TROMBOSIS : DIAGNOSIS & PENATALAKSANAAN

IRZA WAHIDSUBAGIAN 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, TG, Lisosom : Enzim asam hidrolase

C. SISTIM KOAGULASI VS FIBRINOLISIS

NOMENCLATUR FAKTOR PEMBEKUAN DARAH

I FibrinogenII ProtrombinIII Tissue factorIV Ion calsiumV ProaccelerinVI -VII ProconvertinVIII Anti hemophilic factorIX Plasma tromboplastin componentX Stuart factorXI Plasma tromboplastin antecedentXII Hageman factorXIII Fibrin stabilizing factor - High moleculer weight kininogen - Pre kalikrein

Jalur intrinsik

IX

XIaXIHMWK

XIIa

KontakXII

Xa

Tromboplastin Jaringan

X

Ca

VIIa

VII

Jalur Ekstrinsik

PF3, VIII, Ca

IXa

TrombinProtrombin

V, PF3, Ca

Fibrin Polimer Solubel

Fibrin Monomer

Fibrinogen

Fibrin Polimer Insoluber

Ca

XIIIaXIII

Intrinsik Extrinsik Eksogen

XIIa, Kalikrein t-PA Urokinase Aktifator Plasminogen

Plasminogen terikat Plasmin terikat Fibrin

FDP

Plasminogen bebas Plasmin bebas FibrinogenFc 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 PlateletsRBCs

White Thrombus

SLOW FLOW : VENOUS CIRCULATION

Fibrin PlateletsRBCs

Red Thrombus

Incidence of thrombosis in United States of America

Disease US incidence Total in US /year Definable /100.000 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 fisik3. Pemeriksaan Laboratorium4. Pemeriksaan lain:

• Venografi (“Golden Standard”)• USG/ Doppler• Duplex scan• Impedance Plethysmography

FAKTOR RISIKO TROMBOSIS ARTERIHipertensi, hiperkolesterolemia,

hiperlipoproteinemia, merokok, diabetes melitus, hiperhomosisteinemia, trombositosis, polisitemia

FAKTOR RISIKO TROMBOSIS VENAImobilisasi, operasi, trauma jaringan yang luas,

kehamilan, pil kontrasepsi, defisiensi AT3 / protein C/S / Fc XII, PNH

MANIFESTASI KLINIS & PEMERIKSAAN KLINIS

ARTERI / VENAORGAN

ORGAN

• OTAK• MATA• THT• JANTUNG• PARU• ORGAN VISERAL• EXTREMITAS

DVT >< AILPatogenesis, Perjalanan Penyakit,

Komplikasi, Prognosis

DVT AIL

• Dasar STASIS ISKEMIA

• Perjalanan Akut Kronik penyakit (kel. tungkai/tempat lain) Kronik Akut (tromboemboli/trombosis) • Komplikasi akut PE Nekrosis amputasi

• Prognosis Baik / fatal Fatal lokal / sistemik

DVT >< AILDiagnosis: 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, pares- tanda - 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

Fixed dosing

Fast onsetand offset

Predictive kinetics

No coagulationmonitoring

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