Curriculum

Vitae
 Name : dr Dono Antono SpPD-KKV. FINASIM .FICA
 Born :Jogjakarta, 13 April 1964
 Current Position : - Staff Division of Cardiology,
Department of Internal Medicine,
Faculty of Medicine, University of Indonesia

 Medical Student : Faculty of Medicine University of Padjadjaran 1988

 Internist : Faculty of Medicine University of Indonesia 1999
 Cardiovascular Consultant : The Indonesian Society of Internal Medicine , 2008
 Advance Interventional Cardiovascular : The Indonesian Society of Internal Medicine ,
2012
 FINASIM : Fellow The Indonesian Society of Internal Medicine 2009.
 FICA : Fellow International College of Angiology 2011.
Deep Vein Thrombosis
Dr Dono Antono SpPD-KKV. FINASIM. FICA

Divisi Kardiovaskuler
Departemen Ilmu Penyakit Dalam
FKUI/RSCM
Venous Thromboembolism : Definition

• a term used to include

the formation of
thrombus in a vein
which may dislodge
from its site of origin to
travel in the blood, a
phenomenon called
embolism.

NICE Guidelines 2010

Epidemiology

a major health care problem resulting in

significant mortality and morbidity.

The vast majority of these deaths occur in

untreated patients, where the diagnosis is
made post-mortem or undiagnosed

Cancer : 8 – 19 %
Non Cancer : 1,4 %

Heit JA. Atherioscler Thromb Vasc Biol.2008

SPECTRUM OF VTE

Deep Vein Thrombosis

• Distal (Calf) vein Thrombosis : Thrombi remain confined to the deep
calf vein
• Proximal vein Thrombosis : Thrombosis involves the popliteal, femoral or
Iliac Vein
 Provoked DVT : caused by a known event (eg, surgery, hospital
admission, Oral Contraception, immobilitation)
 Unprovoked DVT : no identifiable cause or provoking event for
DVT is evident

Acute Pulmonary Embolism

Kenneth et al. Up to date.2014

Virchow’s triad revisited
• Malignancy • Venous disorders
• Pregnancy and • Venous valvular
peripartum period damage
• Oestrogen therapy • Trauma or surgery
• Inflammatory bowel disease • Indwelling catheters
• Sepsis
• Thrombophilia

Circulatory stasis
• Left ventricular dysfunction
• Immobility or paralysis
• Venous insufficiency or varicose veins
• Venous obstruction from tumour, obesity or pregnancy
Virchow R, ed. Gesammelte Abhandlungun zur Wissenschaftichen Medicin. Von Meidinger Sohn, Frankfurt, 1856;
Blann AD, Lip GYH. BMJ 2006;332:215–219; Geerts WH et al. Chest 2004;126:338S–400S;
Bennet PC et al. Thromb Haemost 2009;101:1032–1040
What is arterial thrombosis ?
Signs of Ischemia
Acute Ischemia
Pale extremities.
Change of temperature with definite border against unaffected area
Pain and paresthesia
Loss of sensation
Cyanotic with definite border, and palor when given pressure.
Paresis to paralysis
Muscle spasticity
Chronic Ischemia
Muscle atrophy
Loss of leg hair
Nail hipertrohy and slow
growth
Weak pulse
Low temperature
Constriction of superficial
veins
Slow capillary refill
Palor
Rubor
What is VTE?
VTE: deep vein thrombosis and
pulmonary embolism
 Thrombosis is the formation PE occurs when parts of the clot
or presence of a thrombus detach and travel in the blood
that may obstruct blood flow to block vessels in the lungs
PE
through a vein or artery1
 VTE occurs when Migration Embolus
thrombosis obstructs blood
flow through a vein
 The term VTE
encompasses:
Thrombus
 DVT
 PE As the venous
clot grows, it
 VTE is a serious health extends along
issue2 the vein

