Noon conference 12 17

VTE:
The most common questions
Steven Kirtland, MD FCCP
Virginia Mason Medical Center
December 17, 2018
That I have been asked…….

© 2014 Virginia Mason Medical Center
Why Venous Thromboembolism
• 900,000 events per year, 1/3 recur in 10 years
• ~100,000 deaths per year, 10-30% in first month
• Most common preventable cause of hospital death
• DVT is associated with long-term complications,
such as post-thrombotic syndrome in up to 50%
• About two-thirds of all VTE events are related to
hospitalization
2

Top 10
5
What anticoagulant should I use?
How long should I treat?
What about cancer?
Provoked vs unprovoked?
What do I do with the “incidental” PE?
UEDVT and PICCS….Treat?
Should I use thrombolytics, CDT/EKOS?
Should I put in an IVC filter?
Should I do a hypercoagulopathy workup?
When can I operate?

Others
Chronic PE
Distal DVT’s
HIT—leave for the hematologist
6

Case 1
53 yo female on HRT with recent THR
3 weeks ago in Orlando now visiting
her grandchildren.
PMH: HTN, CAD, hx of PUD with prior
gi bleed in distant past, breast ca
Meds: metoprolol, HCTZ, ASA
CC: Acute dyspnea, pleuritic chest
pain, 124/80, hr 105
CXR: clear
7

What do you order first?
a. Echocardiogram
b. Chest CTPA
c. V/Q scan
d. D-dimer
e. Troponin
f. CXR
8

Modified Wells criteria

What would you treat her with, for how
long? What if she had cancer? What if she
were pregnant? What if she had a
recurrence? What if she were hypotensive?

What would you treat her
with?
a. LMWH
b. LMWH followed by Vka
c. DOAC
d. aspirin
e. Would not treat
f. I am not sure

Acronym Evolution
TSOAC = Targeted Specific Oral
Anticoagulant
NOAC = Novel Oral Anticoagulant
DOAC = Directed Oral Anticoagulant
13
OOAC = Old Oral Anticoagulant
ROOAC = Really Old Oral Anticoagulant

1. How Long to Treat
15
a. Don’t treat
b. 6 weeks
c. 3 months
d. One year
e. Indefinitely

Provoked proximal DVT/PE (no cancer)
3 mo (longterm) of anticoagulation
(1B)
DOAC > VitKa > LMWH (2B)
Dabigatrin, Endoxiban, require
treatment with LMWH first
All DOACs have shown to be
“noninferior” to VitKa in VTE risk
reduction with less risk of bleeding
VitKa require overlap of >4 days with
2 consecutive INR > 2 17

Rate of DVT/PE at One Year
Rivaroxaban compared with Enox/VitkA

more
Oral agents easier
No injections
Less expensive?
No head to head trials with DOACs
No DOAC vs LMWH trials
21
So which Agent do I choose?

Factors affecting choice
22

DOAC Drug Interactions
23

Can I treat her at home?
(1) clinically stable with good cardiopulmonary
reserve (no inc troponin)
(2) no contraindications such as recent bleeding,
severe renal or liver disease, or severe
thrombocytopenia(ie, <70,000/mm3)
(3) expected to be compliant with treatment
(4) the patient feels well enough to be treated at
home.
(5) PESI score <85 not necessary
In patients with low-risk PE and whose home
circumstances are adequate, we suggest treatment at
home or early discharge over standard discharge
(eg, after the first 5 days of treatment) (Grade 2B). 24

Questions
Why not 6 weeks?
What is Provoked?
What about Cancer?
What if she cannot stop her HRT?
25

Risk of recurrence on therapy
26

What is Provoked?
Surgery
Medication
Inactivity (flight >8 hours)
Cancer
27

Proximal DVT/PE in active cancer
Extended therapy
LMWH > VitKa = DOAC
Recommended with low and medium
bleeding risk
Suggested with high risk
Non-oral, short ½ life
28

Treatment during Pregnancy
LMWH
UFH
VitKa potentially teratogenic
? DOAC (excluded)
29

Rate of recurrence
31

Risk of recurrence
Surgery: 3% at 5 years
Nonsurgical transient: 15% at 5 years
Unprovoked: 30% at 5 years
Cancer: 15%/year
Distal DVT: 1/2 of proximal
2nd Unprovoked: 1.5X
32

Duration: Provoked
Surgical: 3 mo (1B)
Nonsurgical: 3 mo (1B-HR, 2B-LR)
Distal DVT: 3 mo (1B) or none
33

Bleeding Risk
34

Duration: Unprovoked
Initial: high BR: 3 mo (1B) (R)
Low-mod BR: Extended*^ (2B) (S)
Recurrent: HR: 3 mo (2B) (S)
ModR: Extended (2B) (S)
LR: Extended (1B) (R)
*Consider sex, d-dimer
^Reevaluate annually
35

