1. Naturally Occurring Inhibitors
Ahmad Sh. Silmi Msc, FIBMS
IUG
Faculty of Science
Medical Technology Dept

2. Coagulation Inhibitors
The activity of coagulation system must be attenuated.
Numerous inhibitors are found in blood.
Coagulation is controlled by three types of actions.
Inhibition of converting enzymes (e.g., AT III, C1 esterase inhibitor, a2-macroglobulin, a2-antiplasmin, a1-antitrypsin, HC-II).
Act on one or more of the converting enzymes (activated factors).
AT III-heparin pathway: major system - 80% of the thrombin inhibitory action in plasma.
Destruction of protein cofactors (e.g., TM-PC-PS system).
TM-PC-PS system degrades cofactors V & VIII:C, inhibiting prothrombinase and tenase complexes, respectively.
Blocking receptor availability needed for complex formation (e.g., Tissue factor pathway inhibitor (TFPI) and annexin V).

3. Antithrombin III (AT III)
naturally-occuring anticoagulant
binds to factors IXa, Xa, XIa, XIIa (slow)
accelerated by heparin manyfold
Implication:
Heparin has almost NO anticoagulant
action without AT III

4. Proposed Mechanism of AT III-Heparin System
Lysine sites
AT III Th H
Serine site
Arginine
site
Heparin
Thrombin
Antithrombin III H
AT III Th

5. Proposed Mechanism of Thrombomodulin, Protein C and Protein S (TM-PC-PS) System
F-Xa
Prothrombin
Activated
platelet
F-Va PS
Thrombin x
Ca++
Ca++
Protein C
Activated
Protein C
Thrombin
Thrombomodulin

6. Proposed Mechanism of Tissue Factor Pathway Inhibitor (TFPI) Activity
F-Xa
F-Xa
TFPI
TFPI
F-Xa
TFPI
Tissue factor
F-VIIa
Endothelium

7. Anticoagulant Factors

8. INHIBITORS (cont.)