Download The Post Thrombotic Syndrome

The Post Thrombotic Syndrome
Steven M. Dean, DO, FACP, RPVI, FSVM
The Ohio State University College of Medicine
Associate Professor of Medicine
Division of Cardiovascular Medicine
Post Thrombotic Syndrome:
Definition
• A spectrum of chronic clinical
manifestations of venous insufficiency in
patients with prior DVT
• Other terms: “Post phlebitic syndrome” or
“venous stasis syndrome”
How Common is the Post
Thrombotic Syndrome?
Post thrombotic syndrome:
Epidemiology
• The most common chronic complication of
DVT
• >1/3 of cases involve patients > 60 yrs
• Overall incidence of 20-50%
• Severe PTS 5-10%
• Ulcerations 1-2%
Post thrombotic syndrome:
Incidence
Kahn 2008: Two year prospective study of 387
patients with DVT
Cumulative incidence of PTS: 47%
Distal DVT: 41%
Proximal: 52%
(p = 0.03)
Kahn et al. Jn Thromb Haemo 2008;6: 1105-12.
Post thrombotic syndrome:
30%
25%
18%
Prandoni P, Villalta S, Bagatella P, et al . The clinical course of deep-vein thrombosis. Prospective
long-term follow-up of 528 symptomatic patients. Haematologica 1997;82:423-8
What is the Effect of the the PTS
on Quality of Life and Health
Care Costs?
Post Thrombotic Syndrome:
Costs & Quality of Life
• Stasis ulcerations are responsible for the loss of ~ 2
million working days and $ 3 billion/year in the US1
• Chronic venous insufficiency responsible for 1 to
3% of the total health care budget in developed
countries2,3 ( 2% US National Health Care Budget )
• CVI is associated with a reduced QOL which is
proportional to the severity of venous HTN4
• Pts with severe PTS have QOL scores similar to CHF
1. McGuckin. Am J Surg 2002;183:132-7 2. Kurz. Int Angiol 1999;18:83-102
or CA
3. Ruckley. Angiology 1997;48:7-94. Kaplan. J Vasc Surg 2003;37:1047-53.
How does the Post Thrombotic
Syndrome Develop?
Venous valvular reflux
Venous obstruction
How is the Post Thrombotic
Syndrome Diagnosed?
The diagnosis of the post
thrombotic syndrome should
be deferred until 3–6 months
after the index DVT, as
symptoms due to acute DVT
may take this long to
completely resolve
Post Thrombotic Syndrome:
Diagnosis
• PTS is a clinical diagnosis
• No objective test is necessary
• There is no “gold standard” test for the
diagnosis
• Six different scales have been used
Villalta Scale
Villalta et al. Haemostasis 1994;24:158a.
Post Thrombotic Syndrome:
Symptoms
•
•
•
•
•
•
•
Pain
Swelling
Heaviness
Pruritus
Paresthesias
Restless legs syndrome
Venous claudication
>C3 = CVI
Eklöf B et al. Revision of the CEAP classification for chronic
venous disorders: consensus statement. J Vasc Surg 2004;40:1248-52.
Swelling [C3]
Chronic stasis
dermatitis [C4a]
Pigmentation
[C4a]
: Acute (early)
Lipodermatosclerosis
“LDS”
• Acute inflammation
within the distal
medial calf
• DDX: cellulitis,
superficial
thrombophlebitis
Chronic Lipodermatosclerosis
Inverted
“Champagne
Bottle”
or
“Bowling Pin”
Legs
C4B
Identify the abnormality by the
ARROW
1. Venous stasis ulcer
2. Capillary
malformation
3. Atrophie blanche
4. Corona
phlebectatica
Dean SM. In Vascular Disease. Cardiotext 2011. 459-518
Atrophie Blanche (C4b)
Identify the abnormality by the arrow
1. Venous malformation
2. Capillary malformation
3. Reticular veins
4. Corona phlebectatica
“Ankle flare sign”
Dean SM. In Vascular Disease. Cardiotext 2011. 459-518
Corona phlebectatica
“Ankle flare” sign
Best predictor of subsequent occurrence of
skin change in subjects the mild disease
(C0-C3)
The 2 nd best independent predictor for
stasis ulceration after the presence of skin
changes
• Highly significant clinical sign indicative of
Antignani et al. Int Angiol 2012;31:217-8
CVI
C4?
