Venous Disorders

• Moderated by: Prof. Moaath Al Smady

Incidence/Prevelance

• It is estimated that more than 80 million Americans suffer from some form of venous disorder.

• Up to 13 million people in the U.S. suffer from CVI

• Peak incidence occurs in women aged 40-9 and men aged 70-79 years

• Statistics show one in three Americans over the age of 45 is affected by vein disease, and of those, only 4% are

being treated.

• Annual health care cost in the US to treat CVI is about $3billion; about 2 million workdays are lost per year due to venous ulcers

Varicose Veins

• More than 24 million Americans have varicose veins

• Up to 50% of women have varicose veins while 24% of men aged 30-40 and 43% of men over 70 have varicose veins

DVT / PTS

• There are over 200,000 new cases of DVT each year in the U.S.

• The incidence of pulmonary embolism in patients with DVT ranges from 5 – 20% and can be fatal

• After an episode of DVT, 20 – 50% of patients develop Post Thrombotic Syndrome within the first 2 years

Venous Stasis Ulcers

• Affect 2.5 million people in the U.S.

• An estimated 500,000 persons are newly diagnosed each year

Function

• Transport blood back to the

heart

• Prevent intravascular

volume overload

The superficial ,

deep , perforating ,

and communicating

veins 1. The superficial venous system include the reticular veins as well as the great and the small saphenous veins and their tributaries.

2. The reticular veins , a network of veins parallel to the skin surface and lying between the saphenous fascia and dermis, drain the lower extremity skin and subcutaneous tissue.

3. The GSV usually lies directly on the muscular fascia in the saphenous compartment.

4. The saphenous nerve lies anterior to the vein in the calf.

5. A valve is present at the saphenofemoral junction in 94% to 100% of individuals.

6. Approximately 60% of Small Saphenous Veins ( SSV ) join the popliteal vein within 8 cm of the knee joint, 20% join the GSV via anterior or posterior tributaries , and 20% join the femoral, or internal iliac veins.

7. The sural nerve ascends immediately lateral to the vein.

8. The deep venous system of the calf includes the tibial and peroneal veins as well as the soleal and gastrocnemial veins .

9. 64 perforating veins between the ankle and the groin.

10. The calf contain 4 groups of perforators ( medial : paratibial and posterior tibial veins ) , anterior and lateral perforators.

11. Communicating veins connect veins within the same system.

Valves

• Venous valves:

– One way

– Two cusps of CT

skeleton covered by

endothelium

– Closure at > 30cm/s

– Exception: IVC, common

iliacs, portal, cranial

sinus

Etiology

• Pregnancy

• Pelvic obstruction

• Chronic straining

• Prolonged standing

• Prolonged sitting

Etiology

• Wearing constricting clothing

• Obesity

• Hormones

• Heredity risk?

– Both parents = 80%

– 50/50 chance if one parent

– 20% chance if neither parent

SCLEROTHERAPY

Acts by destroying the venous endothelial cells, exposing the subendothelial collagen

fibers, and ultimately, the formation of a fibrotic obstruction.

In the US, FDA approved agents for sclerotherapy include sodium tetradecyl sulphate

(STS), polidocanol, sodium morrhuate, and glycerine which is usually used with

epinephrine.

A recent RCT found no advantage to compression bandaging for > 24 hours when

thromboembolus-deterrent stockings were worn for the remainder of 14 days.

Complications : most complications are minor, and include matting, pigmentation,

pain, allergy, and skin urticaria, these minor complications can be observed in 30% of

patients. Severe complications are very rare <0.01% ( death, anaphylaxis, pulmonary

embolus and stroke)

Sclerotherapy

Before After

10 Week Interval

OPEN VENOUS

SURGERY • Ligation and stripping of the GSV or SSV, combined with excision of large VV, has been the standard of care.

• Recognition of frequent saphenous nerve injury during ankle-to-groin stripping and a better understanding of the venous hemodynamics changed the technique to a limited, groin-to-knee stripping.

TYPES:

1. HIGH LIGATION, DIVISION, AND STRIPPING OF THE GSV OR SSV.

2. MINIPHLEBECTOMY TO REMOVE THE BULGING VV THROUGH A SMALL STAB WOUNDS.

3. CRYOSTRIPPING.

4. POWERED PHLEBECTOMY (TIPP).

5. CHIVA METHOD (reentry perforators).

ENDOVENOUS THERMAL

ABLASION

• Is relatively new, minimally invasive percutaneous procedure with several

advantages over standard open surgery.

• It includes EVLA and RFA; a third technique that recently emerged includes

the use of superheated steam, which destroys the endothelial layer and

causes shrinkage of the collagen.

• Duplex U/S recognition of all refluxing venous segments and their ablation

during procedure is the key to minimizing recurrence of VV.

