VTE Prophylaxis

in the Hospital

Johan Kurnianda
Division of Hematology-Medical Oncology
Department of Internal Medicine
Medical Faculty Gadjah Mada University
Yogyakarta
 VTE : Spectrum of Disease

Post Thrombotic Syndrome

Deep Vein Thrombosis

Pulmonary Embolism Chronic Pulmonary Hypertension

Basic Pathogenesis of VTE :
Virchow’s Triad

Virchow’s Triad

Rudolf Virchow, 1821-1902

VTE Pathogenesis

Key points of VTE :

. Acute thrombogenesis
. Acute (DVT/PE) and chronic (PTS/HAP) complications
. Red-thrombus more prominent, anti-platelet not effective in most cas
 Background
• Hospitalisation causes 50-70% of all
VTE

• 10% of hospital deaths are due to VTE

• Effective prophylaxis reduces VTE by

50 - 90%

• Prophylaxis guidelines are available

 Consequences of
Unprevented VTE
• Symptomatic DVT and PE

• Fatal PE

• Costs of investigating symptomatic patients

• Risks and costs of treating unprevented VTE

• Increased future risk of recurrent VTE

• Chronic post-thrombotic syndrome

 Rationale for
Thromboprophylasis
• High Prevalence of VTE
• Adverse Consequences of VTE
• Efficacy and effectiveness of
thromboprophylaxis
– Highly efficacious in prevention of DVT
– Highly efficacious in prevention of
symptomatic VTE and fatal PE
– DVT prevention prevents PE
– Cost effectiveness has been demonstrated
 Diagnosis
CKS Clinical Topic. Deep Vein Thrombosis. Revised April 2009

• Many cases of VTE are asymptomatic. When seen, clinical

manifestations include:
– DVT: Pain/swelling in one leg, although both legs may be
affected; Tenderness/changes to skin colour and
temperature, and vein distension
– PE: Breathlessness, faintness, chest pain
• Individual symptoms are poorly predictive of DVT
• Where DVT is suspected, refer immediately to hospital if:
– Pregnant or just given birth, IV drug users
– DVT is likely according to the Wells prediction rule
– DVT is unlikely according to the Wells prediction rule but D-
dimer test (carried out on the same day) is positive or same
day D-dimer testing is not available
 DVT Wells Clinical Prediction Rule
(modified version)
CKS Clinical Topic Deep Vein Thrombosis. Revised April 2009
Scarvelis D, Wells PS. CMAJ 2006;175:1087-92

DVT can be effectively ruled out

if the Wells prediction is unlikely
and the D-dimer test is negative

Further tests (venography,

compression ultrasound) for
confirmation

2 likely to have DVT

<2 unlikely to have DVT
PE Wells Clinical Prediction Rule
(modified version)
 VTE Risk Factors
• Risk Factors • Modifiable Risk Factors
– Age > 40 years – Smoking, tobacco
– Prior VTE – Obesity
– Familial and/or acquired thrombophilia – Inactivity
– Active cancer • Therapeutic agents associated with
– Trauma increased risk
– Major surgery
– Hospitalization or prolonged bed rest – Chemotherapy
– Central venous catheter/IV catheter – Estrogen compounds
– Congestive heart failure  HRT/OCP
– Pregnancy  Tamoxifen/Raloxifene
– Regional bulky lymphadenopathy with  Diethylstilbestrol
extrinsic vascular compression – Thalidomide/lenalidomide plus
– Myeloproliferative disorders dexamethasone
– Erythropoietic stimulation agents
– Growth factors
NCCN Practice Guidelines in Oncology. http://www.nccn.org/professionals/physician_gls/PDF/vte.pdf.
Accessed September 2009.
 VTE Risk Factors
1231 Patients Treated for VTE

Risk Factors Patients % Evidence of VTE, %

Age > 40 yrs 88.5
Obesity 37.8
100
History of VTE 26.0 100
Cancer 22.3
80
Immobility 12.0

+DVT (%)
60 50
Major surgery 11.2
36
CHF 8.2 40
24
Varicose veins 5.8 20 11
Stroke 1.8
0
1 or more risks 96.3 1 2 3 4 5
2 or more risks 76.0 Number of Risk Factors
3 or more risks 39.0

Anderson FA, et al. J Vasc Surg. 1992;16:707-714.

