hypofibrinolysis a risk factor for arterial thrombosis and venous thrombosis
TRANSCRIPT
HYPOFIBRINOLYSISA Risk Factor for
ARTERIAL THROMBOSIS AND VENOUS THROMBOSIS
Pertemuan Ilmiah Tahunan VIIKATAN DOKTER INDONESIA
KOTA BOGORBogor, 9 November 2013
Dr Marthino Robinson, SpPDDinas Kesehatan Kota Bogor
RSAD SALAK RSIA MELANIA
What is thrombosis ? The formation or presence of a blood clot inside a blood vessel or cavity of the heart
Triad Virchow1) ALIRAN DARAH2) KOMPOSISI DARAH3) PEMBULUH DARAH
ABNORMALITAS Triad Virchowmendukung terjadinyatrombosis vena
• Trombosis Vena (fibrin-rich “red clots”)Terkait terjadinya ‐ Hiperkoagulabilitas‐ Aliran lambat atau statik
• bermula dibelakang katup
TM thrombomodulin; EPCR endothelial protein C receptor; II prothrombin; IIa thrombin; TF tissue factor; Fgn fibrinogen; RBC red blood cells.
SLOW FLOW : VENOUS CIRCULATION
Fibrin PlateletsRBCs
Red Thrombus
ABNORMALITAS Triad Virchowmendukung terjadinyatrombosis arteri
• Trombosis Arteri (platelet-rich “white clots” ) terbentuk setelah terjadinya- Plak pecah- Pemaparan thd materi procoagulant (seperti lipid-rich
macrophages (foam cells), collagen, tissue factor- kerusakan endotel, kondisi aliran cepat.
TM thrombomodulin; II prothrombin; IIa thrombin; Fgn fibrinogen; TF tissue factor.
HIGH FLOW : ARTERIAL CIRCULATION
Fibrin PlateletsRBCs
White Thrombus
Imbalance ofFactors which activated coagulation (Procoagulant)
Factors which activated control coagulation and fibrinolysis (Protection to developing thrombus).
Pathogenesis of Thrombosis
HEMOSTASISPrimary Hemostasis
Blood vessel contraction Platelet Plug Formation
Secondary Hemostasis Activation of Clotting Cascade Deposition & Stabilization of Fibrin
Tertiary Hemostasis Dissolution of Fibrin Clot Dependent on Plasminogen Activation
KESEIMBANGAN ANTAR SISTEM (Koagulasi dan Fibrinolisis)diperlukan untuk mencegah terjadinya kondisi patologik:
perdarahan atautrombosis
Scheme of thecoagulation-anticoagulation system
Activation of the coagulation systemculminates in generation of thrombin, which cleaves fibrinogen to form fibrin clots with platelets on the site of vascular injury. Coagulation systemis negatively regulated by :• tissue factor pathway inhibitor (TFPI), • antithrombin (AT), and • activated protein C (APC).
Fibrinolytic system also regulates coagulation by generation of plasmin, which dissolves fibrin clots. Fibrinolytic systemis negatively regulated by : • plasminogen activator inhibitor 1 (PAI-1).
Trombosis
Clot Lysis Time (CLT) : Time from the midpoint of clear to maximum turbidity transition
(clot formation) To the midpoint of maximum turbid to clear transition (clot lysis)
Determinants of CLT : Plasminogen activator inhibitor-1 (PAI-1) Plasminogen, thrombin-activatable fibrinolysis inhibitor (TAFI),
prothrombin, and 2-antiplasmin. Fibrinogen, factor VII, X, and XI contributed minimally.
ReferencesReduced plasma fibrinolytic potential is a risk factor for venous thrombosisBLOOD, 1 FEBRUARY 2005
Hypofibrinolysis is a risk factor for arterial thrombosis at young age2009, British Journal of Haematology,
Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1BLOOD, 8 JULY 2010 VOLUME 116, NUMBER 1
HYPOFIBRINOLYSISA Risk Factor for
ARTERIAL THROMBOSIS AND VENOUS THROMBOSIS
HYPOFIBRINOLYSISa Risk Factor forVenous Thrombosis (DVT)We determined the plasma fibrinolytic potential of patients enrolled in the Leiden Thrombophilia Study (LETS),( a population-based case control study on risk factors for DVT). Plasma fibrinolytic potential was determined in 421 patients and 469 control subjects by means of a tissue factor–induced and tissue-type plasminogen activator (tPA)–induced clot lysis assay.
Plasma hypofibrinolysis constitutes a risk factor for venous thrombosis, with a doubling of the risk (at clot lysis times that are present in 10% of the population)
Reduced plasma fibrinolytic potential is a risk factor for venous thrombosisTon Lisman et al. BLOOD, 1 FEBRUARY 2005 VOLUME 105, NUMBER 3
HYPOFIBRINOLYSISa Risk Factor forArterial Thrombosis (CAD, IS, PAD)We determined the plasma fibrinolytic potential of 335 young survivors of a first arterial thrombosis,including CAD (n = 198), IS (n = 103) and PAD (n = 34), enrolled in a population-based case–control study and of 330 healthy individuals.
Clot Lysis Times (CLTs) Pasien secara bermakna lebih tinggi (vs Control)
hipofibrinolisis dijumpai pada 10% populasi umum meningkatkan resiko trombosis arteri
Hypofibrinolysis is a risk factor for arterial thrombosis at young age. 2009 British Journal of Haematology, 145, 115–120
HYPOFIBRINOLYSISa Risk Factor forvenous and arterial thrombosisElevated plasma clot lysis time (CLT) BLOOD, 8 JULY 2010
Hypofibrinolysis
Deposit Fibrin(Mikrotrombus)
BERPOTENSI ATEROGENESISdi setiap tahap perkembangan lesi
meningkatkanpertumbuhan plak
Wien Klin Wochenschr. 1993;105(15):417-24. Fibrinogen and atherosclerosis. Smith EB. Department of Clinical Biochemistry, Medical School, Aberdeen Royal Infirmary, U.K.
MENGATASI HIPOFIBRINOLISISmembantu mencegah aterogenesis
PRINCIPLES THERAPY OF THROMBOSIS BASED ON PATHOGENESISPATHOGENESIS THERAPY
- PLATELET ADHESION
- PLATELET AGGREGATION
- BLOOD COAGULATION ANTI-COAGULANT
THROMBOLYTIC- THROMBOSIS AGENT AND/OR
ANTI-COAGULANT
ANTIPLATELET
Hypofibrinolysis ?
TROMBOLES (Lumbrokinase) MECHANISM OF ACTION1. - directly dissolve fibrinogen and fibrin,
- convert plasminogen to plasmin, - increase endogenous human t-PA activity
2. inhibit platelet activation and aggregation 3. blocks the intrinsic coagulation pathway.
1) Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China, 2) Department of Natural Sciences, Northeastern State University, Broken Arrow, Oklahoma, USA3) Pharmaceutical School, Peking University, Beijing, China
3 in 11. Fibrinolytic
2. Anti Platelet3. Anti Coagulation
Terima Kasih
Pertemuan Ilmiah Tahunan VIIKATAN DOKTER INDONESIA
KOTA BOGORBogor, 9 November 2013
Dr Marthino Robinson, SpPD