Deep Vein Thrombosis:

the danger and how to prevent

What Is Deep Vein Thrombosis (DVT)?

DVT is a blood clot that forms in a vein deep in the body Most often occurs in the deep veins of the legs, either above the knee or below it The blood clot or part of it can break free (called embolism) and become lodged in the blood vessels of the lung, causing pulmonary embolism (PE)

Deep veins of the legs.

Incidence
Likely underestimated - Misdiagnosis - Occult resolve without complication - Non-occlusive - Venous collaterals develop rapidly

DVT: A National Public Health Crisis1

Up to 2 million people in the United States suffer from DVT every year2,3 Complications of DVT, such as PE, kill up to 200,000 people each year, more people than AIDS and breast cancer combined2-6
Some Causes of Death in the US Annual No. of Deaths

PE AIDS Breast cancer

Up to 200,000 16,371 40,580

1. American Public Health Association. Available at: http://www.apha.org/news/press/2003/DVT_whitepaper.pdf. 2. Gerotziafas GT. Curr Opin Pulm Med. 2004;10:356-365. 3. Anderson FA Jr. Arch Intern Med. 1991;151:933-938. 4. Centers for Disease Control. Available at: http://www.cdc.gov. 5. American Cancer Society. Available at: http://www.cancer.org. 6. Bick RL. Clin Appl Thromb Hemost. 1999;5:2-9.

Risk Factors
General
- Age - Immobilization > 3d - Pregnancy / postpartum - Major surgery < 4 weeks - Trip (>4h) in past 4 weeks
- Cancer Trauma - CNS / spinal cord injury - Burns - Lower extremity fractures Hematologic - Thrombocytosis - Anti-thrombin III deficiency - Protein C deficiency - Protein S deficiency - Factor V Leiden Drugs
- OCP - Estrogens

Medical

- Previous DVT - CHF - Sepsis - Nephrotic syndrome

Ref: BMJ 2011;343:d5916 doi: 10.1136/bmj.d5916

Wells Clinical Score for DVT

Clinical Parameter Active cancer Paralysis or recent immobilization of extremities Recently bedridden for > 3 days or major surgery <4 weeks Tenderness along distribution of deep venous system Entire leg swollen Calf swelling > 3cm circumference difference from unaffected leg Pitting edema Previous DVT Collateral superficial veins Alternative diagnosis as likely or more likely than DVT High Probability Moderate Probability Low Probabillity 3 1 or 2 0 Score +1 +1 +1 +1 +1 +1 +1 +1 +1 -2

Who Should We Study?

Ref: Annals of Internal Medicine 2 September 2008

The Life of a Clot

Valve cusps of deep calf veins - Dissolve - Adherence and Organization - 5-10 days - Propagate - Embolize - Chronic Venous Insufficiency

History and Physical

Edema Leg pain Tenderness Superficial thrombophlebitis - Increased risk of DVT Fever

Alternate Diagnosis
Achilles tendinitis Arterial insufficiency Arthritis Cellulitis / lymphangitis Extrinsic vein compression Hematoma Lymphedema Muscle / soft tissue injury Neurogenic pain Postphlebitic syndrome Ruptured Baker cyst Fracture / bony lesions Superficial thrombophlebitis

Phlegmasia cerulea dolens: the entire left leg is swollen and inflamed, with a blue-red aspect. The leg is very painful. It occurs when the whole venous return of the leg is blocked by a deep vein thrombosis. It can ultimately lead to gangrene of the leg

Magnetic resonance venogram

Magnetic resonance venogram showing a thrombus in the left leg extending from the popliteal vein to the common femoral vein; the red arrows point to the position of the thrombus in the vessel

Ref: Annals of Internal Medicine 2 September 2008

One approach to testing for suspected deep venous thrombosis

D-dimer
Fragments - Degradation of fibrin by plasmin Elevated in any condition where clots form - Trauma, recent surgery, cancer, sepsis Low specificity - r/o DVT Elevated for 7 days

Imaging Studies
Study Contrast Venography Notes - Gold standard, 99% sensitive - Allergic reaction, availability, IV contrast, costly - Good for calf, iliac veins, IVC - Useful in pregnancy - Can distinguish acute from chronic - Good for calf, iliac veins - Cost, accessibility - Can do PE study at same time - Good for calf, iliac veins - No radiation, bedside, cost - Non-occlusive thrombi - Cannot distinguish acute from chronic - Poor visualization of calf, iliac veins

MRI

CT Duplex Ultrasonography

Lower Extremity Venous Anatomy

External Iliac Common Femoral Vein - Deep femoral vein - Superficial Femoral Vein - Popliteal Vein - Anterior Tibial Vein - Posterior Tibial Vein - Peroneal Vein

Some Logistics
High frequency linear array probe (7-10MHz) Head of bed to 45 Patient Positioning

What is Duplex Ultrasound?

