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At least 19 recordsLinked to original sources
PubMed1994

Ancrod for the treatment of acute ischemic brain infarction. The Ancrod Stroke Study Investigators.

BACKGROUND AND PURPOSE: There is no acute therapy proven to be of benefit for ischemic stroke. Ancrod is a potentially effective therapy because of the advantageous consequences of fibrinogen lowering. METHODS: We studied the safety and efficacy of ancrod in patients with acute ischemic stroke administered within 6 hours of stroke onset. In a double-blind, randomized, placebo-controlled trial 64 patients received intravenous ancrod and 68 received placebo for 7 days. Neurological outcome, disability, and brain infarct volume were measured. RESULTS: There was no significant difference in overall mean scores on the Scandinavian Stroke Scale. No increase in bleeding occurred in the ancrod-treated patients. The target reduction of plasma fibrinogen levels of less than 100 mg/dL was achieved in only 15 (23%) of 64 ancrod-treated patients. Those patients with ancrod-induced 6-hour fibrinogen levels 130 mg/dL or less had a marginally significantly better neurological outcome on the Scandinavian Stroke Scale, mortality, and Barthel Index than ancrod-treated patients with higher fibrinogen levels. CONCLUSIONS: Ancrod appears safe and potentially effective when administered to patients within 6 hours of onset of ischemic stroke.

Acute Disease↗
PubMed1972

Mechanism of ancrod anticoagulation. A direct proteolytic effect on fibrin.

Fibrin formed in response to ancrod, reptilase, or thrombin was reduced by beta-mercaptoethanol and examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was found that ancrod progressively and totally digested the alpha-chains of fibrin monomers at sites different than plasmin; however, further digestion of fibrin monomers by either reptilase or thrombin was not observed. Highly purified ancrod did not activate fibrin-stabilizing factor (FSF); however, the reptilase preparation used in these experiments, like thrombin, activated FSF and thereby promoted cross-link formation. Fibrin, formed by clotting purified human fibrinogen with ancrod, reptilase, or thrombin for increasing periods of time in the presence of plasminogen, was incubated with urokinase and observed for complete lysis. Fibrin formed by ancrod was strikingly more vulnerable to plasmin digestion than was fibrin formed by reptilase or thrombin. The lysis times for fibrin formed for 2 hr by ancrod, reptilase, or thrombin were 18, 89, and 120 min, respectively. Evidence was also obtained that neither ancrod nor reptilase activated human plasminogen. These results indicate that fibrin formed by ancrod is not cross-linked and has significantly degraded alpha-chains: as expected, ancrod-formed fibrin is markedly susceptible to digestion by plasmin.

Anticoagulants↗
PubMed1991

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↗
PubMed1993

Role of plasminogen activator inhibitor-1 in promoting fibrin deposition in rabbits infused with ancrod or thrombin.

The role of defective fibrinolysis caused by elevated activity of plasminogen activator inhibitor-1 (PAI-1) in promoting fibrin deposition in vivo has not been well established. The present study compared the efficacy of thrombin or ancrod, a venom-derived enzyme that clots fibrinogen, to induce fibrin formation in rabbits with elevated PAI-1 levels. One set of male New Zealand rabbits received intravenous endotoxin to increase endogenous PAI-1 activity followed by a 1-hour infusion of ancrod or thrombin; another set of normal rabbits received intravenous human recombinant PAI-1 (rPAI-1) during an infusion of ancrod or thrombin. Thirty minutes after the end of the infusion, renal fibrin deposition was assessed by histopathology. Animals receiving endotoxin, rPAI-1, ancrod, or thrombin alone did not develop renal thrombi. All endotoxin-treated rabbits developed fibrin deposition when infused with ancrod (n = 4) or thrombin (n = 6). Fibrin deposition occurred in 7 of 7 rabbits receiving both rPAI-1 and ancrod and in only 1 of 6 receiving rPAI-1 and thrombin (P < .01). In vitro, thrombin but not ancrod was inactivated by normal rabbit plasma and by purified antithrombin III or thrombomodulin. The data indicate that elevated levels of PAI-1 promote fibrin deposition in rabbits infused with ancrod but not with thrombin. In endotoxin-treated rabbits, fibrin deposition that occurs with thrombin infusion may be caused by decreased inhibition of procoagulant activity and not increased PAI-1 activity.

Ancrod↗
PubMed1996

Integrin alpha v beta 3 and phospholipase C regulate prostacyclin formation of endothelial cells caused by ancrod-generated fibrin.