DVT, deep vein thrombosis; PE, pulmonary embolism

1. Anderson FA, et al. Center for Outcomes Research, University of Massachusetts Medical Center; 1998
2. Goldhaber SZ. J Am Coll Cardiol 1992
VTE: deep vein thrombosis and
pulmonary embolism

Migration
PE

Embolus

Thrombus

DVT
Classification of PE
 The European Society of Cardiology (ESC) guidelines stratify PE
into levels of risk of early death
 Defined as 30-day risk of death
 PE and risk of early death
 High-risk PE (>15% mortality risk)
 Intermediate-risk PE (3–15% mortality risk)
 Low-risk PE (<1% mortality risk)
 Clinical markers are:
 Shock or hypotension
 Right ventricular dysfunction
 Markers of myocardial injury

Torbicki A et al. Eur Heart J 2008

Clinical presentations of DVT
 DVT occurs when clots form in the deep veins within the muscles of
the leg1
 Less commonly, clots may form in the upper extremities as well2
 DVT-related symptoms may include:1,3
 Leg pain
 Tenderness of the leg
 Cramping that intensifies over several days
 Erythema
 Warmth at the site of DVT
 Edema
 DVT is often asymptomatic, sometimes revealed only after
diagnostic tests4

1. Blann AD, Lip GY. BMJ 2006; 2. Spencer FA. J Gen Intern Med 2006 3. Goldhaber SZ, Morrison RB. Circulation 2002;
4. Anderson FA et al. Center for Outcomes Research, University of Massachusetts Medical Center 1998
Distal or proximal

Proximal
 DVT can be:
 Distal External iliac
─ Below the knee in the deep
veins of the calf
Deep femoral
 Proximal
─ Above the knee, primarily in the Great saphenous
popliteal and femoral veins
Popliteal
 DVT usually begins distally

Distal
 A thrombus may grow and extend to
the proximal veins Anterior tibial
and embolize1 Posterior tibial

Dorsal venous arch

1. Anderson FA, et al. Center for Outcomes Research, University of Massachusetts Medical Center; 1998
Pulmonary embolism
 PE occurs when part of a dislodged thrombus (embolus) passes
into the pulmonary circulation blocking the main artery of the lung
or one of its branches
 May lead to increased pulmonary vascular resistance, impaired
gas exchange (alveolar ventilation with hypoperfusion)
 Increase in pressure on the right heart can cause dilation,
dysfunction, and ischemia of the right ventricular wall1
 PE-related symptoms1–3
 Shortness of breath
 Chest pain, tachypnoe, tachycardia
 Anxiety
 Hemoptysis
 Fever Medical Illustration Copyright © 2007
Nucleus Medical Art. All rights reserved.

1. Goldhaber SZ. N Engl J Med 1998; 2. Goldhaber SZ, et al. Circulation 2002; 3. Stein PD et al. Chest 2001
Post-thrombotic syndrome
 Occurs in nearly one-third of
patients within 5 years after
idiopathic DVT1
 PTS is characterized by:2
 Pain
 Oedema
 Hyperpigmentation
 Eczema
 Varicose collateral veins
 Venous ulceration
 Severe PTS can lead to
intractable, painful venous
leg ulcers requiring ongoing
nursing and medical care3
Reproduced with permission from Dr AT Cohen and Dr T Urbanek
1. Prandoni P et al. Ann Intern Med 1996; 2. Kahn SR. J Thromb Thrombolysis 2006;
3. Kahn SR, et al. J Gen Intern Med 2000
Risk factors for VTE
Exposing risk factors Predisposing risk factors
(acute conditions or trauma, surgery) (patient characteristics)

History of VTE
Chronic heart failure
Advanced age
Surgery
Cancer Varicose veins
Trauma
Obesity
Acute medical illness
Inflammatory Immobility or paresis
Acute heart failure* diseases Myeloproliferative disorders
Acute respiratory failure
Pregnancy/peripartum period
Central venous
catheterization Inherited or acquired
thrombophilia
Hormone therapies
Renal insufficiency