B-mode Imaging + Doppler Ultrasound

Doppler Ultrasound: Color

Doppler Ultrasound: Spectral

Ultrasound for DVT

Major criterion - Failure to compress vascular lumen - Not visualization of lumen - Acute thrombus can be anechoic - Slow flowing blood can have internal echoes Minor criterion - Absence of normal doppler signals - Absence of flow - Absence of respiratory variation in flow - Decreased augmentation with distal compression - Distension of vessel

Major Criteria: Compressibility

Collapse of lumen of vein - Complete apposition of anterior and posterior wall Compress with transducer in transverse - Longitudinal compression slides off vessel wall leading to false negative - Use to follow course of vein May visualize thrombus; not necessary for diagnosis

Compressibility: Normal Findings

A V

Compressibility: DVT

A V

A V

Compressibility

Ultrasound for DVT

Major criterion - Failure to compress vascular lumen - Not visualization of lumen - Acute thrombus can be anechoic - Slow flowing blood can have internal echoes Minor criterion - Absence of normal doppler signals - Absence of flow - Absence of respiratory variation in flow - Decreased augmentation with distal compression - Distension of vessel

Minor Criteria: Flow

Minor Criteria: Respiratory Variation

Minor Criteria: Respiratory Variation

Minor Criteria: Augmentation

Femoral Vein
Begin at inguinal ligament Distally bifurcates into superficial and deep femoral veins Compression in Hunters canal difficult because of depth

Femoral Vein

Popliteal
Positioning Vein superficial to artery Scan to trifurcation point

Popliteal

Diagnostic Difficulties
False negatives - Adductor canal - Complete occlusion - Ilio-femoral DVT - Duplicated vessels - Technical difficulties - obese patients - significant lower extremity edema False positives - Chronic vs. acute - Proximal obstruction limits compressibility - Superficial vein filled with thrombus Operator Dependence

How Good is it?

Noninvasive Diagnosis of Deep Venous Thrombosis - Large review of US for DVT - Proximal DVT: sensitivity 95%, specificity 96% - Calf vein DVT: great variation - Overall: sensitivity 89%, specificity 94% -Kearon C, et al.

Limited Ultrasound
Image entire venous system - Technically difficult - Time Limited Ultrasound - Only B-mode compression - 5 cm inguinal ligament - 5 cm popliteal fossa

How Good is Limited Ultrasound?

Detection of Deep Vein Thrombosis by B-mode

Ultrasonography

- Sole criterion was compressibility of common femoral or popliteal vein - 100% sensitive for proximal DVT - 91% sensitive overall

-Lensing, et.al.

How Good is Limited Ultrasound?

Limited B-mode venous Imaging Versus

Complete Color-flow Duplex Venous Scanning for Detection of Proximal Deep Venous Thrombosis
- time reduction 37 minutes vs. 5.5 minutes - Poppiti et.al.

Are DVT in calf veins ok?

Smaller Propagate Treatment?

Do You Study the Asymptomatic Leg?

Unilateral symptoms - risk in contralateral leg is <1% Assist in difficult anatomic interpretations Does it matter if anti-coagulating anyway?

Other Ultrasound Diagnosis

Lymph node Bakers cyst Superficial thrombophlebitis Popliteal artery aneurysm

Lymph Node

LN A

Baker Cyst

Popliteal Artery Aneurysm

Upper Extremity DVT

Massive PE extremely rare Lower incidence - Fewer venous valves - Higher flow rate - Less frequent immobility - Decreased hydrostatic pressure - Malignancy, catheter induced Clavicle prohibits adequate compression - Evaluate using color or spectral Doppler

What Happens to the Clot?

Clot retracts and becomes echogenic Vein wall becomes thickened, echogenic and resistant to compression In 12-24 months, 50% have complete resolution of thrombus and normal compressibility Difficult to evaluate acute vs. chronic - Post-treatment baseline study for comparison

High Incidence of Venous Thrombosis following Cardiac Surgery

Girish R. Mood, MD, Heather L. Gornik, MD, MHS, Vidyasagar Kalahasti, MD, Donald Hammer, MD, W. H. Wilson Tang, MD, FAHA.