Ancrod-generated fibrin has been shown to stimulate prostacyclin synthesis of human umbilical vein endothelial cells (Chang et al., 1994, Biochem. Biophys. Res. Commun. 203, 1920). We further investigated its mechanism of action. The increment of 6-keto prostaglandin F1 alpha stimulated by ancrod-generated fibrin was almost completely inhibited when endothelial cells were either pretreated with 50 microM 8-(N,N'-diethylamino)octyl-3,4,5- trimethoxybenzoate (TMB-8) or preloaded with 15 microM 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). 6-Keto prostaglandin F1 alpha production during 2 and 10 h incubation period was also inhibited by 1.2 mM ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetraace tic acid (EGTA) (41 +/- 12 and 53 +/- 17% inhibition, respectively). Further, ancrod-generated fibrin caused a rapid-onset increase in [3h]inositol monophosphate (IP1) formation in endothelial cells. This increase in IP1 was significantly inhibited by 1 mM Gly-Pro-Arg-Pro, 1 mM neomycin or 100 ng/ml pertussis toxin. At the same time, neomycin and pertussis toxin also significantly inhibited 6-keto prostaglandin F1 alpha synthesis of endothelial cells stimulated by ancrod-generated fibrin. Additionally, the increment of IP1 production as well as prostacyclin production were significantly inhibited by monoclonal antibodies directed against alpha v beta 3. These results suggest that intra- and extra-cellular Ca2+ participate in prostacyclin synthesis stimulated by ancrod-generated fibrin. Ancrod-generated fibrin stimulates pertussis toxin-sensitive G-protein regulated phosphoinositide breakdown, which is responsible for prostacyclin synthesis. This augmentation in prostacyclin synthesis and phosphoinositide breakdown caused by ancrod-generated fibrin area, at least in part, mediated by fibrin binding to integrin alpha v beta 3 on endothelial cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

MRI study on delayed ancrod therapy of focal cerebral ischaemia in rats.

The therapeutic window for efficient post-treatment of focal cerebral ischaemia with the fibrinogen lowering agent ancrod was studied by magnetic resonance imaging (MRI) in spontaneously hypertensive rats (SHR). Ancrod or vehicle solution (0.9% NaCl) were i.v. infused (0.12 IU/kg per min) via implanted mini pumps starting 0.5, 1.5, 3 or 6 h after permanent proximal middle cerebral artery occlusion and lasting until brain mapping by multislice T2-weighted magnetic resonance imaging in vivo 24 h after middle cerebral artery occlusion. Plasma fibrinogen concentrations were measured before middle cerebral artery occlusion, before pump implantation and after magnetic resonance imaging. Total brain lesion volumes as determined by magnetic resonance imaging 24 h after middle cerebral artery occlusion were 131 +/- 36 (188 +/- 28)*, 151 +/- 39 (194 +/- 39)*, 147 +/- 44 (207 +/- 33)* and 209 +/- 60 (214 +/- 42) mm3 in rats with 0.5, 1.5, 3 and 6 h, respectively, delay of ancrod treatment (means +/- S.D., 8-11 animals/group, corresponding control groups in parentheses, *P < 0.05). Continuous i.v. ancrod infusions reduced plasma fibrinogen levels significantly (P < 0.05) in all ancrod-treated groups as compared to vehicle-treated controls until the end of the experiments 24 h after middle cerebral artery occlusion. In conclusion, significant cerebroprotection was achieved even when the onset of ancrod therapy for lowering of the plasma fibrinogen level was delayed for up to 3 h. To the best of our knowledge no drug efficacy has been reported so far with a therapeutic window of 3 h after permanent middle cerebral artery occlusion in spontaneously hypertensive rats suggesting that ancrod may provide an efficient therapy of acute human stroke.

Ancrod↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1982

Comparative effects of heparin, urokinase, and ancrod on intraglomerular coagulation induced in progressive Masugi nephritis.

Effects of heparin, urokinase, and ancrod were concurrently compared on intraglomerular coagulation using a model of progressive Masugi nephritis. Evaluations were performed with light and immunofluorescent microscopy. Treatment significantly reduced crescent formation, more markedly with ancrod. In contrast, endocapillary proliferation was enhanced in the groups treated with urokinase and, especially, ancrod. Ancrod appeared to be most effective in decreasing the glomerular deposition of fibrinogen-related materials as judged from the immunofluorescence, and a relatively high dose was required for urokinase to be comparable with ancrod. However, in some glomeruli from two of 13 animals given ancrod, mesangiolytic lesion developed. Thus, although promising, ancrod has many problems to be solved before using it to control endocapillary proliferation and mesangiolysis.

Ancrod↗
PubMed1977

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↗
PubMed1987

Ancrod decreases the frequency of cyclic flow variations and causes thrombolysis following acute coronary thrombosis.

