Prothrombin fibrin

Thrombin, the two-chain derivative of the prothrombin molecule, has a molecular weight of approximately 37,000 daltons. Its proteolytic properties induce the conversion of fibrinogen to fibrin to produce the initial visible manifestation of coagulation, the soluble fibrin clot. In addition, thrombin influences the activity of Factors V, VIII, and XIII and plasmin. Thrombin affects platelet function by inducing viscous metamorphosis and the release reaction with subsequent aggregation. 

Factor II. Prothrombin is a vitamin K-dependent compound synthesized by the Hver. When prothrombin is activated it is cleaved at two sites, resulting in a two-chain molecule linked by a disulfide bond that has a molecular weight of 37,000 daltons. Thrombin is the serine protease that initiates the conversion of soluble fibrinogen into fibrin. 

The clear serum of this example is an amber liquid free from prothrombin, thrombin, fibrinogen and fibrin. It contains profibrinolysin and is excellently suited to further purification by salt precipitation fractionation, as given below. 

Initiation of the fibrin clot in response to tissue injury is carried out by the extrinsic pathway. How the intrinsic pathway is activated in vivo is unclear, but it involves a negatively charged surface. The intrinsic and extrinsic pathways converge in a final common path-vray involving the activation of prothrombin to thrombin and the thrombin-catalyzed cleavage of fibrinogen to form the fibrin clot. The intrinsic, extrinsic, and final common pathways are complex and involve many different proteins (Figure 51-1 and Table 51-1). In... 

In the final common pathway, factor Xa, produced by either the intrinsic or the extrinsic pathway, activates prothrombin (factor II) to thrombin (factor Ila), which then converts fibrinogen to fibrin (Figure 51-1). 

A number of laboratory tests are available to measure the phases of hemostasis described above. The tests include platelet count, bleeding time, activated partial thromboplastin time (aPTT or PTT), prothrombin time (PT), thrombin time (TT), concentration of fibrinogen, fibrin clot stabifity, and measurement of fibrin degradation products. The platelet count quantitates the number of platelets, and the bleeding time is an overall test of platelet function. aPTT is a measure of the intrinsic pathway and PT of the extrinsic pathway. PT is used to measure the effectiveness of oral anticoagulants such as warfarin, and aPTT is used to monitor heparin therapy. The reader is referred to a textbook of hematology for a discussion of these tests. 

Thrombin The enzyme formed from prothrombin, which converts fibrinogen to fibrin. It is the principal driving force in the clotting cascade. 

Activated factor X, along with Ca++ ion, factor V, and PF3 (collectively referred to as the prothrombin activator), catalyzes the conversion of prothrombin into thrombin. Thrombin then catalyzes the conversion of fibrinogen into fibrin, an insoluble, thread-like polymer. The fibrin threads form a meshwork that traps blood cells, platelets, and plasma to form the blood clot. The clotting cascade may be elicited by means of two mechanisms (see Figure 16.1) ... 

Both intrinsic and extrinsic pathways generate activated factor X. This protease, in turn, catalyses the proteolytic conversion of prothrombin (factor II) into thrombin (Ha). Thrombin, in turn, catalyses the proteolytic conversion of fibrinogen (I) into fibrin (la). Individual fibrin molecules aggregate to form a soft clot. Factor XHIa catalyses the formation of covalent crosslinks between individual fibrin molecules, forming a hard clot (Figures 12.3 and 12.4). 

Thrombin [EC 3.4.21.5], also known as fibrinogenase, catalyzes the hydrolysis of peptide bonds, exhibiting preferential cleavage for the Arg—Gly peptide bond. The enzyme, a member of the peptidase family SI, activates fibrinogen to fibrin and releases fibrinopeptide A and B. Thrombin, formed from prothrombin, is more selective in peptide hydrolysis than trypsin or plasmin. 

Mechanism of Action A blood modifier that interferes with blood coagulation by blocking conversion of prothrombin to thrombin and fibrinogen to fibrin Therapeutic Effect Prevents further extension of existing thrombi or new clot formation. Has no effect on existing clots. 

Once prothrombinase has been formed, the common pathway is followed. In stage 2, prothrombinase and calcium catalyze the conversion of prothrombin to thrombin. In stage 3, thrombin, in the presence of calcium converts soluble fibrinogen to insoluble fibrin threads. 

Clinical pharmacology Activated factor IX in combination with activated factor VIII activates factor X. This results ultimately in the conversion of prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin, and a clot can be formed. Factor IX is the specific clotting factor deficient in patients with hemophilia B and in patients with acquired factor IX deficiencies. The administration of Coagulation Factor IX (Recombinant) increases plasma levels of factor IX and can temporarily correct the coagulation defect in these patients. 

THROMBIN. A proteolytic enzyme that catalyzes the conversion of fibrinogen to fibrin and thus is essential in the clotting mechanism of blood. It is present in the blood in die form of prothrombin under normal conditions when bleeding begins, the prothrombin is converted to thrombin, which in turn activates the formation of fibrin. 

The enzymes that participate in blood clotting also are activated by partial proteolysis, which again serves to keep them in check until they are needed. The blood coagulation system involves a cascade of at least seven serine proteases, each of which activates the subsequent enzyme in the series (fig. 9.2). Because each molecule of activated enzyme can, in turn, activate many molecules of the next enzyme, initiation of the process by factors that are exposed in damaged tissue leads explosively to the conversion of prothrombin to thrombin, the final serine protease in the series. Thrombin then cuts another protein, fibrin, into peptides that stick together to form a clot. 

Quantification of coagulation factors is notoriously difficult, because of the interrelations among the various components of the coagulation cascade, the broad range of normal values, and considerable inter-laboratory variability (52). This variability is illustrated by a WHO study of users of combined oral contraceptives, conducted on several continents, which showed statistically significant differences among clinical centers in prothrombin time, fibrin plate lysis, plasminogen, and activated partial thromboplastin time (SEDA-16, 464). Effects also vary between different populations, users of different doses, users of different products, and tests performed at different periods of the medication cycle (63,69). 

Both the intrinsic and extrinsic systems ultimately lead to the conversion of prothrombin to thrombin.92 Thrombin is an enzyme that quickly converts the inactive fibrinogen molecule to fibrin. Individual strands of fibrin bind together to form a meshlike structure, which ultimately forms the framework for the blood clot. Other cellular components, especially platelets, help reinforce the clot by sticking to the fibrin mesh. 

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