Analysis of factors affecting the recurrence of thromboembolism off and on anticoagulant therapy

Carter, Stefan A.; McDevitt, Ellen; Gatje, Barbara W.; Wright, Irving S.

doi:10.1016/0002-9343(58)90197-9

Cited by 42 publications

(10 citation statements)

References 10 publications

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“…The concept of rebound hypercoagulable state on abrupt cessation of warfarin was derived from studies which found an increased incidence of rethrombosis in patients after warfarin was stopped abruptly compared with patients who had not been treated with anticoagulants or in whom warfarin had been tailed off (Carter et al 1958;Lieberman & Lindner 1965). The concept of rebound hypercoagulable state on abrupt cessation of warfarin was derived from studies which found an increased incidence of rethrombosis in patients after warfarin was stopped abruptly compared with patients who had not been treated with anticoagulants or in whom warfarin had been tailed off (Carter et al 1958;Lieberman & Lindner 1965).…”

Section: Initiation and Cessation Of Warfarin Therapymentioning

confidence: 99%

Clinical Pharmacokinetic Considerations in the Control of Oral Anticoagulant Therapy

Shetty

Fennerty

Routledge

1989

Clinical Pharmacokinetics

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Aspects of the pharmacokinetics of warfarin that are clinically relevant are reviewed here. Since warfarin is normally completely absorbed, resistance to treatment due to impaired absorption is unusual, even in severe short bowel syndrome. Warfarin is highly albumin-bound; thus, hypoalbuminaemic states result in an increased free fraction of the drug and a decreased half-life but, as might be expected, there is no evidence of altered response at steady-state. Warfarin is completely metabolised by the liver to hydroxy-warfarins and warfarin alcohols, and although the latter have some biological activity they do not contribute significantly to the drug effect. No information is available concerning the metabolism of warfarin in chronic liver disease, but there is evidence of increased sensitivity due to impaired vitamin K-dependent clotting factor synthesis. Impaired renal function does not appear to alter the effect of warfarin. Lowered response to the drug may be secondary to poor compliance, kinetic resistance or pharmacodynamic resistance. These factors can be identified using algorithms based on population values for plasma warfarin concentrations and clearances at steady-state. The pharmacokinetics and pharmacodynamics of warfarin indicate that several days' overlap with heparin on initiation of warfarin, and gradual (rather than sudden) discontinuation of warfarin, might theoretically be necessary. However, those studies which have been performed have indicated that a long overlap and gradual discontinuation are not associated with greater safety or efficacy of the drug. Because of the long elimination half-life of warfarin and the short elimination half-life of vitamin K, many days' treatment with phytomenadione may be required after warfarin overdose. The elimination half-life and therefore the duration of therapy may be reduced by regular oral cholestyramine, although the means by which the latter enhances warfarin elimination is still unknown.

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Section: Initiation and Cessation Of Warfarin Therapymentioning

confidence: 99%

Clinical Pharmacokinetic Considerations in the Control of Oral Anticoagulant Therapy

Shetty

Fennerty

Routledge

1989

Clinical Pharmacokinetics

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“…A number of clinical studies appear to demonstrate a transient increase of thrombotic events after cessation of anticoagulation (Marshall, 1963;Liebermann & Lindner, 1965;Dinon & Vander Veer, 1969;Kuhn et al, 1961;Evans et al, 1970;Hart & Coull, 1983), whereas others do not (Côté et al, 1977;Van Cleve, 1965Kamath & Thorne, 1969;Wright, 1961;De Vries et al, 1980) or are not conclusive in this respect (Carter et al, 1958;Sharland, 1966;Sise et al, 1961;Thomas et al, 1960;Keyes et al, 1956;Nichol et al, 1958;Grip et al, 1991;Michaels, 1970;Pickering et al, 1964). The interpretation is difficult because the prethrombotic state may simply reappear (and is not transient) after a phase of suppression by oral anticoagulants as suggested by one study (Harenberg et al, 1983), or the pathological vascular process has silently proceeded further and becomes overt again; both types of events are not consistent with a transient overshooting of coagulation and subsequent normalization but rather with a 'catching up' to the initial or actual levels (Michaels, 1970;Wright, 1960Wright, , 1961.…”

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confidence: 99%

Rebound after cessation of oral anticoagulant therapy: the biochemical evidence

et al. 1996

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The existence of a phenomenon of rebound hypercoagulability after cessation of oral anticoagulant therapy is controversial. The sensitive procoagulant markers for in vivo thrombin and fibrin formation are potential tools for the reassessment of the presence of each a phenomenon. We examined 19 patients anticoagulated for 6 +/- 2 months (SD, range 3-12) because of venous thromboembolism or myocardial infarction as follows: twice during stable, oral anticoagulation (INR 3.1-3.7) and then on days 1, 2, 3, 4, 5, 7, 9, 11, 13, 15, and > 30 after cessation of oral anticoagulation. Thrombin-antithrombin III complexes (TAT) and fibrinopeptide A (FPA) were measured in addition to the prothrombin times and factors II, V, VII, and X. None of the 19 patients developed clinically manifest thromboembolism within the following 9-18 months. However, the patients' TAT levels increased transiently: rising from 1.5 +/- 0.1 ng/ml (SEM) to 3.0 +/- 0.2 ng/ml on day 4 (P < 0.001), and returned to 1.7 +/- 0.1 ng/ml after day 30 (normals 1.8 +/- 0.33). 17/19 patients showed TAT peak levels above the upper limit of normal between days 3 and 11 (average: day 4), which normalized again after 30 d. 8/19 patients also had transient FPA levels above the upper normal limits ( < 1.81). We conclude that our patients increased their thrombin and fibrin formation transiently and that a subpopulation reached values consistent with a prethrombotic state.

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“…"Rebound" Thromboembolism.-It has been the clinical impression of some au¬ thors 22 that there is a danger in abruptly discontinuing anticoagulant therapy because of a "rebound" increase in the tendency toward recurrent thromboembolism which may exist for a few days or weeks after the drug is stopped. In the present group of 117 patients who stopped anticoagulant therapy during the observation period, 5 patients had a recurrent infarction within 1 month of discontinuing therapy.…”

Section: Resultsmentioning

confidence: 99%