1. Antithrombotic Therapy for VTE: CHEST Guidelines 2016
Jennifer Mah, MD
March 2016

2. Case
A 44-year-old man is evaluated in follow-up for an episode of unprovoked left proximal leg deep venous thrombosis 3 months ago. Following initial anticoagulation with low- molecular-weight heparin, he began treatment with warfarin. INR testing done every 3 to 4 weeks has shown a stable therapeutic INR. He has mild left leg discomfort after a long day of standing, but it does not limit his activity level. He tolerates warfarin well. Family history is unremarkable, and he takes no other medications.
Which of the following is the most appropriate management?
Continue anticoagulation indefinitely
Discontinue warfarin in another 3 months
Discontinue warfarin now
Discontinue warfarin and perform thrombophilia testing
We will come back to this case at the end of the presentation.
[MKSAP17 Heme/Onc question #9]

3. Objectives Recognize subgroups of VTE
Review medications for VTE anticoagulation
Learn guidelines for duration of therapy
Understand differences in therapy based on type of VTE
VTE = venous thromboembolism
Recommendations are classified as strong (Grade 1) and weak (Grade 2) based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.

4. Subgroups of VTE Cancer-associated vs No cancer Provoked vs Unprovoked
Proximal vs Distal DVT
Upper extremity vs Lower extremity DVT
VTE includes DVT and PE. This lecture will focus on DVT. We will go into each of these subgroups in more detail.
For more information on PEs, please refer to the mini lectures “Pulmonary Embolism, Diagnosis” and “Treatment of Acute Pulmonary Embolism.”
DVT = deep venous thrombosis

5. VTE and No Cancer Use NOAC – preferred! (Grade 2B)
Rivaroxaban, apixaban
No bridging needed
Dabigatran, edoxaban
Start with parenteral anticoagulation x5 days
If contraindications to NOAC, then use VKA therapy (warfarin) (Grade 2C)
Overlap with parenteral anticoagulation x5 days,
And INR >2 for 24 hours
Parenteral anticoagulants include: heparin gtt, enoxaparin, fondaparinux, bivalirudin, argatroban, etc.
NOACs = new oral anticoagulants
VKA = vitamin K antagonist

6. Contraindications to NOACs
Extreme BMI (>40)
CrCl <30
Significant increased risk of bleeding
Remember, NOACs are nonreversible!

7. Cancer-Associated Thrombosis
Use LMWH (Grade 2C)
Enoxaparin 1 mg/kg/dose BID
Think back to the CLOT trial.
LMWH = low-molecular-weight heparin

8. Provoking Transient Risk Factors for VTE
Surgery
Estrogen therapy
Pregnancy
Leg injury
Flight >8h

9. Location of VTE Lower extremity DVT Upper extremity DVT
Proximal – Popliteal or more proximal veins
Distal – Calf veins
Upper extremity DVT
Proximal – Axillary or more proximal veins
Catheter-associated

10. Duration of Therapy Proximal DVT or PE Provoked 3 months Unprovoked
(Grade 1B)
Unprovoked
Low bleeding risk
Extended therapy (first VTE - Grade 2B, second VTE - Grade 1B)
Mod bleeding risk
Extended therapy (first VTE - Grade 2B, second VTE - Grade 2B)
High bleeding risk
3 months (first VTE - Grade 1B, second VTE - Grade 2B)
Isolated Distal DVT
Mild symptoms or high bleeding risk
Serial imaging x2 weeks (Grade 2C)
Extending thrombus
Anticoagulate (Grade 1B, 2C)
Severe symptoms or risk for extension
Anticoagulate (Grade 2C)
Cancer-associated
Extended therapy (Grade 1B)
Upper extremity DVT
- Bleeding risk: See next slides.
- Extended therapy = long term anticoagulation with periodic (annual) reevaluation of risks/benefits
For “Anticoagulate,” use the same anticoagulation tree as for patients with acute proximal DVT. (Grade 1B)
Risk factors for extension of isolated distal DVT: See next slides. Basically, this will include anyone who develops distal DVT while inpatient.
 Follow the arrow for special considerations for UE DVT therapy.