• Inappropriate vein size (<2mm and >15mm for RFA), history of superficial

thrombophlebitis resulting in partially obstructed saphenous vein, and

tortuous GSV by U/S are potential C/I; patients with ropy VV or those with

aneurysmal dilatation of SFJ are better served with HL/S. relative C/I

include uncorrectable coagulopathy, liver dysfunction, limited use of local

anesthsia, immobility, pregnancy, and breast feeding.

• Postprocedural care : graduated compression stocking with ankle pressure

of 30-40 mm Hg or an elastic or nonelastic wrap is placed on the leg at the

end of the procedure, recent evidence suggest elastic compression for 1

week (day and night), we suggest duplex U/S 24- 72 hours postprocedural

to exclude any thrombotic event (GRADE 2C).

• COMPLICATIONS:

1. EVLA : in an international endovascular working group registry that

included 3696 procedures (bruising was 75%, parasthesia was 3%,

thrombophlebitis was 1.87%, skin burn was 0.46%, and DVT or heat –

induced thrombosis in 0.27%0.

2. RFA : serious complications such as DVT or thermal skin injury, were not

observed in a multicentre, nonrandomized study .( Parasthesia was

observed in 3.2%, thrombophlebitis in 0.8%, ecchymosis along the course

of GSV in 6.3% and skin pigmentations in 2%).

Chronic Venous Disorders

CLASSIFICATION OF CHRONIC VENOUS DISORDERS: CEAP

• ONE: CLINICAL CLASSIFICATION :

Classification: CEAP *Eklof et al. J of Vasc Surg 2004

Clinical classification

• C0: no visible or palpable signs of venous disease

• C1: telangiectasies or reticular veins

• C2: varicose veins

• C3: edema

• C4a: pigmentation or eczema

• C4b: lipodermatosclerosis or atrophie blanche

• C5: healed venous ulcer

• C6: active venous ulcer

• S: symptomatic, including ache, pain, tightness, skin

• irritation, heaviness, and muscle cramps, and other

• complaints attributable to venous dysfunction

• A: asymptomatic

Compression Stockings

• Worn during the day

• Elastic stockings with

adjustments in pressure

• Lower pressure stockings

(20-30mm Hg) for edema

and DVT prophylaxis

• Higher pressure (30-

40+mm Hg) for ulcers

and significant venous

disease

• Operator dependent

– Difficult to put on

– Physical impediments/Co-

morbidities

• 50% of patients were

unable to them on alone

• 30-65% noncompliance

noted in clinical trials in

venous centers

COMPRESSION

TREATMENT

• It is recommended to decrease ambulatory venous hypertension to patients with CVD in addition to lifestyle modification.

• The different forms include elastic stockings , paste gauze boots (Unna boots), multilayer wraps….

• Pressure to compress the superficial veins in supine position range from 20-25 mmHg. When upright, pressure of 35-40 mmHg have been shown to narrow the superficial veins, and pressure > 60 mmHg are needed to occlude them.

• Most class C1-C2 require pressure 10- 20 mmHg; class C3-C4 require pressure of 20- 30 mmHg; while class C5-C6 require pressure of 30-40 mmHg

• On the basis of high- quality clinical evidence, the Guideline Committee recommends compression therapy for patients with CVI ( class C3 –C6 ) including those with leg ulcers.

• Arterial occlusive disease is contraindation to conventional high- pressure compression treatment. This especially true for patients with ABI < 0.5, in this situation and in those with restricted walking ability, intermittent pneumatic compression pumps may be useful adjunct in ulcer healing.

• Pneumatic compression devices applied primarily at night, are also used in patients with refractory edema and venous ulcers.

• The exact mechanism is unknown. But high pressure bandages do reduce venous reflux and improve calf muscle pump function, and increase subcutaneous tissue pressure may decrease edema thereby improving local metabolism by enhancing oxygen and nutrient diffusion to the skin and subcutaneous tissue. Finally, cytokines, as VEGF and TNF-< have been demonstrated to decrease with compression therapy .

Deep Vein Thrombosis (DVT):

Epidemiology

– Major health issue in industrialized countries

– ~ 200.000 new cases diagnosed each year

•The annual incidence 0.1 percent in young

aduts

•1 percent in adults > 60 years old

– Consequences can be serious and chronic or

fatal

• Pulmonary embolism (major cause of sudden death)

• Postthrombotic syndrome

• Phlegmasia cerulea dolens

Gray HW. Semin Nucl Med. 2002;32(3):159-172. Feied C, Handler J. eMedicine. 2002;3(1). Accessed August 27, 2002.

Mewissen MW, Seabrook GR, Meissner MH, et al. Radiology. 1999;211(1):39-49. Meignan M, Rosso J, Gauthier H, et al.

Arch Intern Med. 2000;160(2):159-164.

