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Current Medical Research and Opinion 2002Ischaemic stroke occurs in over 500,000 US residents each year. Most strokes are due to embolic or thrombotic occlusion of an artery to the brain. Strategies to reduce... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Ischaemic stroke occurs in over 500,000 US residents each year. Most strokes are due to embolic or thrombotic occlusion of an artery to the brain. Strategies to reduce thrombus formation and to improve blood flow in the compromised arterial bed have been have been a major focus of management with the goal of improving the outcome of ischaemic stroke. Ancrod is a biological agent extracted from the venom of the Malayan pit viper that reduces blood fibrinogen levels. This action prolongs blood clot formation and lowers blood viscosity. Ancrod has been studied in a variety of ischaemic conditions including stroke. The clinical studies of ancrod in patients with stroke have shown a benefit with ancrod treatment in neurological outcome with only a modest increase in bleeding risk.
Topics: Aged; Ancrod; Brain Ischemia; Europe; Female; Fibrinolytic Agents; Humans; Male; Placebos; Stroke; United States
PubMed: 12365829
DOI: No ID Found -
The Journal of Neuroscience Nursing :... Dec 1991By increasing local cerebral blood flow to ischemic brain tissue in a timely fashion, impending cerebral infarction can be reversed. Aggressive, early intervention is... (Clinical Trial)
Clinical Trial Review
By increasing local cerebral blood flow to ischemic brain tissue in a timely fashion, impending cerebral infarction can be reversed. Aggressive, early intervention is the key to overall neurological improvement of stroke patients. Ancrod, a purified protein fraction of venom from the Malayan pit viper, has been shown to produce rapid and effective defibrinogenation in humans. A current clinical trial with ancrod in patients with acute or progressing nonhemorrhagic ischemic stroke requires an onset to treatment time of no more than 6 hours. Ancillary hospital personnel, physicians and nurses all play important roles in expediting study treatment. Nurses must assess ancrod study patients for potential bleeding problems. Community awareness and education about the warning signs of impending stroke are factors important to insuring early intervention and improving neurological outcome of stroke victims.
Topics: Ancrod; Cerebral Infarction; Double-Blind Method; Humans; Infusions, Intravenous; Neurologic Examination; Nursing Assessment
PubMed: 1839548
DOI: 10.1097/01376517-199112000-00008 -
Drugs 1997Ancrod converts fibrinogen into soluble fibrin products, resulting in a decrease in plasma fibrinogen and blood viscosity, and also induces the release of endogenous... (Review)
Review
Ancrod converts fibrinogen into soluble fibrin products, resulting in a decrease in plasma fibrinogen and blood viscosity, and also induces the release of endogenous tissue-type plasminogen activator from the vessel wall. These activities suggest that treating patients with acute ischaemic stroke with ancrod might result in improved cerebral blood flow and patient outcome. Two large randomised placebo-controlled studies have evaluated treatment with ancrod in patients with acute ischaemic stroke. In the first, patients were treated within 6 hours of symptom onset: this was not successful in quickly lowering fibrinogen levels to the target range (0.7 to 1.0 g/L) and the results were inconclusive. However, a post hoc analysis suggested that treatment with ancrod was effective in patients whose fibrinogen level was reduced to less than 1.3 g/L within 6 hours of starting treatment. A second larger study is still in progress, but preliminary results in patients treated within 3 hours of onset of ischaemic stroke are available and indicate that the target fibrinogen level of less than 1 g/L within 6 hours of instituting treatment is being achieved in most patients.
Topics: Acute Disease; Ancrod; Brain Ischemia; Clinical Trials as Topic; Fibrinolytic Agents; Humans
PubMed: 9360857
DOI: 10.2165/00003495-199700543-00014 -
Annals of Emergency Medicine Nov 1988Ancrod has been used in Europe for over 15 years for peripheral vascular disease, deep vein thrombosis, and central retinal venous thrombosis, and in patients at risk... (Clinical Trial)
Clinical Trial Randomized Controlled Trial Review
Ancrod has been used in Europe for over 15 years for peripheral vascular disease, deep vein thrombosis, and central retinal venous thrombosis, and in patients at risk for thromboembolism. In a double-blind, randomized, placebo-controlled study at University Hospitals in Cincinnati, 20 acute cerebral infarction patients received a series of IV infusions of ancrod (ten) or placebo (ten) for seven days. Early fibrinolysis with a small decrease in fibrinogen was observed, and d-dimers were elevated at four hours, indicating early clot lysis. At three months, patients with moderate to severe strokes (less than 40 on the Scandinavian Stroke Scale) in the ancrod group showed average improvement by a factor of 3 over the placebo group. No bleeding, abnormal laboratory results, or deaths occurred, but ancrod was discontinued in one patient who had seizures. As a result of this study, a double-blind multicenter international clinical trial to further assess the safety and effectiveness of ancrod is being planned.