Wheeler HB, et al. Arch Surg. 1982;117:1206-1209.
Methods of Prophylaxis
 Aspirin
– Poor study methods
• Acceptable DVT screening – 38%
• ASA alone in only 1/3 of trials
– No significant benefit
– Small increased risk of major bleeding
– Poor results v. LMWH
– Not recommended alone for VTE in any
patient group (Group 1A)
 Unfractionated Heparin &
Low Molecular Weight Heparin
• Most widely used and studied prophylaxis
• Low molecular weight heparin have more
predictable pharmacokinetic and
pharmacodynamic properties due to consistent
binding sites
• Dosing LMWH more cumbersome – Anti – Xa
monitoring
• UFH – needs site specific validation of aPTT
therapeutic range due to variability of reagents
• LMWH – ? Limited uses in renal failure and
obesity – dose adjustments possible
 Low Molecular Weight Heparin
• Reduced anti-factor IIa relative to anti-factor Xa
activity
• More favorable benefit/risk ratio in animal
studies
• Superior pharmacokinetic properties
– SC bioavailability near 100%
– More predicable dose response peak at 3-5 hr
• Monitoring
– Renal failure (CrCl < 30mL/Kg) & obesity
• Four hours post dose - anti-factor Xa level
– Enoxaparin 1.0 IU/mL, Tinzaparin 0.85 IU/mL, Nadroparin 1.3
IU/mL, Dalteparin 1.05 IU/mL
 Vitamin K Antagonists
• Initiation of Oral Dose
– 5-10 mg for first 1-2 days – most patients
– < 5 mg for first days – elderly/elevated bleeding risk/liver
disease/CHF/malnutrition
• Goal
– INR 2.0-3.0
• Monitoring
– Initiation – daily, 2-3 X/wk for 1-2 weeks, when stable 1X/4 weeks
• Reversal
– Elevated INR
• Hold dose v. Oral Vitamin K (1 – 2.5 mg)
– Elective Surgery
• Hold for 4 days
• Hold for 4 days and initiate UFH or LMWH
– Serious/Life threatening Bleeding
• Vitamin K – IV, FFP, protamine, recombinant Factor VIIa
 New Antithrombotic Agents
• Ximelagatran
– Oral direct thrombin inhibitor
– Rapid absorption and conversion to melagatran
– predictable pharmacokinetics, no food interactions
• Hip and knee replacement (Lancet 2002, phase II trial)
• Melagatran 3mg BID/ximelagatran 24mg/d v dalteparin 5000
IU BID
• DVT 15.1 v 28.2%
• Fondaparinux
– synthetic pentasaccharides with selective inhibitor of
activated factor X (NEJM 2001, Lancet 2002)
• RRR 56.4%/59.5% v. enoxaparin q day hip surgery
• RRR 22.6% v enoxaparin BID
• RRR 12.5% in Knee sugery higher bleeding
Both have better efficacy that LMWH for prophylaxis
however cost effectiveness has not yet been proven
 Non Pharmacologic
Treatment for VTE

Graduated Compression Stocking

Intermittent Pneumatic Compression

Inferior Vena Cava Filter

 ACCP VTE Prophylaxis Guidelines 8th Edition

1. Every hospital should develop a formal strategy to prevent

VTE
2. Do not use aspirin alone as prophylaxis for any patient
group
3. Use mechanical prophylaxis primarily for patients at high
bleeding risk
4. Give thromboprophylaxis for
– Major trauma
– Spinal cord injury
– Acute medical illness
– Most ICU patients

Geerts WH, et al. Chest. 2008;133:381S-453S.

