Clinical Relevance of Antithrombin III

Bick, Rodger L.

doi:10.1055/s-2007-1005058

Cited by 141 publications

(94 citation statements)

References 83 publications

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“…Antithrombin 111 activity below 40% ofnorma1 results in no response to heparin therapy in humans with DIC. 74 In addition, heparin administration increases AT I11 consumption, which may potentiate thrombosis in patients with subnormal AT I11 activity.99 Soluble fibrin monomers protect thrombin from inactivation by the heparin-AT I11 complex, and their production is increased in DIC.lOO Heparin therapy instituted after amplification ofthe coagulation cascade and subsequent AT 111 depletion and soluble fibrin monomer formation is not likely to be effective, indicating that therapy should be instituted immediately in horses with severe gastrointestinal disorders. When administered at recommended doses, heparin does not potentiate bleeding complications at surgery, and it may be safely administered preoperatively to horses suspected of having intestinal strangulation-obstruction lesions.…”

Section: Disseminated Intravascular Coagulationmentioning

confidence: 99%

Heparin: A Review of its Pharmacology and Therapeutic Use in Horses

Moore

Hinchcliff

1994

Veterinary Internal Medicne

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Heparin is used clinically in horses to treat hemostatic abnormalities associated with severe gastrointestinal disease, septicemia, and endotoxemia. The primary anticoagulant effect of heparin is through the suppression of thrombin-dependent amplification of the coagulation cascade, and inhibition of thrombin-mediated conversion of fibrinogen to fibrin. Heparin may be of benefit in preventing the complications associated with hypercoagulable states such as jugular vein thrombosis, laminitis, and organ failure. Heparin may also be beneficial in the prevention of intraabdominal adhesions after gastrointestinal surgery, and in amelioration of hernodynamic abnormalities associated with endotoxic shock. Because a sequential rise in serum unique compound with anticoagulant activity was ac-A cidentally discovered in 19 16 by McClean, a medical student, while he was attempting to identify a procoagulant in the liver.' The substance was named heparin because of its abundance in hepatic tissue.' In 1939, Brinkhous discovered that a plasma cofactor was necessary for the anticoagulant activity of h e~a r i n .~ Abildgaard named the cofactor antithrombin 111 (AT 111), and the specific mechanism of action of this cofactor was elucidated shortly thereafter. [4][5][6] Heparin is composed of a family of straight-chain, highly sulfated, anionic polysaccharides, specifically glycosaminoglycuronan sulfate esters, with molecular weights varying from 4,000 to 40,000 d.7-9 The structural unit of this complex molecule is a two hexose sugar that, in 8 to 15 repeating disaccharide subunits, forms a polymer of differing length^.^.' The structure of heparin is markedly heterogenous and varies with respect to the sequence and ratio of the different hexose units, the extent and type of sulfation, and the extent of N-a~etylation.~ The heterogeneity of heparin is not an artifact of preparation, but occurs because of the randomness of the biosynthetic process. lo Endogenous heparin is produced within mast cells of the lung, liver, and intestine.' ' Commercially-available heparin is derived from the mast cells of porcine intestinal mucosa and bovine lung."A small and distinct fraction of the heparin molecule is responsible for its anticoagulant effect. l 3 The active site of the heparin molecule contains a unique glucosamine unit with a specific pentasaccharide ~equence.'~.'~ This distinct fraction of the heparin molecule binds to AT 111, an endog-

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Section: Disseminated Intravascular Coagulationmentioning

confidence: 99%

Heparin: A Review of its Pharmacology and Therapeutic Use in Horses

Moore

Hinchcliff

1994

Veterinary Internal Medicne

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“…In the normal range (70-130%), only moderate decreases in AT have been reported to be associated with thrombosis. [16][17][18] The overall much higher frequency of protein S deficiency (16.6%), which was four times greater than in Western studies 14,15 could be partly attributed to reductions in C4b protein, as a result of higher rates of subclinical infec- tions among Indians. In none of the cases was an underlying cause present; therefore, most of them were considered to consist of inherited deficiencies of anticoagulant proteins.…”

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confidence: 99%

Prevalence of common thrombophilia markers and risk factors in Indian patients with primary venous thrombosis

Mishra

Bedi

2010

Sao Paulo Med. J.

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CONTEXT AND OBJECTIVE: Venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. DESIGN AND SETTING: This was a cross-sectional study carried out in Mumbai. METHODS: Samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and β2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). RESULTS: The popliteal vein was the most commonly involved site. Forty-four samples (56%) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9% each), followed by low protein S (16.6%). CONCLUSIONS: This study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.

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“…inhibits factors XIIa, XIa, IXa, Xa, plasmin, and thrombin (5). Healthy premature and full term infants have low levels of a normally functioning AT-I11 molecule at birth (30-50% of adult values) (3,7,13,16,22,35) but do not develop spontaneous thrombosis as do adults with similar inherited low levels of AT-111.…”

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confidence: 99%

Dysfunctional Antithrombin III in Sick Premature Infants

et al. 1985

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ABSTRAm. Antithrombin 111, a major inhibitor of activated coagulation factors has low immunologic levels in the human infant. The objective of this study was to deermine if the antithrombin 111 molecule is fully functional in sick premature infants. The populations studied included: adult controls (n = 20), full term healthy infants (n = 18), sick premature infants on day 1 (n = 16) and at >7 days of age (n = lo), and infants with disseminated intravascular coagulation (n = 11). This was diagnosed in the presence of prolonged screening tests, decreased levels of fibrinogen, and platelets along with elevated fibrin degradation products. Plasma antithrombin 111 levels were measured biologically (chromogenic substrate S2238) and immunologically (radialimmunodiffusion), and expressed as a percent of adult pooled plasma. Crossed immunoelectrophoresis were performed in the presence and absence of heparin. The antithrombin 111 biologic/immunologic ratios for adults, healthy full term infants, and sick premature infants on day 1 of life were all near unity. In contrast sick premature infants beyond the 1st wk of life and infants with disseminated intravascular coagulation had lower biologic activity compared to immunologic (B/I = 0.77 f 0.28, 0.78 f 0.17, p < 0.01), respectively. In all groups, the antithrombin 111 molecule was normal on crossed immunoelectrophoresis except for one infant with disseminated intravascular coagulation. Sick premature infants may acquire a dysfunctional antithrombin 111 molecule in the postnatal period. (Pediatr Res 19: 237-239, 1985) Abbreviations AT-111, antithrombin 111 RDS, respiratory distress syndrome BPD, bronchopulmonary dysplasia DIC, disseminated intravascular coagulation CIE, cross-immunoelectrophoresis APTT, activated partial thromboplastin time PT, prothrombin time TcT, thrombin clotting time EACA, €-amino caproic acid Normal hemostasis depends on a delicate balance between the procoagulant and fibrinolytic systems and their respective inhibitors. AT-111, the major inhibitor for the coagulation system

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Clinical Relevance of Antithrombin III

Cited by 141 publications

References 83 publications

Heparin: A Review of its Pharmacology and Therapeutic Use in Horses

Heparin: A Review of its Pharmacology and Therapeutic Use in Horses

Prevalence of common thrombophilia markers and risk factors in Indian patients with primary venous thrombosis

Dysfunctional Antithrombin III in Sick Premature Infants

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