11. Special Considerations for Upper Extremity DVT
Proximal
Anticoagulate
Catheter-associated
Catheter functional?
Catheter still needed?
Leave catheter in and anticoagulate
Remove and anticoagulate x3 months
Yes No
These recommendations are based on MKSAP and are not addressed in the CHEST guidelines. No
Yes

12. Risk Factors for Bleeding on Anticoagulant Therapy
Age >65
Anemia
Age >75
Antiplatelet therapy
Previous bleeding
Poor anticoagulant control
Cancer
Comorbidity and reduced functional capacity
Metastatic cancer
Renal failure
Recent surgery
Liver failure
Frequent falls
Thrombocytopenia
Alcohol abuse
Previous stroke
NSAID use
Diabetes
You might be tempted to use the HAS-BLED score. However it is used for assessing the risk of bleeding in atrial fibrillation management.
Low risk
0 risk factors
Moderate risk
1 risk factor
High risk
≥2 risk factors

13. Risk Factors for Extension of Distal DVT
Positive D-dimer
Extensive thrombus
>5cm long, involves multiple veins, >7mm diameter
Thrombus close to proximal veins
No reversible provoking factor
Active cancer
History of VTE
Inpatient status

14. What if my patient stops anticoagulation?
Aspirin is NOT a reasonable alternative to anticoagulation for extended therapy
Much less effective at preventing recurrent VTE
However, aspirin is better than nothing (Grade 2B)

15. Recurrent DVT on Anticoagulation
If on therapeutic warfarin or NOAC, then switch to enoxaparin temporarily (minimum 1 month) (Grade 2C)
Is this really recurrent VTE?
Is my patient compliant with therapy?
Is there underlying malignancy?
If on enoxaparin and compliant, then increase the dose by 25-33% (Grade 2C)
- While you are temporarily on lovenox, reassess the patient’s case with the above listed 3 points.
- Current guidelines recommend against IVC filter in patients with acute DVT or PE who are treated with anticoagulants (Grade 1B).

16. Case Revisited
A 44-year-old man is evaluated in follow-up for an episode of unprovoked left proximal leg deep venous thrombosis 3 months ago. Following initial anticoagulation with low- molecular-weight heparin, he began treatment with warfarin. INR testing done every 3 to 4 weeks has shown a stable therapeutic INR. He has mild left leg discomfort after a long day of standing, but it does not limit his activity level. He tolerates warfarin well. Family history is unremarkable, and he takes no other medications.
Which of the following is the most appropriate management?
Continue anticoagulation indefinitely
Discontinue warfarin in another 3 months
Discontinue warfarin now
Discontinue warfarin and perform thrombophilia testing
Also, do you agree with using warfarin for anticoagulation?

17. Duration of Therapy Proximal DVT or PE Provoked 3 months Unprovoked
Low to moderate bleeding risk
Extended therapy
High bleeding risk
Isolated Distal DVT
Mild symptoms or high bleeding risk
Serial imaging x2 weeks
Extending thrombus
Anticoagulate
Severe symptoms or risk for extension
Cancer-associated
Upper extremity DVT

18. Case Revisited
A 44-year-old man is evaluated in follow-up for an episode of unprovoked left proximal leg deep venous thrombosis 3 months ago. Following initial anticoagulation with low- molecular-weight heparin, he began treatment with warfarin. INR testing done every 3 to 4 weeks has shown a stable therapeutic INR. He has mild left leg discomfort after a long day of standing, but it does not limit his activity level. He tolerates warfarin well. Family history is unremarkable, and he takes no other medications.
Which of the following is the most appropriate management?
Continue anticoagulation indefinitely
Discontinue warfarin in another 3 months
Discontinue warfarin now
Discontinue warfarin and perform thrombophilia testing
This patient had an unprovoked DVT and has a low-bleeding risk. He should be placed on extended therapy, with reassessment every year.
NOAC is actually preferred over warfarin.

19. Summary NOACs are preferred over warfarin for anticoagulation
Except if VTE is cancer-associated, then use enoxaparin
Duration of therapy is usually 3 months, with extended therapy based on risk factors for recurrent VTE

20. References
Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy For VTE Disease: CHEST Guideline And Expert Panel Report. CHEST. 2016;149(2): doi: /j.chest
MKSAP 17