PubMed HealthSearch

SEARCH · PubMed Health

Results for “Ancrod”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia.

In order to determine the efficacy and safety of ancrod, a rapid acting defibrinogenating drug, for patients with heparin-induced thrombocytopenia, 11 consecutive patients who required anticoagulant therapy because of venous thromboembolism and who developed acute heparin-induced thrombocytopenia or had a history of heparin-induced thrombocytopenia were treated with ancrod. Heparin therapy was discontinued (in patients receiving heparin) and ancrod started at a dose of 1 to 2 U/kg every 24 hours with subsequent daily doses adjusted to maintain fibrinogen levels between 0.5 and 1.0 g/L. Ancrod was continued until warfarin had become effective. The platelet count increased to more than 150 x 10(9)/L within 2 to 10 days in all thrombocytopenic patients. Two patients with a history of heparin-induced thrombocytopenia maintained normal platelet counts while receiving ancrod. Two patients had recurrent venous thrombosis while receiving warfarin, 10 days after ancrod was discontinued: one of these patients had metastatic pancreatic carcinoma and developed phlegmasia cerulea dolens and the other patient developed a venographically proven extension of her deep venous thrombosis. One patient suffered a bleeding episode into the thigh with a 16-g/L decrease in her hemoglobin level while receiving ancrod therapy. No other side effects were noted. Our experience indicates that ancrod therapy is a reasonable approach for patients with heparin-induced thrombocytopenia who require anticoagulant therapy.

Aged

Ancrod improves survival in murine systemic lupus erythematosus.

The effect of ancrod, a defibrinating agent, on murine lupus glomerulonephritis in the male BXSB mouse was studied to determine the relationship between macrophage procoagulant activity (PCA), fibrin deposition and glomerulonephritis. Marked renal disease and fibrin deposition were noted by three months of age in control mice, whereas little or no disease was seen in ancrod treated mice until five months of age. Similar high titers of anti-DNA antibodies and renal deposition of IgG were seen in both groups of mice. PCA rose with age in both ancrod treated and untreated mice, although it was significantly higher in control animals than in the ancrod treated group. Furthermore, ancrod therapy resulted in a decrease in plasma PCA inducing activity (PIF) and a decrease in the effectiveness of PIF to induce PCA in peritoneal macrophages in vitro. No mortality was observed in the 20 ancrod treated mice, whereas 10 of 20 control animals died. We conclude that defibrination with ancrod delays the development of renal fibrin deposition and glomerulonephritis and improves survival in BXSB mice. This was associated with a decrease in plasma PCA inducing activity and with an inhibitory effect on PCA induction. These results suggest that PCA contributes to injury in murine lupus glomerulonephritis by promoting fibrin deposition.

Ancrod

Ancrod causes rapid thrombolysis in patients with acute stroke.

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.

Acute Disease

Stimulation of fibrinogen synthesis by thrombin in rabbits with ancrod-induced afibrinogenemia.

The effect of intravenous infusions of thrombin on fibrinogen synthesis was evaluated in rabbits rendered afibrinogenemic by ancrod. Fibrinogen production and catabolism were measured simultaneously with 75Se-labeled selenomethionine (75SeM) and with 125I-labeled fibrinogen injected 5, 12, 18, or 26 h after ancrod. In normal rabbits the infusion of ancrod (2 U/kg body mass during 1 h) did not alter fibrinogen synthesis nor did it affect the rate of fibrinogen catabolism measured during a period of 5-120 h after ancrod administration. Normal rabbits that received purified bovine thrombin (100 U/kg body mass during 1 h) exhibited a twofold stimulation of fibrinogen synthesis as measured by the incorporation of 75SeM injected 5 h after thrombin. Rabbits made afibrinogenemic by infusion of ancrod 5 h before thrombin also showed a twofold increase in fibrinogen synthesis, as did animals that received ancrod immediately after thrombin. These experiments show that ancrod alone has no effect on fibrinogen production, and that thrombin stimulates fibrinogen synthesis in afibrinogenemic rabbits to the same extent as in controls.

Afibrinogenemia

Subcutaneous ancrod in prevention of deep-vein thrombosis after operation for fractured neck of femur.

