฆไป˜ ACS PCI
  • Ticagrelor (Brilinta): ๅฅไฟๆขไปถ็ตฆไป˜ ACS / PCI
  • Cilostazol (Pletaal): ๅฅไฟๆขไปถ PAD
  • GPIIb/IIIa (abciximab, tirofiban, eptifibatide): ๅฅไฟๆขไปถ็ตฆไป˜ PCI
  • Vorapaxar: ่‡ช่ฒป
123.3.0.3.2 ๆŠ—ๅ‡
  • UFH: ๅฅไฟ acute hospital
  • LMWH (Enoxaparin/Clexane, Dalteparin/Fragmin): ๅฅไฟๆขไปถ็ตฆไป˜
  • Fondaparinux (Arixtra): ๅฅไฟๆขไปถ็ตฆไป˜ HIT alternative + VTE prophy
  • Argatroban: ๅฅไฟๆขไปถ็ตฆไป˜ HIT
  • Bivalirudin (Angiomax): ๅฅไฟๆขไปถ็ตฆไป˜ HIT/PCI
  • Warfarin: ๅฅไฟ๏ผˆๆœ€ไพฟๅฎœ๏ผŒๅคš generic๏ผ‰๏ผ›INR ็›ฃๆธฌ frequent
  • Dabigatran (Pradaxa): ๅฅไฟๆขไปถ็ตฆไป˜ AF + VTE
  • Rivaroxaban (Xarelto): ๅฅไฟๆขไปถ็ตฆไป˜
  • Apixaban (Eliquis): ๅฅไฟๆขไปถ็ตฆไป˜
  • Edoxaban (Lixiana): ๅฅไฟๆขไปถ็ตฆไป˜
  • Idarucizumab (Praxbind): ๅฅไฟๆขไปถ็ตฆไป˜๏ผˆ็ทŠๆ€ฅ dabigatran reversal๏ผ‰
  • Andexanet alfa: ่‡ช่ฒป๏ผˆๆฏๅŠ‘ NT$ ๆ•ธๅ่ฌ๏ผŒๅชๅœจ็ทŠๆ€ฅ critical bleed ็ตฆ๏ผ‰
  • 4F-PCC (Kcentra): ๅฅไฟๆขไปถ็ตฆไป˜ warfarin reversal + DOAC reversal alternative
123.3.0.3.3 Fibrinolytic
  • Alteplase (Actilyse): ๅฅไฟๆขไปถ็ตฆไป˜ stroke / STEMI / PE
  • Tenecteplase (Metalyse): ๅฅไฟๆขไปถ็ตฆไป˜ STEMI
  • Streptokinase: ็ฝ•็”จ
123.3.0.3.4 Lab + ็›ฃๆธฌ
  • ๅฅไฟ๏ผšaPTT, INR, anti-Xa level, factor activity assays
  • ๅฅไฟ๏ผšD-dimer
  • ๅฅไฟๆขไปถ๏ผšCYP2C19 / CYP2C9 / VKORC1 genotyping for hard-to-control AC
123.3.0.3.5 ๅœจๅœฐๅˆ†ๅธƒ
  • DOAC ๆ™ฎๅŠ๏ผš่‡ช 2012 ่ตทๅฅไฟ่ฆ†่“‹๏ผ›็พๅคš้†ซๅธซ prefer over warfarin
  • Warfarin ็”จ้‡ โ†“๏ผšไป็”จๆ–ผ mech valve, APS, DOAC ไธ้ฉ็—…ไบบ
  • NOAC clinic ๅธธ่จญๆ–ผๅฟƒ่‡Ÿ็ง‘ / ็ฅž็ถ“็ง‘
  • Asian dose adjustment: dabigatran 110 mg in elderly Asian (RE-LY-Asian subgroup); apixaban + edoxaban Asian-specific data ๆ”ฏๆŒ lower-dose
  • ๅญธๆœƒ๏ผšๅฐ็ฃ่ก€ๆ “ๆšจๆญข่ก€ๅญธๆœƒ + ไธญ่ฏๆฐ‘ๅœ‹ๅฟƒ่‡Ÿๅญธๆœƒ + ไธญ่ฏๆฐ‘ๅœ‹็ฅž็ถ“ๅญธๆœƒ NOAC ๅ…ฑ่ญ˜
123.3.0.3.6 ๅœจๅœฐ่ก›ๆ•™
  • DOAC ่ฆๅพ‹ๆœ่—ฅ๏ผˆๅคš BID ๆœ่—ฅ้ †ๅพžๆ€งๆ˜ฏ่ญฐ้กŒ๏ผ‰
  • DOAC ๅœ่—ฅๅ‰ procedure ่ซฎ่ฉข้†ซๅธซ๏ผˆไธๅฏ่‡ช่กŒๅœ๏ผ‰
  • Warfarin ็—…ไบบ INR ่ฆๅพ‹ + drug-food interaction ๆ•™่‚ฒ
  • ๆŠ—่ก€ๅฐๆฟ + ๆŠ—ๅ‡ๅˆ็”จ GI bleed ้ขจ้šช โ†‘โ†‘ โ†’ PPI prophy
  • ็ทŠๆ€ฅๆ™‚ๅ‘Š็Ÿฅ่ก€ๆถฒ็จ€้‡‹่—ฅ

