Dr. dr.

Ikhwan Rinaldi, SpPD, K-HOM

Tempat Tanggal lahir: Jakarta, 24 Agustus 1973
Pendidikan :
S1, FKUI 1998
S2, PPDS1 Dept. Ilmu PD FKUI/ RSCM 2005
Konsultan HOM, Dept. IPD FKUI / RSCM 2014
Doktor bidang ilmu kedokteran

Pekerjaan :
Staf Divisi Hematologi Onkologi Medik Dept.
IPD FKUI/RSCM
ARTERIAL - VENOUS THROMBO EMBOLY:
PERIPHERAL ARTERIOVASCULAR DISEASE
& PULMONARY EMBOLY

Department of Internal Medicine

Cipto Mangunkusumo General Hospital - FKUI
 WHAT DAMAGE CAN A CLOT DO ?
Stroke
Thromboembolism in
atrial fibrillation

Coronary artery
Plaque rupture
unstable angina Pulmonary embolism
Myocardial infarction
(MI) / heart attack
(PE)

Deep vein
thrombosis (DVT)

PAD
 PATHOPHYSIOLOGY & MECHANISM OF
THROMBOSIS FORMATION
Triad of Virchow

Abnormality of Abnormality of Abnormality of

Vessel wall Blood flow The blood

Plaque Venous Shears stress Venous Platelet Hyper

ruptures Hypotonia Shears rate stasis hyper coagulability state
Turbulence aggregation Thrombophilic state
Fibrinolysis deficient
Thrombocytosis

Thrombosis
Arterial Venous Arterial Venous Arterial
Thrombosis Thrombosis Thrombosis Thrombosis

Endothelial Hyper Venous

Perturbation viscosity Thrombosis
Hyper
fibrinogenemia
TYPICAL OVERLAPP OS VASCULAR DISEASE
Common Pathophysiology: VTE and Arterial Thrombus

Atherosclerosis

Piazza, Goldhaber. Circulation 2010;121: 2146

Th.: thalidomide,lenalidomide ; TAM;raloxine; EPO
 VTE Risk Factors:
Numerous and common
Exposing Factors :
Table 3 : VTE risk factors Surgery1
include:
Protein C deficiency 1 Trauma2
Protein S deficiency1 Malignant disease1
Antithrombin deficiency1 Acute MI3,4
Activated protein C resistance1 Acute infection3,4
Prothrombin G20210A1 Acute heart failure2
High factor VIII concentration1 Acute respiratory failure3,4
Hyperhomocysteinemia1 Antiphospholipid syndrome1
Age1,8 Stroke2
Congestive heart failure2
Hypertension5
Lack of identification of the Myeloproliferative disorders1,8

patients overall risk profile Nephrotic syndrome2,8

Inflammatory bowel disease2,8
may lead to unexpected events.2,7 Obesity2
Varicose veins2
1. Rosendaal FR. Semin Hematol 1997;34:17187 Immobility1
2. Clagett GP, et al. Chest 1998;114 Suppl 5:53160S Long-distance travel6
3. Fraisse F, et al. Am J Respir Crit Care Med 2000;161:110914 Pregnancy and puerperium1
4. Samama MM, et al. N Engl J Med 1999;341:793800 Previous venous thrombosis1,8
5. Goldhaber SZ, et al. JAMA 1997;277:6425
6. Cruickshank JM, et al. Lancet 1988; 2:4978 Cancer therapy
7. Hirsh J, Hoak J. Circulation1996; 93:221245
CVP 8
8. ACCP 8th
ARTERIAL ANATOMY :
Classified into three catagories:
1. Large or elastic arteries ( ec : aorta and its
proximal branches )
2. Medium size or musc.arteries ( ec: just distal
to elastic art.: common femoral, axillary &
carotid )
3. Small arteries ( < 2 mm )

PAD : is a disease in medium to small art.

 PATHOPHYSIOLOGY:
Basic process of PAD
1. Athereosclerosis 5. Inflamation
2. Aneurysme 6. Trauma
3. Embolism 7. Vasospasm
4. Thrombosis 8. Arteriovenous fistula
MOST of PAD cause by atherosclerosis & thrombosis
ANATOMIC & RESPONSE TO VASCULAR INJURY
Cont. :
 Peripheral Arterial Disease ( PAD )
Define as :
Any disease of the arteries out side of the
cranium, the coronary circulation and aortic arch
Conventional :
Arteriosclerotic disease involving the arteries
supplying circulation to the lower extremities

