Heparin therapy: A randomized prospective study

Wilson, John R.; Lampman, James H.

doi:10.1016/0002-8703(79)90349-1

Cited by 124 publications

(26 citation statements)

References 6 publications

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“…Patients with thromboembolic disease require larger doses, even when infused continuously, than those without such disease (White et aI., 1979). The divergent opinions about the utility of continuous monitoring of heparin therapy with periodic clotting tests cannot yet be resolved, because of differences among the study protocols employed and because insufficient data pertaining to relative dose have been reported in conjunction with concomitantly measured clotting times (Glazier and Crowell, 1976;Mant et al, 1977;Norman and Provan, 1977;Salzman et aI., 1975;Verska, 1977;Wilson and Lampman, 1979). It seems highly probable that the wide interindividual variation in response to the anticoagulant, especially when influenced by thrombogenesis, contributes to the diverse interpretations of the available data.…”

Section: Choice Ofa Mode Of Heparin Administrationmentioning

confidence: 99%

Clinical Pharmacokinetics of Heparin

1980

Clinical Pharmacokinetics

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Heparin binds reversibly to its target sites of action, antithrombin and the other serine proteases involved in coagulation, especially activated factor X. It also binds to other plasma proteins, including fibrinogen, plasmin, albumin, and lipases. The volume of distribution of heparin is then, under most circumstances, limited to the plasma volume. Heparin has a very short half-life, about 1.5 hours, which is dose-dependent and varies with the assay method employed for its measurements. It is not eliminated enzymatically nor by glomerular filtration or renal tubular secretion. In all likelihood, the anticoagulant is transferred to reticuloendothelial cells, which may also provide the means for its degradation. Many of the difficulties inherent in assessing the kinetic properties of heparin, as well as its clinical efficacy, may be attributed to: (1) its molecular heterogeneity; (2) its wide spectrum of binding sites and their respective kinetic properties and dissociation constants; (3) differences among methods for measuring heparin effect and concentration; (4) the dose dependence of the drug's half-life; (5) variation in patient response to heparin; (6) the specific cation associated with it; and (7) the presence of hypercoagulation syndromes associated with deficits of antithrombin. Neither renal nor hepatic disease, nor the biological tissues from which heparins are extracted commercially, seem to influence the drug's kinetic properties as much as variations in clearance and response to heparin among individual patients. Many comparisons among available studies are difficult because of the wide variation in the assay methods employed in them. It would appear that optimum therapy with heparin can be achieved only when the individual patient's response to, and rate of elimination of, heparin are taken into account concurrently.

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Section: Choice Ofa Mode Of Heparin Administrationmentioning

confidence: 99%

Clinical Pharmacokinetics of Heparin

1980

Clinical Pharmacokinetics

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“…Haemostasis 1998;28(suppl 3): [8][9][10][11][12][13][14][15][16] Hull/Pineo/Raskob impact of treating 37% of the patients as outpatients with a discharge from the hospital on day 2. The 95% confidence limits were also used for this proportion in the sensitivity analysis to evaluate the effect of varying the proportion treated as outpatients on the conclusions of cost-effectiveness analysis.…”

Section: Intravenous Heparin 12mentioning

confidence: 99%

The Economic Impact of Treating Deep Vein Thrombosis with Low-Molecular-Weight Heparin: Outcome of Therapy and Health Economy Aspects

Hull

Pineo

Raskob

1998

Pathophysiol Haemos Thromb

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Subcutaneous low-molecular-weight heparin (LMWH) is at least as safe and effective as classical intravenous heparin therapy for the treatment of proximal vein thrombosis. Anticoagulant monitoring and intravenous administration are not required with LMWH treatment, therefore this therapy may offer economic advantages. An economic evaluation of these therapeutic approaches was performed comparing the costs and effectiveness. The evaluation was aimed at helping decision-makers to maximize the health of the population served, subject to available resources. The American-Canadian Thrombosis Study was a multicentre, randomized, double-blind clinical trial that compared treatment by initial continuous intravenous infusion of heparin (followed by 3 months of warfarin therapy) with a once-daily dose of subcutaneous LMWH, tinzaparin sodium (followed by 3 months of warfarin treatment) in patients with acute proximal deep vein thrombosis. In the LMWH-treated group, the cost incurred for 100 patients was $399,403 (Canadian) or $335,687 (US) with a frequency of objectively documented recurrent venous thromboembolism of 2.8%. In the intravenous heparin-treated group, the cost incurred for 100 patients was $414,655 (Canadian) or $375,836 (US), with a frequency of objectively documented recurrent venous thromboembolism of 6.9%. These results show a cost saving of $15,252 (Canadian) or $40,149 (US) with the use of LMWH. Multiple sensitivity analyses did not alter the findings of the study which indicated that LMWH therapy is at least as safe and effective but less costly than intravenous heparin treatment. The potential for outpatient therapy in up to 37% of patients who are receiving LMWH would substantially augment the cost-saving. The cost-effectiveness findings presented in this paper are based on the assumption that all costs are covered by a single payer. Outpatient management in many countries will shift the healthcare costs from the healthcare payer to the patient, increasing the economic burden to the patient.

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“…The classic treatment for acute deep-vein thrombosis (DVT) is initial therapy with con tinuous intravenous heparin [1][2][3][4][5] followed by long-term oral anticoagulant therapy [6][7][8][9], Improvements in the methods of clinical trials and the use of accurate objective tests to detect venous thromboembolism [10][11][12][13][14] have made it possible to perform a series of randomized trials [1-5, 7. 8.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Use of Low-Molecular-Weight Heparins

Hull

Pineo²

1993

Pathophysiol Haemos Thromb

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Accumulating evidence indicates that certain low-molecular-weight (LMW) heparins administered subcutaneously may replace classic intravenous heparin therapy. LMW heparins do not require monitoring and may be safer and more effective than unfractionated heparin. The decreased mortality rate, evident in two randomized trials, which was particularly striking in patients with metastatic carcinoma, requires confirmation. The simplified care offered by LMW heparin therapy raises the possibility of transferring care from in-hospital to out of hospital in uncomplicated patients with deep-vein thrombosis [Salzman EW: Low-molecular weight heparin and other new antithrombotic drugs. N Engl J Med 1992;326: 1017-1019]. The advantages to the patient of avoiding in-hospital care and its associated hazards are obvious. Outpatient LMW heparin therapy will likely prove to be highly cost-effective. It is uncertain at present whether the findings associated with an individual LMW heparin preparation can be extrapolated to a different LMW heparin. For this reason the findings of clinical trials apply only to the particular LMW heparin evaluated and cannot be generalized to the LMW heparins at large.

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Heparin therapy: A randomized prospective study

Cited by 124 publications

References 6 publications

Clinical Pharmacokinetics of Heparin

Clinical Pharmacokinetics of Heparin

The Economic Impact of Treating Deep Vein Thrombosis with Low-Molecular-Weight Heparin: Outcome of Therapy and Health Economy Aspects

Therapeutic Use of Low-Molecular-Weight Heparins

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