Topics: Ancrod; Cerebral Infarction; Clinical Trials as Topic; Humans
PubMed: 3056131
DOI: 10.1016/s0196-0644(88)80071-4 -
Critical Reviews in Oncology/hematology Aug 1993
Review
Topics: Ancrod; Contraindications; Drug Evaluation; Drug Tolerance; Fibrinolysis; Glomerulonephritis; Hemorrhage; Heparin; Humans; Myocardial Ischemia; Thrombocytopenia; Thromboembolism
PubMed: 8240705
DOI: 10.1016/1040-8428(93)90018-y -
Seminars in Vascular Surgery Dec 1996
Review
Topics: Ancrod; Animals; Anticoagulants; Blood Coagulation; Coronary Artery Bypass; Fibrinogen; Fibrinolysis; Heparin; Humans; Pulmonary Embolism; Thrombocytopenia; Thrombosis; Vascular Surgical Procedures
PubMed: 8958607
DOI: No ID Found -
The Quarterly Journal of Medicine Nov 1988
Topics: Ancrod; Glomerulonephritis; Humans
PubMed: 3271333
DOI: No ID Found -
The American Journal of the Medical... May 1990Clot lysis is desirable in patients with thrombi in arteries and arterioles by a safe rapidly-acting thrombolytic agent. Ancrod cleaves fibrinogen; the resulting... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Clot lysis is desirable in patients with thrombi in arteries and arterioles by a safe rapidly-acting thrombolytic agent. Ancrod cleaves fibrinogen; the resulting circulating ancrod-fibrin stimulates fibrinolysis. Ancrod action and effect were studied in 20 patients with acute developing stroke in a double-blind, placebo-controlled study. Patients were randomly assigned to one of two treatment groups, and received either normal saline or ancrod 0.5 mu/kg in normal saline administered as a constant-rate intravenous infusion over 6 hours. Subsequent doses of ancrod (or saline placebo) were determined daily thereafter for a total treatment period of 7 days. Neither bleeding nor re-thrombosis occurred within the 90 day follow-up period. That ancrod acted rapidly was shown by a significant decrease in functional plasminogen activator inhibitor (PA-I) within 60 minutes, and by significant elevations of fibrin(ogen) degradation products (FDP) and D-dimer within 3 and 4 hours. The biological effect of fibrinolysis in ancrod infused patients was demonstrated by a greater improvement in stroke score when compared to those infused with saline.
Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Ancrod; Cerebrovascular Disorders; Double-Blind Method; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Intracranial Embolism and Thrombosis; Middle Aged; Pilot Projects; Plasminogen; Plasminogen Activators; Plasminogen Inactivators; Protein C; Randomized Controlled Trials as Topic; Time Factors; alpha-2-Antiplasmin
PubMed: 2186630
DOI: 10.1097/00000441-199005000-00006 -
JAMA May 2000
Topics: Ancrod; Fibrinolytic Agents; Humans; Stroke; Tissue Plasminogen Activator
PubMed: 10815092
DOI: 10.1001/jama.283.18.2440 -
Stroke Nov 2011Ancrod, derived from Malayan pit viper venom, has been tested as ischemic stroke treatment in clinical trials with inconsistent results. We studied the actions of ancrod... (Comparative Study)
Comparative Study
BACKGROUND AND PURPOSE
Ancrod, derived from Malayan pit viper venom, has been tested as ischemic stroke treatment in clinical trials with inconsistent results. We studied the actions of ancrod on fibrinolysis pathways in patient plasma samples and endothelial cell culture systems.
METHODS
We analyzed fibrinogen levels during the first 6 hours of ancrod infusion in patients entered in the Stroke Treatment with Ancrod Trial. For the in vitro study, human brain microvascular endothelial cells incubated with plasminogen or with human brain microvascular endothelial cell-conditioned medium were co-incubated with ancrod and fibrinogen under normal or oxygen-glucose deprivation conditions over 6 hours.
RESULTS
Fibrinogen levels decreased both in vivo and in vitro. Ancrod generated fibrinopeptide A, caused visible clot formation, and reduced levels of tissue-type plasminogen activator antigen in the human brain microvascular endothelial cell system and in a cell-free system with conditioned media.
CONCLUSIONS
The in vitro results indicate that ancrod causes local fibrin formation and secondary depletion of tissue-type plasminogen activator by binding to fibrin clot. Ancrod-induced fibrin formation could result in cerebral microvascular occlusion and may explain the suboptimal clinical effects of ancrod in human stroke trials.
Topics: Ancrod; Cells, Cultured; Culture Media, Conditioned; Endothelium, Vascular; Fibrin; Humans; Stroke
PubMed: 21868728
DOI: 10.1161/STROKEAHA.111.622753