Atrophie Blanche
[C4b]
Posterior or Lateral Calf
Stasis ulceration =
Small Saphenous Vein
Reflux
Dean SM. In Vascular Disease. Cardiotext 2011. 459-518
What are the Risk Factors for
the Post Thrombotic Syndrome
?
Post thrombotic syndrome:
Risk factors
Well established risk factors:
 Recurrent ipsilateral DVT (6-10 fold increase)
 Proximal DVT (especially iliofemoral)
 Obesity (BMI > 30 kg/m2)
 Varicose veins prior to DVT
Rabinovich. Pol Arch Med 2014;124:410-15..
Post thrombotic syndrome:
Risk factors
Probable risk factors (more studies needed):
Residual DVT symptoms 1 month after dx
Residual venous obstruction
Valvular reflux or incompetence
> 20% of time with a subtherapeutic INR during the
1st few months of anticoagulation
• Type of anticoagulation
• Elevated inflammatory markers (CRP, IL-6)
• Elevated D-dimer
•
•
•
•
Rabinovich. Pol Arch Med 2014;124:410-15..
Post thrombotic syndrome:
Risk factors
NOT risk factors:
• Thrombophilia
• Type of DVT (provoked vs unprovoked)
• Duration of anticoagulation
Rabinovich. Pol Arch Med 2014;124:410-15..
Post thrombotic syndrome:
Prevention
1. Prevent the occurrence of DVT with
appropriate thromboprophylaxis
2. Prevent DVT recurrence by administering
anticoagulation of appropriate intensity
3. Consider catheter directed thrombolysis
(iliofemoral DVT)
4. Class II knee high gradient compression
stockings?
Medical compression stockings
prevent PTS
Musani MH et al. Am J Med. 2010 Aug;123(8):735-40
Kanaan AO et al. Thrombosis 2012.
Compression stockings to prevent
post-thrombotic syndrome: a
randomised placebo-controlled trial.
(SOX-trial)
Kahn S et al
www.thelancet.com Published online December 6, 2013
http://dx.doi.org/10.1016/S0140-6736(13)61902-9
After proximal DVT (all first event):
6 months- 2 years
• 410 ECS 30-40 mmHg vs 396 Placebo-stockings
• Primary outcome:
– PTS (Ginsberg)= pain and swelling > 1 month
• Secondary outcome:
– Villalta scale = subjective signs and symptoms
– Popliteal reflux (12 months), QOL, recurrent VTE
• CONCLUSION: „ECS did not prevent PTS after a first
proximal DVT, hence our findings do not support
routine wearing of ECS after DVT“
Post thrombotic syndrome:
Management
1. Class II knee high gradient compression
stockings to reduce swelling & symptoms
2. Consider pentoxifylline and/or venotonic
medications (diosmiplex)
3. Assess for remedial superficial and/or
perforating vein reflux
4. Endovascular therapy (iliac vein)
5. Supportive care (weight loss/skin care)
[email protected]
“Phlebolymphedema”
Steven M. Dean, DO, FACP, RPVI
Program Director- Vascular Medicine
Associate Professor of Internal Medicine
Division of Cardiovascular Medicine
The Ohio State University
Disclosures
Potential Conflict: Scientific Advisory
Board - Tactile Medical Systems
Phlebolymphedema:
Definition
A condition of mixed venous AND
lymphatic insufficiency that leads
to the accumulation of protein
rich fluid in the interstitial space
“Dual outflow system failure”
Lymphedema:
(Patho)physiology
An Intimate Relationship…
Superficial Medial Bundle
Copyright © The Worlds of David Darling
Mechanisms of Lymphatic Failure
or “Lymphedema”
1. Normal microvascular
filtration w/dysfunctional
lymphatics (primary;
secondary- CA; surgery;