The potential use of ancrod, a purified isolate from the venom of the Malaysian pit viper, Agkistrodon rhodostoma, in decreasing the frequency of cyclic flow variations in severely stenosed canine coronary arteries and causing thrombolysis of an acute coronary thrombus induced by a copper coil was evaluated. Open-chest, anesthetized dogs were used. Ancrod was given intravenously (8 U/kg) over 1 hour and caused a significant reduction in the frequency of cyclic flow variations (5.8 +/- 0.7 to 3.6 +/- 0.8 cyclic flow variations per 30 minutes, p less than 0.05), whereas control animals failed to decrease the frequency of their cyclic flow variations over the same time period (5.3 +/- 0.3 to 5.0 +/- 0.4 cyclic flow variations per 30-minute period). Twenty-seven dogs had a coronary thrombus induced by a copper coil positioned directly in a major coronary artery; of these, four died of ventricular fibrillation prior to treatment, eight received an infusion of saline and showed no thrombolysis over 5 hours, and three died of ventricular fibrillation during the initial part of an intravenous infusion of ancrod. The remaining 12 dogs received ancrod intravenously (16 U/kg); six demonstrated lysis of the coronary thrombus (mean time to lysis, 65 +/- 20 minutes). The concentrations of ancrod used in these studies produced a severe decrease in systemic fibrinogen concentration and a significant decrease in the inhibitor of plasminogen activator levels. Thus, ancrod decreases the frequency of cyclic flow variations in stenosed canine coronary arteries and may cause coronary thrombolysis in approximately 50% of animals within 65 +/- 20 minutes of its intravenous administration.

Acute Disease↗
PubMed1996

Sensitivity of experimental venous and arterial thrombosis and bleeding to ancrod-induced defibrinogenation.

The effect of ancrod-induced defibrinogenation on thrombosis and bleeding time was determined in anesthetized rats. Functional plasma fibrinogen levels were reduced 42, 71, 94 and 93% by ancrod doses of 5, 10, 20 and 30 U/kg, respectively, while a 2.5 U/kg dose was without significant effect. Ancrod inhibited vena cava thrombosis induced by partial stasis of blood flow combined with mild vascular injury. Thrombus weight was decreased 85 and 93% by the 10 and 20 U/kg doses, but was unaffected at lower doses. In contrast, ancrod doses of up to 30 U/kg did not significantly decrease carotid artery thrombi formed in response to oxidative transmural vessel injury. Ancrod caused a dose-dependent increase in bleeding time measured by puncturing small mesenteric arteries with a hypodermic needle. The bleeding time increase was approximately 38% in response to the 2.5 and 5 U/kg doses, and 182% in response to the 10 U/kg dose. These studies demonstrate that ancrod-induced reductions in plasma fibrinogen more effectively inhibit venous compared to arterial thrombosis, although these activities require doses that also increase bleeding time in small arteries.

Ancrod↗
PubMed1995

The morphologic change of endothelial cells by ancrod-generated fibrin is triggered by alpha v beta 3 integrin binding and the subsequent activation of a G-protein coupled phospholipase C.

The mechanism of morphologic change of human cultured umbilical vein endothelial cells (HUVECs) caused by fibrin was investigated. Ancrod, a thrombin-like enzyme, did not cause morphologic alteration of HUVEC by itself at concentrations ranging from 0.01 to 10 U/ml. However, when 0.02 U/ml of ancrod was added to cultured HUVEC monolayers in the presence of citrated plasma, it caused pronounced morphologic change of HUVEC after 6-10 h incubation period. Gly-Pro-Arg-Pro (4 mg/ml), an inhibitor of fibrin polymerization, prevented the morphologic alteration, indicating that the morphologic alteration was caused by the polymerized fibrin. The morphologic change of HUVEC caused by ancrod-generated fibrin was not observed in the presence of an intracellular calcium mobilization inhibitor TMB-8 (50 microM), and the morphologic alteration was also less pronounced with BAPTA(15 microM)-loaded HUVECs and HUVECs pretreated with EGTA (1.2 mM). Ancrod (in Medium 199) itself did not stimulate phosphoinositide breakdown of HUVEC. However, when ancrod was present in plasma, it caused an increase of [3H]IP1 of HUVECs preloaded with [3H]myoinositol. This IP1 increment was inhibited by Gly-Pro-Arg-Pro. The increase of IP1 was significantly inhibited by the pretreatment of monoclonal antibodies 23C6 and 7E3 directed against alpha v beta 3 integrin. Neomycin (1 mM) and pertussis toxin (100 ng/ml), but not aspirin or mepacrine, blocked this enhanced phosphoinositide breakdown. The morphologic change was also prevented by the monoclonal antibodies, 23C6 and 7E3. These results suggest that both intra- and extra-cellular calcium participate in the event of morphologic change of HUVEC caused by ancrod-generated fibrin, and the morphologic change is mediated, at least in part, by fibrin binding to integrin alpha v beta 3 on HUVECs, causing the subsequent activation of the endogenous G-protein coupled phospholipase C.

