1) The document summarizes a presentation on hypofibrinolysis as a risk factor for arterial and venous thrombosis. Hypofibrinolysis refers to impaired fibrinolysis, or the breakdown of blood clots. 2) It discusses Virchow's triad, the factors that promote thrombosis, including blood flow abnormalities, blood composition changes, and damaged blood vessels. It also explains the pathogenesis of arterial versus venous clots. 3) The presentation finds that hypofibrinolysis doubles the risk of venous thrombosis and is a risk factor for arterial thrombosis in young patients. Increased clot lysis times are associated with elevated levels of proteins that inhibit fibrinolysis.

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. What is thrombosis ?
 The formation or presence of a blood clot
inside a blood vessel or cavity of the heart

3. Triad Virchow
1) ALIRAN DARAH
2) KOMPOSISI DARAH
3) PEMBULUH DARAH

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. SLOW FLOW : VENOUS CIRCULATION
Fibrin
RBCs
Red Thrombus
Platelets

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. HIGH FLOW : ARTERIAL CIRCULATION
Fibrin
White Thrombus
RBCs
Platelets

8. Pathogenesis of Thrombosis
Imbalance of
Factors which activated coagulation (Procoagulant)
Factors which activated control coagulation and
fibrinolysis (Protection to developing thrombus).

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. 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. Trombosis

13. 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.

14. 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

15. 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

16. 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

17. HYPOFIBRINOLYSIS
a Risk Factor for
venous and arterial thrombosis
Elevated plasma clot lysis time (CLT)
BLOOD, 8 JULY 2010

18. 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.

19. 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 ?

21. 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

23. Pertemuan Ilmiah Tahunan VI
IKATAN DOKTER INDONESIA
KOTA BOGOR
Bogor, 9 November 2013
Terima Kasih
Dr Marthino Robinson, SpPD