The Natural Course of Defibrination Syndrome Caused by Echis Colorata Venom in Man

1974 ◽  
Vol 31 (03) ◽  
pp. 420-428 ◽  
Author(s):  
M Fainaru ◽  
S Eisenberg ◽  
N Manny ◽  
C Hershko
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Major Bleeding ◽  
Renal Damage ◽  
Specific Treatment ◽  
Natural Course ◽  
Factor V ◽  
Thrombocyte Count

SummaryThe natural course of defibrination syndrome caused by Echis colorata venom (ECV) in five patients is reported. All patients developed afibrinogenemia within six hours after the bite. Concomitantly a depression in factor V was recorded. Factor VIII and thrombocyte count in blood were normal in most patients. In the light of the known effects of ECV on blood coagulation in vivo and in vitro it is concluded that the afibrinogenemia is due to intravascular clotting.Four patients had transient renal damage, manifested by oliguria, azotemia, albuminuria and cylindruria, ascribed to microthrombi in the renal glomeruli.After the bite, the natural course was benign, no major bleeding was observed, and all signs of coagulopathy reverted to normal within 7 days. Therefore we recommend no specific treatment for this condition. In the case of heavily bleeding patients, administration of antiserum against ECV and/or heparin should be considered.

scholarly journals Experimental Hemostasis in Normal Dogs and Dogs with Congenital Disorders of Blood Coagulation

Blood ◽  
1967 ◽  
Vol 30 (5) ◽  
pp. 636-668 ◽  
Author(s):  
T. HOVIG ◽  
H. C. ROWSELL ◽  
W. J. DODDS ◽  
L. JØRGENSEN ◽  
J. F. MUSTARD
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Bleeding Time ◽  
Light And Electron Microscopy ◽  
Factor Ix ◽  
Surrounding Tissue ◽  
Factor Vii ◽  
Congenital Defects

Abstract Hemostasis was examined after transection of vessels, 50-200 microns in diameter, both in normal dogs and in dogs with congenital defects of either factor VII, factor IX, or factor VIII. The formation of the hemostatic platelet plugs was observed by direct microscopy in vivo, and sections of the plugs were prepared for both light and electron microscopy 10 to 30 minutes after transection. Furthermore, the reaction of platelets from normal and abnormal dogs with adenosine diphosphate, collagen and thrombin was tested in vitro by a turbidimetric technic. In normal and factor VII deficient dogs the initial arrest of bleeding took place about 3 minutes after transection, and rebleeding was infrequently observed. Their platelet plugs were composed of densely packed platelets, anchored to the vascular and perivascular tissue and surrounded by a cap of fibrin. In factor IX deficient dogs there was no definite prolongation of the initial bleeding time, but rebleedings were frequent. In factor VIII deficient dogs the initial bleeding time was prolonged and the intensity of the bleeding had a wave-like characteristic. The plugs in the hemophilic dogs were larger than normal, were rich in channels, and had areas of loosely packed platelets and an incomplete fibrin cap. Treatment of factor IX deficient dogs with Dicumarol did not further impair hemostatic plug formation in the doses used. Treatment of factor VII deficient dogs with heparin, or factor IX deficient dogs with phenylbutazone, prolonged the bleeding time markedly, delayed the building up of the plug, and gave fragile, loosely packed plugs. Treatment of normal dogs with phenylbutazone did not alter the hemostatic process at the dosage used. In the in vitro studies, platelets from the dogs with congenital coagulation defects reacted normally with the aggregating stimuli. It is concluded that the initial platelet interaction wih the vessel wall and surrounding tissue is not dependent upon blood coagulation. An intact intrinsic pathway of coagulation is necessary for the stabilization of the hemostatic plug after it is formed.

Effects of fibrinolytic agents and heparin on blood coagulation in dogs

1964 ◽  
Vol 207 (5) ◽  
pp. 1049-1052 ◽  
Author(s):  
Jessica H. Lewis ◽  
Mitsuru Shirakawa
Keyword(s):  
Blood Coagulation ◽  
Coagulation Factors ◽  
In Vivo Studies ◽  
Factor V ◽  
In Vitro Experiments ◽  
Fibrinolytic Agents ◽  
Dog Plasma ◽  
Viii And Ix

In vitro experiments demonstrated that incubation of dog plasma with Thrombolysin or Actase caused marked falls in factors I, VIII, and IX, a moderate fall in factor V, and the appearance of a heat-labile clot inhibitor. Incubation of dog plasma with streptokinase (SK), staphylokinase, trypsin, bromelain, or dog fibrinolysin in amounts similar to those used in in vivo studies had little effect on these coagulation factors. If the streptokinase concentration were increased 10- to 15-fold results similar to those found with Thrombolysin were observed. Intravenous infusions of Thrombolysin or Actase resulted in marked depressions of factors I, VIII, and V, minimal depressions of factors II, VII, and IX, and the development of a clot inhibitor. Seven dogs who received SK showed no coagulation changes, while three showed moderate fibrinogenolysis and inhibitor formation.