Ancrod↗
PubMed1978

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↗
PubMed1989

Ancrod (Arvin) as an alternative to heparin anticoagulation for cardiopulmonary bypass.

Heparin is the anticoagulant used during cardiopulmonary bypass (CPB). Both the use of heparin and the reversal of its effect with protamine have well-documented complications. Ancrod is a defibrinogenating enzyme that has been used as an anticoagulant in humans, but its use as an anticoagulant for CPB has been limited to studies in animals. Twenty patients for elective aortocoronary bypass surgery were anticoagulated by means of an intravenous infusion of ancrod pre-operatively. Target plasma fibrinogen concentrations of 0.40-0.80 g/l were achieved within 13.3 +/- 2.5 h using an average dose of ancrod of 1.65 +/- 0.55 U/g. All perfusions were without incident. Postoperative blood loss (2286 +/- 1311 cc) was compared to that of 20 matched controls (1737 +/- 973 cc), as was blood product use; 4.1 +/- 2.1 U of packed cells versus 2.5 +/- 2.3 U (P less than 0.05) and 5.6 +/- 3.1 U of plasma versus 2.6 +/- 2.9 U (P less than 0.05) in the ancrod and heparin-treated groups, respectively. There were no differences in the postoperative courses or recovery periods of the ancrod-treated and control patients. This study confirms the efficacy and feasibility of ancrod as an alternative form of anticoagulation for CPB.

Adult↗
PubMed1996

Enoxaparin for unstable angina and ancrod for cardiac surgery following heparin allergy.

OBJECTIVE: To describe a patient who presented with heparin allergy and required alternate anticoagulation for unstable angina and coronary artery bypass surgery. To review therapeutic alternatives to porcine heparin for patients with hypersensitivity or intolerance to standard heparin anticoagulation. CASE SUMMARY: A 74-year-old man with a 15-year-old coronary artery bypass graft presented to the emergency room with unstable angina and was scheduled for urgent coronary artery revascularization. A bolus dose of porcine heparin was administered followed by a continuous infusion. Shortly afterward the patient developed a type I allergic reaction to the porcine heparin that was confirmed by rechallenge. Three alternatives to porcine heparin were tried, including bovine lung heparin, low-molecular-weight heparin (enoxaparin), and ancrod. The patient was found to be cross-sensitive to bovine lung heparin, but tolerated enoxaparin for unstable angina without cross-sensitivity. Anticoagulation for cardiopulmonary bypass was achieved with an infusion of ancrod that was later reversed with cryoprecipitate. The patient was discharged postoperatively on day 5 without the complication of excessive bleeding. DISCUSSION: Type I allergic reaction to unfractionated heparin is a rare occurrence and could be the result of a variety of factors. Possible causes for the reaction include a porcine protein, a preservative contained in the heparin solution, or a hapten formed between heparin and a plasma protein. We considered four alternatives to heparin anticoagulation: rush desensitization, bovine lung heparin, low-molecular-weight heparin, and ancrod. The patient was cross-sensitive to bovine lung heparin, but was able to tolerate low-molecular-weight heparin (enoxaparin). This was unexpected because enoxaparin is derived from unfractionated porcine heparin. Testing for cross-sensitivity had no value in this case, as two negative subcutaneous test doses were followed by dramatic reactions when the drugs were given intravenously. Although enoxaparin has been used for anticoagulation during bypass surgery, there is more experience with ancrod as an alternative to heparin. Repeat bypass surgery, which normally results in above-average blood loss, was successfully performed with a very low fibrinogen concentration (< 0.15 g/L) during ancrod anticoagulation. CONCLUSIONS: We conclude that ancrod was a safe and effective alternative to heparin for coronary artery bypass surgery in this patient in whom a heparin product had caused a hypersensitivity reaction. We discovered on two occasions that a negative subcutaneous test dose for heparin allergy did not predict a severe type I allergic reaction when the heparin was later administered intravenously. Furthermore, we found that a low-molecular-weight heparin administered subcutaneously for a short period of time did not cause cross-sensitivity in a patient with a type I allergy to unfractionated heparin.

Aged↗
PubMed1991

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↗
PubMed1977

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↗