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KP 2.2.3.

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
Risiko trombosis arterial
Kelainan vaskular Kelainan aliran Kelainan koagulasi
Aterosklerosis Aterosklerosis Antiphospholipid syndrome
Merokok Hyperviscosity Sticky platelet syndrome
Hypertensi syndromes Cancer procoagulant (CP)
Diabetes Mellitus Hyperglisemia Protein S defects
Obesitas Hyperlipidemia Protein C defects
Riwayat keluarga positif Polycythemia APC resistance (factor V Leiden)
High Lipoprotein(a) Leukostasis Antithrombin defects
High Low-density syndromes Heparin cofactor II defects
lipoprotein Dysfibrinogenemia Plasminogen defects
High Kolesterol Tissue plasminogen activators
Hypertriglyceridemia defects
Defisiensi estrogen Plasminogen activator inhibitor
Hyper Homocystinemia defects
Kepribadian (stress) 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;45:369375


2. Girard P, et al. Chest. 1999;116:903908
Complications of VTE:
Leg ulcer, a severe consequence

Annual incidence of leg ulcer after a DVT = 12%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):83102
2. Blair SD, et al. BMJ. 1988;297:11591161
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
COAGULATION FUNCTION TEST
MANAGEMENT TREATMENT
PREVENTION
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