In a randomised double-blind controlled trial 53 patients received 5 daily subcutaneous injections of ancrod ('Arvin') after operation for fractured neck of femur, and 52 patients received saline fractured neck of femur, and 52 patients received saline injections. Deep-vein thrombosis (D.V.T.) was detected by bilateral ascending venography or necropsy 6--16 days after surgery. The frequency of D.V.T. and bilateral D.V.T. was significantly lower in the ancrod group (P less than 0.01). The frequency of major D.V.T. (thrombi in veins proximal to the calf, or calf-vein thrombi more than 3 cm long) was also significantly lower in the ancrod group (P less than 0.001). No complications of ancrod prophylaxis occurred. Ancrod reduced plasma-fibrinogen, and hence plasma and blood viscosity, during the first week after surgery; preoperative levels of fibrinogen and viscosity were not associated with post-operative D.V.T. Subcutaneous ancrod is a simple and effective alternative to oral anticoagulants for the reduction of the frequency of D.V.T. after operation for hip fracture, and merits assessment in other high-risk groups of patients.

Adult

Effects of ancrod and rtPA on fibrin accumulation, glomerular inflammation and renal function in nephrotoxic nephritis.

We have compared the effects of ancrod and recombinant tissue plasminogen activator (rtPA) on nephrotoxic nephritis induced in pre-immunized rabbits by the administration of nephrotoxic globulin (NTG; sheep anti-rabbit glomerular basement membrane). We used three different doses of NTG: in each experiment three groups of six rabbits were preimmunized with normal sheep globulin and given NTG: group A received no further treatment; group B received rtPA, 2 mg/kg 12 hourly; group C received ancrod 2 U/kg 12 hourly. Animals were bled daily for estimation of plasma fibrinogen and serum creatinine, then killed on day 5 and kidneys removed for histology. 1 ml/kg of NTG caused massive glomerular necrosis, all three groups having severe renal failure. With 0.5 ml/kg of NTG, ancrod and rtPA both effectively prevented fibrin deposition in Bowman's space, but all animals had severe proliferative glomerulonephritis and marked renal failure. With 0.25 ml/kg of NTG, control animals developed severe proliferative nephritis and advanced renal failure, ancrod provided almost complete protection, and the rtPA group had renal injury and functional impairment intermediate between the other two groups. We conclude that renal failure in severe nephrotoxic nephritis is fibrin-independent, but in less fulminant nephritis renal function can be protected by defibrination with ancrod. rtPA is capable of reducing glomerular fibrin accumulation as effectively as ancrod, but provides inferior protection of renal function.

Ancrod

Comparison of polymerization of ancrod and thrombin fibrin monomers.

The polymerization of thrombin and ancrod fibrin monomers was studied with a standardized technique that evaluated turbidity changes and protein incorporation into the clot. Ancrod fibrin monomers were found to polymerize more slowly and form less turbid clots (at identical protein concentrations). Changes in ionic strength and pH influences ancrod fibrin monomer polymerization to a greater extent than thrombin fibrin monomer polymerization. Benzyltriethylammonium chloride was shown to be a potent inhibitor of fibrin monomer polymerization, with a greater inhibitory effect on ancrod fibrin monomers than on thrombin fibrin monomers. The differences between ancrod and thrombin fibrin may play a role in the infrequent thrombotic complications reported with ancrod therapy.

Ancrod

Therapeutic defibrinogenation by ancrod: effect on limb blood flow in peripheral vascular disease.

Reduction of blood viscosity by venesection may improve peripheral blood flow but similar haemorheological changes have not been conclusively demonstrated following reduction of plasma viscosity by defibrinogenation. Ancrod is a defibrinogenating enzyme from the venom of the Malayan pit viper. We studied six male patients with severe intermittent claudication before, during and after treatment with ancrod for 48 h. Ancrod was given by initial infusion of 2 U/kg over 6 h and four subsequent bolus i.v. injections of 2 U/kg. Skin blood flow in feet and toes were measured repeatedly by laser Doppler velocimetry and calf blood flow by electronic plethysmography both before and after 2 min arterial occlusion. Plasma fibrinogen [median (range)] fell from 2.3(1.4-3.9) to 0.1(0.1-0.3) g/l and plasma viscosity from 1.81(1.61-1.90) to 1.49(1.45-1.72) cp. Dorsal foot and toe skin blood (resting or post-ischaemic) flows were not changed significantly by ancrod. Resting calf blood flow fell significantly after 49 h treatment with ancrod (P less than 0.04). Brachial and ankle blood pressures remained unchanged and haematocrit was not changed. Thus, treatment with ancrod for 48 h did not improve peripheral blood flow in patients with peripheral vascular disease. The fall observed in calf blood flow could be related to increased circulating fibrin/fibrinogen high-molecular-weight complexes and degradation products.

Adult

The effects of ancrod, the coagulating enzyme from the venom of Malayan pit viper (A. rhodostoma) on prothrombin and fibrinogen metabolism and fibrinopeptide A release in man.

