MEDICINAL CHEMISTRY

fibrin monomer by the action of thrombin (IIa) formed from its inert precursor
prothrombin (II). These smaller peptides unite end to end and side to side to form
insoluble strands of fibrin. These fibrins entangle blood cells and platelets to form the
solid clot.
Fig. 2: Schematic presentation of blood coagulation and fibrinolysis
The conversion of prothrombin to thrombin is achieved by activated factor X (Xa) in the
presence of Va, calcium ions and platelets or phospholipids. The formation of Xa may
take place through two pathways. In the intrinsic pathway, clotting is initiated in vitro
when XII, prekallikrein and kininogen interact with glass or any other surface to produce
small amounts of XIIa. This is followed by activation of XI to XIa and IX to IXa. IXa
then converts X to Xa with the help of VIIIa, calcium ions and phospholipids. The
extrinsic pathway initiates coagulation in vivo. In this pathway activation of factor X to
Xa is by VIIa in the presence of tissue factor and calcium ions. The Xa formed activates
factor VII to VIIa. Factor VII itself possesses proteolytic activity, though less than 1%
that of VIIa, and is sufficient to initiate coagulation in the presence of tissue factor.
Tissue factor, which is available at the site of injury, accelerates the activation of factor X
by VIIa (or VII), phospholipids and calcium ions about 30,000 fold. It is likely that tissue
factor plays a major role in haemostasis during injury. The activated VII can also cause
conversion of IX to IXa in the presence of tissue factor and calcium ions, supplementing
the process by intrinsic pathway.
Blood clots are removed from the vascular system by breakdown of fibrin by proteolytic
enzyme plasmin, which is formed from its inactive precursor plasminogen by the action