Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Ancrod improves survival in murine systemic lupus erythematosus. 229 6

Analysis of fatal sensitivity to 0.2 microgram of S. enteritidis lipopolysaccharide in cycloheximide-treated mice identified two independent lethal elements. First, an absolute requirement for steroid supplementation to ensure survival suggests a crucial role for cycloheximide-mediated inhibition of steroidogenesis. The second factor is the development of virtually total bilateral renal cortical necrosis, itself a consequence of glomerular capillary occlusion with fibrin-like material. The survival of cycloheximide and endotoxin-challenged mice requires both hydrocortisone treatment and defibrination with ancrod. Cycloheximide and a smaller dose of endotoxin (0.1 microgram per mouse) is also fatal, but here steroid deficiency is not a crucial factor, protection being conferred by ancrod defibrination alone.
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PMID:Factors involved in the fatal susceptibility to submicrogram doses of endotoxin in cycloheximide-treated mice. 264 18

The effect of a low-dosage regimen of ancrod in the prevention of postoperative deep vein thrombosis was assessed in 24 patients having surgical repair of fractured neck femur and compared with 25 control patients who did not receive therapy. The objective of the therapy was to lower the preoperative fibrinogen level and produce a low concentration of fibrin degradation products yet avoid the haemorrhagic complications of total defibrination. Ancrod therapy proved feasible to carry out, was not associated with haemorrhagic complications, and produced sustained, predictable reductions in fibrinogen concentration. There were seven thromboembolic complications in the control patients compared to one such complication in the ancrod-treated patients. Five deaths occurred in the control group and one in the treated group. Though the incidence of deep vein thrombosis was not apparently affected by ancrod it appeared on venography that the thrombi in the treated patients were less extensive than those in the control patients. Finally, some discrepancies in the diagnosis of deep vein thrombosis by the three techniques of clinical examination, (125)I-fibrinogen scanning, and ascending venography were identified.
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PMID:Low-dosage ancrod for prevention of thrombotic complications after surgery for fractured neck of femur. 460 45

Glomerular thrombi occur frequently in active lupus nephritis. Their presence has been correlated with low platelet counts and with subsequent development of glomerular sclerosis. We have examined the plasma PGI2 generating capacity of 8 patients with active lupus nephritis with thrombi that were to undergo defibrination therapy with ancrod. PGI2 generation by these plasma samples was significantly decreased as compared both to normals and to 6 individuals with lupus nephritis and no glomerular thrombi. Significant improvement in the capacity to generate PGI2 was seen in the post-ancrod treatment plasma samples. the pathogenesis of this defect is discussed.
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PMID:Deficiency of a plasma factor stimulating vascular prostacyclin generation in patients with lupus nephritis and glomerular thrombi and its correction by ancrod: in-vivo and in-vitro observations. 675 85

Antithrombin III (At III) levels in plasma samples were determined by incubation of diluted plasma with thrombin, either with or without heparin. Followed by measurement of residual thrombin using clotting and amidolytic methods. All assays were of multidose bioassay design suitable for parallel line analysis. Assays without heparin showed only a small difference between amidolytic and clotting methods, which was not significant at the 95% level. Assays with heparin showed a much larger difference between clotting and amidolytic methods which is shown to be attributable to the heat defibrination step used in the clotting assay. Heat defibrination and ancrod defibrination methods are compared using the amidolytic heparin cofactor assay and it is shown that heat defibrination can cause the loss of nearly 50% of the functional At III in a reconstituted freeze-dried plasma which was used as a standard. No loss occurs when ancrod is used for defibrination. It is an advantage of the amidolytic heparin cofactor assay that defibrination is not required.
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PMID:Comparison of antithrombin III assays using biological and chromogenic substrates. 705 31

Plasma fibronectin (FN) binds fibrin in vitro by both noncovalent and covalent bonds and is decreased in DIC. In rabbits, conventionally purified 125I-FN had a complex blood clearance with a late t1/2 of 71 hr. A large portion was apparently altered, as evinced by rapid clearance and an intravascular/total body ratio (C1) of 0.28-0.51. 3H-labeled FN, made in vivo by injection of 3H amino acids, had a t1/2 of 73 hr. Crosstransfusion of 131I-FN and 3H-FN into a second set of animals gave similar t1/2s and C1s of 0.74-0.82, indicating the altered 125I-FN was biologically screened in the first animals. Other animals were given 125I-fibrinogen and "screened" 131I-FN. Intravenous thrombin (50-60 U/kg/1 hr) caused a 25%-50% decrease in both 125I-fibrinogen and 131I-FN. Ancrod injection reduced fibrinogen by greater than 90% but had no effect on 131I-FN. 131I-FN levels did not change when thrombin was given after ancrod. No cross-linked FN-fibrinogen alpha-chain was found in the plasma, nor was the thrombin-induced fall in FN affected by spermidine blockade. These experiments demonstrate that FN and fibrin bind in vivo during defibrination and are rapidly cleared from the blood. The abnormal fibrin resulting from ancrod either does not bind FN in vivo or does so reversibly.
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PMID:Fibronectin: blood turnover in normal animals and during intravascular coagulation. 710 86

