Factor thromboplastin

III Tissue factor (thromboplastin) Extrinsic Accessory tissue protein which initiates extrinsic pathway... 

Tissue factor/thromboplastin xi Plasma thromboplastin antecedent (PTA) 3.4.27.27... 

Zeldis, S.M., Nemerson, Y., Pitlick, F.A. Tissue factor (thromboplastin) Localization to plasma membranes by peroxidase-conjugated antibodies. Science 175, 766-768 (1972)... 

Bleeding Bleeding time Platelet numbers, in vitro bleeding, platelet aggregation, clotting factors, thromboplastin time, partial thromboplastin time... 

Extrinsic Pathway. Coagulation is initiated when tissue extracts with Hpid—protein properties are released from the membranes of endothehal cells following injury or insult. These substances, collectively designated tissue thromboplastin, complex with circulating Factor VII and in the presence of calcium ions subsequentiy activate Factor X (Fig. 1). In vitro evidence suggests that Factor X can be activated less rapidly through the interaction of kaUikrein [9001-01-8] with Factor VII. 

Prothrombin time (PT) is a coagulation assay, which measures the time for plasma to clot upon activation by thromboplastin (a mixture of tissue factor and phospholipids). 

Antihemophilic factor B, Christmas factor, plasma thromboplastin component (PTC)... 

FIGURE 7.2 LMWH inhibits factor Xa and minimally affects factor Ha thus, activated partial thromboplastin time is not used to measure its anticoagulant activity. (Reprinted from the American Family Physician published by the American Academy of Family Physicians, February 15th, 1999, in an article entitled Low-molecular-weight heparin in outpatient treatment of DVT. )... 

Activated partial thromboplastin time aPTT is performed by adding calcium phospholipids and kaolin to citrated blood and measures the time required for a fibrin clot to form. In this manner, aPTT measures the activity of intrinsic and common pathways. Prolongation of aPTT may be due to a deficiency or inhibitor for factors II, V, VIII, IX, X, XI, and XII. It also may be due to heparin, direct thrombin inhibitors, vitamin K deficiency, liver disease, or lupus anticoagulant. 

Prothrombin time PT is performed by adding thromboplastin (tissue) factor and calcium to citrate-anticoagulated plasma, recalcifying the plasma, and measuring the clotting time. The major utility of PT is to measure the activity of the vitamin K-dependent factors II, VII, and X. The PT is used in evaluation of liver disease, to monitor warfarin anticoagulant effect, and to assess vitamin K deficiency. 

Thromboplastin A substance that triggers the coagulation cascade. Tissue factor is a naturally-occurring thromboplastin and is used in the prothrombin time test. 

The extrinsic mechanism of blood coagulation begins when a blood vessel is ruptured and the surrounding tissues are damaged. The traumatized tissue releases a complex of substances referred to as tissue thromboplastin. The tissue thromboplastin further complexes with factor VII and Ca++ ions to activate factor X directly. 

Progressive liver damage (shock liver) manifests as elevated serum hepatic transaminases and unconjugated bilirubin. Impaired synthesis of clotting factors may increase prothrombin time (PT), international normalized ratio, and activated partial thromboplastin time (aPTT). 

An overview of the coagulation cascade and sites of action for coumarins and heparin is shown in A. There are two ways to initiate the cascade (B) 1) conversion of factor XII into its active form (Xlla, intrinsic system) at intravascular sites denuded of endothelium 2) conversion of factor VII into Vila (extrinsic system) under the influence of a tissue-derived lipoprotein (tissue thromboplastin). Both mechanisms converge via factor X into a common final pathway. 

In the extravascular pathway (right), tissue thromboplastin (factor 111), a membrane protein in the deeper layers of the vascular wall, activates coagulation factor Vll. The activated form of this (Vila) autocatalytically promotes its own synthesis and also generates the active factors IXa and Xa from their precursors. With the aid of factor Villa, PL, and Ca factor IXa produces additional Xa, which finally— with the support of Va, PL, and Ca ""—releases active thrombin. 

Pharmacology Vitamin K promotes the hepatic synthesis of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X). The mechanism by which vitamin K promotes formation of these clotting factors involves the hepatic post-translational carboxylation of specific glutamate residues to gamma-carboxylglutamate residues in proteins involved in coagulation, thus leading to their activation. 

Extrinsic pathway Coagulation is activated by release of tissue thromboplastin, a factor not found in circulating blood. Clotting occurs in seconds because factor III bypasses the early reactions. 

Pharmacology Enoxaparin, tinzaparin, and dalteparin are LMWHs. These agents enhance the inhibition of Factor Xa and thrombin by binding to and accelerating antithrombin activity. They preferentially potentiate the inhibition of Factor Xa, while only slightly affecting thrombin and clotting time (activated partial thromboplastin time [APTT] or PT). 

Increased prothrombin time, partial thromboplastin time, platelet aggregation time, platelet count, and factors II, VII, VIII, IX, X, XII, Vll-X complex, ll-VII-X complex, and -thromboglobulin decreased antithrombin III, antifactor Xa increased fibrinogen, plasminogen, norepinephrine-induced platelet aggregability. 

Vitamin K activity is associated with several quinones, including phylloquinone (vitamin Kj), menadione (vitamin K3), and a variety of menaquinones (vitamin K2). These quinones promote the synthesis of proteins that are involved in the coagulation of blood. These proteins include prothrombin, factor VII (proconvertin), factor IX (plasma thromboplastin), and factor X (Stuart factor). A detailed discussion of blood coagulation is found in Chapter 22. The vitamin K quinones are obtained from three major sources. Vitamin K is present in vari-... 

Extrinsic pathway This pathway has fewer steps than the intrinsic pathway and occurs rapidly, within a matter of seconds if the trauma is severe. It is called the extrinsic pathway because a protein tissue factor, also called thromboplastin or coagulation factor III, takes into the blood stream from outside and initiates the formation of prothrombinase. Tissue factor is released from the surface of the damaged cells. It activates factor VII. Factor VII combines with factor X, activating it. Factor X in the presence of Ca combines with factor V to give active enzyme prothrombinase. 

---