*New York Heart Association classification III and IV

Risk factors from Geerts WH et al. Chest 2004
 Provoked and unprovoked VTE
Transient/
Continuing/
reversible factors No identifiable
irreversible factors
e.g. surgery or cause
e.g. cancer
hospitalization

Unprovoked
Provoked VTE (idiopathic)
VTE

ACCP guidelines recommend at least 3 months’ VKA therapy after

provoked VTE or longer after unprovoked (idiopathic) VTE3

ACCP, American College of Chest Physicians; VKA, vitamin K antagonist

1. Zhu T et al. Arterioscler Thromb Vasc Biol 2009; 2. Gensini GF et al. Semin Thromb Hemost 1997;
3. Kearon C et al. Chest 2012
The Bad News Is …………
 VTE: A Silent Killer, Often Detected Too Late

 ~ 80% of cases of DVT are clinically silent

 < 50% of all cases of fatal PE are detected prior to death

At least 70% of fatal PE

detected post-mortem
30% was not suspected
or diagnosed1,2

At autopsy,
approximately 63% of
DVT cases were
70% clinically undiagnosed2

1. Stein PD, et al. Chest 1995;110:978-981.
2. Sandler DA, et al. J R Soc Med 1989;82:203-205.
A post-mortem
Goldhaber SZ, et al. Am. J. Med. 1982; 73: 822-826 DVT
Lensing AWA, et al. Lancet 1999; 353: 479-485
Lethen H, et al. Am. J. Cardiology 1997; 80: 1066-1069
Giradr P, et al. Chest 1999; 116: 903-908
The diagnosis of symptomatic VTE is
often delayed
Patients enrolled in the MASTER registry (N=2,047)
>10 days from onset

25
of symptoms (%)
Diagnosis of VTE

20
15
10
5 23% 16%
0
DVT PE
 DVT: multiple signs or symptoms, pain and previous VTE are associated
with earlier diagnosis
 PE: only multiple signs or symptoms and transient risk factors are
associated with an earlier diagnosis

Agnelli G et al. Thromb Res 2008; Ageno W et al. Thromb Res 2008
What Is The Situation Now ?
VTE is a leading cause of death worldwide
VTE is estimated to cause >500,000 deaths
Europe every year1

An estimated
300,000
VTE-related
deaths occur in
the US VTE is estimated to cause at least
each year2
3 million deaths a year worldwide
1. Cohen AT et al. Thromb Haemost 2007; 2. Heit JA et al. Blood 2005
Incidence of VTE increases with age
 A population-based study shows Incidence rates of DVT and PE in
the incidence rate of VTE patients treated in short-stay hospitals1
increases exponentially 350
with age1 DVT

Rate per 100,000 patients

300
 Risk increases by a factor of PE
~200 between the ages of 20 250
and 80 years1
200
 Patients aged 60 years or
over represent ~65% of those 150
with PE2
100

50

Age

1. Anderson FA, Jr et al. Arch Intern Med 1991; 2. Torbicki A et al. Eur Heart J 2008
VTE is a major cause of death in Europe
600,000 Deaths resulting from VTE
543,454
500,000
Number of deaths per annum

400,000

300,000
Combined deaths
209,926
200,000 Transport accident

Prostate cancer
100,000
Breast cancer
AIDS
0

AIDS, acquired immune deficiency syndrome

Cohen AT et al. Thromb Haemost 2007
Healthcare burden of VTE
 US
 Estimated total costs to healthcare system of managing VTE:
>$1.5 billion per year1
 Estimated cost of managing:
─ An initial episode of DVT: $10,8042
─ An initial PE event: $16,6442
─ Recurrent VTE: $11,862 (DVT) and $14,722 (PE)2
─ Treatment of PTS: additional annual cost of approximately $11,7001
 UK
 Total costs of managing VTE: ~£640 million3
 ~20% of costs attributable to the chronic care costs of PTS3

