thrombus

1. October 6, 2018
R E A C H I N G N E W H E I G H T S I N C A R D I O V A S C U LA R C A R E

2. A Primer on management of venous
thromboembolic disease.
Medical and endovascular options.
Ashish Gupta, MD, PhD
Interventional Cardiologist, Peripheral Vascular Disease
Specialist
Orlando Health Heart Institute Cardiology Group
Assistant Professor of Medicine, UCF College of Medicine.

3. VTE is a Spectrum of Disease
Not all VTE are created equally
Patients require individual assessment and management plans

4. VTE: A Major Source of Mortality and Morbidity
Over 200,000
deaths per year due to
PE annually in the
U.S. alone.
Over 600,000
patients diagnosed with
DVT annually in the US
alone
More than HIV,
MVAs & Breast
Cancer combined
10% of Hospital Deaths
most common
preventable death
Huge Costs
and Morbidity
Recurrence of DVT, post-
thrombotic syndrome and
chronic PE / PAH are long
term sequelae
Some Causes of Death in the US Annual Number of Deaths
PE Up to 200,000
AIDS 16,371
Breast Cancer 40,580

5. Venous Thromboembolism (VTE) remains a
major health problem
In addition to the risk of sudden death
30% of survivors
develop recurrent VTE
within 10 years
28% of survivors
develop venous stasis
syndrome within 20 years
5

6. 6
VTE incidence increasing
First-time occurrence

7. VTE and the risk our patients face:
Age > 40
Immobility
CHF
Stroke
Paralysis
Spinal Cord injury
Hyperviscosity
Polycythemia
Severe COPD
Anesthesia
Obesity
Varicose Veins
Cancer
High estrogen states
Inflammatory Bowel
Nephrotic Syndrome
Sepsis
Smoking
Pregnancy
Thrombophilia
Surgery
Prior VTE
Central lines
Trauma
Most hospitalized patients have at least one risk factor for DVT
Stasis Hypercoagulability Endothelial
Damage
7

8. How do we treat VTE?
Who needs inpatient therapy?

9. Contraindications to outpatient treatment of
venous thromboembolism
Active or high risk of bleeding
Recent surgery (within 7 days)
Cardiopulmonary instability
Severe symptomatic venous obstruction
High risk pulmonary embolism*
Thrombocytopenia (platelets < 50,000/µL)
Other medical or surgical condition requiring inpatient management
Medical non-compliance
Geographical or telephone inaccessibility
Poor hepatic function (International Normalized Ratio (INR) ≥ 1.5)
Unstable renal function (e.g. rising serum creatinine)
Poor home health care support environment

10. Who needs inpatient Rx
• Suspected or proven concomitant PE
• Significant cardiovascular or pulmonary comorbidity
• Iliofemoral DVT, symptomatic distal calf DVT or UE axillary-
subclavian DVT
• Contraindications to anticoagulation
• Familial or inherited disorder of coagulation: antithrombin III (ATIII)
deficiency, prothrombin 20210A, protein C or protein S deficiency,
or factor V Leiden
• Familial bleeding disorder
• Pregnancy
• Morbid obesity (>150 kg)
• Renal failure (creatinine >2 mg/dL)

11. Rx is guided by underlying condition
Suggested Anticoagulant Regimen∗
Stage IV renal failure Prefer conventional treatment∗
Concomitant treatment with verapamil or
dronedarone
Prefer conventional treatment or rivaroxaban
Concomitant treatment with carbamazepine,
phenobarbital, phenytoin
Prefer conventional treatment
Active cancer LMWH or conventional treatment or NOACs
Isolated distal DVT If to be treated, prefer conventional treatment or LMWH or
NOACs
Unsuspected VTE If to be treated, treat as symptomatic VTE
Upper arm Treat as lower-limb VTE
Splanchnic or cerebral vein thrombosis Prefer conventional treatment
APLA Prefer conventional treatment
Patients with vena cava filter Prefer conventional treatment

14. NOACs and DVT
• Xarelto – Einstein-DVT trial 2010 – Non inferiority trial to
VKA
• Syvasa (Edoxaban) - Hokusai-VTE study - Non inferiority
trial to VKA
• Apixiban (Eliquis) – AMPLIFY trial – Non inferior to
Lovenox and VKA
• Pradaxa – REMEDY and RECOVER trial – Non inferior
to VKA
All trials required parenteral anticoagulation for 72h to
9d. Post thrombotic syndrome patients were NOT studied.

15. From: Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European society of cardiology working
groups of aorta and peripheral vascular diseases and pulmonary circulation and right ventricular function
Eur Heart J. Published online February 17, 2017.

