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
Kontak XIIa HMWK XI XIa IX IXa PF3, VIII, Ca X

VII
Ca Tromboplastin Jaringan

VIIa

Xa V, PF3, Ca Fibrinogen

Protrombin

Trombin

Fibrin monomer
Fibrin polimer Solubel XIII Ca XIIIa Fibrin polimer InSolubel

Intrinsik

Extrinsik

Eksogen

XIIa, Kalikrein

t-PA Aktifator Plasminogen

Urokinase

Plasminogen terikat

Plasmin terikat

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

RBCs

Platelets

White Thrombus

SLOW FLOW : VENOUS CIRCULATION

Fibrin

RBCs

Platelets

Red Thrombus

Incidence of thrombosis in United States of America

Disease US incidence /100.000 Total in US /year Definable cases reason

Deep Vein Thrombosis 159/100.000 398.000 80% Pulmonary Embolus 139/100.000 347.000 80 % Fatal Pulmonary Emb. 94/100.000 235.000 80 % Myocardial Infarction 600/100.000 1.500.000 67 % Fatal MI 300/100.000 750.000 67 % Cerebrovascular thromb. 600/100.000 1.500.000 30 % Fatal Cereb. Trhromb. 396/100.000 990.000 30 % Total serious thromb. In US 1498/100.000 3.742.000 50 % Total deaths from above thrmb. 790/100.000 1.990.000 50 % Bick RL, Clin Appl Throm Hemos 3, Suppl 1, 1997

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 STASIS Akut

AIL
ISKEMIA Kronik (kel. tungkai/tempat lain) Akut (tromboemboli/trombosis) Nekrosis amputasi

Kronik Komplikasi akut Prognosis

PE

Baik / fatal

Fatal lokal / sistemik

DVT >< AIL Diagnosis: Keluhan dan Tanda

DVT AIL Keluhan (stasis) (iskemia) utama/awal - edema tungkai nyeri: biasanya unilateral - tromboemboli: onset akut - silent DVT - trombotik: pelan-pelan - nyeri dan keras (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 Fixed administration dosing Fast onset and offset Predictive No coagulation kinetics monitoring

Warfarin Heparin LMWH

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