In Vivo Evidence of Modulation of the Hemophilia Phenotype by the Factor V Leiden.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 693-693
Author(s):  
Alexander Schlachterman ◽  
Jianhua Liu ◽  
Yi-Lin Liu ◽  
Katherine High ◽  
Valder Arruda
Keyword(s):  
Factor Viii ◽  
Thrombus Formation ◽  
Factor V Leiden ◽  
Factor Ix ◽  
Platelet Glycoprotein ◽  
Factor V ◽  
Severe Hemophilia ◽  
Fvl Mutation

Abstract The amelioration of hemophilia phenotype or delayed onset of the bleeding episodes in subjects with severe hemophilia A (FVIII deficiency) has been associated with inherited resistance to activated protein C due to factor V Leiden (R506Q), FVL. These observations were confirmed by in vitro systems in which homozygous phenotype of FVL increased thrombin formation in presence of < 1% FVIII by nearly 5-fold (Blood 90:3067). Here we provide in vivo evidence of the beneficial interaction of FVL on the hemophilia phenotype in mice. Animals with severe deficiency of factor VIII due to deletion of intron 16 of factor VIII gene (HA) or large gene deletion of factor IX (HB) were crossed with FVL homozygous mice [+/+] on C57Bl6 strain [Cui et al. (Blood 96:4222)] We used a modified activated partial thromboplastin time (aPTT) assay to compared clotting times among male HA (n=30), HA/FVL [+/+] (n=7), FVL [+/+] (n=5), and litermate WT mice (n=6) with age ranging from 6–12 weeks. Blood samples were collected by tail vein transection into 3.8% sodium citrate. Values for the aPTT in male HA were 67.3 ± 4 sec, and among WT or FVL [+/+] values were 37 ± 4 sec or 31± 2 sec, respectively. Whereas intermediate aPTT values of 53 ± 3.7 sec were determined in HA/FVL [+/+], which differs from HA mice (p<0.0001) but also from WT or FVL (p<0.0001). A similar shortening of aPTT was also determined among HB/FVL[+/+] which were compared to HB, 55 ± 7 sec vs. 64 ± 0.9. Hemostatic challenge by tail clipping assay failed to revealed differences in bleeding times/blood loss among hemophilia animals with or without FVL mutation. To test whether a more sensitive technique would provide further evidence of the improved hemostasis in HA/FVL mice, we assessed real-time in vivo thrombus formation by confocal and widefield microscopy. Mice were anesthetized and the cremaster muscle was exposed for intravital microscopy. Infusion of fluorescently labeled antibody to murine platelet glycoprotein IIb/IIIa complex via the jugular vein allowed monitoring of platelet deposition upon laser-mediated endothelial injury at several sites of the arterial vessel wall. No thrombus formation was observed in severe HA mice following successive vascular injuries, a finding also common in severe HB mice. However, infusion of factor VIII concentrated clearly induced the thrombi formation upon vascular injury. HA/FVL mice tested presented thrombus formation in a comparable fashion of HA-FVIII transfused mice. These in vivo data provide support to the hypothesis that the FVL mutation has the potential to improve the phenotype of severe hemophilia and may offer a novel therapeutic target for hemophilia.

Ancylostoma caninum Anticoagulant Peptide Blocks Metastasis In Vivo and Inhibits Factor Xa Binding to Melanoma Cells In Vitro

1998 ◽  
Vol 79 (05) ◽  
pp. 1041-1047 ◽  
Author(s):  
Kathleen M. Donnelly ◽  
Michael E. Bromberg ◽  
Aaron Milstone ◽  
Jennifer Madison McNiff ◽  
Gordon Terwilliger ◽  
...  
Keyword(s):  
Active Site ◽  
Thrombin Generation ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Melanoma Cells ◽  
Factor V ◽  
Ancylostoma Caninum ◽  
Metastatic Activity