Background:
Absolute risk of DVT in hospitalized patients

General Surgery Major gynecologic surgery Major urologic surgery Neurosurgery Hip or Knee surgery Spinal cord surgery Critical care patients

15-40% 15-40% 15-40% 15-40% 40-60% 60-80% 10-80%

Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, Ray JG. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):338S-400S

Deep venous thrombosis after open heart surgery:

10,638 patients (1975-1988)
7,979 (75%) had CABG 2,659 had valve CABG
Patients with LE edema, pain, temp underwent Imaging studies

77 (0.7%) had DVT

36 patients had DVT without PE

41 patients had PE

16 patients had DVT being treated with heparin

25 patients without DVT

DeLaria GA, Hunter JA. Deep venous thrombosis. Implications after open heart surgery. Chest. 1991 Feb;99(2):284-8

Management

Are there any new treatments under study for iliofemoral DVT?
Combined mechanical and chemical thrombolysis
(A and B) The EKOS Endowave Peripheral Lysis System consists of a multi-lumen infusion catheter with removable, coaxial ultrasound core and a control unit that simultaneously delivers high frequency (2.2 MHz), low energy (0.45 W) ultrasound energy and thrombolytic drug into the thrombus. (C) The Trellis-8 catheter directed thrombolysis device combines balloon containment of a thrombus with chemical and mechanical thrombolysis. The thrombus is isolated after placing the catheter by inflating the proximal and distal balloons. (D) The Angiojet Power Pulse system uses a complex mixture of rapid fluid streaming and hydrodynamic forces to fracture the thrombus, allowing extraction at the catheter tip as a result of negative pressure.

Mechanical Prophylaxis

Overview
Mechanical Compression No convincing evidence of mortality value over placebo. DVT in 21.0% plantar vs. 6.5% calf (p = 0.009). Equivalent effect w improved compliance in KL group. OR 0.46 (CI 0.16-1.29) for all heparin vs. mechanical Plantar vs. Calf Knee-length vs. Thigh-length Mechanical vs. Chemical

Gregory et al. J Trauma 1999; 47:1

Compression

Roderick et al. HTA, 2005; 9

Compression

Roderick et al. HTA, 2005; 9

Chemical Prophylaxis

Overview
Aspirin Not recommended for DVT prophylaxis Aspirin vs. LMWH 63% RRR among 205 ortho pts LMWH vs. ASA. Among hip trauma pts, 44% vs. 28% ASA vs. LMWH

UFH and LMWH UFH decreases incidence of DVT by 20% over placebo LMWH decreases incidence of DVT by 30% over UFH.

Mechanism of Heparins

Unfractionated heparin inactivates both Factor IIa and Xa

LMWH has increased affinity for Factor Xa Fondiparinux is only a pentasaccharide sequence

Weitz. NEJM, 1997; 337:688

Pharmokinetics

Tran and Lee. Ann Pharm 2003; 37: 1632.

DVT Recommendations
DVT, % Level of Risk PE, % Successful Prevention Strategies Calf Proximal Clinical Fatal

Low risk Minor surgery in patients < 40 yr with no additional risk factors Moderate risk Minor surgery in patients with risk factors High risk Surgery in patients > 60 yr Highest risk Surgery in patients with multiple risk factors, Trauma, Ortho

0.4

0.2

<0.01 No specific prophylaxis; early and "aggressive" mobilization

10 20

24

12

0.1 0.4 LDUH (q12h), LMWH ( 3,400 U daily), GCS, or IPC

20 40

48

24

0.4 1.0 LDUH (q8h), LMWH (> 3,400 U daily), or IPC

40 80

1020

410

0.25 LMWH (> 3,400 U daily), fondaparinux, oral VKAs (INR, 23), or IPC/GCS + LDUH/LMWH

Geerts et al. Chest, 2004; 126:338S

DVT prophylaxis
Bariatric surgery: recommend higher dosages of lmwh or lduh than for non- obese patients (2c) Extended prophylaxis for major abdominal/pelvic cancer surgery for up to 4 weeks. Hip/knee 10-35 days Stroke, SCI & major trauma prefer lmwh & consider continuing during rehab Renal Failure and UFH vs LMWH

Thank You