Recurrence risk off therapy
37

Effect of Sex on recurrence rate
39

Treatment of Recurrent VTE
41
LMWH

What about Aspirin?
2 trials
Initial unprovoked VTE treated with 3-
18 mo of AC (Vka), no inc BR
Reduced risk of recurrence by 33%
(compared with 80%)
Increased bleeding but not significant
42

Aspirin?
In patients with an unprovoked proximal DVT
or PE who are stopping anticoagulant therapy and
do not have a contraindication to aspirin, we
suggest
aspirin over no aspirin to prevent recurrent VTE
(Grade 2B).
43

Hypercoagulation workup?
Thorough history and physical examination combined with routine
laboratory testing.
Testing for inherited thrombotic disorders and malignancy can lead to
the discovery of risk factors, but does not improve mortality
For unselected patients with a diagnosis of VTE, we suggest not
routinely testing for hypercoagulable disorders and malignancy
(Grade 2C).
For patients with VTE who have at least one first degree relative with
documented VTE before the age of 45 years, we suggest testing for
all five inherited thrombotic disorders (antithrombin, protein S and C
deficiencies, factor V Leiden and prothrombin gene mutations)
(Grade 2C).
For patients with VTE who are <45 years old, we also suggest testing
for all five inherited thrombotic disorders as well as for
antiphospholipid syndrome (Grade 2C).
44

Cont
In patients with a first episode of unprovoked VTE, we suggest
limited testing for cancer, including a history and physical
examination, complete blood count, serum chemistries, liver function
tests and urinalysis, routine age-appropriate cancer screening, and
chest radiography (Grade 2C)
In patients with recurrent thrombosis, multiple thromboses, and
thrombosis in unusual vascular beds (eg, hepatic or portal vein
thrombosis), we suggest testing for inherited thrombotic disorders,
antiphospholipid syndrome, and malignancy (Grade 2C).
Additionally, patients with hepatic or portal vein thrombosis should
be evaluated for JAK2 mutations and paroxysmal nocturnal
hemoglobinuria
In patients with VTE who have a history of warfarin-induced skin
necrosis, we suggest testing for protein C deficiency (Grade 2C).
In patients with arterial thrombosis, we suggest testing for markers
of the antiphospholipid syndrome (Grade 2)
45

Did I forget to mention her
recent subdural hematoma
and massive GI bleed?
46

IVC filters
47

PREPIC-2 Trial
48
Effect of a Retrievable Inferior Vena Cava
Filter Plus Anticoagulation vs
Anticoagulation Alone on Risk of Recurrent
Pulmonary Embolism: A Randomized
Clinical Trial
Primary efficacy outcome was symptomatic
recurrent pulmonary embolism at 3 months.
Secondary outcomes were recurrent
pulmonary embolism at 6 months,
symptomatic deep vein thrombosis, major
bleeding, death at 3 and 6 months, and
filter complications
By 3 months, recurrent pulmonary embolism
had occurred in 6 patients (3.0%; all fatal) in
the filter group and in 3 patients (1.5%; 2 fatal)
in the control group (relative risk with filter,
2.00 [95% CI, 0.51-7.89]; P = .50). Results
were similar at 6 months.
JAMA. 2015;313(16):1627-1635.

IVC Recommendation
In patients with acute DVT or PE who are treated
with anticoagulants, we recommend against the use
of an IVC filter (Grade 1B)
49

?IVC
50

UEDVT
Reviewed VTE cases (00-09)
Accounts for 50% of DVT (1.4/1000)
Underestimate
PE in 14%
CVC: 14x increased risk (25% of pts)
PICC: OR 13
Younger, leaner
51
Journal of Thrombosis and Haemostasis.
13: 2155-2160

UE Deep Venous System
52

UEDVT
In patients with acute upper extremity DVT
(UEDVT) that involves the axillary or more proximal
veins, we suggest anticoagulant therapy alone over
thrombolysis (Grade 2C).
CDT is recommended over systemic
Anticoagulation for 3 mo is recommended
regardless
Good candidates for CDT: <14 d, SC or axillary,
good life expectancy, low bleeding risk
53

PICC associated DVT
Vessel size
Catheter size
Picc most trombogenic
55

Catheter-related risk factors
-malplacement of catheter tip (not at
atriocaval junction),
-left-sided catheter p lacement,
-large number of catheter lumens,
-several attempts to place catheter,
-prior central venous catheterization,
-open-ended (vs. closed) catheter,
-catheter infection,
-polyvinylchloride or polyethylene (vs.
silicone or polyurethane)catheter material
56