16. Therapy for DVT

17. Treatment of Venous Thromboembolism With New Anticoagulant
Agents - Practical tips
Follow-up patients on NOACs Check renal function and blood cell count at 1 month , then every 6 months
Switch from VKAs INR <2: NOACs can be initiated immediately
INR 2.0–2.5: better to start NOACs the next day
INR >2.5: take into account the actual INR value and the half-life of the VKA. A new
INR can be scheduled before starting the NOAC
Recurrent VTE on NOAC treatment Verify compliance to NOAC treatment
Reassess concomitant medications
Consider change to a different NOAC or to conventional treatment
Overdosing With active bleeding: Manage as patients with bleeding complications
In the absence of bleeding: Consider activated charcoal if <2 h
Withhold the next dose
Missing dose In bid regimens: take if <6 h from scheduled intake
In od regimens: take if <12 h from scheduled intake

18. Treatment of Distal DVT
• Serial imaging if no severe sxs for 2 weeks.
• OAC if there is extension of thrombus, or patient has
high risk for VTE.

19. Compression stockings for DVT
• No indication to prevent PTS
• Use only if patient has severe dependent edema.

20. Upper extremity DVT
• Axillary or more proximal veins: Anticoagulation is
preferred, however, CDT can be considered if bleeding
risk is low and there is access to CDT.
• Duration – three months

21. Peripheral Endovenous Interventions for
DVT

22. Endovascular management – Contemporary
data
• Three clinical trials in last 6 years
– TORPEDO trial - 2010, 183 patients with symptomatic DVT were randomized
to receive PEVI plus anticoagulation vs anticoagulation alone. At 30-month
follow-up recurrent VTE developed in 4.5% of the PEVI group vs 16% of the
control group (P=.02). PTS developed in 6.8% of the PEVI group vs 29.6% of
the control group (P<.001).
– Catheter-Directed Venous Thrombolysis in Acute Iliofemoral Vein Thrombosis
(CaVenT) trial - 2012, enrolled 209 patients. PTS was noted in 41.1% of the
CDT vs 55.6% of the control group at 24 months (P=.047). Ileofemoral patency
at 6 months was noted in 65.9% of the CDT vs 47.4% of the control group
(P=.012).
– The ATTRACT trial, a multicenter NHLBI study – no benefit in reducing PTS in
patients with femoral DVT. DID NOT STUDY MASSIVE ILIOFEMORAL DVTs

23. Peripheral endovascular intervention for
DVT (PEVI)
• Encompasses all modalities that can be employed for the
invasive diagnosis and treatment of venous disease when
performed through a percutaneous approach, which is the
usual practice. Includes:
– Catheter directed thrombolysis
– Pharmacomechanical thrombectomy,
– Balloon venoplasty, stenting, and imaging with intravascular ultrasound (IVUS).

24. Indications for PEVI
• Phlagmesia cerulea dolens
• IVC thrombosis
• Subacute and chronic iliofemoral DVTs
• Acute iliofemoral or femoropopliteal DVT treatment

25. 44y male with massive iliofemoral DVT and
PTS

26. Day 2 post 12h EKOS

27. 52y female with acute LLE extensive DVT
with 15y old filter
Caval Venoplasty followed by thrombectomy and stenting to crush
the old fractured filter to improve venous outflow

28. Day 2 – LLE PEVI
Thrombectomy using PENUMBRA device with complete restoration of antegrade flow and
resolution of LLE edema

29. Pulmonary Embolism

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PE risk stratification
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31. 31
PE patient population profile
Registry. Lancet 1999;353:1386-1389
MINOR PE

32. 32
Adverse outcomes associated with
RVD – 3x higher mortality if RV/LV ≥ 0.9
―

33. 33
Adverse outcomes associated with RVD
– increased mortality risk
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34. 34
Adverse outcomes associated with RVD
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35. 35
Standard PE therapy
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36. 36
Rationale for thrombolysis in acute PE
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37. 37
Meta-analysis suggests reduced risk of
recurrent PE or death from thrombolysis
compared with heparin

38. 38
Review and meta-analysis on systemic thrombolysis
for PE weighed risks and benefits

39. 39
Metaanalysis showed consistent recovery of
hemodynamics among patients treated using
EKOS®
―
First author and year of
publication
No. of
patients
Patients with
high-risk PE
Total rt-PA
dose (mg)
Total
thrombolysis
duration (h)
RV/LV ratio
Mean pulmonary artery
pressure (mmHg)

40. 40
Metaanalysis demonstrated a favorable safety
profile among patients treated using EKOS®
−
First author and year of
publication
No. of
patients
Patients with
high-risk PE
Total rt-PA
dose (mg)
Total thrombolysis
duration (h)
Bleeding Complications Mortality at 3
months

41. Sub segmental PE
• In patients with subsegmental PE (no involvement of
more proximal pulmonary arteries) and no proximal
DVT in the legs who have:
• low risk for recurrent VTE - Clinical surveillance
• High risk for recurrent VTE – anticoagulation.

42. EKOS catheter directed thrombolysis for PE
Thrombus in
pulmonary arteries
Right Left
EKOS catheter in each PA