123.3.0.4 ๐ŸŽ“ ๅ…งๅฐˆๅฟ…ๆ‡‚ (10)

  1. Antiplatelet pharmacology + DAPT ๅ€‹ๅˆฅๅŒ– (TWILIGHT, PEGASUS, DAPT score)
  2. Warfarin pharmacogenomics + CYP2C9 / VKORC1
  3. DOAC drug interactions (P-gp + CYP3A4) + perioperative management
  4. Reversal agents: idarucizumab vs andexanet vs 4F-PCC + cost-benefit
  5. HIT alternative anticoagulants: argatroban, bivalirudin, fondaparinux, DOAC
  6. Cancer-associated thrombosis 22E choice algorithm
  7. Mechanical valve ๆŠ—ๅ‡ (warfarin INR target + bridge)
  8. Pregnancy ๆŠ—ๅ‡ (LMWH dose-adjusted by anti-Xa)
  9. Factor XI inhibitors mechanism + trials + future
  10. Fibrinolytic for stroke (4.5 hr, extended 9 hr) + STEMI + PE + ๅ่ฝ‰

123.3.0.5 ๐Ÿ”ฌ ้€ฒ้šŽๆฉŸ่ฝ‰

123.3.0.5.1 Factor XI Inhibitor Hypothesis
  • FXI ไธป่ฆ amplifies thrombin generation in pathologic thrombosis
  • Hemostasis (cut, surgery, vessel injury) FXI ่ง’่‰ฒ็›ธๅฐ minor
  • Dual-mechanism: โ†“ thrombosis without compromising hemostasis
  • Clinical evidence: FXI deficiency ็—…ไบบ thrombosis ้ขจ้šช โ†“ ไฝ† bleed risk ไธๅขž
123.3.0.5.2 DOAC Pharmacology
Dabigatran Rivaroxaban Apixaban Edoxaban
Target IIa Xa Xa Xa
Bioavailability 6-7% 80-100% 50% 62%
Half-life 12-14 hr 5-13 hr 12 hr 10-14 hr
Renal excretion 80% 33% 25% 50%
Food None with food (15+ mg) None None
CYP3A4 None + (P-gp + CYP) + (P-gp + CYP) (P-gp)

โ†’ Apixaban ๅคš prefer due ่ผƒๅฐ‘ renal dependence + balanced PK

123.3.0.5.3 Reversal Agent Mechanism
Drug Mechanism
Idarucizumab Humanized Fab fragment binds dabigatran > 350x affinity than thrombin
Andexanet alfa Recombinant modified Xa (catalytically inactive) binds Xa inhibitors as decoy
4F-PCC 4-factor (II, VII, IX, X) + protein C + S concentrate

123.3.0.6 โš ๏ธ ๅ…งๅฐˆๆ˜“้Œฏ้ปž

  • DAPT ไธๅ€‹ๅˆฅๅŒ–: high bleed risk ๅ…จ 12 mo โ†’ bleed ้ขจ้šช โ†‘โ†‘
  • CYP2C19 PM ็—…ไบบ clopidogrel ๅคฑๆ•ˆไธๆ› prasugrel/ticagrelor โ†’ ๅ่ฆ† stent thrombosis
  • Warfarin pregnancy + ๅฆŠๅจ  โ†’ teratogenic
  • DOAC mech valve / triple+ APS / pregnancy โ†’ contraindicated
  • DOAC drug interaction (azole, HIV PI, amiodarone) ไธ dose-adjust
  • Severe renal failure ็”จ dabigatran (80% renal excretion)
  • HIT ็ตฆ LMWH โ†’ trigger
  • HIT warfarin ็›ดๆŽฅ transition without alternative AC โ†’ limb gangrene
  • tPA ไธๆŸฅ contraindications + BP before infusion โ†’ ICH
  • tPA + ACE inhibitor combined orolingual edema ไธ่ญฆ่ฆบ
  • Heparin resistance ไธๆŸฅ antithrombin โ†’ escalating dose ไป ineffective
  • DOAC perioperative ไธ hold based on procedure bleed risk
  • Andexanet routinely for warfarin reversal โ†’ ไธ้ฉ (only Xa inhibitor)
  • 4F-PCC for dabigatran reversal ไธๆ•ˆ๏ผˆๆ‡‰็”จ idarucizumab๏ผ‰

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