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Nature of Venous Thromboembolism

Dr. Mika Lumbantobing, SpPD-KHOM


Sub Bag Hematologi-Onkologi Medik
Bagian Ilmu Penyakit Dalam
FK UNDIP RS Dr. Kariadi
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:
DVT Thrombus
PE
As the venous
VTE is a serious health clot grows, it
issue2 extends along
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
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
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
Total hospitalization costs for recurrent DVT are
~20% higher compared with first DVT

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

$11,862

$9,805

First Recurrent First Recurrent


DVT DVT PE PE

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
DVT Rates in Asia
Incidence is perceived as
low in Asian populations,
1
1988
2. but has increased
7 in some patient groups b
~ 6 fold in the past decad
19.3
2
1999

0 5 10 15 20 25
Incidence of DVT per 10,000
hospital patients
1
Woo KS, et all. Singapore Med J.1988 Aug:Aug29(4)357-359
2
Lee LH. New Insights and unresolved issue in the prevention of DVT/VTE in Asia. March 2001.Phuket.Thailand
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


PREVALENCE OF CLINICAL DVT BASED ON RISK
FACTORS (Dr Sardjito Hospital Data) 2011-2012

40

35

30

25

20

15

10

0 DVT
No DVT

Wulansih et al 2012 presented on KOPAPDI XII


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

*New York Heart Association classification III and IV


Risk factors from Geerts WH et al. Chest 2004
Virchows triad revisited
Malignancy Venous disorders
Pregnancy and Venous valvular
peripartum period damage
Oestrogen therapy Trauma or surgery
Inflammatory bowel disease Indwelling catheters
Sepsis
Thrombophilia Hypercoagu Endothelial
lable State Injury

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; Geerts WH et al. Chest 2004; Bennett PC et al. Thromb Haemost 2009
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) VTE 3

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
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
Patients aged 60 years or 200
over represent ~65% of those 150
with PE2
100

50

30 9
40 9
50 9
60 9
70 9
9
20 9
10 9

0
2
3
4
5
6
7
1
0

8
Age

1. Anderson FA, Jr et al. Arch Intern Med 1991; 2. Torbicki A et al. Eur Heart J 2008
The diagnosis of symptomatic VTE is
often delayed
Patients enrolled in the MASTER registry (N=2,047)
>10 days from onset
of symptoms (%)
Diagnosis of VTE

23% 16%

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
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
DVT PROBABILITY : WELLS SCORE SYSTEM
Active cancer (treatment ongoing, within previous 6 +
months, palliative) 1
Paralysis, paresis or recent plaster immobilization of the +
lower extremities 1
Recently bedridden > 3 days, or major surgery within 12 +
weeks requiring 1
general or regional anesthesia
Localized tenderness along the distribution of the deep +
venous system 1
Entire leg swollen +
1
Calf swelling > 3 cm compared to asymptomatic leg +
(measured 10 cm 1
below
0 : tibial
LOWtuberosity)
1Pitting
or 2 edema
: INTERMEDIATE
confined to the symptomatic leg +
3 : HIGH 1
Collateral superficial veins (non-varicose)
Venous Thromboembolism +
Diagnosis & Treatment Guideline. Group Health. 2
PEMERIKSAAN KONFIRMASI DIAGNOSTIK

1. USG Doppler
2. Venografi
3. D-Dimer
APPROACH TO SUSPECTED DVT
Sign &
symptoms

Wells score
probability
test

Low Intermediate High

D-dimer Doppler USG Doppler USG

(+) (-) (+) (-) (+) (-)

Doppler Alternativ DVT D-dimer DVT Venograp


USG e (+) hy
7
diagnosis
days
Doppler
USG
ALTERNATIVE DIAGNOSIS AT LEAST AS LIKELY AS DVT

superficial phlebitis postphlebitic syndrome


cellulitis muscle strain or tear
leg swelling in paralized venous insufficiency
limb
edema due to systemic external venous
cause obstruction
(CHF, cirrhosis) (due to tumor)
lymphangitis or popliteal (Bakers) cyst
lymphedema
hematoma pseudoaneurysm
knee abnormality