Pathophysiology

Virchow’s Triad : 1856

Venous thrombosis

Phlegmasia dolens

Mondor’s disease

Venous Insuffenciency

Variceal hemorrhage

Pulmonary thromboembolism

Paradoxical embolism

Blood Clotting

• Vascular Phase

• Platelet Phase

• Coagulation Phase

• Fibrinolytic Phase

Vascular Phase

• Vasoconstriction

• Exposure to tissues activate Tissue

factor and initiate coagulation

Tissue Factor

Platelet phase

• Non-nucleated - arise from magakaryocytes

• blood vessel wall (endothelial cells) prevent platelet adhesion and aggregation

• platelets contain receptors for fibrinogen and von Willebrand factor

• after vessel injury Platelets adhere and aggregate.

• Release permeability increasing factors (e.g. vascular permeability factor, VPF)

• Loose their membrane and form a viscous plug

m

Coagulation Phase

• Two major pathways – Intrinsic pathway

– Extrinsic pathway

• Both converge at a common point

• 13 soluble factors are involved in clotting

• Biosynthesis of these factors are dependent on Vitamin K1 and K2

• Most of these factors are proteases

• Normally inactive and sequentially activated

• Hereditary lack of clotting factors lead to hemophilia -A

Risk Factors

• AMI

• Antithrombin III deficiency

• Behcet’s disease

• Blood type A

• Burns

• Catheters

• Chemotherapy

• Estrogen replacements

• Fibrinogen abnormality

• Fractures

• Hemolytic anemias

• Heparin-associated thrombocytopenia

• Homocysteinuria

• Hyperlipidemias

Immobilization

Inflammatory bowel disease

Malignancy

Obesity

Old age

Plasminogen activator abnormality

Polycythemia

Postoperative

Pregnancy

Protein C deficiency

Protein S deficiency

Superficial phlebitis

Trauma

Varicose veins

Venous stasis

Warfarin (first few days of therapy)

Presentation

Conditions that mimic DVT

Diagnosis

DOPPLER ULTRASONOGRAPHY

D-DIMER TESTS

HELICAL COMPUTED TOMOGRAPHY

CONTRAST VENOGRAPHY

IMPEDANCE PLETHYSMOGRAPHY

EMERGING TECHNOLOGIES

Thrombosis of the vena cava. A, Direct imaging. B, Digitally subtracted

imaging. A vena cava filter is present at the cephalic aspect of the thrombus,

having captured mboli from the lower extremity.

A Bad PE !

Pulmonary Embolism

Treatment of Venous Thrombosis and

Pulmonary Embolism : Goals

• Prevent death from PE

• Prevent post-thrombotic characterized by chronic deep venous insufficiency, chronic pain,

venous stasis, recurrent cellulitis, and lower extremity ulceration.

• Prevent recurrent venous thromboembolism (VTE)

• Achieve these objectives with minimal side effects and

inconvenience

Treatment of VTE : modalities

• Anticoagulants

• Thrombolytic therapy

• Caval interruption

• Surgical removal

Anticoagulants

• Initial treatment with heparin is necessary.

• Induction period with heparin therapy can be reduced to 5 days.

• Treatment following hospital discharge is necessary.

• LMWH is a major advance.

• Optimal therapeutic range with warfarin established.

• Optimal duration of warfarin therapy still to be established.

• New oral small-molecule direct thrombin inhibitor.*

Thrombolytic Therapy

• Not often indicated in venous thrombosis

• Useful in major PE

• Possible new indication in PE

Caval Filter

• A single randomized trial has defined

advantages and drawbacks of caval filters.

The results indicate that inferior venacaval

filters:

a) Prevent recurrent PE in short term

b) Increase the risk of recurrent deep venous

thrombosis (DVT) in the long term

Anticoagulants

• Heparin

• Vitamin K antagonists (warfarin)

• LMWH

• Danaparoid*

• Hirudin*

• Pentasaccharide*

• Oral small-molecule direct thrombin inhibitor*

*Danaparoid is not approved by the FDA for use in the treatment of thrombosis or HIT. Natural hirudin is not approved by the

FDA for any indication; recombinant hirudin (lepirudin) is approved for the treatment of thrombosis associated with HIT.

Pentasaccharide and the new oral small-molecule direct thrombin inhibitor do not have FDA approval for any indication.

Oral: Multiple clinical trials Small molecule DTI†*

Injection: Phase 3 Pentasaccharide*

Injection Hirudin*

Injection Danaparoid*

Oral Warfarin

Injection LMWH

Injection Heparin

Anticoagulants

• Initial treatment with heparin is necessary.

• Induction period with heparin therapy can be reduced to 5 days.

• LMWH can replace heparin and is now treatment of choice.

• Continued treatment following hospital discharge is necessary.