VTE risk assessment
for surgery
 Post surgical risk of DVT
Type of operation Incidence of DVT
Knee surgery 75%
Hip fracture surgery 60%
Elective hip surgery 50-55%
Retropubic prostatectomy 40%
General abdominal surgery 30-35%
Gynaecological surgery 25-30%
Neurosurgery 20-30%
Transurethral resection of prostate 10%
Inguinal hernia repair 10%
 Incidence of DVT according to
length of surgery and age

Incidence of DVT (%)

Length of surgery (hours)
1–2 20
2–3 46.5
>3 62.5

Age (years)
40–60 20.1
61–70 36.4
> 71 62.5

Borow M, Goldson H. Am J Surg. 1981;141:245-51.

VTE Prevention in
General Surgery
 VTE Levels of Risk
DVT Risk Without
Levels of Risk Prophylaxis
Suggested Options

Low risk • No specific

• Mobile minor surgery patients < 10%
thromboprophylaxis
• Fully mobile medical patients • Early and “aggressive”
ambulation
Moderate risk
• Most general, open gynecologic • LMWH, UFH bid or tid,
fondaparinux
or urologic surgery
10-40%
• Medical patients, bed rest or sick • Mechanical prophylaxis if
• CHF risk of bleeding is high
• COPD, pneumonia
High risk • LMWH, fondaparinux, VKA
• Hip or knee arthroplasty, HFS (INR 2-3)
• Major trauma, SCI • Mechanical prophylaxis
• Abdominal/pelvic cancer surgery 40-80% may be used if risk of
bleeding is high; switch to
anticoagulants when risk
decreases
Adapted from Geerts WH, et al. Chest. 2008;133:381S-453S.
 Quantifying Risk
Patient Intake Form Northwestern University Physician Assessment
Joseph A. Caprini, MD, MS, FACS, RVT
Louis W. Biegler Professor of Surgery,

The Feinberg School of Medicine;

Professor of Biomedical Engineering,
Northwestern University;
Email: j-caprini2@aol.com

1. Personal History of DVT or PE Website: venousdisease.com

Venous Thromboembolism Risk Factor Assessment

2. Family History of DVT or PE
3. Malignancy: Current or Previous
4. Personal History of Recent MI or stroke (<
1 month)
5. Recent Major Surgery (< 1 month)
6. Currently on BCP, HRT, or hormonal
therapy for Breast or Prostate Cancer
7. Current or recent acute inflammatory or
infectious process (< 1 month)
8. Currently immobile (unable to ambulate
in the in-patient setting)
9. History of unexplained stillborn infant,
recurrent spontaneous abortion. premature
birth with preeclampsia or growth-restricted
Patient’s Name:_________________ Age: ___ Sex: ___ Wgt:___lbs Joseph A. Caprini, MD, MS, FACS, RVT
Choose All That Apply
Each Risk Factor Represents 1 Point
 Age 41-60 years
 Minor surgery planned
 History of prior major surgery
 Varicose veins
 History of inflammatory bowel disease
 Swollen legs (current)
 Obesity (BMI >30)
 Acute myocardial infarction (< I month)
 Congestive heart failure (< 1 month)
 Sepsis (< 1 month)
 Serious lung disease incl. pneumonia (< 1
month)
 Abnormal pulmonary function (COPD)
 Medical patient currently at bed rest
 Leg plaster cast or brace
 Other risk factors____________________
Each Risk Factor Represents 3 Points
Each Risk Factor Represents 2 Points
 Age 60-74 years
 Major surgery (> 60 minutes)
 Arthroscopic surgery (> 60 minutes)
 Laparoscopic surgery (> 60 minutes)
 Previous malignancy
 Central venous access
 Morbid obesity (BMI >40)
Each Risk Factor Represents 5 Points
 Elective major lower extremity arthroplasty
 Hip, pelvis or leg fracture (< 1 month)
 Stroke (< 1 month)
 Multiple trauma (< 1 month)
 Acute spinal cord injury (paralysis)(< 1
month)
 Major surgery lasting over 3 hours

infant.  Age over 75 years

10. Swollen legs 

Major surgery lasting 2-3 hours
BMI > 50 (venous stasis syndrome)
For Women Only (Each Represents 1 Point)