1. Dobesh PP. Pharmacotherapy 2009; 2. Spyropoulos AC, Lin J. J Manag Care Pharm 2007; 3. House of
Commons Health Committee Second Report of Session 2004–2005
Total hospitalization costs for recurrent DVT are
~20% higher compared with first DVT

p=0.38
N=14,108
16000
p=0.006 $14,146 $14,722
14000
Total average cost
per patient (US$)

$11,862
12000
$9,805
10000
8000
6000
4000
2000 First Recurrent First Recurrent
DVT DVT PE PE
0

 No significant difference in hospitalization costs for recurrent versus first PE

Spyropoulos AC, Lin J. J Manag Care Pharm 2007

VTE : A Western Disease ?
Data From Asia
VTE Incidence : Asian vs Caucasian

Cohen A, et al. Thromb Res 2012

In Asia ………………

• It is becoming evidence that Asians are at

much higher risk of VTE than was
supposed.

Cohen A, et al. Thromb Res 2012

What About Indonesia ?
Data From Indonesia – From 13 Patients
Undergoing Major Orthopedic Surgery

• Asymptomatic VTE was found in

69,2% patients at hospital discharge
• Symptomatic VTE was found in 23,1%
patients
• No thromboprophylaxis were given to
patients

Med J Indones 2009;18:249-56

What can be done ?
General rules

• use short-term anticoagulation during periods of high risk

(eg, hospitalization for acute medical illness, following major
surgery)
• LMWH and Fondaparinux are all reasonable options.
• The choice depends on whether the patient is hospitalized or
outpatient, cost, availability, and patient-specific factors.
• Mechanical prophylaxis is an option for hospitalized patients
for whom the risk of bleeding is considered high

Kenneth AB, Uptodate 2017

Inpatient Prophylactic Anticoagulation

• Patients with critically ill, cancer and reduced mobility,

suggest using an anticoagulant rather than mechanical
prophylaxis or no anticoagulation
• Studies have uniformly found a benefit from LMWH or
Fondaparinux in VTE prevention for patients at high VTE risk
• Hospitalized cancer patients without immobility may also
benefit from pharmacologic thromboprophylaxis based on
their increased VTE risk due to malignancy alone.

Kenneth AB, Uptodate 2017

Outpatient Prophylactic Anticoagulation

• For most ambulatory outpatients with cancer, suggest that

routine anticoagulation not be used.
• Prophylactic anticoagulation may be appropriate in
condition with :
• Multiple myeloma – treated with thalidomide or
lenalidomide-containing regimens
• High Khorana score – Prophylactic anticoagulation could be
considered for selected higher-risk ambulatory patients (eg,
those with a Khorana score ≥3).
• History of unprovoked VTE – with a prior history of
unprovoked VTE unrelated to their tumor who are not
already on chronic anticoagulation.

Kenneth AB, Uptodate 2017

Doses of LMWH, UFH and Fondaparinux for VTE
prevention in adults with cancer

Kenneth AB, Uptodate 2017

DVT treatment:

The initial treatment objective:

 To prevent thrombus extention.

 To prevent PE.
 To prevent early & late recurrence of VTE.
 To prevent or minimize the risk of the post
thrombotic syndrome (PTS).
The long-term treatment objective:

 To complete of the acute episode of VTE.

 To prevent of new episode VTE.

Kearon C, et al. Chest 2012; 133:454s-545s.

