DVT: among Asians: From myth to current data

TROMBOSIS : DIAGNOSIS &
PENATALAKSANAAN
IRZA WAHID
SUBAGIAN HEMATOLOGI & ONKOLOGI MEDIK
FK UNAND / RS DR M DJAMIL PADANG
HEMOSTASIS - DIATESIS HEMORAGIS
- TROMBOSIS
Vaskular
Trombosit
Koagulasi
A. VASKULAR
* Vasokonstriksi
* Aktifasi trombosit
* Aktifasi faktor Koagulasi
B. TROMBOSIT
* Adesi
* Agregasi
* RX pelepasan isi trombosit
 Granula padat : ADP, ATP, Ca, Epinefrin, Norepinefrin,
 Granula alfa : Fibrinogen, vWF, FV, PF 4, bTG,
 Lisosom
: Enzim asam hidrolase
C. SISTIM KOAGULASI VS FIBRINOLISIS
NOMENCLATUR FAKTOR PEMBEKUAN DARAH
I
II
III
IV
V
VI
VII
VIII
IX
X
XI
XII
XIII
-
Fibrinogen
Protrombin
Tissue factor
Ion calsium
Proaccelerin
Proconvertin
Anti hemophilic factor
Plasma tromboplastin component
Stuart factor
Plasma tromboplastin antecedent
Hageman factor
Fibrin stabilizing factor
High moleculer weight kininogen
Pre kalikrein
Jalur
intrinsik
Jalur
Ekstrinsik
XII
VII
Kontak
XIIa
HMWK
XI
Tromboplastin
Jaringan
Ca
XIa
IX
IXa
PF3, VIII, Ca
VIIa
X
Xa
V, PF3, Ca
Protrombin
Trombin
Fibrinogen
Fibrin Monomer
Fibrin Polimer
Solubel
XIII
XIIIa
Ca
Fibrin Polimer
Insoluber
Intrinsik
XIIa, Kalikrein
Plasminogen terikat
Extrinsik
Eksogen
t-PA
Aktifator Plasminogen
Plasmin terikat
Urokinase
Fibrin
FDP
Plasminogen bebas
Plasmin bebas
Fibrinogen
Fc V, Fc VIII
Anti Plasmin
TROMBOSIS
What is thrombosis ?
• Thrombosis is the formation or presence
of a blood clot inside a blood vessel or
cavity of the heart
*
Triad Virchow
 Kelainan dinding pembuluh darah
* kerusakan endotel : hipertensi,
kateterisasi, anoksis , rokok,
RX
ag – ab, hiperkolesterolemia,
hiperhomosisteinemia
 Perubahan aliran darah  kerusakan endotel, perlambatan
 Perubahan daya beku darah : Ggn keseimbangan sisitim
koagulasi dan
fibrinolisiss
Pathophysiology thrombosis
Thrombosis
•
•
Arterial thrombosis (white thrombus)
Venous thrombosis (red thrombus)
HIGH FLOW : ARTERIAL CIRCULATION
Fibrin
White Thrombus
RBCs
Platelets
SLOW FLOW : VENOUS CIRCULATION
Fibrin
RBCs
Red Thrombus
Platelets
Incidence of thrombosis in United
States of America
Disease
US incidence
/100.000
•
•
•
•
•
•
•
•
•
Deep Vein Thrombosis
Pulmonary Embolus
Fatal Pulmonary Emb.
Myocardial Infarction
Fatal MI
Cerebrovascular thromb.
Fatal Cereb. Trhromb.
Total serious thromb. In US
Total deaths from above thrmb.
•
Bick RL, Clin Appl Throm Hemos 3, Suppl 1, 1997
159/100.000
139/100.000
94/100.000
600/100.000
300/100.000
600/100.000
396/100.000
1498/100.000
790/100.000
Total in US /year Definable
cases
reason
398.000
347.000
235.000
1.500.000
750.000
1.500.000
990.000
3.742.000
1.990.000
 80%
 80 %
 80 %
 67 %
 67 %
 30 %
 30 %
 50 %
 50 %
Diagnosis
1. Anamnesis  Riwayat penyakit (Faktor risiko
medis & bedah), Manifestasi klinis
2. Pemeriksaan fisik
3. Pemeriksaan Laboratorium
4. Pemeriksaan lain:
• Venografi (“Golden Standard”)
• USG/ Doppler
