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| __NOTOC__
| | #REDIRECT [[Antithrombin III#Pharmacology]] |
| {{Anti[[thrombin]] III}}
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| {{CMG}}, {{AE}}{{JH}}
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| ==Clinical Pharmacology==
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| Anti[[thrombin]] III, an alpha2-glycoprotein of molecular weight 58,000, is normally present in human [[plasma]] at a concentration of approximately 12.5 mg/dL(6,7) and is the major [[plasma]] inhibitor of [[thrombin]].(8) Inactivation of [[thrombin]] by ATIII occurs by formation of a covalent bond resulting in an inactive 1:1 stoichiometric complex between the two, involving an interaction of the active serine of [[thrombin]] and an arginine reactive site on ATIII.(8) ATIII is also capable of inactivating other components of the coagulation cascade including factors IXa, Xa, XIa, and XIIa, as well as [[plasmin]].(8)
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| The neutralization rate of serine proteases by ATIII proceeds slowly in the absence of heparin, but is greatly accelerated in the presence of heparin.(8) As the therapeutic antithrombotic effect in vivo of heparin is mediated by ATIII, heparin is ineffective in the absence or near absence of ATIII.(8–12)
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| The prevalence of the hereditary deficiency of ATIII is estimated to be one per 500 to 5000 in the general population.(8,11,13) The pattern of inheritance is [[autosomal dominant]]. In affected individuals, spontaneous episodes of thrombosis and [[pulmonary embolism]] may be associated with ATIII levels of 40%–60% of normal.(14,15) These episodes usually appear after the age of 20, the risk increasing with age and in association with surgery, pregnancy and delivery. The frequency of thromboembolic events in hereditary ATIII deficiency during pregnancy has been reported to be 70%, and several studies of the beneficial use of Anti[[thrombin]] III (Human) concentrates during pregnancy in women with hereditary deficiency have been reported.(16–18) In many cases, however, no precipitating factor can be identified for venous thrombosis or pulmonary embolism.(11) Greater than 85% of individuals with hereditary ATIII deficiency have had at least one thrombotic episode by the age of 50 years.(11) In about 60% of patients thrombosis is recurrent. Clinical signs of pulmonary embolism occur in 40% of affected individuals.(11) In some individuals, treatment with oral anticoagulants leads to an increase of the endogenous levels of ATIII, and treatment with oral anticoagulants may be effective in the prevention of thrombosis in such individuals.(10,11)
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| In clinical studies of THROMBATE III conducted in 10 asymptomatic subjects with hereditary deficiency of ATIII, the mean in vivo recovery of ATIII was 1.6% per unit per kg administered based on immunologic ATIII assays, and 1.4% per unit per kg administered based on functional ATIII assays.(14) The mean 50% disappearance time (the time to fall to 50% of the peak [[plasma]] level following an initial administration) was approximately 22 hours and the biologic half-life was 2.5 days based on immunologic assays and 3.8 days based on functional assays of ATIII.(14) These values are similar to the half-life for radiolabeled Anti[[thrombin]] III (Human) reported in the literature of 2.8–4.8 days.(19–21)
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| In clinical studies of THROMBATE III, none of the 13 patients with hereditary ATIII deficiency and histories of thromboembolism treated prophylactically on 16 separate occasions with THROMBATE III for high thrombotic risk situations (11 surgical procedures, 5 deliveries) developed a thrombotic complication. Heparin was also administered in 3 of the 11 surgical procedures. Eight patients with hereditary ATIII deficiency were treated therapeutically with THROMBATE III as well as heparin for major thrombotic or thromboembolic complications, with seven patients recovering. Treatment with THROMBATE III reversed heparin resistance in two patients with hereditary ATIII deficiency being treated for thrombosis or thromboembolism.
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| During clinical investigation of THROMBATE III, none of 12 subjects monitored for a median of 8 months (range 2–19 months) after receiving THROMBATE III became antibody positive to [[human immunodeficiency virus]] (HIV-1). None of 14 subjects monitored for ≥ 3 months demonstrated any evidence of [[hepatitis]], either non-A, non-B hepatitis or [[hepatitis B]].<ref>{{Cite web | last = | first = | title = THROMBATE III (ANTI[[thrombin]] III) KIT [GRIFOLS USA, LLC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b2a9f856-3ef7-8da4-920c-f738e4f1f7d7 | publisher = | date = | accessdate = 7 March 2014 }}</ref>
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| ==References==
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| {{Reflist}}
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| {{FDA}}
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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