T H ROMBOSIS

IRZA WAHID
SUBDIVISION OF HEMATOLOGY & MEDICAL ONCOLOGY
DEPARTEMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE ANDALAS UNIVERSITY
KP 2017
 HEMOSTASIS : Hemo + Stasis

Vaskular

Trombosit Koagulasi
HEMOSTASIS : Hemo + Stasis
A. VASKULAR
* Vasokonstriksi
 Reflektoris  dipertahankan oleh Fc lokal
: 5-HT, serotonin, epinefrin

* Trombosit
 adhesi , aktivasi, agregasi  sumbat trombosit

* Aktifasi faktor Koagulasi

 via jalur intrinsik & ekstrinsik
 B. TROMBOSIT
Adesi
 Vaskular robek , sel endotel rusak, subendotel terbuka
 Trombosit lengket dg ddg vaskular terutama kolagen
 Sangat tergantung fc vWF yg disintesis sel endotel & megakariosit

Aktivasi
•Release granula trombosit
 Granula padat : ADP, ATP, Ca, Epinefrin, Norepinefrin,
 Granula alfa : Fibrinogen, vWF, FV, PF 4, bTG,
 Lisosom : Enzim asam hidrolase
• perubahan bentuk trombosit menjadi cakram

Agregasi
 trombosit lengket satu sama lain
 Dihubungkan oleh GPIIB – IIIA dan fibrinogen
C. SISTIM KOAGULASI
NOMENCLATUR FAKTOR KOAGULASI
I Fibrinogen
II Protrombin
III Tissue factor
IV Ion calsium
V Proaccelerin
VI -
VII Proconvertin
VIII Anti hemophilic factor
IX Plasma tromboplastin component
X Stuart factor
XI Plasma tromboplastin antecedent
XII Hageman factor
XIII Fibrin stabilizing factor
- High moleculer weight kininogen
- Pre kalikrein
TEORI CASCADE ATAU WATERFALL
(BY Mac Farlane, Davie & Ratnoff)

 Tiap Fc koagulasi diubah menjadi bentuk aktif oleh Fc sebelumnya

 Dimulai dari 2 jalur yakni :

* Jalur intrinsik
 vaskular robek  permukaan asing(kolagen) kontak dg Fc XII

* Jalur ekstrinsik :
 vaskular robek  tromboplastin jar. + Ca kontak dg Fc VII

 Diakhiri dengan jalur bersama

* Aktifasi Fc X
 FIBRINOLISIS

Proses penghancuran deposit fibrin oleh sistim fibrinolitik sehingga aliran

darah terbuka kembali

3 komponen utama :

* Plasminogen  plasmin
* Aktifator plasminogen
* Inhibitor plasmin
Intrinsik Extrinsik Eksogen

XIIa, Kalikrein t-PA Urokinase

Aktifator Plasminogen

Plasminogen terikat Plasmin terikat Fibrin

FDP

Plasminogen bebas Plasmin bebas Fibrinogen

Fc V, Fc VIII

Anti Plasmin
• Thrombosis is the formation or presence of
a blood clot inside a blood vessel or cavity
of the heart

 Arterial thrombosis (white thrombus)

 Venous thromboembolism (red thrombus)

* Deep vein thrombosis

* Pulmonary embolism
 High Flow Slow Flow

Fibrin RBCs Platelets Fibrin RBCs Platelets

White Thrombus 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

 Pathophysiologic of Thrombosis

Triad of Virchow

Abnormality of Abnormality of Abnormality of

Vessel wall Blood flow The blood

Plaque Venous Shears stress  Venous Platelet Hyper

ruptures Hypotonia Shears rate  stasis hyper coagulability state
Turbulence aggregation Thrombophilic state
Fibrinolysis deficient
Thrombocytosis

Arterial Venous Arterial Venous Arterial

Thrombosis Thrombosis Thrombosis Thrombosis Thrombosis

Endothelial Hyper Venous

Perturbation viscosity Thrombosis
Hyper
fibrinogenemia
TROMBOSIS ARTERI

- OTAK
- TELINGA
- MATA
- JANTUNG
- EXTREMITAS
 Risiko trombosis arterial
Kelainan vaskular
• Aterosklerosis
• Merokok
• Hypertensi
• Diabetes Mellitus
• Obesitas
• Riwayat keluarga positif
• High Lipoprotein(a)
• High Low-density
lipoprotein
• High Kolesterol
• Hypertriglyceridemia
• Defisiensi estrogen
• Hyper Homocystinemia
• Kepribadian (stress)
Kelainan aliran Kelainan koagulasi
• Aterosklerosis • Antiphospholipid syndrome
• Hyperviscosity • Sticky platelet syndrome
syndromes • Cancer procoagulant (CP)
• Hyperglisemia • Protein S defects
• Hyperlipidemia • Protein C defects
• Polycythemia • APC resistance (factor V Leiden)
• Leukostasis • Antithrombin defects
syndromes • Heparin cofactor II defects
• Dysfibrinogenemia • Plasminogen defects
• Tissue plasminogen activators
defects
• Plasminogen activator inhibitor
defects
• Factors XII defects
TROMBOSIS VENA (VTE)

- DVT
- PE
 VTE: A strong relationship between
DVT and PE

Almost 50% of patients with

proximal DVT of the leg Migration
have asymptomatic PE1

Embolus
DVT (mainly asymptomatic)
is found in around 80% Thrombus
of patients with PE2