• Optimal therapeutic range with warfarin is an INR of 2.0 to 3.0.

• Optimal duration of warfarin therapy still to be established.

Established Guidelines

Unfractionated Heparin (UFH)

• Sulphated carbohydrate

• Purified from bovine lungs

• Active in vitro and in vivo

• Binds to a variety of cells and plasma proteins, leading to

unpredictable effects

• Short half-life : 1 - 5 hrs - monitor aPTT

• Increased risk of heparin-induced thrombocytopenia (HIT)

• Administration - parenteral- Do not inject IM - only IV or deep s.c.

• Adverse effect - hemorrhage - antidote - protamine sulphate

LMWH: A Major Advance

• Weight-adjusted subcutaneous dosing predictable (Handeland et al,1990; Bratt et al, 1990)

• Mechanism of more predictable dose response (Young et al, 1993, 1994)

• Less osteopenia than UFH (Shaughnessy et al, 1995; Monreal et al, 1994)

• Less HIT than UFH (Warkentin et al, 1995)

• Once-daily subcutaneous dosing effective in DVT (Hull et al, 1992)

• Outpatient treatment effective and safe (Levine et al, 1996; Koopman et al, 1996)

• Treatment of PE effective and safe (Columbus Investigators, 1997; Simonneau et al, 1997)

• Improved subcutaneous (SC) bioavailability compared with UFH allows more convenient administration

• Dosing in obese patients and in renal

insufficiency

• Dosing in pregnancy

• Protamine reversal

• Interchangeability of different

preparations

LMWH: Outstanding Questions

Oral anticoagulants : warfarin,

dicumarol

• Coumarins - warfarin, dicumarol

• Isolated from clover leaves

• Structurally related to vitamin K

• Inhibits production of active clotting factors

• Absorption rapid - binds to albumin

• Clearance is slow - 36 hrs

• Delayed onset 8 - 12 hrs

• Overdose - reversed by vitamin K infusion

• Can cross placenta - do not use during late pregnancies

Optimal Duration of Anticoagulant Therapy for Symptomatic Venous

Thrombosis: Recommendations

Indication Duration

Proximal thrombosis: reversible cause

Idiopathic proximal vein thrombosis

Idiopathic calf-vein thrombosis

Calf-vein thrombosis: reversible cause

3 to 6 months

6 months to >1 year

6 months to 1 year

6 weeks to 3 months

Potential Indications for

Indefinite Anticoagulant Therapy • Inherited thrombophilia: AT, protein C and S deficiency

not factor V Leiden or prothrombin mutation

• Antiphospholipid syndrome

• Recurrent idiopathic VTE

• Malignancy

• Thromboembolic pulmonary hypertension

AT = antithrombin

Thrombolytic Therapy

DVT • Thrombolytic therapy achieves complete early lysis

in 30% to 40% of cases (heparin 10%).

• Increases bleeding threefold.

• Probably reduces the incidence of post-thrombotic syndrome. However, risk of severe post-thrombotic syndrome about 10% with adequate anticoagulation.

• Catheter-directed thrombolysis with administration into thrombus claimed to be more effective, but further study is required.

Thrombolytic Therapy

PE

• Two-hour high-dose t-PA or urokinase effective.

• Improves resolution at 24 hours but not at 7 days.

• Role in massive embolism accepted.

• Role in submassive, major embolism controversial.

Classification of Acute PE

• Massive PE with shock or syncope

• Major PE with right-ventricular dysfunction

• Major PE with normal right-ventricular

function

• Minor PE

Recommended Treatment of

Acute PE

• Massive PE with shock or syncope – Thrombolysis or surgery

• Major PE with right-ventricular dysfunction – Anticoagulants (Dalen) – Thrombolysis (Goldhaber)

• Major PE without right-ventricular dysfunction – Anticoagulants

• Minor PE

Thrombolysis for Massive PE

Heparin (10,000 U bolus + 1000 U/hr IV) versus

streptokinase (1.5 million U IV over 60 min) + heparin

Patients (8)

• Cardiogenic shock; HR 124; Pa02 46

(4/4 heparin patients had already deteriorated on heparin)

Heparin Streptokinase + Heparin

Mortality 4/4 0/4

Jerjes-Sanchez et al, 1995

Ha

Pulmonary Embolectomy

• Can be life saving in patients with massive

PE.

• In consecutive series of 96 patients,

mortality was 37% (Meyer et al, 1991).

• Cardiac arrest and associated

cardiopulmonary disease were

independent predictors of death.

• Elective pulmonary embolectomy was life

saving in selected patients with chronic

thromboembolic pulmonary hypertension

(Moser et al, 1990).

Fibrinolysis

• Enhance degradation of clots

• Activation of endogenous protease

• Plasminogen (inactive form) is converted

to Plasmin (active form)

• Plasmin breaks down fibrin clots