Thromboplastin inhibition

Mechanism of action Activates plasma antithrombin, blocks thromboplastin Inhibits the synthesis of factors II, VII, IX, and X by... 

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. )... 

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). 

Therapy with heparin occurs in an inpatient setting. Heparin inhibits both in vitro and in vivo clotting of blood. Whole blood clotting time and activated partial thromboplastin time (aPTT) are prolonged in proportion to blood heparin concentrations. 

I 10 Day KC, Hoffman LC, Palmier MO, et al, Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit. Blood 1990 76 1538-1545. 

It was found that rivaroxaban competitively inhibits human FXa and prothrombinase activity (/C50 = 2.1 nM). It inhibits endogenous FXa more potently in human and rabbit plasma (/C50 = 21 nM) than in rat plasma (/C50 = 290 nM). Rivaroxaban has demonstrated anticoagulant effects in human plasma, doubling the prothrombin time (PT) and activated partial thromboplastin time (APTT) at 0.23 and 0.69 pM, respectively. In vivo, rivaroxaban reduced venous thrombosis dose dependency (EDS0 = 0.1 mg/kg i.v.) in a rat venous stasis model. The pharmacological actions of rivaroxaban have been described in more detail by Perzbom et al.12... 

Antithrombin, in presence of low molecular weight heparin, produces anticoagulation by inhibition of factor Xa. Enoxaparin causes less inactivation of thrombin, inhibition of platelets, and bleeding than standard heparin. Does not significantly influence bleeding time, prothrombin time (PT), activated partial thromboplastin time (APTT). 

Several new compounds have been reported that affect the formation of a fibrin clot. Aromatic diamidines, such as, 21, were reported to inhibit several proteolytic enzymes including thrombin.74 Concanavalin A (a globulin protein from the jack bean) inhibits fibrin formation by inhibiting the lipoprotein cofactor in the production of thrombin and thus decreasing the rate of thrombin production.75 Several antibiotics (penicillins and cephalosporins) have been reported to affect fibrin clot formation as well as platelet function. Cephalothin (22) has been shown to delay fibrin polymerization and thus prolong the activated partial thromboplastin time (APTT) and thrombin time tests.78... 

Inhibition of Clotting. In all species studies, phosphorothioate oligodeoxynucleotides induce a transient, apparently self-limited, peak plasma concentration-related inhibition of clotting, manifested as an increase in activated partial thromboplastin... 

Mechanism and effects Regular heparin binds to and activates endogenous antithrombin 111 (ATlIl). The heparin-ATIll complex combines with and inactivates thrombin (activated factor 11) and several other factors, especially factor X. In the presence of heparin, antithrombin III inhibits the coagulation factors approximately 1000-fold faster than in its absence. Low doses of heparin also coat the endothelial walls of vessels and reduce the activation of clotting elements by these cells. Because it acts on preformed blood components, heparin is also active in vitro—almost instantaneously. The action of heparin is monitored with the activated partial thromboplastin time laboratory test (aPTT or PTT). 

I. Pharmacology. Protamine is a cationic protein obtained from fish sperm that rapidly binds to and inactivates heparin. The onset of action after intravenous administration is nearly immediate (30-60 seconds) and lasts up to 2 hours. It also partially neutralizes low-molecular-weight heparins (LMWHs) and can act as an anticoagulant itself by inhibiting thromboplastin. 

When blood is lost or clotting is initiated in some other way, a complex cascade of biochemical reactions is set in motion, which ends in the formation of a network or clot of insoluble protein threads enmeshing the blood cells. These threads are produced by the polymerisation of the molecules of fibrinogen (a soluble protein present in the plasma) into threads of insoluble fibrin. The penultimate step in the chain of reactions requires the presence of an enzyme, thrombin, which is produced from its precursor prothrombin, already present in the plasma. This is initiated by factor lit (tissue thromboplastin), and subsequently involves various factors including activated factor Vn, DC, X, XI and XII, and is inhibited by antithrombin in. Platelets are also involved in the coagulation process. Fibrinolysis is the mechanism of dissolution of fibrin clots, which can be promoted with thrombolytics. For further information on platelet aggregation and clot dissolution, see Antiplatelet drugs and thrombolytics , (p.697). 

In healthy volunteers orally administered garlic capsules at the manufacturer s recommended dose (amount not specified) daily for two weeks, no effects on platelet function or other hematological parameters were observed, including prothrombin time, partial thromboplastin time, thrombin time, bleeding time, the collagen/epinephrine assay, or the collagen/adenosine diphosphate assay. Aspirin was used as a positive control and markedly inhibited platelet function (Beckert et al. 2007). 

Steroidal saponins isolated from anemarrhena inhibited platelet aggregation and activated partial thromboplastin time in human blood (Zhang et al. 1999). Another saponin inhibited PAF-induced platelet aggregation in rabbit blood (Dong and Han 1991). 

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