Venous Thromboembolism Diagnosis & Treatment Guideline. Group Health. 2


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 symptoms13
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
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 (315% 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


PULMONARY EMBOLISM PROBABILITY :
WELLS SCORE SYSTEM
CLINICAL CHARACTERISTIC SCORE
Previous DVT or PE + 1.5
Heart rate > 100 beats per minute + 1.5
Recent surgery or immobilization + 1.5
Clinical signs of DVT + 3.0
PE judged to be the most likely diagnosis*) + 3.0
Hemoptysis + 1.0
Active cancer (treatment ongoing or within + 1.0
previous 6
months, or palliative)
TOTAL
POINTS
HIGH pretest probability >7
INTERMEDIATE pretest probability 2-6
LOW (PE
tive diagnosis unlikely)
less pretest
likely than probability
PE: myocardial 0-1
infarction, pericarditis, pn
othorax, chest wall pain, congestive heart failure, pleuritis, pericardial t
PERC RULE FOR ASSESSING PE RISK
CLINICAL CHARACTERISTIC MEETS CRITERIA
(YES/NO)
Age < 50 years
Heart rate < 100 beats/minute
O2 saturation on room air >
94%
No prior history of DVT or PE
No recent trauma or surgery
No hemoptysis
No exogenous estrogen
No clinical signs suggesting
rule only applies if all eight criteria are met. Accordin
DVT
study, there is less than 2% risk of PE in this patient
PEMERIKSAAN KONFIRMASI DIAGNOSTIK

1. CT pulmonary angiography
2. V/Q (ventilation-perfusion) lung scan
3. D-Dimer
APPROACH
Clinical symptoms
TO
SUSPECTE Wells probability test
D PE
Low Intermediate High

PERC CT angiography CT angiography


(+) (+) (-) (-) (+)
Alternativ
e PE D-dimer D-dimer PE
diagnosis Therapy therapy
(+) (+) (-)
Probabilitas Probabilitas Probabilitas tinggi
lemah tinggi
Bila pemeriksaan
belum selesai US dupleks +
Alternative kompresi pada
diagnosis dalam 4 jam
Therapy tungkai
(+) (-)
VTE Resiko PE rendah
ALTERNATIVE DIAGNOSIS LESS LIKELY THAN PE

myocardial infarction chest wall pain


pericarditis congestive heart failure
pneumonia pleuritis
pneumothorax pericardial tamponade

Venous Thromboembolism Diagnosis & Treatment Guideline. Group Health. 2


HASIL POSITIF PALSU PEMERIKSAAN D-DIMER

Usia > 50 Trauma


tahun
Wanita hamil Penyakit liver
Kanker aktif Pembedahan yang baru dilakukan
Infeksi Imobilitas lama/permanen
Penyakit DIC (disseminated intravascular
jantung coagulation)
Imobilisasi
Potential complications
and goal of treatment

DVT complications:1,2
PE
Damage to valves in the deep veins
Venous reflux
Post-thrombotic syndrome (PTS)
Goal of treatment
Prevent embolization to the lungs
Prevent extension into larger veins
Prevent recurrence
Avoid the chronic complications

1. Kearon C. Circulation 2003; 2. Ginsberg JS, et al. Arch Intern Med 2000
Chronic thromboembolic
pulmonary hypertension
Serious complication of PE
Up to 5% of patients with PE are
reported to develop chronic
thromboembolic pulmonary
hypertension (CTPH)1
Initial phase of disease often
asymptomatic and followed by
progressive dyspnoea and
hypoxaemia2
Right heart failure can frequently
occur2
Progressive condition associated
with mortality rates of 420%2
Chest axial with a clot on the left (patients right side); a
tongue of white contrast can be seen extending into the
clot (PE)
Reproduced with permission from Professor AT Cohen
1. Kearon C. Circulation 2003; 2. Torbicki A et al. Eur Heart J 2008
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
Conclusion
VTE incidence year by year to be increased
DVT diagnosis starting from clinical symptoms, Wells probability
test, and confirmed diagnosis
PE diagnosis starting from clinical symptoms, Wells probability
test, and confirmed diagnosis
VTE is not merely a western disease its also rise number in Asia
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


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