 Oral contraceptives or hormone

11. Varicose Veins 

History of SVT, DVT/PE
Family history of DVT/PE replacement therapy
 Pregnancy or postpartum (<1 month)
12. Obesity (BMI > 30) 

Present cancer or chemotherapy
Positive Factor V Leiden  History of unexplained stillborn infant,
recurrent spontaneous abortion (≥ 3),
13. Age 

Positive Prothrombin 20210A
Elevated serum homocysteine premature birth with toxemia or growth-
 Positive Lupus anticoagulant restricted infant
 Elevated anticardiolipin antibodies
 Heparin-induced thrombocytopenia (HIT)
 Other thrombophilia Total Risk Factor Score
Type______________________________

Bahl V, et al. Ann Surg. 2009 Sept 22 Please see Following Page for Prophylaxis Safety Considerations Revised November 4, 2006

[epub ahead of print].

 VTE Risk and Suggested
Prophylaxis for Surgical Patients
Incidence of
Risk score Risk level Prophylaxis Regimen
DVT
No specific measures; early
0–1 < 10% Low risk
ambulation
ES, IPC, LDUH (5,000 U bid), or
2 10–20% Moderate risk LWMH
(< 3,400 U)
IPC, LDUH (5.000U tid), or LMWH
3–4 20–40% High risk
(> 3,400 U)
Pharmacological: LDUH, LMWH
40–80% (> 3,400 U), warfarin, or FXa
5 or more Highest risk
1–5% mortality alone or in combination with ES or
IPC

ES = elastic stockings; IPC = intermittent pneumatic compression; LDUH = low-dose

unfractionated heparin; LMWH = low-molecular-weight heparin; FXa I = factor X inhibitor

Bahl V, et al. Ann Surg. 2009 Sept 22 [epub ahead of print].

VTE risk assessment
for medical patients
 Prevalence
• 3 out of 4 hospital pts dying from PE have
NOT had recent surgery…
• 2.5% of medical patients immobilized with
multiple clinical problems suffer fatal PE.
• National DVT Free Registry
– 60% of patients dx with acute DVT were in the
peri-hospitalization period
– 60% of cases were in non-surgical patients!

Haas, S. Seminars in Thrombosis and Haemostasis, 2002; Goldhaber, SZ

Am J Cardiol 2004.
 VTE Risk Factors for
Medical Patients (1)
• Heterogeneous population!
• Need to consider:
– Acute medical condition (MI, pneumonia,
etc.)
– Underlying risk factors (h/o VTE, estrogen
use, etc.)
– Medical interventions (central venous
catheters, chemotherapy, etc.)
• Relative contribution of various risk
factors still being defined.
 VTE Risk Factors for
Medical Patients (2)

• Acute medical conditions well accepted as

high risk:
– MI (24% VTE risk)
– Decompensated CHF (40% VTE risk)
– Acute Stroke (30-75% VTE risk)
– Spinal Cord Injury (up to 100%)
– ICU admission (13-33*% VTE risk, *½ of these
were proximal leg vein thromboses)
– Central venous catheters (25-46% VTE risk)
– Malignancy

Haas, S. Seminars in Thrombosis and Hemostasis, 2002; Pendleton, Amer J Hematology, 2005.
Abstracted from
Pendleton, R. Amer J
Hemat 2005.
VTE Risk Assessment
in Medical Patients
VTE Preventions in
Medical Patients
 ENDORSE: Is Prophylaxis Used?
• 68,183 hospitalized patients, multinational
• Surgical 45%, medical 55%
• 52% at risk for VTE
– 41% of surgical at-risk patients don’t receive ACCP prophylaxis
– 60% of medical at-risk patients don’t receive ACCP prophylaxis
• Overall, 50% of at-risk patients receive prophylaxis
At-Risk Patients, %

100

80

60 No Px
26 41%
40 Receive Px
25 60%
20 38
17
0
Surgical Medical

Cohen AT, et al. Lancet. 2008;371:387-394.