1. Venous Thromboembolism
Rony D. Gorges, MD
Invasive Cardiologist
Metro Heart and Vascular

2. No Disclosures (Unfortunately)

3. Incidence of VTE 75 to 269 per 100K patients
200 to 700 per 100K patients 70 or older
600K Hospitalizations in U.S.
300K Deaths/Year in U.S.
LAST in the US we have about 600,000 hospitalizations for VTE and 300,000 deaths/year from VTE

4. Incidence of VTE Incidence on the rise Aging population
Risk of VTE doubles every decade over the age of 40
Better diagnostic accuracy
Readily available tests
FIRST its a big problem and its growing

5. Recurrence 10-year recurrence rate of VTE is 25%
Recurrence peaks in the first 6 months
DVTs tend to recur as DVTs
PEs tend to recur as PEs
2ND SENTENCE and trends down for 3 years before stabilizing at 2% per year.
So the average yearly recurrence rate is about 4% per year for years 1-3 and 2% for years 4-10

6. Death Rates 30-day case-fatality: 10% for VTE
1-year case-fatality: 23% for VTE
30-day mortality: 3% for initial DVT
30-day mortality: 31% for initial PE

7. Cost Average LOS 4.7 for DVT Average LOS 5.1 for PE
Treatment & Diagnosis
$15.5 Billion
2011, LOS for joint replacement

8. Thrombus Genesis Blood pooling in valves
“think cusps” or “little appendages”
Avg. 23 min. IV contrast to clear
+/- Tissue factor
Vessel damage
1ST Blood stasis, concentrated coagulation factors and platelets.
3RD High inflammatory states, active cancer, autoimmune diseases, IBS

9. RISK
Transient obstructions/impedance to flow are risk factor for a first and hopefully last VTE, whereas chronic issues tend to cause recurrence

10. Physical Exam Bancroft’s/Mose’s sign Homans sign Lisker’s sign
Louvel’s sign
Lowenberg’s sign
Peabody’s sign
Pratt’s sign
Rose’s sign
Cord sign
I don’t know anyone who knows or uses these physical exam findings and I’m sure there are even less that are willing to diagnose and treat a DVT based on these, but on the other hand we have to make keen our other skills like history taking and awareness of signs, symptoms and risk factors for VTE

11. VTE Detection Ultrasound is the standard for DVT diagnosis
If clinical suspicion remains high do serial exams
Venography, “gold standard”
Limited indications, invasive
D-Dimer - Fibrin Degradation Product (FDP)
99.6% Negative Predictive Value
Specificity of 50%

12. VTE Detection Multidetector Computed Tomography Angiogram (CTA)
Standard
Ventilation/Perfusion Scan (V/Q)
Inhale radioactive isotope and inject radioactive isotope
Not gonna work well if significant lug disease
Pulmonary angiogram ‘gold standard”
Limited indications, invasive
v/q not as binary

13. Treatment Duration No clear guidelines on duration of treatment
Provoked DVT treat for 3 months
Provoked PE treat for 6 months
Unprovoked PE or DVT treat lifelong
2nd provoked VTE treat lifelong
Heritable clotting disorder and VTE treat life long
LAST I do not refer patients with provoked DVT for hyper coagulable w/u unless they have a family history of a coagulable disorder.

14. anticoagulation treatment of VTE includes 3 phases (look up)
anticoagulation treatment of VTE includes 3 phases (look up). Traditionally we used rapid onset IV or SQ anticoagulants and this is to achieve therapeutic levels to avoid early recurrence

15. VKA to NOAC INR <2.0 can start NOAC now
INR wait 24 hours and then start NOAC
INR >2.5, consider value, retest follow above

16. Major Trials
Non-inferiority, recurrence and VTE related deaths were the primary efficacy outcomes

17. MECHANISMS OF ACTION TF-tissue factor
TFPI-tissue factor protein inhibitor - RCT 1700 patients thought to help in severe sepsis with high inflammation high levels of TF, they get more end organ damage, hyper coagulable, no effect on mortality, increased bleeding
Andexanet - reversed Xarelto in 2 minutes, safely reverses xarelto and elquis, phase III

18. Untested Clinical Scenerios
FIRST Use of apixiban/eliquis in renal severe/end stage failure patients. about 75% cleared by the intestine and about 25% by the liver. We do now that there are increased levels in ESRD patients.

