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Mechanistic Deep Dive
Factor V Leiden
- G1691A mutation (R506Q)
- Activated protein C cannot cleave factor Va â prolonged active Va
- Heterozygous: 5x risk
- Homozygous: 50x risk
- More common in Caucasians
APS Mechanism
- Antibodies against phospholipid-binding proteins (β2-GPI, prothrombin)
- Disrupt anticoagulant pathways (protein C, antithrombin)
- Activate platelets, endothelium, complement
- Catastrophic APS: multiple organ thrombosis in days
HIT Pathophysiology
- IgG antibody against PF4-heparin complex
- Binds platelets â activation â microthrombi
- Platelet count â (50% from baseline) by day 5-10 of heparin
- Stop heparin immediately, use argatroban/bivalirudin/fondaparinux
Recent Trials & Updates
EXTRACT-PE (2021) and FLAME (2023)
- Mechanical thrombectomy (Indigo, FlowTriever) for intermediate-high and high-risk PE
- â major bleeding vs lysis
- â procedural success and RV recovery
- 2024 ESC PE Guideline: Class IIa for catheter therapies
HI-PEITHO (2024)
- Ultrasound-assisted CDT vs anticoagulation in intermediate-high PE
- â death, hemodynamic deterioration, recurrent PE
- Strong support for CDT in submassive
ATTRACT (2017)
- CDT for proximal DVT
- No reduction in overall PTS
- Reduced moderate-severe PTS in iliofemoral DVT
- Practice: CDT in young iliofemoral with severe symptoms
CLOT-DVT (2024) Iliofemoral
- Pharmacomechanical CDT for iliofemoral DVT
- Improved patency and reduced PTS
Caravaggio (2020)
- Apixaban vs dalteparin in cancer-VTE
- Non-inferior, less bleeding (especially with apixaban)
- DOAC first-line in cancer-VTE
TRAPS (2018)
- Rivaroxaban vs warfarin in triple-positive APS
- â recurrence with DOAC
- Warfarin preferred in triple-positive APS
PEITHO + Long-Term (2017)
- Submassive PE: full-dose tPA
- â death/hemodynamic deterioration but â major bleeding (especially ICH in elderly)
- Use half-dose or CDT in selected
High-Yield Specialist Points
CTPH (Chronic Thromboembolic Pulmonary Hypertension)
- Persistent dyspnea + PH after PE (3-5% of survivors)
- V/Q scan most sensitive screening
- Right heart cath + pulmonary angiography for diagnosis
- Pulmonary endarterectomy (PEA): curative for proximal disease
- Riociguat (sGC stimulator) for inoperable or persistent
- Balloon pulmonary angioplasty (BPA): for distal disease
Distal DVT
- Calf DVT controversial
- Surveillance vs anticoagulation
- 3 mo AC if symptomatic, risk factors, or extending
- Otherwise serial US for 2 weeks
Upper Extremity DVT
- 5-10% of DVT
- Catheter-related (~ 70%)
- Effort thrombosis (Paget-Schroetter) â young athletes
- Anticoagulate; catheter removal if not needed; CDT for severe
IVC Filters
- Indication: contraindication to AC, recurrent VTE despite therapeutic AC
- Not adjunctive to AC routinely
- Retrievable preferred
- High retrieval rate failure â tracking system
PERT (Pulmonary Embolism Response Team)
- Class I for severe PE
- Cardio + pulmonology + vascular IR + ICU + surgery
- Faster, more appropriate therapy
Pregnancy + VTE Workup
- D-dimer often elevated in pregnancy (less reliable)
- Compression US first
- V/Q < CTPA fetal radiation, less breast dose
- LMWH preferred treatment
Thrombophilia Testing
- Donât test routinely (Choosing Wisely)
- Indications:
- Unprovoked VTE in young
- Recurrent VTE
- Family hx
- Pregnancy loss recurrent
- Tests should be done OFF anticoagulation + after acute phase
COVID-19 + VTE
- Increased risk during acute infection
- Prophylactic AC in hospitalized
- Therapeutic AC in select severe (REMAP-CAP, ATTACC, ACTIV-4)
Andexanet Alfa (Reversal)
- For Xa inhibitor reversal (apixaban, rivaroxaban)
- Approved for life-threatening bleeding
- ANNEXA-4 study
Idarucizumab (Reversal)
- For dabigatran reversal
- Monoclonal antibody, monolayer
Pearls
- Wells + D-dimer â US (DVT) or CTPA (PE)
- Massive PE: thrombolysis (alteplase 100 mg) OR CDT/FlowTriever; PERT
- DOAC first-line for most VTE; warfarin for APS triple-positive + mechanical valve
- Cancer-VTE: DOAC (Caravaggio) or LMWH (GI/GU)
- Pregnancy: LMWH; never DOAC
- CTEPH: post-PE PH; PEA curative; riociguat / BPA
- PERT for high/intermediate-high PE
- EXTRACT-PE + HI-PEITHO: CDT and mechanical thrombectomy gaining ground vs systemic lysis