TROMBOSIS : DIAGNOSIS & PENATALAKSANAAN IRZA WAHID SUBAGIAN HEMATOLOGI & ONKOLOGI MEDIK FK UNAND / RS DR M DJAMIL PADANG

HEMOSTASIS - DIATESIS HEMORAGIS - TROMBOSIS Vaskular TrombositKoagulasi

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 IFibrinogen IIProtrombin IIITissue factor IVIon calsium VProaccelerin VI- VIIProconvertin VIIIAnti hemophilic factor IXPlasma tromboplastin component XStuart factor XIPlasma tromboplastin antecedent XIIHageman factor XIIIFibrin stabilizing factor -High moleculer weight kininogen -Pre kalikrein

Jalur intrinsik IX XIaXI HMWK XIIa Kontak XII 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-PAUrokinase Aktifator Plasminogen Plasminogen terikat Plasmin terikatFibrin FDP Plasminogen bebas Plasmin bebasFibrinogen 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 White Thrombus

SLOW FLOW : VENOUS CIRCULATION

Incidence of thrombosis in United States of America Disease US incidence Total in US /year Definable / cases reason Deep Vein Thrombosis 159/  80% Pulmonary Embolus 139/  80 % Fatal Pulmonary Emb. 94/  80 % Myocardial Infarction 600/  67 % Fatal MI 300/  67 % Cerebrovascular thromb. 600/  30 % Fatal Cereb. Trhromb. 396/  30 % Total serious thromb. In US 1498/  50 % Total deaths from above thrmb. 790/  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 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 >< 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, 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 onset and offset Predictive kinetics No coagulation monitoring Warfarin Heparin LMWH

Dose and administration UFH : initial dose: bolus 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 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