XRT; late CVI)
2. Increased microvascular
filtration w/normal but
overwhelmed lymphatics
(Right HF; TR;NS; cirrhosis;
early CVI) –reversible
early; irreversible late
Phlebolymphedema:
Pathophysiology
Venous
hypertension
Phleblolymphedema
(C4-6)
Lymphatic
destruction
Increased
microfiltration
Phleblolymphedema
(C3)
“In the U.S., the most common cause of
secondary lymphedema is malignancies
and their related treatment (i.e.,
surgery, radiation)”
Lymphedema: Secondary
Causes
“The most common form of
lymphedema worldwide may be
filarial infection but the most
common in the Western world is
phlebolymphedema”
Farrow. Phlebolymphedema- A Common Underdiagnosed & Undertreated
Problem in the Wound Care Clinic. J Am Col CWS 2010;2: 14-23
There is a conspicuous lack
of data on the prevalence
of secondary lymphedema!
Venous-lymphatic disease:
Lymphoscintigraphic
abnormalities in CVI
Silva. Jn Vasc Bras. vol.8 no.1 Porto Alegre Jan./Mar. 2009
“Dermal Backflow”
Silva. Jn Vasc Bras. vol.8 no.1 Porto Alegre Jan./Mar. 2009
CA vs CVI:
Secondary Lymphedema




ACS 2012: ~ 3 million survivors of invasive breast cancer
currently living the United States (600,000)
Siegel 2013: ~1 million gynecologic cancer survivors
currently living in the United States (250,000)
Medscape 2012: 2-5% of all Americans have some
changes associated with CVI (6-16 million x 50% with
+LSC = 3- 8 million with 20 lymphedema from CVI )
VDF 2012: 6 million have skin changes associated with
CVI / 500,000 with venous stasis ulcerations
(~ 3,400,000 )
Petrek JA: L. Cancer 92:1368-1377, 2001
Siegel. Cancer statistics, 2013. CA Cancer J Clin 2013, 63:9-11.
Lymphedema
Buffalo
Hump”
Dean SM. Ann Vasc Surg. 2014 Jul;28(5):1314.e1-3.
Exaggerated
skin creases
Hypoplastic
Toenails
Chronic venous
insufficiency
Swelling
Chronic eczematous
stasis dermatitis
Late Chronic
Lipodermatosclerosis
Inverted
“Champagne
Bottle”
or
“Bowling Pin”
Legs
Clinically evident
Phlebolymphedema
Phlebolymphedema
Lymphedema vs
Phlebolymphedema
Dean SM. Ann Vasc Surg. 2014 Jul;28(5):1314.e1-3
Elephantiasis Nostras Verrucosa:
An Institutional Analysis of 21
Cases
Steven M. Dean, DO, Matthew J. Zirwas, MD, Anthony Vander Horst BA, BS, MA
Results:
All 21 pts were obese (91% were morbidly
obese) with a mean BMI of 55.8 [34.6-79.1].
Average maximal calf circ = 63.7 cm [43.2106.7]
Concurrent CVI- 71%
Bilateral- 86%
Cellulitis/lymphangitis [prior/current]- 86%
J Am Acad Dermatol 2011. 64;(6):1104-10
Phlebolymphedema with
Congenital Vascular Malformations
Phlebolymphedema
Phlebolymphedema:
A Vulnerable Skin Area
Ruocco. Clin Dermat 2012;30:541-43
Phlebolymphedema:
Management
1. Gradient compression stockings or Velcro
based wraps
2. Medications: pentoxifylline, venotonic
medications (Daflon 500), and judicious
diuresis
3. Endovenous ablation GSV (RFA, EVLT)
4. Endovascular therapy (iliocaval)
5. Supportive care (skin care)
Phlebolymphedema:
Management
Conclusions:
Phlebolymphedema-Pathophysiology
Venous
hypertension
Phleblolymphedema
(C4-6)
Lymphatic
destruction
Increased
microfiltration
Phleblolymphedema
(C3)
Conclusions:
1. The venous & lymphatic systems are
mutually interdependent. When
dysfunctional, dual outflow system failure
ensues.
