Deep Vein Thrombosis of the Legs: New Therapy by Mean of Low Molecular Weight Heparins

Zanghì, M; Morici, V; Costanzo, Mario; Astuto, L.; Salanitri, G.

doi:10.1177/030006058801600610

Cited by 23 publications

(7 citation statements)

References 15 publications

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“…Twenty‐six randomized controlled trials were identified from the bibliographic search by following the methodology previously described in Study identification (above) [5–30]. All of them compared the efficacy of UFH and LMWH in patients with DVT.…”

Section: Resultsmentioning

confidence: 99%

“…All of them compared the efficacy of UFH and LMWH in patients with DVT. Ten clinical trials with no venographic assessment [21–30], and three trials with a follow‐up period of < 2 months [5–7] were excluded. Finally, 13 randomized controlled clinical trials were included [8–20].…”

Section: Resultsmentioning

confidence: 99%

“…Centralized and blinded assessment of Marder score by at least two independent experts is the venographic score most commonly used in clinical trials comparing low‐molecular‐weight heparins (LMWHs) and unfractionated heparin (UFH) [5–20]. A lower number of clinical trials used clinical assessment only [21–30]. The validity of venographic scores as surrogate endpoints of clinical outcomes has been supported by the results of isolated clinical trials [19, 31], but no previous meta‐analyses have been performed to analyze the correlation between both outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Correlation between thrombus regression and recurrent venous thromboembolism. Examining venographic and clinical effects of low‐molecular‐weight heparins: a meta‐analysis

Gómez-Outes

Lafuente-Guijosa

Martínez‐González

et al. 2004

Journal of Thrombosis and Haemostasis

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SpainTo cite this article: Gó mez-Outes A, Lecumberri R, Lafuente-Guijosa A, Martínez-Gonzá lez J, Carrasco P, Rocha E. Correlation between thrombus regression and recurrent venous thromboembolism. Examining venographic and clinical effects of low-molecular-weight heparins: a meta-analysis. Summary. We analyzed the correlation between thrombus regression on control venography performed after discontinuation of heparin therapy and recurrent venous thromboembolism (VTE) detected during clinical follow-up in randomized trials comparing low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in patients with deep vein thrombosis (DVT). Data were abstracted from MEDLINE, conference abstracts and reference lists of previous reviews. Randomized, controlled trials comparing LMWH and UFH for the treatment of DVT using a combined venographic and clinical assessment and with at least 2 months of follow-up were selected. The proportions of patients with thrombus regression on control venography performed soon after discontinuation of heparin therapy and recurrent VTE at 2-6 months were independently collected by two researchers. Thirteen studies met the inclusion criteria. There was a strong inverse correlation between thrombus regression and recurrent VTE (r ¼ ) 0.70; P ¼ 0.008). The venographic effect varied between the different LMWHs (P ¼ 0.013). A very strong correlation was found when the results were pooled by the type of LMWH used (r ¼ ) 0.84; P ¼ 0.037). No influence of the dose interval used on the venographic effect (P ¼ 0.156) or on recurrent VTE (P ¼ 0.218) was shown. The lack of thrombus regression in venography, performed soon after heparin discontinuation, was correlated with clinical recurrence. Non-invasive imaging techniques should be relevant to identify non-responders and to assess the optimal duration of initial heparin treatment in daily clinical practice.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Correlation between thrombus regression and recurrent venous thromboembolism. Examining venographic and clinical effects of low‐molecular‐weight heparins: a meta‐analysis

Gómez-Outes

Lafuente-Guijosa

Martínez‐González

et al. 2004

Journal of Thrombosis and Haemostasis

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“…Overall, 22 randomized studies that fulfilled our inclusion criteria were identified, where LMWH was compared with UFH for the initial treatment of VTE. [3][4][5][6][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Twelve studies were excluded for the following reasons: inadequate or incomplete follow-up or the inavailability of 3-month mortality figures for cancer patients [21][22][23][24][25][26][27][28][29][30] ; duplicate report 31 ; or because the study was primarily a dose-finding study 32 . The recently published study by Decousus and colleagues was also excluded because of its factorial study design and the absence of cancer patient-specific data in the main article.…”

Section: Meta-analysismentioning

confidence: 99%

Do Heparins Do More than Just Treat Thrombosis? The Influence of Heparins on Cancer Spread

