1. 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines

2. Grade 1 Recommendations GradeRisk/ Benefit Methodologic StrengthStrength of Recommendation 1AClearRCTs w/o significant limitations Strong; applies to most patients and circumstances 1C+ClearNo RCTs; strong results extrapolated or strong observational studies Strong; most patients, circumstances 1BClearRCTs with limitationsStrong; most patients 1CClearObservational studiesIntermediate RCT = randomized controlled trial

3. Grade 2 Recommendations GradeRisk/ Benefit Methodologic StrengthStrength of Recommendation 2AUnclearRCTs w/o important limitations Intermediate; action depends on circumstances, values 2C+UnclearNo RCTs; strong results extrapolated or strong observational studies Weak; action depends on circumstances, values 2BUnclearRCTs with limitationsWeak; alternatives likely better for some 2CUnclearObservational studiesVery weak RCT = randomized controlled trial

4. Treatment of Venous Thromboembolic Disease

5. Initial Therapy for Acute DVT of the Leg We recommend that patients receive anticoagulants as soon as the diagnosis of DVT is confirmed Interim treatment should be started if suspicion is high and confirmation is delayed We recommend that patients receive anticoagulants as soon as the diagnosis of DVT is confirmed Interim treatment should be started if suspicion is high and confirmation is delayed

6. Guidelines for Initial Treatment CLINICAL SITUATIONRECOMMENDED TREATMENT Confirmed acute DVT of the legOptions: SC LMWH, IV UFH, or SC UFH (all Grade 1A) High suspicion of DVT of the legAnticoagulants, while awaiting the outcome of diagnostic tests (Grade 1C+)

7. Initial UFH or LMWH Therapy SELECTIONRECOMMENDED TREATMENT IV UFHContinuous infusion; adjust dosage to prolong the APTT to a range that corresponds to a plasma heparin level of 0.3 to 0.7 IU/mL antifactor Xa activity by amidolytic antifactor Xa assay (Grade 1C+) If therapeutic levels of APTT are not reached despite large daily doses of UFH: measure antifactor Xa levels for dosage guidance (Grade 1B)

8. Initial UFH or LMWH Therapy, continued SELECTIONRECOMMENDED TREATMENT SC UFHSC UFH is an alternative to IV UFH (Grade 1A); initial dose 35,000 U/24 h, then maintain the APTT within therapeutic range (Grade 1C+) SC LMWHWe recommend initial treatment with SC LMWH qd or bid, over UFH, as outpatient therapy if possible (Grade 1C), as inpatient therapy if necessary (Grade 1A) We recommend against routinely monitoring antifactor Xa levels (Grade 1A)

9. Systemic Thrombolysis as Initial Therapy THERAPYRECOMMENDATIONS IV thrombolytic therapyWe recommend against routine use (Grade 1A) We suggest use in selected patients* (Grade 2C) Catheter-directed thrombolysis We recommend against routine use (Grade 1C) We suggest confining use to selected patients, eg, those requiring limb salvage (Grade 2C)

10. Systemic Thrombolysis as Initial Therapy, continued THERAPYRECOMMENDATIONS Venous thrombectomy We recommend against routine use (Grade 1C) We suggest use in selected patients* (Grade 2C) Placement of a vena cava filter We recommend against routine use in most patients during anticoagulant therapy (Grade 1A) We suggest use in patients with a contraindication for, or complication of, anticoagulant therapy (Grade 2C), and those with recurrent thromboembolism despite adequate anticoagulant therapy (Grade 2C)

11. Long-term Therapy for DVT of the Leg PATIENT CHARACTERISTICSRECOMMENDED TREATMENT First DVT episode, secondary to a transient (reversible) risk factor (proximal vein thrombosis or symptomatic DVT confined to calf veins) VKA therapy for 3 months, over use for shorter periods (Grade 1A) First episode of idiopathic DVTVKA therapy for ≥ 6 to 12 months (Grade 1A) Consider giving anticoagulants indefinitely (Grade 2A)

12. Long-term Therapy for DVT of the Leg, continued PATIENT CHARACTERISTICSRECOMMENDED TREATMENT DVT and cancerLMWH for the first 3 to 6 months of anticoagulant therapy* (Grade 1A) We recommend giving anticoagulants indefinitely, or until the cancer is resolved (Grade 1C) *Established LMWH regimens for long-term treatment: dalteparin, 200 IU/kg body weight qd for 1 month, then 150 IU/kg qd; or tinzaparin, 175 IU/kg body weight SC qd.

13. Long-term Therapy for DVT of the Leg, continued PATIENT CHARACTERISTICSRECOMMENDED TREATMENT First DVT episode and either documented antiphospholipid antibodies (APLAs) or two or more thrombophilic conditions, eg, combined factor V Leiden and prothrombin 20210 gene mutation VKA therapy for 12 months (Grade 1C+) We suggest giving anticoagulants indefinitely (Grade 2C)

14. Long-term Therapy for DVT of the Leg, continued PATIENT CHARACTERISTICSRECOMMENDED TREATMENT First DVT episode and any of the following: documented antithrombin deficiency, deficiency of protein C or protein S, factor V Leiden, prothrombin 20210 gene mutation, homocystinemia, factor VIII levels > 90 th percentile of normal VKA therapy for 6 to 12 months (Grade 1A) We suggest continuing treatment indefinitely (Grade 2C) 2 or more episodes of documented DVTWe suggest continuing treatment indefinitely (Grade 2A)