Defibrination with ancrod has been shown to be a successful form of treatment for certain types of experimental glomerulonephritis. The effect of ancrod on reticuloendothelial function has received little attention. In the present studies the blood clearance and reticuloendothelial uptake of injected preformed BSA-anti-BSA complexes were studied in defibrinated and control mice. 3 h after their injection, the blood levels and the hepatic and splenic uptakes were significantly different in experimental and control groups. It may be concluded that the reticuloendothelial clearance of injected immune complexes is not impaired by defibrination.
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PMID:Defibrination with ancrod: effect on reticuloendothelial clearance of circulating immune complexes. 711 Apr 62

Ancrod is a purified coagulant venom which renders blood incoagulable by cleaving fibrinopeptide A (FPA) from fibrinogen, but the mechanism involved in the clearance of fibrin from the circulation is unknown. To investigate the fibrinolytic response to ancrod, and to increase understanding of clearance mechanisms, six patients with peripheral vascular disease causing claudication were infused with ancrod at 2 u/kg over 6 h followed by 2 u/kg at 12 h intervals for 38 h. Venous blood samples were taken at time 0, 3, 6, 25 and 49 h for assay of fibrinogen (Fbg), fibrinopeptide A (FPA), total fibrin(ogen) degradation products (TDP), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (tPA), urinary type plasminogen activator (u-PA), plasminogen, alpha 2 antiplasmin (alpha 2 AP) and plasminogen activator inhibitor-1 (PAI-1). Fibrinogen (median and range) was 2.3 (1.4-3.90) g/l at time 0 and thereafter was undetectable. FPA rose from 2.5 (1.8-3.6) to 600 and 188 pmol/l at 3 h and 6 h and remained elevated. TDP, FbDP and FgDP increased greatly following ancrod while there was no evidence of XL-FDP. The surprising increase in FgDP during defibrination suggests either that fibrinogen is digested following its incorporation into circulating fibrin protofibrils or that some of the fibrin subunits in the photofibril retain one of the two fibrinopeptide A's. tPA and uPA remained unchanged. Plasminogen fell from 125 (100-155)% to 79 (40-118)% at 49 h and alpha 2 AP fell from 91 (75-107)% to 24 (10-35)% at 49 h. The level of PAI-1 was depressed during defibrination, with the exception of the 6 h data. The results demonstrate that ancrod removes FPA from fibrinogen to produce non-cross-linked (soluble) fibrin. This is cleared from the circulation without evidence of an increase in the circulating activities of the plasminogen activators, tPA or UK, but with evidence of plasminogen activation and consumption.
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PMID:The fibrinolytic response to ancrod therapy: characterization of fibrinogen and fibrin degradation products. 845 76

The aim of this study was to investigate the influence of the activation of the complement and coagulation systems on bacterial clearance and killing capacity of the reticuloendothelial system in rabbits. To enable quantification of the clearance process, defined numbers of exogenous Escherichia coli (1.3 x 10(8) colony-forming units) were injected intravenously, after complement activation with inulin-activated rabbit serum (n = 6), after complete defibrination with the snake toxin ancrod (n = 6), and in sham-operated animals (controls, n = 6). During the following 180 min observation period, parameters monitored were arterial pressure, fibrinogen, blood gases, and bacterial counts in blood and tissue samples of liver, kidney, spleen, and lung. Defibrination produced a significant delay in blood clearance (p < .05) compared with controls, coupled with up to four times higher bacterial counts in organ homogenates. Complement activation did not affect bacterial elimination kinetics, but was associated with accumulation of E. coli in lung and kidney (up to 100-fold of control values, p < .001). The impaired bacterial clearance associated with increased organ colonization after activation of the complement and coagulation systems reflect reticuloendothelial system dysfunction, thus pointing toward a weaker resistance against bacterial infection.
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PMID:Impaired bacterial clearance after activation of the complement and coagulation systems. 898 35

Alistair Reid was an outstanding clinician, epidemiologist and scientist. At the Penang General Hospital, Malaya, his careful observation of sea snake poisoning revealed that sea snake venoms were myotoxic in man leading to generalized rhabdomyolysis, and were not neurotoxic as observed in animals. In 1961, Reid founded and became the first Honorary Director of the Penang Institute of Snake and Venom Research. Effective treatment of sea snake poisoning required specific antivenom which was produced at the Commonwealth Serum Laboratories in Melbourne from Enhydrina schistosa venom supplied by the Institute. From the low frequency of envenoming following bites, Reid concluded that snakes on the defensive when biting man seldom injected much venom. He provided clinical guidelines to assess the degree of envenoming, and the correct dose of specific antivenom to be used in the treatment of snake bite in Malaya. Reid demonstrated that the non-clotting blood of patients bitten by the pit viper, Calloselasma rhodostoma [Ancistrodon rhodostoma] was due to venom-induced defibrination. From his clinical experience of these patients, Reid suggested that a defibrinating derivative of C. rhodostoma venom might have a useful role in the treatment of deep vein thrombosis. This led to Arvin (ancrod) being used clinically from 1968. After leaving Malaya in 1964, Alistair Reid joined the staff of the Liverpool School of Tropical Medicine, as Senior Lecturer. Enzyme-linked immunosorbent assay (ELISA) for detecting and quantifying snake venom and venom-antibody was developed at the Liverpool Venom Research Unit: this proved useful in the diagnosis of snake bite, in epidemiological studies of envenoming patterns, and in screening of antivenom potency. In 1977, Dr H. Alistair Reid became Head of the WHO Collaborative Centre for the Control of Antivenoms based at Liverpool.
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PMID:Hugh Alistair Reid OBE MD: investigation and treatment of snake bite. 963 63


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