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Summary of 2016 CHEST Guidelines: Antithrombotic Therapy for VTE Disease Strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B) and low- (Grade C) quality evidence 1. Non Cancer patients i. Direct Oral Anticoagulants (DOAC) is recommended over vitamin K antagonist (VKA) (Grade 2B) ii. VKA is recommended over lower molecular weight heparin (LMWH) (Grade 2C) iii. LMWH (Grade 2C) 2. Cancer patients i. LMWH (Grade 2C) ii. VKA is equivalent to DOAC 3. Proximal DVT of leg, arm or PE a. Duration of Therapy i. 3 months for VTE secondary to 1. surgery (Grade 1B) 2. nonsurgical transient risk factor (estrogen therapy, pregnancy, leg injury, flight.>8 hours) (Grade 1B) 3. unprovoked DVT (isolated distal or proximal) or PE (Grade 1B) a. after 3 months weigh risk versus benefit of extended therapy b. patient sex and D-dimer measured 1 month after stopping anticoagulant therapy can further stratify the risk of recurrence i. men have a ~75% (1.75 fold) risk of recurrence compared to women ii. positive D-dimer result have double the risk of recurrence. D-dimer testing will often influence a female’s decision but not a male’s decision. iii. predictive value of 2 risk factors additive c. first or second unprovoked & high risk of bleeding (>2 bleeding risk factors) d. if patient declines extended anticoagulant therapy & there are no contraindications to aspirin, suggest indefinite ASA 100mg/day i. not equivalent to other anticoagulants but reduced recurrent VTEs in first unprovoked patients by 1/3 (in patients who completed 3-18 months of anticoagulation) ii. Lifelong (extended) duration for VTE in the following scenarios: 1. First unprovoked proximal DVT or PE with low (no bleeding risk factors, see table 11) or moderate (1 risk factor) risk of bleeding (Grade 2B) 2. Second unprovoked & low (Grade 1B) or moderate (Grade 2B) risk of bleeding 3. Cancer-associated thrombosis irrespective of bleeding risk factor in patients with active cancer 4. Distal DVT a. To treat or not to treat? i. 15% of untreated distal DVT expected to extend into the popliteal vein & may cause PE ii. Risk factors for extension & hence favor anticoagulation in patients with 1. Positive D-dimer 2. Extensive thrombosis 3. Thrombosis close to proximal veins 4. No reversible provoking factor for DVT 5. Active cancer 6. History of VTE 7. Inpatient status 8. Thrombosis that involves the axial (true deep, peroneal, tibial) veins 9. Severe symptoms 10. High bleeding risk favors surveillance iii. Without severe symptoms or risk factors, recommend serial imaging of deep veins for 2 weeks over anticoagulation (Grade 2C) 1. Patients at high risk for bleeding are more likely to benefit from serial imaging 2. Patients who place a high value on avoiding the inconvenience of repeat imaging & a low value on inconvenience of treatment & on the potential for bleeding are likely to choose initial anticoagulation over serial imaging 3. No anticoagulation if thrombus does not extend (Grade 1B) iv. Anticoagulation if: 1. Severe symptoms or risk factors (Grade 2C) 2. Thrombus extends but remains confined to distal veins (Grade 2C) 3. Thrombus extends to proximal veins (Grade 2C) b. Prevention of complications i. Do not use compression stockings to prevent post-thrombotic syndrome (Grade 2B) 5. Catheter-Directed Thrombolysis for acute DVT of the leg i. Proximal DVT 1. Anticoagulant therapy alone over catheter directed thrombolysis (Grade 2C) 6. IVC in addition to anticoagulation for acute DVT or PE i. Not recommended (Grade 1B) 7. Sub-segmental PE & no proximal DVT in the legs who have i. If low risk for recurrent VTE, consider surveillance (serial LE u/s or UE if central venous catheter) over anticoagulation (Grade 2C) 1. Patient should return for re-evaluation if symptoms persist or worsen ii. If high risk for recurrent VTE, consider anticoagulation (Grade 2C) 1. inpatient 2. low mobility 3. active cancer 4. no reversible risk factor 5. low cardiopulmonary reserve 8. Treatment of Acute PE out of hospital i. Low risk PE, treatment at home or early discharge ok if: 1. Clinically stable with good cardiopulmonary reserve 2. No contraindications such as recent bleeding, severe renal or liver disease or severe thrombocytopenia (<70K) 3. Expected to be compliant with treatment 4. Patient feels well enough to be treated at home 5. Absence of right ventricular dysfunction or increased cardiac biomarker levels should discourage treatment out of hospital 9. Systemic thrombolytic therapy is recommended for patients with i. Acute PE associated with hypotension (SBP<90 mmHg for 15 minutes) & without high risk of bleeding (Grade 2C) ii. Acute PE & cardiopulmonary deterioration after starting anticoagulant therapy but have to yet develop hypotension & low bleeding risk (Grade 2C) iii. Use systemic thrombolytic therapy using a peripheral vein over catheter directed thrombolysis (CDT) 10. Catheter directed thrombolysis is recommended for patients with i. high risk of bleed ii. failed systemic thrombolysis or shock that is likely to cause death before systemic thrombolysis can take effect (eg within hours) 11. Catheter based mechanical disruption/removal may be considered at centers that have expertise in these modalities (VM has expertise in catheter directed therapy [thrombolysis and mechanical disruption/removal]; activate the pulmonary embolism response teamPERT). 12. Anticoagulation alone is recommend over catheter directed thrombolysis for proximal DVT of the leg 13. UEDVT that involves the axillary or more proximal veins i. Anticoagulation over thrombolysis (Grade 2C) 14. Management of Recurrent VTE while on anticoagulation therapy i. Risk factors: 1. Treatment factors a. Higher risk during 1st week (or month) vs 2nd week (or month) ie risk diminishes with time b. Was LMWH used? c. Patient compliant? d. VKA sub therapeutic e. Was anticoagulant therapy prescribed correctly? f. DOAC Drug Interaction? (For interactions refer to the anticoagulation manual in VNet) g. Anticoagulant dose (other than VKA) reduced? h. Taking other medications that increase risk of thrombosis (estrogen, cancer chemo) 2. Patient’s Intrinsic Risk a. Active cancer b. Antiphospholipid syndrome (under dosing of VKA due to spurious increases in INR results) c. Taking other medications that can increase the risk of thrombosis ii. If on VKA or DOAC switch to LMWH (Grade 2C) iii. If on LMWH, increase dose by 25 to 30% (influenced by LMWH prefilled syringe dose options). Change from once a day to twice a day dosing. (Grade 2C) iv. If no reversible cause for recurrent VTE & anticoagulation intensity cannot be increased because of risk of bleeding, consider vena caval filter placement (last resort) Table 1 Risk Factors for bleeding with anticoagulant therapy and estimated risk of major bleeding in low, moderate and high risk categories Risk Factors Age >65 years Age >75 years Previous bleeding Cancer Metastatic Cancer Renal failure Liver failure Thrombocytopenia Previous Stroke Diabetes Anemia Antiplatelet therapy Poor anticoagulant control Co-morbidity and reduced functional capacity Recent surgery Frequent falls Alcohol abuse Non-steroidal anti-inflammatory drug Categorization of Risk of Bleeding Estimated absolute risk of major bleeding Low risk Moderate risk High risk (0 risk factors) (1 risk factor) (> 2 risk factors) Anticoagulation 0-3 months Baseline risk (%) 0.6 1.2 4.8 Increased risk (%) 1.0 2.0 8.0 Total risk (%) 1.6 3.2 12.8 Anticoagulation after firs 3 months Baseline risk (%) Increased risk (%) Total risk (%) 0.3 0.5 0.8 0.6 1.0 1.6 >2.5 >4.0 >6.5 Table 2- Recommended Duration of Secondary Prevention of VTE Length of Therapy Indication ACCP 2016 3 Months Provoked distal or proximal DVT or PE (surgery, estrogen therapy, pregnancy, leg injury, flight>8 hours) 1B 1B First unprovoked proximal or distal DVT or PE with high risk of bleeding At least 3 months Extended Therapy Second unprovoked VTE and high risk of bleeding First unprovoked DVT or PE Evaluate for risk-benefit of extended therapy at 3 months First unprovoked proximal DVT or PE and low or moderate bleeding risk 2B 1B 2B Second unprovoked VTE and low risk of bleeding 1B Second unprovoked VTE and moderate risk of bleeding 2B DVT or PE and active cancer and low and moderate risk of bleeding 1B DVT or PE and active cancer and high risk of bleeding 2B References: 1. Kearon C, Akl E, et al. Antithrombotic Therapy for VTE Disease CHEST Guideline and Expert Panel Report. CHEST 2016; 149(2): 315-352.