Update on the clinical use of the low-molecular-weight heparin, parnaparin

Camporese, Giuseppe; Bernardi, Enrico; Noventa, Franco

doi:10.2147/vhrm.s3430

Cited by 15 publications

(7 citation statements)

References 26 publications

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“…It is a sodium salt obtained by hydrogen peroxyde and cupric salt depolimerization of unfractionated heparin from pig intestine with a 4.000–6.000 D molecular weight and a mean anti‐Xa to anti‐IIa activity ratio of 2.3–2.4 [16,18]. Parnaparin has been evaluated in RCTs for the prevention and treatment of venous thromboembolism [19].…”

Section: Introductionmentioning

confidence: 99%

A randomized double‐blind study of low‐molecular‐weight heparin (parnaparin) for superficial vein thrombosis: STEFLUX (Superficial ThromboEmbolism and Fluxum)

Cosmi

Filippini

Tonti

et al. 2012

Journal of Thrombosis and Haemostasis

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Summary. Background: Optimal doses and duration of lowmolecular-weight heparin (LMWH) for the treatment of superficial vein thrombosis (SVT) are still uncertain. Objectives: To compare the efficacy and safety of different doses and durations of LMWH parnaparin for symptomatic lower limb SVT. Patients and methods: Outpatients with at least a 4-cmlong SVT of long or short saphenous veins or their collaterals were randomized to receive parnaparin either 8500 UI once daily ( o.d.) for 10 days followed by placebo for 20 days (group A) or 8500 UI o.d. for 10 days followed by 6400 UI once daily (o.d.) for 20 days (group B) or 4250 UI o.d. for 30 days (group C) in a double-blind fashion in 16 clinics. Primary outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT), symptomatic pulmonary embolism (PE) and relapse and/or symptomatic or asymptomatic SVT recurrence in the first 33 days with 60 days followup. Results: Among 664 patients, primary outcome occurred in 33/212 (15.6%), 4/219 (1.8%) and 16/217 (7.3%) subjects in groups A, B and C, respectively (B vs. A: absolute risk reduction [ARR]: 13.7%, 95% confidence intervals [CI]: 8-18.9 P < 0.001; B vs. C: ARR: 5.5%; 95% CI: 1.6-9.4 P = 0.011; C vs. A: ARR: 8.2%, 95% CI: 2-14 P = 0.012). During days 0-93, the event rate was higher in group A (22.6%) than either in group B (8.7%; P = 0.001) or C (14.3%, P = 0.034). No major hemorrhages occurred. Conclusions: An intermediate dose of parnaparin for 30 days is superior to either a 30-day prophylactic dose or a 10-day intermediate dose for lower limb SVT treatment.

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Section: Introductionmentioning

confidence: 99%

A randomized double‐blind study of low‐molecular‐weight heparin (parnaparin) for superficial vein thrombosis: STEFLUX (Superficial ThromboEmbolism and Fluxum)

Cosmi

Filippini

Tonti

et al. 2012

Journal of Thrombosis and Haemostasis

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“…After administration of a dose of 5 mg/kg, the area under the curve for MCCS was 100 times smaller than that for UFH, which may explain the almost 10-times lower aXa activity of MCCS. Increases in plasma Xa activity have been demonstrated previously using a test analogous to the ReaClot Heparin test [19,20] after s.c. administration of parnaparin to healthy volunteers and after administration of enoxaparin to monkeys. Thus, the large value for antithrombin activity (70 U/mg) and the link between the antithrombin activity of rabbit plasma and microcrystalline cellulose sulfate (molecular weight 86 kDa, extent of sulfur substitution 1.63) on s.c. administration may allow this compound to be positioned as a potential anticoagulant (after studies using i.v.…”

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confidence: 67%

Effects of Subcutaneous Microcrystalline Cellulose Sulfate Extracted from the Wood of the Siberian Fir (Abies sibirica Ledeb) on the Clotting of Rabbit Plasma

