TROMBOSIS DIAGNOSIS PENATALAKSANAAN IRZA WAHID SUBAGIAN HEMATOLOGI ONKOLOGI
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, v. WF, FV, PF 4, b. TG, Lisosom : Enzim asam hidrolase C. SISTIM KOAGULASI VS FIBRINOLISIS
NOMENCLATUR FAKTOR PEMBEKUAN DARAH I II IV V VI VIII IX X XI 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 PF 3, VIII, Ca VIIa X Xa V, PF 3, Ca Protrombin Trombin XIIIa Ca Fibrinogen Fibrin Monomer Fibrin Polimer Solubel 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. 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 • Bick RL, Clin Appl Throm Hemos 3, Suppl 1, 1997 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 % 67 % 30 % 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 AT 3 / 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 Kronik • Komplikasi akut • Prognosis PE Baik / fatal AIL ISKEMIA Kronik (kel. tungkai/tempat lain) Akut (tromboemboli/trombosis) Nekrosis amputasi 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 < 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/kg. BB followed by continous infusion to achieve a. PTT between 1. 5 to 2. 5 times control • LMWH : 1 mg/kg. BB or 0. 1 ml/10 kg. BB sc twice daily • Fondaparinux : 7. 5 mg for 50 -100 kg. BB 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
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