Low-dose low–molecular-weight heparin is anti-inflammatory during venous thrombosis

Downing, L.; Strieter, Robert M.; Kadell, Amy M.; Wilke, Carol A.; Greenfield, Lazar J.; Wakefield, Thomas W.

doi:10.1016/s0741-5214(98)70060-6

Cited by 100 publications

(70 citation statements)

References 26 publications

(32 reference statements)

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“…[27][28][29][30][31][32] Although the mechanisms behind the anticancer activity of LMWH remain poorly understood, these could involve an effect on the host immune response. [33][34][35][36][37][38] However, this hypothesis was not confirmed by the results of the current study, in which none of the measured cytokines was found to correlate with the beneficial survival effects of nadroparin. 28 Although a change in these cytokine concentrations would have given an indication of the general immune system activity against the tumor, the lack of such an effect cannot exclude a possible influence of LMWH on other immune markers or on immune pathways not reflected in circulating markers.…”

Section: Discussioncontrasting

confidence: 65%

“…[27][28][29][30][31][32] The beneficial effects of LMWH on survival could be related to an effect on the host immune response, although data are limited, with discordant results published across the studies, possibly due to differences in experimental conditions. [33][34][35][36][37][38] Another possible mechanism with which to explain the anticancer activity of LMWH could be that LMWH interferes with the cross-talk between platelets and tumor cells. Platelets have the potential to promote several steps of the tumor progression and markers of platelet activation have been correlated with a worse prognosis in patients with cancer.…”

mentioning

confidence: 99%

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Plasma cytokine and P‐selectin levels in advanced malignancy

Nisio¹,

Niers²,

Reitsma³

et al. 2005

Cancer

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BACKGROUNDThe survival benefit described in patients with cancer treated with low molecular weight heparin (LMWH) may result from a LMWH‐mediated effect on the immune system or on the cross‐talk between platelets and tumor cells.METHODSPlasma levels of interleukin (IL)‐10, IL‐6, interferon (IFN)‐γ, and P‐selectin were measured in patients with advanced stage malignancy who were randomized to receive standard cancer care with or without the addition of LMWH.RESULTSPatients with IL‐6 levels above the median had a median survival of 6.5 months versus 8.8 months for those with values below this cutoff (P = 0.02). IL‐10 levels were found to be similarly correlated with survival such that IL‐10 concentrations above the detection limit of the assay were associated with a doubled risk of dying in comparison to undetectable IL‐10 (P = 0.02). No significant association was found between survival and circulating levels of IFN‐γ. For P‐selectin, patients with values below the fourth quartile had a median survival of 8.8 months versus 6.5 months for patients with levels above the fourth quartile (P = 0.02). In multivariate analysis, IL‐10 remained an independent unfavorable prognostic factor (hazard ratio, 2.13; 95% confidence interval, 1.08–4.20). In patients treated with LMWH, the plasma levels of IL‐6, IL‐10, IFN‐γ, and P‐selectin demonstrated similar correlations with survival. However, none of the markers was associated with the beneficial survival effects observed with the administration of LMWH.CONCLUSIONSIL‐10, IL‐6, and P‐selectin levels predicted a poor outcome in patients with advanced stage malignancy. The prolongation in survival observed with LMWH in patients with cancer apparently cannot be explained by a LMWH effect on these circulating markers. Cancer 2005. © 2005 American Cancer Society.

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Section: Discussioncontrasting

confidence: 65%

mentioning

confidence: 99%

Plasma cytokine and P‐selectin levels in advanced malignancy

Nisio¹,

Niers²,

Reitsma³

et al. 2005

Cancer

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“…A dose-response effect was noted such that patients who spent more time in the subtherapeutic INR range had the highest incidence of PTS. There has been interest in whether low-molecular-weight heparins (LMWHs), which have anti-inflammatory and anticoagulant properties, 86 could have a role in preventing PTS. In a systematic review of 5 randomized trials that compared longterm (≥3 months) LMWH with warfarin for DVT treatment, Hull et al 77 reported a risk ratio of 0.66 (95% CI, 0.57-0.77) in favor of LMWH for complete recanalization of thrombosed veins, and LMWH-treated patients had a lower incidence of venous ulceration.…”

Section: Optimizing Anticoagulation Delivery To Prevent Ptsmentioning

confidence: 99%

The Postthrombotic Syndrome: Evidence-Based Prevention, Diagnosis, and Treatment Strategies

Kahn¹,

Comerota²,

Cushman³

et al. 2014

Circulation

484

410

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“…Earlier studies by our group have demonstrated a severely impaired skin capillary circulation in the feet of diabetic patients with PAOD (5), to which hemorheological disturbances related to a high plasma fibrinogen concentration might contribute. LMWH and unfractionated heparin are potent antithrombotic agents that also enhance the fibrinolytic activity and have anti-inflammatory effects (23)(24)(25)(26). LMWH also stimulates angiogenesis and improves the arterial circulation, e.g., the coronary circulation (27,28).…”

Section: Biochemical Variablesmentioning

confidence: 99%

Effect of Dalteparin on Healing of Chronic Foot Ulcers in Diabetic Patients With Peripheral Arterial Occlusive Disease

et al. 2003

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OBJECTIVE—Chronic foot ulcers are a common, severe, and expensive complication threatening life and limb in patients with diabetes. The aim of the present study was to investigate the effect of dalteparin on ulcer outcome in patients with diabetes, peripheral arterial occlusive disease, and chronic foot ulcers. RESEARCH DESIGN AND METHODS—A total of 87 patients were investigated in a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized to treatment with subcutaneous injection of 5,000 units dalteparin (Fragmin, Pharmacia Corporation; n = 44) or an equivalent volume of physiological saline (n = 43) once daily until ulcer healing or for a maximum of 6 months. Ulcer outcome was investigated by evaluating the number of patients 1) who healed with intact skin; 2) in whom the study ulcer was improved, unchanged, or impaired; or 3) who were amputated above or below the ankle level, as compared with control subjects. RESULTS—Two patients, one on dalteparin and one on placebo, dropped out of the study. Ulcer outcome was significantly better (P = 0.042, two-sided χ2 test for trend) in the dalteparin group (n = 43) compared with the placebo group (n = 42). A total of 29 patients healed with intact skin (n = 14) or decreased the ulcer area ≥50% (n = 15) in the dalteparin group compared with 20 (n = 9 and 11, respectively) in the placebo group. Five patients in each group showed impaired ulcer healing, i.e., the ulcer area increased ≥50%. Two patients in the dalteparin group were amputated compared with eight in the placebo group. Time to healing with intact skin was 17 ± 8 weeks in the dalteparin group compared with 16 ± 7 weeks in placebo group (NS). CONCLUSIONS—The results of the present study indicate that dalteparin improves the outcome of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease.

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Low-dose low–molecular-weight heparin is anti-inflammatory during venous thrombosis

Cited by 100 publications

References 26 publications

Plasma cytokine and P‐selectin levels in advanced malignancy

Plasma cytokine and P‐selectin levels in advanced malignancy

The Postthrombotic Syndrome: Evidence-Based Prevention, Diagnosis, and Treatment Strategies

Effect of Dalteparin on Healing of Chronic Foot Ulcers in Diabetic Patients With Peripheral Arterial Occlusive Disease

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