Hettiarachchi¹,

Smorenburg²,

Ginsberg³

et al. 1999

Thromb Haemost

202

102

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IntroductionThe influence of unfractionated heparin (UFH) and other anticoagulants on the spread of cancer has been reported since the early 1960s.1 However, clinical studies investigating the use of heparins in cancer patients have not produced consistent results.2 Intravenous, adjusted-dose UFH for 5 to 10 days has been the standard initial treatment for venous thrombosis. More recently, subcutaneous, fixed-dose, low molecular weight heparins (LMWHs), which are fractions of the parent compound, have been shown to be safe and effective alternatives to UFH in the initial treatment for venous thromboembolism.3-5 In one of our randomized clinical trials comparing LMWH and UFH in the initial treatment of deep vein thrombosis (DVT), we observed an unexpected difference in 6-month mortality among cancer patients in favor of LMWH, which could not be attributed to a difference in the incidence of thrombotic or bleeding complications.6 A similar observation in favor of LMWH was reported in a subsequent study and in a meta-analysis of trials.7,8 The number of cancer patients included in these studies was small, and adjustment of the observed effect for the baseline characteristics of the cancer patients was not possible. However, these findings suggested an inhibitory effect of LMWH on tumor growth or metastasis, which is less apparent or absent for UFH, resulting in a beneficial effect on the survival of cancer patients. This hypothesis is supported by the observations, in experimental studies, that LMWH and low molecular weight heparan sulfate, in comparison to UFH, effectively suppressed angiogenesis, a process necessary for tumor growth and metastasis.9,10 On the other hand, animal studies that investigated the effect of chemically-modified heparins on the spread of cancer did not detect a superior anti-tumor effect of LMWH compared to UFH; both were found to inhibit metastasis.11,12 To date, the effect of LMWH on cancer survival in humans has not been investigated as a primary objective. If a consistent and beneficial effect of LMWH on mortality is indeed present, such a study would be warranted.We performed a meta-analysis of all available randomized clinical trials where LMWH was compared with UFH in the treatment of venous thromboembolism (VTE) to estimate the crude treatment effect of LMWH on mortality in cancer patients compared to UFH. Subsequently, we adjusted this treatment effect for age, gender, and primary malignancy site by reanalyzing data from three of those trials.3-5 This effect was further adjusted for other prognostic factors, including cancer histology, tumor stage, presence of metastases, duration of cancer, and concomitant use of cancer treatment, by analyzing individual patient data from the largest randomized trial.5

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“…The following LMW heparins have been investi gated and compared with unfractionated heparin for the treatment of DVT in prospective and randomized stud ies: nadroparin (Fraxiparin, Sanofi Winthrop), 6,7 CY 222 (Sanofi Winthrop), 8 dalteparin (Fragmin, Pharma cia Upjohn), [9][10][11][12][13][14][15][16] enoxaparin (Clexane, Rhone Poulenc Rorer), 4,5,17-20 certoparin (Mono-Embolex, Sandoz), 2122 logiparin (Innohep, Braun Melsungen), 23,24 and OP 2123 (Fluxum, Alfa Wassermann). [25][26][27] An overview of the studies and their treatment groups until June 1996 is given in Table 3.…”

Section: Treatment Of Dvt With Lmw Heparinmentioning

confidence: 99%

Treatment of Deep Vein Thrombosis with Low-Molecular-Weight Heparins: A Consensus Statement of the Gesellschaft für Thrombose-und Hämostaseforschung (GTH)

Harenberg

Schmitz-Huebner²,

Breddin³

et al. 1997

Semin Thromb Hemost

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Recent studies have led to a new concept for the management of deep vein thrombosis. The German Society on Thrombosis and Haemostasis decided to work up the clinical studies in this field published until June 1996 for a consensus statement. The consensus group concluded that (1) high-dose, APTT-controlled subcutaneous administration of unfractionated heparin is as effective as high-dose, APTT-controlled continuous intravenous infusion of unfractionated heparin (grade B recommendation); (2) the anticoagulation with heparin may start at day 1 or 2, overlapping with oral anticoagulants for 7 to 10 days (grade C recommendation); (3) high-dose subcutaneous low-molecular-weight heparins are almost as effective and safe as continuous intravenous infusion of unfractionated heparins (grade B recommendation); (4) no agreement was obtained for the other concomitant treatments of DVT, such as duration of bed rest, use of antiphlogistic drugs, whether LMW heparins are comparable, and whether outpatient treatment can be recommended using LMW heparins.

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Deep Vein Thrombosis of the Legs: New Therapy by Mean of Low Molecular Weight Heparins

Cited by 23 publications

References 15 publications

Correlation between thrombus regression and recurrent venous thromboembolism. Examining venographic and clinical effects of low‐molecular‐weight heparins: a meta‐analysis

Correlation between thrombus regression and recurrent venous thromboembolism. Examining venographic and clinical effects of low‐molecular‐weight heparins: a meta‐analysis

Do Heparins Do More than Just Treat Thrombosis? The Influence of Heparins on Cancer Spread

Treatment of Deep Vein Thrombosis with Low-Molecular-Weight Heparins: A Consensus Statement of the Gesellschaft für Thrombose-und Hämostaseforschung (GTH)

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