1. Pesavento R, et al. Minerva Cardioangiologica. 1997;45:369–375

2. Girard P, et al. Chest. 1999;116:903–908
 Complications of VTE:
Leg ulcer, a severe consequence
Annual incidence of leg ulcer after a DVT = 1–2%1

Venous ulcer, a highly chronic condition:1

Cases not healed at 4 months: 50%
2 years: 20%
5 years: 8%
Around 60% of patients have two or more recurrences of venous
ulcer

Venous ulcer, a very costly disease:

Direct medical costs if no healing at 12 weeks
US$10,0002
1. Kurz X, et al. Int Angiol. 1999;18(2):83–102
2. Blair SD, et al. BMJ. 1988;297:1159–1161
 Diagnosis

1. Anamnesis  Riwayat penyakit (Faktor risiko

medis & bedah), Manifestasi klinis
2. Pemeriksaan fisik
3. Pemeriksaan Laboratorium
4. Pemeriksaan lain:
• ANGIOGRAFI (“Golden Standard”)
• USG/ Doppler
• Duplex scan
• Impedance Plethysmography
 PLATELET FUNCTION TEST
* LIGHT THROMBOCYTE AGGREGOMETRY (LTA)
 STILL A GOOD STANDARD
AGONIS : ADP, AA, EPINEPHRIN, RISTOCETIN, COLAGEN

* FLOWCYTOMETRY
 GLYCOPROTEIN IA, IIA, VI, THROMBIN RESEPTOR (PAR 1)
 CLASSICAL AGONIS, DENSE GRANUL, ANIONIC PHOSPOLIPID

* MEASUREMENT OF ADENIN NUCLEOTIDES

* WB AGGREGOMETRY

* ELISA / RIA / WESTERN BLOT

 THROMBOGLOBULIN BETA
 PLATELET FC IV
 COAGULATION FUNCTION TEST
* PROTHROMBIN TIME (PT)  INR
 FIRST PROPOSED BY QUICK IN 1935
 FUNCTION OF THE TISSUE FACTOR PATHWAY ( EXTRINSIC PATHWAY’).
 ADDING TISSUE FACTOR AND PHOSPHOLIPIDS TO PLASMA AND THEN MEASURING
THE TIME IN SECONDS TO CLOT FORMATION FOLLOWING THE ADDITION OF CALCIUM.
* ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT)
 FUNCTION OF THE CONTACT-FACTOR’ PATHWAY ( INTRINSIC’ PATHWAY )
FVIII, FIX, FXI, AND FXII), AS WELL AS THE COMMON PATHWAY (I, FII, FV, FX).
THE APTT IS THE TIME TO CLOT IN SECONDS WHEN CONTACT ACTIVATOR AND
PHOSPHOLIPIDS ARE ADDED TO PLASMA IN THE PRESENCE OF CALCIUM
* THROMBIN TIME (TT)
 ADDING EQUAL VOLUMES OF PLASMA AND THROMBIN AND MEASURING THE
AMOUNT OF TIME UNTIL A CLOT FORMS.
THE TT IS SENSITIVE TO HEPARIN, DIRECT THROMBIN INHIBITORS AND TO DEFECTS AND
DEFICIENCIES OF FIBRINOGEN.
* FIBRINOGEN
* D- DIMER
* FRACTION PROTROMBIN 1 + 2
* ENDOGENOUS THROMBIN POTENTIALE
MANAGEMENT  TREATMENT
 PREVENTION
- NON FARMAKOLOGI

- FARMAKOLOGI
* ANTI PLATELET
* ANTIKOAGULAN
* TROMBOLITIK

- BEDAH
 Targets for Anticoagulants
Intrinsic pathway Extrinsic pathway
(surface contact) (tissue damage)

XII XIIa Tissue factor

XI XIa
Heparins and
LMWH2 IX IXa VIIa VII
Vitamin K antagonists3
VIII VIIIa
Direct thrombin inhibitors4
X Xa
Factor Xa inhibitors5
1Adapted with permission from V Va
Petitou M, et al. Nature. 1991;350(suppl):30-33.
2Hirsh J, et al. Chest. 2001;119(suppl):64S-94S.
3Hirsh J, Fuster V. Circulation. 1994;89:1449-1468.
II IIa
IIa (Thrombin)
4Weitz JI, Hirsh J. Chest. 2001;119(suppl):95S-107S.
5Herbert JM, et al. Cardiovasc Drug Rev. 1997;15:1.
Fibrinogen Fibrin
COMPARATIVE CHARACTERISTICS
OF ANTICOAGULANTS
Oral
Fixed Fast onset Predictive No coagulation
administration dosing and offset kinetics monitoring

Warfarin 
dabigatran     

Heparin 
LMWH    
 TROMBOLITIK

 STREPTOKINASE
 STAPILOKINASE
 UROKINASE
 CONCLUSION

•Thrombosis is formation or presence of a blood

clot inside a blood vessel ( arteri / vein ) or cavity
of the heart
• Pathophysiologic of Thrombosis depend on
abnormality of vessel wall, vessel flow &
blood
• Gold standard to make diagnosis of thrombosis
by angiography
• Farmacology of antithrombotic consist of
antiplatelet, anticoagulant & thrombolitic