et al. 2015

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The anticoagulant activity of the microcrystalline cellulose sulfate (MCCS) extracted from the wood of Abies sibirica Ledeb (molecular weight 86,000, sulfur substitution level 1.63) were studied in vitro and ex vivo. The antithrombin activity was 87.4 ± 0.7 U/mg and activity against activated factor X was 18.3 ± 0.2 U/mg. S.c. administration of high doses (5, 20, and 40 mg/kg) of MCCS to rabbits increased plasma antithrombin activity. A cellulose sulfate dose of 10 mg/kg produced the same area under the pharmacodynamic curve for plasma antithrombin activity as unfractionated heparin (5 mg/kg).The sulfated polysaccharide unfractionated heparin (UFH), a glycosaminoglycan, is used in the treatment of thromboses [1]. The UFH molecule consists of a chain of repeating disaccharide units consisting of a-D-glucosamine and uronic acid connected by 1 -4 glycoside bonds (® 4-a-IdoA2S-1 ® 4-a-GlcNS6S-1 ® ) [2]. The rate of inhibition of clotting factors Ia, Xa, and IXa by antithrombin (AT) increases on interaction with UFH [3]. The anticoagulant (AC) activity of UFH includes roles for both the negatively charged sulfate groups and the glycan of the main chain of the molecule, operating as the "substrate" for the inhibitor, which is an enzyme [4]. Some investigators have demonstrated methods for increasing the anticoagulant activity of heparin [5], though side effects and the sources of UFH (mammalian tissues) [1] point to the need to develop alternative, plant-derived, AC, such as chemically modified cellulose. Cellulose is a linear homoglycan built of glucose residues joined by b(1 ® 4) bonds. Carboxymethylcellulose sulfate, like UFH, accelerated the inhibition of the AT activity of clotting factors, due to a specific sequence of 13 sugar residues simultaneously binding the protease and the inhibitor [6]. Microcrystalline cellulose (MCC) is known to have greater reactivity in alkylation and esterification reactions taking place in both alkaline and acidic conditions than the initial cellulose, so its use in sulfation reactions yields water-soluble derivatives in mild conditions [7].The aim of the present work was to analzye the effects of microcrystalline cellulose sulfate (MCCS) extracted from the wood of the Siberian fir (Abies sibirica Ledeb) on the clotting of rabbit plasma after s.c. administration. EXPERIMENTAL CHEMICAL SECTIONMCC was prepared and sulfated using methods developed at the Institute of Chemistry and Chemical Technology, Siberian Branch, Russian Academy of Sciences [8,9]. At the first stage, 10 g of fir sawdust dried at 105°C to constant weight was placed in a 0.2-liter stainless steel reactor and supplemented with to 150 ml of aqueous solution containing 25.8% acetic acid, 4.2% hydrogen peroxide, and 2% sulfuric acid. The reactor was placed in a heater and held at 130°C for 2 h. The mixture was then cooled and filtered, and the resulting fibrous product was washed with water to neutral pH. At the second stage, the fibrous product was subjected to solvolysis in 150 ml of aqueous solution containing 23.6% ...

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“…Parnaparin is a LMWH successfully employed in the prevention and treatment of venous thromboembolism (VTE) and chronic venous disorders (CVD) [31,32]. In the present study, parnaparin was administered not as a bridge, but as an alternative to oral anticoagulation therapy and without prior prolonged treatment.…”

Section: Discussionmentioning

confidence: 99%

Low molecular weight heparin (parnaparin) for cardioembolic events prevention in patients with atrial fibrillation undergoing elective electrical cardioversion: a prospective cohort study

et al. 2010

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Systemic thromboembolism is a severe complication in patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Vitamin K antagonists greatly reduce the risk of thromboembolic events, but the administration scheme before ECV is troublesome as difficulties in reaching and maintaining the target therapeutic range for 3 weeks often delay the restoration and likelihood of maintaining sinus rhythm. Low molecular weight heparins (LMWHs) do not need dose adjustment, and may be preferable in this clinical setting. In this multicentre study, the LMWH parnaparin was used at a dose of 85 anti-factor Xa U/kg b.i.d. 2 weeks before and 3 weeks after ECV of AF. In an intention to treat analysis of 102 patients, there was no systemic thromboembolism or major bleeding (0%, 95% CI 0-3.6). Two clinically relevant non-major bleeds (2.5%, 95% CI 0.7-8.8) and three minor bleeds (3.8%, 95% CI 1.3-10.6) were recorded. No heparin-induced thrombocytopenia or other major adverse events were recorded. Parnaparin appears effective and safe for thromboprophylaxis of elective ECV in patients with AF.

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Update on the clinical use of the low-molecular-weight heparin, parnaparin

Cited by 15 publications

References 26 publications

A randomized double‐blind study of low‐molecular‐weight heparin (parnaparin) for superficial vein thrombosis: STEFLUX (Superficial ThromboEmbolism and Fluxum)

A randomized double‐blind study of low‐molecular‐weight heparin (parnaparin) for superficial vein thrombosis: STEFLUX (Superficial ThromboEmbolism and Fluxum)

Effects of Subcutaneous Microcrystalline Cellulose Sulfate Extracted from the Wood of the Siberian Fir (Abies sibirica Ledeb) on the Clotting of Rabbit Plasma

Low molecular weight heparin (parnaparin) for cardioembolic events prevention in patients with atrial fibrillation undergoing elective electrical cardioversion: a prospective cohort study

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