TROMBOSIS : DIAGNOSIS & PENATALAKSANAAN
IRZA WAHIDSUBAGIAN HEMATOLOGI & ONKOLOGI MEDIK
FK UNAND / RS DR M DJAMIL PADANG
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
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
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
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
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)
Recommended