15. Initial Therapy for PE: LMWH Or UFH Therapy CLINICAL SITUATIONRECOMMENDATION Confirmed, non-massive PESC LMWH or IV UFH (both Grade 1A) High suspicion of PEAnticoagulants, while awaiting test outcomes (Grade 1C+) Coexisting severe renal failureIV UFH over LMWH (Grade 2C)

16. Initial Therapy for PE: Thrombolytic Agents CLINICAL SITUATIONRECOMMENDATION Most patientsWe recommend clinicians not use systemic thrombolytic therapy (Grade 1A) Selected patients, eg, hemodynamically unstable patients Systemic thrombolytic therapy (Grade 2B)* Patients receiving thrombolytic therapy We suggest regimens with a short infusion time over those with a prolonged infusion time (Grade 2C)

17. Initial Therapy for PE: Additional Recommendations INITIAL TREATMENT OF PERECOMMENDATION Most patientsWe recommend against mechanical approaches (Grade 1C) We recommend against pulmonary embolectomy (Grade 1C) Selected, highly compromised patients (those who are unable to receive thrombolytic therapy, or whose critical status does not allow enough time for infusion) Mechanical approaches may be used (Grade 2C) Pulmonary embolectomy may be used (Grade 2C)

18. Initial Therapy for PE: Additional Recommendations, continued INITIAL TREATMENT OF PERECOMMENDATION Patients with a contraindication for, or complication of, anticoagulant treatment; or patients with recurrent thromboembolism, despite adequate anticoagulation therapy We suggest clinicians place an IVC filter (Grade 2C)

19. Long-Term Therapy for PE: VKA Therapy PATIENT CHARACTERISTICSRECOMMENDATION First episode of PE, secondary to a transient (reversible) risk factor VKA therapy for ≥ 3 months (Grade 1A) First episode of idiopathic PEVKA therapy for ≥ 6 to 12 months (Grade 1A) Consider giving anticoagulants indefinitely (Grade 2A) Concomitant cancerMost patients: LMWH for 3 to 6 months (Grade 1A); then anticoagulants indefinitely, or until the cancer is resolved (Grade 1C)

20. Long-Term Therapy for PE: VKA Therapy, continued PATIENT CHARACTERISTICSRECOMMENDATION First episode of PE, and either documented APLAs or ≥ 2 thrombophilic conditions (eg, combined factor V Leiden and prothrombin 20210 gene mutations) Treat for 12 months (Grade 1C+) ;We suggest giving anticoagulants indefinitely (Grade 2C) First episode of PE, and any of the following: documented antithrombin deficiency, protein C or protein S deficiency, factor V Leiden, prothrombin 20210 gene mutation, homocystinemia, high factor VIII levels (> 90 th percentile of normal) Treat for 6 to 12 months (Grade 1A) We suggest giving anticoagulants indefinitely (Grade 2C)

21. Long-Term Therapy for PE: VKA Therapy, continued PATIENT CHARACTERISTICSRECOMMENDATION ≥ 2 episodes of documented PEWe suggest giving anticoagulants indefinitely (Grade 2A)

22. Postthrombotic Syndrome THERAPEUTIC GOALRECOMMENDATION Prevent postthrombotic syndromeGCS (ankle pressure 30 to 40 mm Hg) for 2 yr after a DVT episode (Grade 1A) Treat severe edema of the legA course of therapy with an IPC device (Grade 2B) Treat mild edema of the legGCS (Grade 2C) or rutosides (Grade 2B)

23. Other Thrombotic Conditions PATIENT CHARACTERISTICSRECOMMENDATION Chronic thromboembolic pulmonary hypertension Selected patients, ie, those with central disease being treated by experienced surgical & medical team: pulmonary thrombo- endarterectomy (Grade 1C) After pulmonary thromboendarterectomy, and for patients who are ineligible: life- long VKA therapy (INR 2.0 to 3.0) (Grade 1C) We suggest placing a vena cava filter before or at the time of pulmonary thrombo- endarterectomy (Grade 2C) Superficial thrombophlebitis, as a complication of infusion Topical diclofenac gel (Grade 1B) or oral diclofenac (Grade 2B)

24. Other Thrombotic Conditions, continued PATIENT CHARACTERISTICS RECOMMENDATION Spontaneous superficial thrombophlebitis Intermediate doses of UFH or LMWH for ≥ 4 wk (Grade 2B) Acute upper-extremity DVT (initial treatment) UFH or LMWH (both Grade 1C+) Initial treatment for selected patients: Those with a low risk of bleeding and symptoms of recent onset: short course of thrombolytic therapy (Grade 2C) Those with failure of anticoagulant or thrombolytic treatment, and persistent symptoms: surgical embolectomy or catheter extraction (both Grade 2C)

25. Other Thrombotic Conditions, continued PATIENT CHARACTERISTICSRECOMMENDATION Acute upper-extremity DVT (initial treatment) Continued: Those with a contraindication for anticoagulant treatment: consider a superior vena cava filter (Grade 2C) Acute upper-extremity DVT (long- term treatment) VKA therapy (Grade 1C+) (for duration of treatment, see recommendations for acute DVT) Persistent edema and painElastic bandages, for symptomatic relief (Grade 2C)