19. Isolated Distal DVT DVTs below the level of the popliteal vein
No definitive guidelines available
2 Approaches
Treat as proximal DVT
Repeat US in 1 week
CACTUS trial: 2015
LAST CACTUS TRIAL about 250 patients 6 weeks of SC LMWH versus placebo DVT extension/PE at 6 weeks and 90 days was primary end points 7 had recurrence in placebo arm, 4 had recurrence in LMWH arm and 5 had major or clinically relevant bleeding all in the LMWH arm

20. Patients with Cancer 2.5% - 9.4% in clinical trials had cancer
About 20% of patients with VTE have cancer
Meta-analysis of the 6 major trials
VTE recurrence 3.9% in patients on NOACs
VTE recurrence 6% in patients on VKA
Despite these findings NOACs were compared to VKA and not LMWH which is the treatment of choice.

21. NOAC Follow-up Normal renal function/abnormal renal function
Cr/GFR/CBC at 1 month then q6 months
More frequent testing needed for patients with renal function close to recommended adjustment dose values
LAST and obviously those with fluctuating values

22. Post-Thrombotic Syndrome
20-50% of patient after DVT
Destruction of valves
Deep venous reflux
Chronic thromboembolic pulmonary HTN (CTEPH) %
First varicose veins, lipodermatoscelrosis,
LAST CTEPH this large margin of error is probably due to referral bias, absence of early symptoms, and the occasional difficulty in differentiating acute PE from an episode superimposed on pre-existing CTEPH
CTEPH should be ruled out in patients with persistent dyspnea after acute PE and at least 3 months of anticoagulation treatment; however, routine screening for CTEPH is not recommended in asymptomatic survivors of PE

23. Advanced Treatment TPA for massive PE (5% of all PEs)
15+ mins of hypotension, SBP <90 mmHg
HR <40 BPM with signs of hypo-perfusion
1 in 5 will have a major/clinically relevant bleed
6% will have intracranial hemorrhage
Catheter directed thrombolysis +/- thrombectomy
Symptomatic DVTs
Submassive PEs
40% of PE, 55% are low risk, only 5% are massive

24. Submassive PE Hemodynamically stable (SBP >90 mmHg)
Acutely symptomatic
Elevated troponin
Right Ventricular Dysfunction (RVD)
RV/LV ratio >0.9 (CT/ECHO)
RV dysfunction on echocardiogram
ECG changes of RV strain (new RBBB)

25. PE Death Spiral

26. Importance of RV Dysfunction
Strong independent predictor of poor outcomes
Increased mortality
Increased VTE recurrence
Increased adverse outcomes (CTEPH)

27. Adverse outcomes associated with
RVD – 3x higher mortality if RV/LV ≥ 0.9
Registry of 1,416 patients
Mortality rate:
1.9% RV/LV < 0.9
6.6% RV/LV >/= 0.9
Mortality

28. RVD Increases Mortality
Retrospective analysis
120 patients
Hemodynamically stable PEs
PE related 90 days
17% RV/LV >/= 1.5
8% RV/LV <1.5
0% RV/LV <1.0

29. Presence of RV hypokinesis associated with 57% increase in mortality rate at 3 months
Prospective study of 2,454 consecutive PE patients at 52 hospitals in 7 countries
Mortality rates at 3 months
21% with hypokinesis
15% with no hypokinesis

30. Adoption of IV thrombolysis hampered by elevated risk of severe bleeds
In randomized trials, systemic PE thrombolysis is associated with a 11.5% risk of major bleeding and a 6.3% risk of intracranial hemorrhage1
In clinical practice, systemic PE thrombolysis is associated with a 19.2% risk of major bleeding and a 5% risk of intracranial hemorrhage2
In clinical practice, systemic thrombolysis is withheld in up to two thirds of patients with high-risk (massive) PE3
Meyer G et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014;370:
Fiumara, K et al. Predictors of Major Hemorrhage Following Fibrinolysis for Acute PE. Am J Cardiol 2006;97:127-9
Kucher, N et al. Massive PE. Circulation 2006;113:577-82

31. Emerging Treatment USING ULTRASONIC ENERGY TO DISSOLVE CLOT
Ultrasonic energy causes fibrin strands to thin, exposing plasminogen receptor sites and fibrin strands to loosen
Thrombus permeability and lytic penetration are dramatically increased
Ultrasound pressure waves force lytic agent deep into the clot and keep it there