2016 Updated VTE Guidance Statements
Anticoagulant therapy remains the
mainstay of DVT treatment1

1. Streiff et al. J Thromb Thrombolysis (2016) 41:32–67

VTE treatment consideration

 Cancer-associated vs No cancer
 Provoked vs Unprovoked
 Proximal vs Distal DVT
 Supervicial vs deep vein thrombosis
 Upper extremity vs Leg DVT

Choice of Anticoagulant

Kearon C, et al. Chest. 2012; 141(2)(Suppl):e419S–e494S

Properties of an ideal anticoagulant
Oral Food/Drug Predictable No routine Fixed No risk
interactions response monitoring dosing of HIT
Ideal      

LMWH    

UFH 
Fondaparinux     

VKAs  

Rivaroxaban      

Dabigatran      

Apixaban      

Eerenberg ES et al. Circulation. 2011;124:1573-1579.

VTE Treatment

In patients with acute DVT of the leg treated with VKA therapy,
we recommend initial treatment with parenteral
anticoagulation (LMWH, fondaparinux, UFH) over no such
initial treatment (Grade 1B).

Kearon C et al. Chest 2012; 133:454s-545s.

UFH
LMWH
Fondaparinux
Initial treatment
Long term treatment
Extended treatment
5-10 At least 3 months indefinite
days
Kearon C, et al. Chest. 2012; 141(2)(Suppl):e419S–e494S
 Role of Fondaparinux
for the treatment of VTE
 AT Enhancers: Mechanism of Action
Unfractionated Heparin (UFH)
•Inhibits Thrombin (IIa), IXa, Xa, XIa
and XIIa
•Therapeutic action: Xa, thrombin

Low Molecular Weight Heparin

(LMWH)
•Predominantly inhibit factor Xa

Fondaparinux
•Purely inhibits factor Xa

Am J Health-Syst Pharm. 2002.

 Heparin, LMWH, Fondaparinux

• Antithrombin (AT) inhibits factor Xa

and thrombin
• UFH, LMWH, and Fondaparinux
bind to AT, causing a
conformational change.
• Activated complex increases
Factor Xa inactivation by several
fold over endogenous AT
• Longer chain polysaccharides:AT
complexes irreversibly binds to an
inhibits the active site of thrombin

Am J Health-Syst Pharm. 2002.

 Heparin, LMWH, Fondaparinux
Heparin LMWH (enoxaparin) Fondaparinux
Source Endogenous Derived from UFH Synthetic
Polysaccharide (small molecule)
(bovine and porcine)
Chain Length ~45 saccharide units ~15 saccharide units 5 saccharide units
Route IV, Subcutaneous Subcutaneous, IV Subcutaneous, IV
Time to Cmax SC: 20-30 min SC: 3-4.5 hours SC: 2-3 hours
(erratic absorption) (predictable absorption) (predictable absorption)
Half Life 0.5 to 2 hours ~4 to 7 hours 15-17 hours
(Daily to BID dosing) (Daily SC dosing)
Dosing in Renal No adjustment needed; Adjust doses; Adjust doses;
Impairment Preferred agent for Not recommended for Contraindicated when
ESRD/dialysis patients dialysis patients CrCl<30 mL/min
Laboratory aPTT, ACT, Not routinely Not routinely
monitoring anti-factor Xa recommended; optional recommended; optional
Platelet monitoring anti-factor Xa assay anti-factor Xa assay
Platelet monitoring

Am J Health-Syst Pharm. 2002.

Heparin, LMWH, Fondaparinux
Heparin LMWH (enoxaparin) Fondaparinux
Additional Proteins, macrophages, Less protein, osteoblast, No additional binding
Binding platelets, osteoblasts platelet binding than UFH
Bleeding Higher than LMWHs 0-13% Any bleeding 2-3 % Minor bleeding
Incidence (rates vary based on 0-4% Major bleeding 1-3% Major bleeding
indication and patient)
Incidence of 1-5% HIT <1%HIT 0% HIT
thrombocytopenia 30% Non-HIT 3-5% Non-HIT 3% Non-HIT
Pregnancy Preferred anticoagulant Preferred anticoagulant Category B
(not routinely used)
Body Weight Caution with obese Caution in extremes of Treatment dose tiered
Initial doses often weight according to body
capped, and/or adjusted (<45kg and >~180kg) weight.
body weights are used Actual body weight used
for weight-based doses
Reversal Protamine (100%) Protamine (~60 to 75%) No specific reversal
agent available

Am J Health-Syst Pharm. 2002.