The action of ancrod on fibrinogen and prothrombin metabolism was studied in six healthy individuals by the use of 131I-fibrinogen and 125I-prothrombin and by measurement of blood levels of fibrinopeptide A. Two untreated healthy controls were studied at the same time. Rapid defibrinogenation occurred during the initial 3 hr ancrod infusion, and fibrinogen levels were maintained near zero throughout the study. Large quantities of non-thrombin-clottable TCA-precipitable 131I material could be demonstrated in the circulation, reaching a maximum 3 to 6 hr after ancrod infusion and clearing with a half-life of 6 hr. Gel filtration of 6 hr plasmas demonstrated the presence of complexes larger than fibrinogen, as well as degradation products of fibrinogen-fibrin. Prothrombin concentration and metabolism were unchanged by ancrod treatment. Fibrinopeptide A levels in the ancrod group were greather than 4,000 ng/ml during the initial defibrinogenation, declined to greater than 80 ng/ml, and then increased to high levels after 3 days. These studies provide explanations of previous observations concerning the specificity of ancrod and demonstrate that rapid clotting of fibrinogen and dissolution of fibrin can occur in vivo without recruitment of the classic coagulation mechanism.

Adult

Treatment of severe foot ischaemia by defibrination with ancrod: a randomized blind study.

Forty-two patients, mean age 68 years, with severe leg ischaemia were randomly treated with placebo or by controlled defibrination with ancrod for 3 weeks. Plasma fibrinogen concentration was kept at about 20% of normal in the ancrod treated group. The two groups proved to be well matched regarding factors which could affect the degree of ischaemia. Objective measurements showed a significant rise in ankle and toe systolic blood pressure in the ancrod group lasting for 3 months. There was no rise in distal blood pressure in the control group. In the ancrod treated group the toe and ankle systolic pressures rose about 8 mmHg, but this was not accompanied by an improvement in the clinical course.

Aged

Therapeutic defibrination with ancrod does not protect canine myocardium from reperfusion injury.

The purpose of this study was to determine whether normal fibrinogen contributes to the development of myocardial reperfusion injury by acting as a substrate in vivo for neutrophil adhesion. This was tested in a dog model of acute myocardial infarction that used pentobarbital anesthetized dogs subjected to 90 min regional myocardial ischemia and 5 h reperfusion. Dogs were treated with 1 unit/kg Ancrod (venom from the Malayan pit viper, Agkistrodon rhodostoma) or vehicle i.v. 60 min after left circumflex coronary artery occlusion. Therapeutic defibrination was verified in Ancrod-treated dogs by measurements of clottable fibrinogen, alpha-2 antiplasmin and plasminogen, by the activated partial thromboplastin time and by immunoelectrophoresis. Fibrinogen was depleted to below detectable limits of the assay (less than 0.05 mg/ml) after treatment with Ancrod. The defibrination effect was accomplished by the expected activation of the fibrinolytic system: alpha-2 antiplasmin was decreased by 10% and plasminogen activity was decreased by 30% with Ancrod treatment. There were no measureable differences between the two treatment groups in heart rate, mean arterial blood pressure, rate pressure product or circumflex coronary blood flow throughout the 90 min of regional ischemia or during the 5 h of reperfusion. The relative severity of ischemia between the two treatment groups was similar when assessed with radiolabeled microsphere measurement of myocardial blood flow. The accumulation of neutrophils (measured by myeloperoxidase activity) within the myocardium after reperfusion was not reduced by prior depletion of fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Ancrod

Heparin-associated thrombocytopenia and thrombosis: optimal therapy with ancrod.

Heparin-associated thrombocytopenia and thrombosis (HATT) is an infrequent occurrence but may have disastrous consequences. Continued therapy with heparin must be avoided and anticoagulation achieved by alternative means. Among the few alternatives to heparin in critically ill patients, the best is ancrod. Depletion of fibrinogen with ancrod results in anticoagulation comparable to therapy with heparin within 12 hours. In a small series, nine patients with HATT were treated with ancrod; one underwent angiographic assessment, angioplasty and subsequent vascular reconstruction. Ancrod therapy was not associated with bleeding complications. It appears to provide optimal therapy for patients suspected of having HATT.

Ancrod

Amino acid sequence determination of ancrod, the thrombin-like alpha-fibrinogenase from the venom of Akistrodon rhodostoma.

