Intravenous and Subcutaneous Administration of Fragmin in Deep Venous Thrombosis

The aim of the present study was to gain clinical experience with different dose levels of dalteparin, a low-molecular-weight heparin, following thrombolytic therapy in acute myocardial infarction. Compared to heparin, dalteparin has a longer half-life and a greater and highly predictable bioavailability, which would suggest dalteparin to be a convenient alternative. Twenty patients with ECG signs of acute transmural myocardial ischemia received streptokinase (1.5 million IU for 60 min) and were allocated to a control group or to open treatment with 50, 75 or 100 IU of dalteparin/kg b.w. s.c. b.i.d., starting 4 h later, for 6 days. Each group consisted of 5 patients. Except for the control group, aspirin was withheld during dalteparin treatment. Anti-factor-Xa (anti-FXa) values increased dose-dependently during the first 24 h and were maintained throughout the study period. On day 6, anti-FXa levels after 100 IU/kg b.w. were 0.79 (0.59-1.00) IU/ml (median, min.-max.) 4 h after administration of dalteparin, and 0.51 (0.34-0.82) IU/ml before the subsequent dose of dalteparin. In conclusion, our results indicate that a dalteparin dose slightly higher than 100 IU/kg b.w. is required in order to obtain the presumed therapeutic range of anti-FXa (0.6-1.0 IU/ml).

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Anticoagulant Effects of Low-Molecular-Weight Heparin following Thrombolytic Therapy in Acute Myocardial Infarction: A Dose-Finding Study

Strandberg

Kahan

Lundin

et al. 1996

“…In another study by Lockner et al [51], 120 anti-Xa units/kg Fragmin given subcuta neously 2 times daily to 13 patients with DVT resulted in adequate anti-Xa activity but with a tendency for accumulation of the Fragmininduced activity. Subcutaneous injections of Fragmin 2 times daily also appeared to effec tively prevent the progression of thrombosis.…”

Section: Randomized Clinical Trials Evaluating Lm W Heparinmentioning

confidence: 95%

“…In 1986, Lockner et al [51] compared intravenous infusions of unfractionated hepa rin with LMW heparin (Fragmin). Fifty-four patients with venographically verified DVT were randomized to treatment with either in travenous infusions of 240 anti-Xa units/kg/ 12 h of unfractionated heparin or 240 or 120 anti-Xa units/kg/12h of the LMW heparin Fragmin.…”

Section: Randomized Clinical Trials Evaluating Lm W Heparinmentioning

confidence: 99%

Therapeutic Use of Low-Molecular-Weight Heparins

Hull

Pineo²

1993

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.

“…Initial treatment lasted 5 to 10 days in all studies, and patients received at least 3 months of vitamin K antagonists for prevention of recurrent symptomatic VTE thereafter. A total of 24 studies were excluded for the following reasons: it was impossible to extract the clinical data from the published material [7][8][9][10][11][12][13]; they were reports of studies that were later published in full [14-17]; LMWH doses were adjusted or it was a dose-ranging study [18][19][20][21][22][23][24][25]; clinical outcomes were not objectively confirmed [22,23,26]; follow-up lasted less than 3 months [22, 23]; fixed-dose UFH was used [26][27][28]; it was a duplicate report [29]; and data were earlier published in full [30].…”

Section: Identification Of Trialsmentioning

confidence: 99%

Low-Molecular-Weight Heparins: Are They Interchangeable?

Heijden

Prins²,

Büller³

2000

Unfractionated heparin (UFH) has been used as an antithrombotic agent in the treatment of various clinical entities for over 60 years. Low-molecular-weight heparin (LMWH) com- pounds have gradually replaced UFH for these indications as they have several advantages, including subcutaneous administration and the lack of need for laboratory monitoring. Ever since their introduction, there has been discussion about whether LMWH compounds differ in their efficacy and safety. The best answer is given by direct comparison of two or more preparations; however, such trials are very scarce. Comparison using classical meta-analysis is limited as only a small number of trials with the respective low-molecular-weight heparin compounds are available. The objective of the present analysis has been to use a novel way of plotting the odds ratios of the different studies to compare the efficacy and safety of different LMWH compounds in the initial treatment of patients with venous thromboembolism. Classical meta-analysis revealed reductions in safety and efficacy of 30–40% in favour of LMWHs. Contrasting the log odds ratios of efficacy and safety indicated that there is no conclusive evidence that LMWHs have intrinsic different safety and efficacy profiles.