FONDAPARINUX FOR PREVENTION OF VTE
ARixtra for ThromboEmbolism prevention in a Medical
Indications Study (ARTEMIS)

Objective:
 To determine the efficacy and safety of the anticoagulant fondaparinux
in older acute medical inpatients at moderate to high risk of venous
thromboembolism

Method:
ARTEMIS, a randomized, double-blind, placebo-controlled study, was
carried out at 35 centers in 8 countries (Australia, Canada, Denmark,
France, The Netherlands, Poland, the United Kingdom, and the United
States) on 849 patients aged ≥ 60 years. About 36% of patients had
been hospitalized with congestive heart failure (NYHA class III/IV),
44% had acute respiratory disease, and 50% had acute infection or
inflammatory disease. All patients required ≥ 4 days of bed rest
Study Design

n = 425
Fondaparinux 2.5 mg, SC, Once-daily
n=849
from 35 R Double-blind randomized placebo controlled trial
centers of 8
countries
Placebo
n = 414
*

6 - 14 Days

Primary Efficacy outcome was venous thromboembolism Secondary outcomes were bleeding and death. Patient
detected by routine bilateral venography along with were followed up at one month
symptomatic venous thromboembolism up to day 15
Result

1.80% 1.67%
12.0%
n=84
10.5% 1.60%
n=84
9
9

10.0% 46.7% 1.40% 58.1%

Incidence of Fatal PE (%)

Incidence of Fatal VTE (%)

RRR*
8.0% P=0.02 1.20%
9
1.00%
6.0% 5.6%
0.80% 0.70%
4.0% 0.60%
2.0% 0.40%
0.20%
0.0%
Placebo Arixtra ™ 0.00%
Placebo Arixtra™
n=323** 2.5 mg/day n=420 2.5 mg/day
n=321** n=429

Adapted from Cohen AT et al. The ARTEMIS™ investigator. Efficacy and safety of fondaparinux for the
prevention of venous thromboembolism in older acute medical patients; randomized placebo
controlled trial. BMJ 2006; 332; 325-29
Fondaparinux treatment of VTE

Background

Current standard initial

therapy in DVT is body
weight adjusted LMWH s.c.

Objective
To evaluate whether
fondaparinux has efficacy
and safety similar to those
of enoxaparin in patients
with deep venous
thrombosis.

N Engl J Med 2003;349:1695-702.

Ann Intern Med. 2004;140:867-873.
 Study Design
MATISSE DVT

patients  5 days Fondaparinux* 7.5 mg once-daily + VKA (INR

with DVT 2-3)
5 mg if body weight < 50 kg
(N=2.205) R
from 154 Double- 10 mg if body weight > 100 kg

centres of 23 blind
countries
 5 days SC enoxaparin (1 mg/kg, bid) + VKA (INR
2-3)

90 ± 7
Days

Primary Efficacy Outcome (3 months) Principal Safety Outcome (initial treatment)

•Recurrent symptomatic non-fatal PE or DVT • Major bleed
•Fatal PE / unexplained death • Clinically relevant non-major bleed
 Study Design
MATISSE PE
 5 days Fondaparinux* 7.5 mg once-daily + VKA (INR 2-3)
patients with
PE + DVT
(N=2.213) R Open-Label
From 214
centres of 20
countries  5 days IV UFH (aPTT 1.5-2.5) + VKA (INR 2-3)

* 5 mg if body weight < 50 kg

90 ± 7 Days
10 mg if body weight > 100 kg

Primary Efficacy Outcome (3 months) Principal Safety Outcome (initial treatment)