The thrombin-like serine protease and antithrombotic agent, Ancrod, was rapidly purified from the crude venom of Akistrodon rhodostoma by agmatine-Sepharose affinity chromatography followed by MonoQ anion exchange chromatography. N-Terminal sequencing and analysis of overlapping proteolytic fragments of purified Ancrod by automated Edman degradation in combination with tandem mass spectroscopy allowed the determination of the 234 amino acid sequence of the protease. Glycosylation sites at all five canonical N-linked glycosylation sites were inferred from the appearance of blank sequencer cycles in the amino acid sequence and were confirmed by mass spectroscopic analysis of the N-glycanase-treated peptides. Monoclonal antibodies raised against the denatured protein and HF-deglycosylated protein recognized Ancrod on Western blots. Sequence comparison to other thrombin-like serine proteases and reptilian fibrinogenases revealed a number of similarities, most notably the catalytic triad and many conserved cysteine positions.

Amino Acid Sequence

Comparison of ancrod and heparin as anticoagulants following endarterectomy in the dog.

An experimental model of surgically-induced arterial thrombosis was devised using the femoral arteries of dogs. Within 7 days, 67% of the arteries became completely thrombosed and only 12% remained compeletly patent. In the group of dogs that received low-dose heparin, 69% of the vessels were completely thrombosed and 6% remained completely patent. In the group of dogs treated with low-dose Ancrod to induce partial defibrination, 75% remained completely patent while only 19% of their femoral arteries were completely thrombosed. Although the ancrod was effective in preventing arterial thrombosis, 88% of the wounds showed moderate to severe separations. Most likely the absence of a fibrin lattice, necessary for the securement and growth of fibroblasts as the wound heals, explains this latter effect. Thus while Ancrod may become useful as an anticoagulant in certain clinical situations, it should not be used in proximity to surgery. Finally, in these studies of acute arterial thromboses, low-dose heparin therapy offered no protective effect.

Ancrod

Experimental ancrod (Arvin) for acute ischemic stroke: nursing implications.

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.

Ancrod

Role of fibrinopeptide B release: comparison of fibrins produced by thrombin and Ancrod.

The gelation time, opacity, light scattering, and elastic moduli of human fibrin gels clotted in the presence of thrombin, Ancrod, and Reptilase have been compared. At low ionic strength lateral association to thick fibers is observed in all cases. At all ionic strengths thrombin fibrin forms thicker fibers than does Ancrod fibrin. We have demonstrated that an increase in the extent of lateral association is linked to an increase in its velocity and to a decrease in the gelation time. One may consider the removal of fibrinopeptide B to act as a switch: after it is removed fibrin assembles rapidly to thick fibers and gelation is fast; but when this peptide is still attached, there is a slow assembly of thin fibers, and gelation, especially of dilute fibrin, is delayed. We believe that this delay is critical for the complete digestion by plasmin of fibrin formed during in vivo defibrination with Ancrod and of fibrin produced by very small amounts of thrombin (which would still contain fibrinopeptide B), and that slow release of fibrinopeptide B is part of a control mechanism for the regulation of fibrin formation and the prevention of intravascular coagulation.

Ancrod

Subcutaneous ancrod after operation for fractured hip--a dose-ranging and feasibility study.

We have conducted a dose-ranging and feasibility study of daily subcutaneous injections of ancrod (Arvin) as a potential antithrombotic method in 28 patients following operation for fractured neck of femur. Sustained, predictable fibrinogen depletion during the first post-operative week was induced by four different regimes. A total dose of 10 units/kg weight, given in divided doses starting on the day of operation, is suggested as a possible antithrombotic regime. Ancrod treatment produced a rise in fibrinogen/fibrin degradation products, prolongation of the thrombin clotting time, and a fall in plasminogen, plasma fibrinogen and corrected blood viscosity were observed in 14 control patients. Plasma fibrinogen was correlated with plasma viscosity and corrected blood viscosity. No adverse effects of treatment occurred. Subcutaneous ancrod appears to be a simple, safe, and feasible potential antithrombotic method, and merits trials of efficacy in the prevention of post-operative thromboembolism.

Adult

Defibrination with ancrod in nephrotoxic nephritis in rabbits.

Defibrination with ancrod in nephrotoxic nephritis in rabbits. In rabbits with nephrotoxic nephritis, defibrination with ancrod provided protection when administered during the autologous phase, after extensive glomerular fibrin deposition had occurred and crescents and renal failure were developing. When further glomerular fibrin deposition was prevented by defibrination, deposited fibrin was rapidly removed, indicating that glomerular fibrin-clearing mechanisms are retained in crescentic nephritis. Defibrination had no effect on the extent of glomerular C3 deposition or on the amount of proteinuria.

Ancrod