2. Phlebolymphedema, not cancer & its Rx,
is the most common cause of lower
extremity secondary lymphedema in
Western countries
3. Remember the manifestations of the
clinically phlebolymphedematous limb
Dean- Phlebolymphedema
Objectives
Understand how the lymphatic and venous systems interact at a large and small
vessel level
Be aware that phlebolymphedema is the most common secondary cause of
lower extremity lymphedema
Recognize the characteristic clinic features of the phlebolymphedematous leg
Review treatment options for phlebolymphedema
Dean
Questions for the Post Thrombotic Syndrome Lecture
Which of the following is a well-validated risk factor for the post thrombotic
syndrome:
1. Duration of anticoagulation
2. Presence of thrombophilia
3. Morbid obesity
4. Absence of varicose veins
Correct answer: 3- Morbid obesity
Which of the following clinical manifestations most likely predicts the subsequent
development of a stasis ulceration in a patient with the post thrombotic syndrome?
1. Edema
2. Corona phlebectatica
3. Calf varicose veins
4. Large thigh spider veins
Correct answer: 2- corona phlebectatica.
Dean-Phlebolymphedema
Questions
1. What is the most common cause of secondary lower extremity lymphedema in
the United States??
A. Radiation
B. Trauma
C. Cancer surgery
D. Chronic venous insufficiency
Correct answer #D. Chronic venous insufficiency
2. Which of the following manifestations of chronic venous disease is most likely to
have associated secondary lymphedema?
A. Diffuse thigh telangiectasias
B. Large calf varicose veins
C. Medial calf stasis hyperpigmentation
D. Medial calf lipodermatosclerosis
Correct answer #D. Lipodermatosclerosis
Dean
Post thrombotic syndrome
References
Galanaud JP, Kahn SR. Postthrombotic syndrome: a 2014 update.
Curr Opin Cardiol. 2014 Nov;29(6):514-9.
doi: 10.1097/HCO.0000000000000103.
Rabinovich A, Cohen JM, Kahn SR. Predictive value of markers of inflammation
in the postthrombotic syndrome: a systematic review: Inflammatory biomarkers
and PTS. Thromb Res. 2015 Aug;136(2):289-97.
doi: 10.1016/j.thromres.2015.06.024. Epub 2015 Jun 20.
Perrin M, Eklöf B. Does prescription of medical compression prevent
development of post-thrombotic syndrome after proximal deep venous
thrombosis? Phlebology. 2015 May 5. pii: 0268355515585437. [Epub ahead of
print]
Vazquez SR, Kahn SR. Advances in the Diagnosis and Management of Post
Thrombotic Syndrome. Best Pract Res Clin Haematol 2012;25(3):391-402
Dean. Phlebolymphedema
References:
Nisha Bunke, Katherine Brown and John Bergan. Phlebolymphemeda: Usually
Unrecognized, Often Poorly Treated. Perspect Vasc Surg Endovasc Ther 2009;
21; 65
DOI: 10.1177/1531003509337155
P.S. Mortimer. Implications of the Lymphatic System in CVI-Associated Edema.
Angiology 2000; 51; 3
DOI: 10.1177/000331970005100102
Farrow W. Phlebolymphedema-a common underdiagnosed and undertreated
problem in the wound care clinic. J Am Col Certif Wound Spec. 2010 Apr
22;2(1):14-23.
doi: 10.1016/j.jcws.2010.04.004. eCollection 2010.