Is a marker of systemic atherosclerosis disease

Prevalence 12% in adult population; men >
women
Involving : Lower extr. ,
Art. Mesenteric ,
Aortic Abdominal & Renal arteries
The clinical symptoms :
1.May vary from intermitten claudicatio, atypical
leg pain, rest pain, ischemic ulcer, or gangrene to
NO symptoms at all.
Symptoms : results from arterial stenosis or
occlusion reduction distal blood
6P : pain, pulse less , pallor, poikilothermia,
parasthesias, and paralysis
(- or (-) depend on severity and times of the
disease )
Continue :
If base on clinical peripheral arterial
palpation under or over diagnosed
Need other diagnostic tools to reveals
with: accurate detection & local area with
the reduced blood flow
a. Arterial Doppler signal
b. ABI ( more accurate )
c. TPI ( Toe pressure index < 40 )
 Ankle Brachial Index (ABI)
By ultra sound doppler
( N ) : 0,91- 1,3
Mild obstruction: 0,71-0,9
Mod. obstruction 0,41 0,7
Severe obstruction < 0,4
Most pts with claudicatio intermt. : 0,5
0,9
ABI > 0,5 : ABI < 0,5 : Mortality rate 7yr
24% compare to 69 %
TANDA ISKEMIA :
Iskemi akut
Ekstremitas pucat pada posisi istirahat.
Perubahan temperatur dengan garis batas yang sangat jelas.
Nyeri dan parastesia
Sensasi menurun
Sianotik dengan batas tegas dan jika ditekan menjadi pucat.
Parese sampai paralisis
Muskulus spastik dan keras.

Iskemi kronik
Muskulatur atrofi
Bulu kaki rontok
Kuku hipertrofi dan pertumbuhan lambat
Nadi lemah
Temperatur
Vena superfisial menciut
Pengisian kapiler lambat
Pucat lebih lama dengan elevasi
Rubor
Skin gangrene in left hand and functional salvageable Th/ Amputation
ACC/AHA2005 ; TASCII,
CLINICAL STAGE :
 TABLE 3 : CLASSIFICATION OF ACUTE LIMB
ISCHEMIA (ALI)
Catagory Description/Prognosis LOSS Doppler Test
Sensory Muscle Arterial Venous
I. Viable Not immediately None None Audible Audible
threatened
II Threatened
a. Marginally Salvageable if None or None In audible Audible
promptly treated min.(toes)
b. Immediately Salvageable if More than Inaudible Audible
imm.revascularization Mild,mod
toes, assc.
rest pain
III.Irreversible Major tissue Profound Prof.para Inaudible Inaudible
loss,permanent nerve Anesth. Lysis(rigor)
damaged

Rutherford RB ,Baker JD,Ernst C,et al. J Vasc Surg 1997

Shiny skin, dystrophic nail changes and Atherosclerosis with severe,
dependent rubor associated with PAD occlusive disease limited to the
the patient's right foot. aorta and common iliac arteries.
Peripheral Arterial Disease ( PAD )
 DIAGNOSIS ARTERIAL THROMBOSIS:
1. Anamnesis dan klinis
2. Laboratorium hemostasis, agregasi trombosit
dan indikator metabolik lain
3. Ultra Sound Doppler
4. MRA ( Magnetic Radiologic Angiografi)
5. CTA ( Computerized Tomography Arteriography
6. Arteriografi
Bedakan : arteriosklerosis, trombus,
emboli atau KOMBINASI?
 Arterial duplex Imaging Combines :
B-mode USG with pulsed-wave Doppler
INFORMATION: hemodynamic & anatomic
peripheral arteries
Arteriography ( + contrast ) : RESERVED in
whom a decision has been made for
revascularization BE IT PERCUTANEOUS /
OPEN revascularization
MRA :
non invasive ; need NOT IV contrast ;
IMPROVED with Gadolinium enhanced MRA
 CAUSES ART. OCCLUSSION AND IC :
ACUTE OCCLUSSION CHRONIC OCCL.

TASCII
 DIFFERENTIAL DIAGNOSIS:
ACUTE OCCLUSSION CHRONIC OCCLUSSION
Acute Limb Ischemia : PAD
Arteria Embolism
Arterial Thrombosis Buerger Disease
Aneurysm of the
Blue Toe Syndr Popliteal art.
/Atheroembolism
Peripheral Art. AneurysmPopliteal Entrap Syndr.
Vasospastic Disorder (
Raynauds disease )
Thoracic Outlet Syndr.
APROACH & DIAGNOSIS :

ACC/AHA 2005; TASCII

TASCII
CLI
ACC/AHA2005 ;TASCII
ALI :