•Recurrent symptomatic non-fatal PE or DVT • Major bleed
•Fatal PE / unexplained death • Clinically relevant non-major bleed
The MATISSE- DVT
Treatment VTE ( DVT & PE )

Once-daily FONDAPARINUX ... With similar incidence of

was as effective as twice-daily major bleeding
enoxaparin for the treatment of DVT
Ann Intern Med. 2004;140:867-873.
 The MATISSE- PE
treatment VTE ( DVT & PE )

Once-daily FONDAPARINUX With similar incidence of major

was as effective as a bolus plus bleeding
continuous infusion of UFH in the
treatment of PE
 Parenteral Anticoagulants Dosing

UFH
80 U/kg IV bolus followed by 18 U/kg/hr
5000U IV bolus followed by 1000 U/hr

Enoxaparin
1 mg/kg SQ Q12H
1.5 mg/kg SQ QD
CrCl < 30: 1 mg/kg SQ Q24H

Fondaparinux
< 50kg: 5mg SQ QD
50-100kg: 7.5mg SQ QD
> 100kg: 10mg SQ QD

Alwquwaizini M, et al. Curr Emerg Hosp Med Rep (2013) 1:83–97

 Oral Anticoagulants Therapy

Vitamin K Antagonist - warfarin

Started on day 1 or 2 of parenteral anticoagulation
Maintain overlap for at least 5 days.
INR goal = 2-3

OR

NOAC
Rivaroxaban, Apixaban, Edoxaban, Dabigatran
 Contraindication of anticoagulation

Absolute
 Active bleeding
 Recent hemorrhagic CVA
 History of heparin sensitivity
 History of Heparin-induced thrombocytopenia (HIT)
 Underlying bleeding diathesis
 Intracranial pathology e.g subdural hematoma
• Relative
 Active peptic ulcer disease
 Recent major trauma
Kakkos SK et al.2014.Eur j Vasc Endovasc Surg;48(5):565-575
Patient populations potentially
at higher risk of bleeding

 Elderly
 Patients with renal impairment
 Patients with hepatic impairment
 Patients receiving certain co-medications
 Genetic
 Duration of use
 Drug-drug interaction

Alexander Turpie et al. J Thromb Haemost 2012;108

Contraindications to
outpatient treatment of VTE

Active or high risk of bleeding

 Recent surgery (within 7 days)

 Cardiopulmonary instability
 Severe symptomatic venous obstruction
 High risk pulmonary embolism*
 Thrombocytopenia (platelets \50,000/lL)
 Other medical or surgical condition requiring inpatient management
 Medical non-compliance
 Geographical or telephone inaccessibility
 Poor hepatic function (International Normalized Ratio (INR) C 1.5)
 Unstable renal function (e.g. rising serum creatinine)
 Poor home health care support environment

* High risk PE is characterized by systolic blood pressure \90 mmHg or a systolic blood pressure drop of
C40 mmHg for [15 min not due to an arrhythmia, hypovolemia or sepsis

J Thromb Thrombolysis (2016) 41:32–67

Summary

 Anticoagulation options for acute VTE include unfractionated

heparin, low molecular weight heparin, fondaparinux and the
direct oral anticoagulants (DOACs).

 Various clinical scenarios determine the choice of

anticoagulant therapy.

 Fondaparinux has been proven to be at least as safe and

effective as treatment of DVT and pulmonary embolism (PE)
as LMWH and UFH.
 The MATISSE DVT trial confirmed that fondaparinux and
enoxaparin have similar safety and efficacy for the initial
treatment of DVT.
Overall summary
 VTE is a serious and potentially life-threatening
condition
 VTE is not merely a western disease
 Data from Indonesia showed high rate of VTE,
when patients undergoing major orthopedic
surgery were not given thromboprophylactic.
Also high prevalence of VTE among cancer and
bedridden patients

VTE is a REAL DISEASE