HYPOFIBRINOLYSIS A Risk Factor for ARTERIAL THROMBOSIS AND VENOUS THROMBOSIS

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HYPOFIBRINOLYSIS
A Risk Factor for ARTERIAL THROMBOSIS AND VENOUS THROMBOSIS
Dr Marthino Robinson, SpPD | Dinas Kesehatan Kota Bogor | RSAD SALAK | RSIA MELANIA

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HYPOFIBRINOLYSIS A Risk Factor for ARTERIAL THROMBOSIS AND VENOUS THROMBOSIS

  1. 1. Pertemuan Ilmiah Tahunan VI IKATAN DOKTER INDONESIA KOTA BOGOR Bogor, 9 November 2013 HYPOFIBRINOLYSIS A Risk Factor for ARTERIAL THROMBOSIS AND VENOUS THROMBOSIS Dr Marthino Robinson, SpPD Dinas Kesehatan Kota Bogor RSAD SALAK RSIA MELANIA
  2. 2. What is thrombosis ?  The formation or presence of a blood clot inside a blood vessel or cavity of the heart
  3. 3. Triad Virchow 1) ALIRAN DARAH 2) KOMPOSISI DARAH 3) PEMBULUH DARAH
  4. 4. ABNORMALITAS Triad Virchow mendukung terjadinya trombosis 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.
  5. 5. SLOW FLOW : VENOUS CIRCULATION Fibrin RBCs Red Thrombus Platelets
  6. 6. ABNORMALITAS Triad Virchow mendukung terjadinya trombosis 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.
  7. 7. HIGH FLOW : ARTERIAL CIRCULATION Fibrin White Thrombus RBCs Platelets
  8. 8. Pathogenesis of Thrombosis Imbalance of Factors which activated coagulation (Procoagulant) Factors which activated control coagulation and fibrinolysis (Protection to developing thrombus).
  9. 9. HEMOSTASIS Primary 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
  10. 10. KESEIMBANGAN ANTAR SISTEM (Koagulasi dan Fibrinolisis) diperlukan untuk mencegah terjadinya kondisi patologik: perdarahan atau trombosis Scheme of the coagulation-anticoagulation system Activation of the coagulation system culminates in generation of thrombin, which cleaves fibrinogen to form fibrin clots with platelets on the site of vascular injury. Coagulation system is 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 system is negatively regulated by : • plasminogen activator inhibitor 1 (PAI-1).
  11. 11. Trombosis
  12. 12. 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.
  13. 13. HYPOFIBRINOLYSIS A Risk Factor for ARTERIAL THROMBOSIS AND VENOUS THROMBOSIS References Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis BLOOD, 1 FEBRUARY 2005 Hypofibrinolysis is a risk factor for arterial thrombosis at young age 2009, British Journal of Haematology, Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1 BLOOD, 8 JULY 2010 VOLUME 116, NUMBER 1
  14. 14. HYPOFIBRINOLYSIS a Risk Factor for Venous 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 thrombosis Ton Lisman et al. BLOOD, 1 FEBRUARY 2005 VOLUME 105, NUMBER 3
  15. 15. HYPOFIBRINOLYSIS a Risk Factor for Arterial 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
  16. 16. HYPOFIBRINOLYSIS a Risk Factor for venous and arterial thrombosis Elevated plasma clot lysis time (CLT) BLOOD, 8 JULY 2010
  17. 17. MENGATASI HIPOFIBRINOLISIS membantu mencegah aterogenesis Hypofibrinolysis Deposit Fibrin (Mikrotrombus) BERPOTENSI ATEROGENESIS di setiap tahap perkembangan lesi meningkatkan pertumbuhan 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.
  18. 18. PRINCIPLES THERAPY OF THROMBOSIS BASED ON PATHOGENESIS PATHOGENESIS THERAPY - PLATELET ADHESION - PLATELET AGGREGATION ANTIPLATELET - BLOOD COAGULATION ANTI-COAGULANT - THROMBOSIS THROMBOLYTIC AGENT AND/OR ANTI-COAGULANT Hypofibrinolysis ?
  19. 19. TROMBOLES (Lumbrokinase) MECHANISM OF ACTION 1. - directly dissolve fibrinogen and fibrin, 2. 3. 1) 2) 3) - convert plasminogen to plasmin, - increase endogenous human t-PA activity inhibit platelet activation and aggregation blocks the intrinsic coagulation pathway. 3 in 1 1. Fibrinolytic 2. Anti Platelet 3. Anti Coagulation Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China, Department of Natural Sciences, Northeastern State University, Broken Arrow, Oklahoma, USA Pharmaceutical School, Peking University, Beijing, China
  20. 20. Pertemuan Ilmiah Tahunan VI IKATAN DOKTER INDONESIA KOTA BOGOR Bogor, 9 November 2013 Terima Kasih Dr Marthino Robinson, SpPD

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