ACC/AHA2005 ; TASCII
 PAD MANAGEMENT :
Non pharmacologic :
1. Smoking cessation
2. Exercise therapy
Pharmacologic :
Thrombolytic Hyperhomocyteinemia
Antiplatelet therapy Hypertension
Diabetes Dislipidemia Anticoagulant :
UFH IV 80/kg BW or 5000U IV INFUS 18 U/kg/hr
; aPTT : 0,3 0, 7 IU/ml a Xa activity /1,52 X C OR
FIXED dose : IV 333 u / kg 250 U /kg bid
OR LMWH target aXA activity 0,3 0,7
 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: 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
Table II : Classical risk factors for
venousthromboembolism.
Strong risk factors (odds ratio >10)
trauma or fractures
major orthopaedic surgery
oncological surgery

Moderate risk factors (odds ratio 2-9)

non-oncological surgery
oral contraceptives and hormone replacement therapy
pregnancy and puerperium
hypercoagulability
previous venous thromboembolism

Weak risk factors (odds ratio <2)

age
bed rest (> 3 days)
prolonged travel
metabolic syndrome
air pollution
( Cont. ) :

Approximately 30% of apparently

isolated episodes of PE are
associated with silent DVT,

and in patients presenting with

symptoms of DVT, the frequency of
silent PE ranges from 40 to 50%.

Turkstra F, Kuijer PM, van Beek EJ, et al.. Ann Intern Med 1997;126:775-81.
Meignan M, Rosso J, Gauthier H, et al.. Arch Intern Med 2000;160:159-64.
Dobromirski M, Chen AT..Blood. 2012;120: 1562-9
 Pulmonary Embolism
Diagnosis
Requires clinical suspicion!
High clinical suspicion demands immediate evaluation
Recognize Virchows Triad in every patient. Remember,
risk of acute death from PE 30% if untreated
Sign and symptoms neither sensitive nor specific.
Only 20% of patients with suspected PE will be found by
objective examinations to have PE

Classic triad of dyspnea, pleuritic chest pain and

hemoptysis

Clinical presentation depends on clot burden & underlying

health status of patient. Dyspnea common but nonspecific.
Massive or submassive PE cause pulmonary apoplexy or
sudden syncope or cardiac arrest without much dyspnea
 Sistim Sirkulasi Arteri Vena Pulmonalis
Dan Emboli Paru

Pada EP, 30% pasien tidak diketahui/tak terdeteksi adanya faktor provoking
Hipoksemia tipikal pada EP AKUT is, TETAPI 40% pasien O2 SATURASI normal dan 20%
normal alveolar-arterial O2 gradien
 Differential diagnosis of PE
Acute Myocardial Infarction
Aortic Dissection
Muskuloskeletal disorders
Obstructive pulmonary disease
Pericardial disease
Pneumonia
Pneumothorax
 SIGN & SYMPTOMS:
Signs of right ventricular
dysfunction and pulmonary
hypertension, such as a loud
P2, right ventricular heave, and
elevated neck veins.

Auscultation to detect a loud P2

is best done with the diaphragm
of the stethoscope placed over
the pulmonic area. P2 should be
considered abnormally loud if it
is louder than A2 in the
pulmonic area or if P2 is heard
in the vicinity of the mitral valve.

The presence of a heave is best

appreciated by pressing the
base of the hand firmly over the
right ventricular area while
keeping the fingertips off the left
ventricular area
 Predicting Pre-test probability for PE

Clinical signs and Hemoptysis 1.0

symptoms of DVT 3 Cancer (treatment
Heart rate < 100 / minute
1.5
on-going or within
Immobilization (for > 3 6 months, or
consecutive days) 1.5 palliative) 1.0
Surgery in the previous 4 PE as likely or
weeks 1.5
more likely than
other diagnosis
3.0
Low Probability <2.0 Moderate Probabilty : 2-6.0
High Probability > 6.0
Table 5:Geneva & Wells Prediction Rules for Pulmonary Embolism
PULMONARY EMBOLY :
D/: Pulmonary Angiography (BAKU EMAS)
NB: filling deffect, amputation
Q/C Lung
MDCT : Sn 83%, Sp 96%
MRI: low sensitivity
ECHO. :
Pulmonal HT
Trombus RV
NPV 40 - 50 %

Gold standard
Invasive
Contrast dye
Availability
Karakteristik Klinis Pasien EP di Emergensi Unit