• Duplex scan
• Impedance Plethysmography
FAKTOR RISIKO TROMBOSIS ARTERI
Hipertensi, hiperkolesterolemia,
hiperlipoproteinemia, merokok, diabetes melitus,
hiperhomosisteinemia, trombositosis, polisitemia
FAKTOR RISIKO TROMBOSIS VENA
Imobilisasi, operasi, trauma jaringan yang luas,
kehamilan, pil kontrasepsi, defisiensi AT3 / protein C/S
/ Fc XII, PNH
MANIFESTASI KLINIS &
PEMERIKSAAN KLINIS
ARTERI / VENA
ORGAN
ORGAN
•
•
•
•
•
•
•
OTAK
MATA
THT
JANTUNG
PARU
ORGAN VISERAL
EXTREMITAS
DVT >< AIL
Patogenesis, Perjalanan Penyakit,
Komplikasi, Prognosis
DVT
• Dasar
• Perjalanan
penyakit
• Komplikasi akut
• Prognosis
STASIS
AIL
ISKEMIA
Akut
Kronik
(kel. tungkai/tempat lain)
Kronik
Akut
(tromboemboli/trombosis)
PE
Nekrosis  amputasi
Baik / fatal
Fatal lokal / sistemik
DVT >< AIL
Diagnosis: Keluhan dan Tanda
DVT
• Keluhan
(stasis)
utama/awal - edema tungkai
biasanya unilateral
- silent DVT
- nyeri dan keras
AIL
(iskemia)
nyeri:
- tromboemboli: onset akut
- trombotik: pelan-pelan
(intermittent claudication)
• Keluhan & - nyeri
- “6 Ps”: pain, pallor, parestanda
- pitting edema
thesia,paralysis,pulseless- flebitis:inflamasi
ness, poikylothermia
- dilatasi v.superfisial - awal: nyeri & parestesia
- sianosis (ileofemoral) - palpasi denyut arteri -
PEMERIKSAAN LABORATORIUM
• DVT: - D-dimer:
- D-dimer < 500 ng/ml  menyingkirkan DVT
atau PE
- nilai prediktif negatif pada DVT & PE: 98 %
- sensitif tetapi tidak spesifik: pasca bedah,
DIC, infeksi, dll  D-dimer (+)
- metoda ELISA: cepat dan akurat
- Pemeriksaan hemostasis lain: kelainan
dasar DVT ?  trombofilia herediter/didapat ?
(defisiensi AT III, Protein C, APS, dll)
 penentuan lamanya terapi antitrombosis
PENATALAKSANAAN
- MEDIS
- BEDAH
ANTITHROMBOTIC DRUGS:
• ANTIPLATELET DRUGS
• ANTICOAGULANT DRUGS
• THROMBOLYTIC AGENTS
ANTIPLATELET DRUGS
• ASPIRIN
• DIPYRIDAMOL
• CLOPIDOGREL AND TICLOPIDINE
ANTICOAGULANT DRUGS
• WARFARIN
• HEPARIN
• HIRUDIN AND DIRECT THROMBIN INHIBITORS
COMPARATIVE CHARACTERISTICS
OF ANTICOAGULANTS
Oral
administration
Warfarin
Fixed
dosing
Predictive
kinetics
No coagulation
monitoring




Heparin
LMWH
Fast onset
and offset


Dose and administration
• UFH : initial dose: bolus 75-100 u/kgBB
followed by continous infusion
to achieve aPTT between
1.5 to 2.5 times control
• LMWH :1 mg/kgBB or 0.1 ml/10kgBB sc
twice daily
• Fondaparinux : 7.5 mg for 50-100 kgBB
sc daily
Warfarin - Action
• Inhibits the synthesis of (in order of potency)
– Factor II
– Factor X
– Factor VII
– Factor IX
Conversion from Heparin to Warfarin
• May begin concomitantly with heparin therapy
• Heparin should be continued for a minimum of four
days
– Time to peak antithrombotic effect of warfarin is delayed
96 hours (despite INR)
• When INR reaches desired therapeutic range,
discontinue heparin (after a minimum of four days)
THROMBOLYTIC AGENTS
• STREPTOKINASE
• TISSUE PLASMINOGEN ACTIVATOR