Antithrombotic activity of a polydeoxyribonucleotidic substance extracted from mammalian organs: A possible link with prostacyclin

Niada, R; Mantovani, M; Prino, G; Pescador, Rodolfo; Berti, F.; Omini, C.; Folco, Giancarlo

doi:10.1016/0049-3848(81)90013-x

Cited by 80 publications

(42 citation statements)

References 14 publications

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“…3,15 Fibrinolysis was among the first pharmacologic actions of defibrotide observed in in vitro, animal, and clinical studies, 2,3,[15][16][17][18] whereas aptamers from defibrotide have been identified and shown to inhibit thrombin in vitro.…”

Section: Key Pharmacologic Actions and Characteristicsmentioning

confidence: 99%

“…2,3 Renamed defibrotide, this substance was determined to be a polydisperse mixture of predominantly single-stranded polydeoxyribonucleotide sodium salts 4,5 and is currently derived via controlled depolymerization of porcine intestinal mucosal DNA. [6][7][8][9] Compared with other oligonucleotides, defibrotide has a particularly complex mechanism of action.…”

Section: The Development Of Defibrotide Origins and Drug Profilementioning

confidence: 99%

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The use of defibrotide in blood and marrow transplantation

et al. 2018

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propensity analysis-estimated between-group difference: 23%; P 5 .0109). The most common adverse events (AEs) were hypotension and diarrhea; rates of common hemorrhagic AEs were similar in the defibrotide and historical control group (64% and 75%, respectively). In a phase 3 prophylaxis trial, defibrotide was found to lower incidence of VOD/SOS in children (not an approved indication) and reduce the incidence of graftversus-host disease. This review describes the development and clinical applications of defibrotide, focusing on its on-label use in patients with VOD/SOS and MOD/MOF after HSCT.

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Section: Key Pharmacologic Actions and Characteristicsmentioning

confidence: 99%

Section: The Development Of Defibrotide Origins and Drug Profilementioning

confidence: 99%

The use of defibrotide in blood and marrow transplantation

et al. 2018

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“…However, the precise chemical structure of the compound is not yet known. Defibrotide has significant profibrinolytic (Pescador et al, 1983) and plasminogen-activating properties (Mussoni et al, 1979), eventually resulting in the dissolution of preformed arterial and venous platelet thrombi in vivo (Niada et al, 1981;Grodzinska et al, 1987). Most notably, Lobel & Schror (1985) have demonstrated an increase of coronary vascular prostacyclin forma- ' Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

Defibrotide reduces infarct size in a rabbit model of experimental myocardial ischaemia and reperfusion

Thiemermann

Thomas

Vane

1989

British J Pharmacology

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1 Defibrotide, a single-stranded polydeoxyribonuncleotide obtained from bovine lungs, has significant anti-thrombotic, pro-fibrinolytic and prostacyclin-stimulating properties. 2 The present study was designed to evaluate the effects of defibrotide on infarct size and regional myocardial blood flow in a rabbit model of myocardial ischaemia and reperfusion. 3 Defibrotide (32 mg kg -bolus + 32 mg kg-1 h -1, i.v.) either with or without co-administration of indomethacin (5mg kg-' x 2, i.v.) was administered 5min after occlusion of the left anteriorlateral coronary artery and continued during the 60 min occlusion and subsequent 3 h reperfusion periods. 4 Defibrotide significantly attenuated the ischaemia-induced ST-segment elevation and abolished the reperfusion-related changes (R-wave reduction and Q-wave development) in the electrocardiogram. In addition, defibrotide significantly improved myocardial blood flow in normal and in ischaemic, but not in infarcted sections of the heart. The improvement in blood flow in normal perfused myocardium, but not in the ischaemic area was prevented by indomethacin. 5 Although the area at risk was similar in all animal groups studied, defibrotide treatment resulted in a 51% reduction of infarct size. Indomethacin treatment abolished the reduction of infarct size seen with defibrotide alone. 6 The data demonstrate a considerable cardioprotective effect of defibrotide in the reperfused ischaemic rabbit myocardium. This effect may be related, at least in part, to a stimulation of endogenous prostaglandin formation. Other possible mechanisms are discussed.

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“…This drug is a polydeoxyribonucleotide salt (MW about 50,000 daltons) obtained from deoxyriboucleic acid of mammalian lung by controlled depolymerization [4]. This substance has been shown to display considerable antithrombotic activity in various experimental models of venous as well as arterial throm bosis [5], including experimentally induced local Swartzman reaction [6].…”

Section: Introductionmentioning

confidence: 99%

Effect of a New Antithrombotic Agent (Defibrotide) in Acute Renal Failure Due to Thrombotic Microangiopathy

Bonomini

Frascà

Raimondi

et al. 1985

Nephron

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8 patients with thrombotic microangiopathy were treated with a new antilfcrombotic agent, defibrotide. This drug displays considerable fibrinolytic and antithrombotic activity, and induces generation and release of a prostacyclin-like substance from vascular tissue. At admission all patients presented severe renal involvement and coagulation abnormäÄies. Neurological manifestations were present in 6. Defibrotide admiu&tration was followed by recovery of renal function in 6, disappearance of neurological Symptoms and coagulation abnormalities in all p9l!ajits. The use of defibrotide was not associated with side effects. On the basis of the results obtained in these patients, we suggest that defibrotide might be considered as a valuable drug in the management of patients with thrombotic microangiopathy.

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Antithrombotic activity of a polydeoxyribonucleotidic substance extracted from mammalian organs: A possible link with prostacyclin

Cited by 80 publications

References 14 publications

The use of defibrotide in blood and marrow transplantation

The use of defibrotide in blood and marrow transplantation

Defibrotide reduces infarct size in a rabbit model of experimental myocardial ischaemia and reperfusion

Effect of a New Antithrombotic Agent (Defibrotide) in Acute Renal Failure Due to Thrombotic Microangiopathy

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