ESC, guideline 2014. Pollack, et al.2011

DIAGNOSTIC APROACH
ECG

ECG:
 Wanita , 40 thn KU: pleuritic chest pain
S1Q3T3; prominent S lead I, gel.Q & inverted T lead III, ST,
T inverted: leads V1 - V3, RBBB, defleksi amplitudo rendah
TREATMENT APPROACH :NT
ALGORITHM
 TYPES AND AVAILABLE
ANTICOAGULANT / ANTITHROMBOTICS DRUGS

ANTIPLATELETS ANTICOAGULANT THROMBOLYTIC

ORAL PARENTERAL ORAL PARENTERAL PARENTERAL

Aspirin GPIIb/IIIa Coumarin Heparin
Dypiridamol Antagonist: (Warfarin) LMWH Streptokinase
Clopidogrel Abcicimab Melagatran Hirudin Urokinase
Cilostazol Rivaroxaban Argatroban t - PA
Dabigatran Fondaparinux
Apixaban Idaparinux
Edoxaban
 ANTICOAGULANT
Table IV : TYPE LMWH :
N LMWH Merek Cara produksi Approved RatioAnti
o market Xa :IIa
1. Ardeparin Normiflo Depolimerisasi oksidatif H202 USA 1,9
sodium
2. Certoparin Sandopari Deaminative cleavage Jerman
sodium n dengan isoamilnitrit
3. Dalteparin Fragmin Deamiratine cleavage dengan USA,Japan, 2,7
sodium nitrous acid UK,Jerma
n
4. Enoxaparin Lovenox Eliminating cleavage ester USA,Jerman, 3,8
sodium benzil heparin dengan Spanyol
terapi alkaline
5. Nadroparin Fraxiparin Deaminative cleavage Perancis,Jer 3,6
sodium dengan nitrous acid man
6. Parnaparin Fluxum Depolimerisasi oksidatif Itali >3
sodium dengan Cu dan H202
7. Reviparin Clivarin Depolimerisasi cleavage Canada 3,5
sodium dengan nitrous acid ,Jerman
8. Tinzaparin Innohep Eliminating cleavage dengan Jerman, 1,9
sodium heparinase Denmark,
USA
MECHANISM OF ACTION (1)

76
 Targets for new-generation antithrombotic
agents in the coagulation cascade1 (2)
Initiation Tissue factor/VIIa Vitamin K antagonist:
Tecarfarin (Ph II completed)2

X IX
Indirect Factor Xa
inhibitors:
Direct Factor Xa inhibitors: VIIIa Idraparinux
Apixaban (Ph III completed)5,6 IXa (Ph III terminated)3
Rivaroxaban (Ph III completed)7 SSR 126517
Edoxaban (Ph III ongoing)8 Va (withdrawn 2009)4
Betrixaban (Ph II completed)9
Xa AT
Direct thrombin inhibitors:
Propagation Dabigatran etexilate
(Ph III completed)10
Fibrin formation II Thrombin Ximelagatran
(withdrawn 2006)11,12
AZD0837 (Ph II completed)13
Fibrinogen Fibrin
AT= antithrombin; Ph = Phase
1. Adapted from Turpie AG. Eur Heart J 2008;29:15565; 2. Ellis DJ et al. Circulation 2009;120:102935;
3. Bousser MG et al. Lancet 2008;371:31521; 4. NCT00580216; available at www.ClinicalTrials.gov; accessed March
2012; 5. Connolly SJ et al. N Engl J Med 2011;364:80617; 6. Granger CB et al. N Engl J Med 2011;365:98192;
7. Patel MR et al. N Engl J Med 2011;365:88391; 8. NCT00781391; available at www.ClinicalTrials.gov; accessed
March 2012; 9. NCT00742859; available at www.ClinicalTrials.gov; accessed March 2012; 10. Connolly SJ et al. N
Engl J Med 2009;361:113951; 11. Olsson SB et al. Lancet 2003;362:16918; 12. Albers GW et al. JAMA
2005;293:6908; 13. Lip GY et al. Eur Heart J 2009;30:2897907
Disclaimer: Apixaban and Edoxaban are not approved for clinical use in stroke prevention in atrial fibrillation. Rivaroxaban is approved in this indication only in the USA.
Dabigatran etexilate is now approved for clinical use in stroke prevention in atrial fibrillation in certain countries. Please check local prescribing information for further details
Evolving Anticoagulation Strategies

LMWH/Warfarin UFH/Warfarin
Overlapping
Bridge Bridge

LMWH to LMWH to
Switching Dabigatran Edoxaban
(RE-COVER) (HOKUSAI)
(N=8,250)

Oral Rivaroxaban Apixaban

Monotherapy (3 week loading dose) (1 week load)
(EINSTEIN) (AMPLIFY)
Table 1
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