PICC associated thrombosis in UE and LE

PICC Algorithm
58

True or False
Incidental PE’s should be
anticoagulated.
59
MAYBE

Incidental PE

Incidental PE
2.5% prevalence
Occurring more commonly
~30% segmental/subsegmental
45-91% treated in multiple studies
Significant recurrence if not treated in
some
No RCT’s
Need to treat dependent upon size and
absence of proximal DVT and risk of
recurrence 61

Caveats
May want to do serial US
Recurrence: immobility, cancer,
idiopathic
More apt to follow if good
cardiopulmonary reserve and high risk
of bleeding
Grade: 2c
62

Case 3
73 yo male with DM and hx of prior
DVT 7 years ago, 6 weeks post
laminectomy, sudden heart pounding
and sense of distress. No sob, cp
Tachycardic, brief syncope, sbp 110
Elevated troponin, BNP, creat
PAP 54 ml, dilated RV with poor funct.
RV:LV 1:3
63

Treatment
a. UFH + VitKa
b. LMWH + VitKa
c. UFH + systemic TPA
d. UFH + EKOS
e. Surgical thrombectomy
f. DOAC
65

Should they be treated the same?
66

PE and Risk of Death
67

PE Physiology
68

Massive indications
Mortality of ~50%
Sbp <90 or drop of 40 mmHg for
more than 15 min…reduces mortality
Benefit > bleeding risk in most
CPR
? Extensive Clot (MOPPETT trial)
?Free floating atrial clot with PFO
69

Intermediate Risk
Normotensive, tachycardic
RV distention
Increased Troponin, BNP
70

PEITHO study
1006 pts with RVD and elevated troponin
Randomized to heparin vs tenectaplase
Reduction in mortality or hemodynamic
decompensation
Increased Bleeds (11.5% vs 2.4%) 11 more CVA
No difference in overall mortality (1.2% vs 1.8%)
Meta-analysis: reduces PE related death but not
overall mortality
* 5% decompensated 1.8 days after admission
71

CHEST Recommendations
In patients with acute PE associated with
hypotension (eg, systolic BP < 90 mm Hg) who do not
have a high bleeding risk, we suggest systemically
administered thrombolytic therapy over no such
therapy (Grade 2B).
In most patients with acute PE not associated
with hypotension, we recommend against systemically
administered thrombolytic therapy (Grade 1B).
In selected patients with acute PE who
deteriorate after starting anticoagulant therapy but
have yet to develop hypotension and who have a low
bleeding risk, we suggest systemically administered
thrombolytic therapy over no such therapy
(Grade 2C).
72

Risk of Bleeding
73

Left side
76

CDT
77

Submassive PE

PERT
Pulmonary Embolism Response Team
Elevated BNP, troponin
HR >120
Severe hypoxia
RV:LV >0.9
CCU MD, IR,
PCP, Cardiology, Vascular surgery
79

What about CTEPH?
Unclear etiology
Vascular remodeling in smaller vessels
RF: VA shunts, infected pacemakers,
splenectomy, APLAS, malignancy,
thyroid replacement therapy, recurrent
VTE, massive PE
Echocardiography, V/Q scan in at risk
and/or persistently symptomatic
81

? Followup Studies
Large
Persistent symptoms
High risk for recurrence
82

CDT for DVT
Studies are poor and results variable as to benefit and risk
In patients with acute proximal DVT of the leg,
we suggest anticoagulant therapy alone over CDT
(Grade 2C).
83
“patients who are most likely to
benefit from
CDT have iliofemoral DVT,
symptoms for <14 days,
good functional status, life
expectancy of >1 year, and a
low risk of bleeding”

Distal DVT
In patients with acute isolated distal DVT of the
leg and (i) without severe symptoms or risk factors for
extension (see text), we suggest serial imaging of the
deep veins for 2 weeks over anticoagulation (Grade 2C),
and (ii) with severe symptoms or risk factors for
extension (see text), we suggest anticoagulation over
serial imaging of the deep veins (Grade 2C).
3 months of anticoagulation if it extends
84

Other Recommendations
In patients who have recurrent VTE on VKA
therapy (in the therapeutic range) or on dabigatran,
rivaroxaban, apixaban, or edoxaban (and are believed
to be compliant), we suggest switching to treatment
with LMWH at least temporarily (Grade 2C).
In patients who have recurrent VTE on longterm
LMWH (and are believed to be compliant), we
suggest increasing the dose of LMWH by about onequarter
to one-third (Grade 2C).
85

Additional Recommendations
In patients with acute DVT of the leg, we suggest
not using compression stockings routinely to
prevent PTS (Grade 2B).
86

Thank You for your Attention
87

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