SummaryWe evaluated the in vivo anti-metastatic activity of recombinant Ancylostoma caninum Anticoagulant Peptide (rAcAP), a potent (Ki = 265 pM) and specific active site inhibitor of human coagulation factor Xa originally isolated from bloodfeeding hookworms. Subcutaneous injection of SCID mice with rAcAP (0.01-0.2 mg/mouse) prior to tail vein injection of LOX human melanoma cells resulted in a dose dependent reduction in pulmonary metastases. In order to elucidate potential mechanisms of rAcAP’s anti-metastatic activity, experiments were carried out to identify specific interactions between factor Xa and LOX. Binding of biotinylated factor Xa to LOX monolayers was both specific and saturable (Kd = 15 nM). Competition experiments using antibodies to previously identified factor Xa binding proteins, including factor V/Va, effector cell protease receptor-1, and tissue factor pathway inhibitor failed to implicate any of these molecules as significant binding sites for Factor Xa. Functional prothrombinase activity was also supported by LOX, with a half maximal rate of thrombin generation detected at a factor Xa concentration of 2.4 nM. Additional competition experiments using an excess of either rAcAP or active site blocked factor Xa (EGR-Xa) revealed that most of the total factor Xa binding to LOX is mediated via interaction with the enzyme’s active site, predicting that the vast majority of cell-associated factor Xa does not participate directly in thrombin generation. In addition to establishing two distinct mechanisms of factor Xa binding to melanoma, these data raise the possibility that rAcAP’s antimetastatic effect in vivo might involve novel non-coagulant pathways, perhaps via inhibition of active-site mediated interactions between factor Xa and tumor cells.

Purification of the Antihemophilic Factor by Gel Filtration on Agarose

1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Large Scale ◽  
Gel Filtration ◽  
Large Scale Preparation ◽  
Scale Preparation ◽  
Antihemophilic Factor

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.

Acquired Haemophilia: Functional Study of Antibodies to Factor VIII

1981 ◽  
Vol 45 (03) ◽  
pp. 285-289 ◽  
Author(s):  
J P Allain ◽  
A Gaillandre ◽  
D Frommel
Keyword(s):  
Factor Viii ◽  
Functional Study ◽  
Factor Viii Inhibitor ◽  
Acquired Haemophilia ◽  
Viii Inhibitor ◽  
Kinetics Of ◽  
Antibody Function ◽  
Native Plasma

SummaryFactor VIII complex and its interaction with antibodies to factor VIII have been studied in 17 non-haemophilic patients with factor VIII inhibitor. Low VIII:C and high VIIIR.Ag levels were found in all patients. VIII:WF levels were 50% of those of VTIIRrAg, possibly related to an increase of poorly aggregated and electrophoretically fast moving VIIIR:Ag oligomers.Antibody function has been characterized by kinetics of VIII :C inactivation, saturability by normal plasma and the slope of the affinity curve. Two major patterns were observed:1) Antibodies from 6 patients behaved similarly to those from haemophiliacs by showing second order inhibition kinetics, easy saturability and steep affinity slope (> 1).2) Antibodies from other patients, usually with lower titres, inactivated VIII :C according to complex order kinetics, were not saturable, and had a less steep affinity slope (< 0.7). In native plasma, or after mixing with factor VIII concentrate, antibodies of the second group did not form immune complexes with the whole factor VIII molecular complex. However, dissociation procedures did release some antibodies from apparently low molecular weight complexes formed in vivo or in vitro. For appropriate management of non-haemophilic patients with factor VIII inhibitor, it is important to determine the functional properties of their antibodies to factor VIII.

Comparison of the Actions of Thrombin and the Thrombin-Like Venom Enzymes Ancrod and Batroxobin

1976 ◽  
Vol 36 (01) ◽  
pp. 009-013 ◽  
Author(s):  
D. L Aronson
Keyword(s):  
Factor Viii ◽  
Fibrinopeptide A ◽  
Enzymic Reaction

SummaryThrombin acts on several coagulant proteins to produce products with physiologic, pharmacologic and pathologic potential. The most sensitive thrombin substrate seems to be factor VIII. Some thrombin dependent reactions studied in vitro and proposed as control reactions seem too insensitive to the action of thrombin to be of in vivo significance.The only enzymic reaction the thrombin-like venom enzymes, Ancrod and Batroxobin, have in common with thrombin is the removal of fibrinopeptide A.

The Development of Homologous (Canine/Anti-Canine) Antibodies in Dogs with Haemophilia A (Factor VIII Deficiency): A Ten-Year Longitudinal Study

1993 ◽  
Vol 69 (01) ◽  
pp. 021-024 ◽  
Author(s):  
Shawn Tinlin ◽  
Sandra Webster ◽  
Alan R Giles
Keyword(s):  
Factor Viii ◽  
Canine Model ◽  
Significant Inhibition ◽  
Human Condition ◽  
Haemophilia A ◽  
Variable Expression ◽  
The Family ◽  
Over Time

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

scholarly journals The Therapeutic Effect of Extracellular Vesicles on Asthma in Pre-Clinical Models: A Systematic Review Protocol

2021 ◽  
Vol 1 (1) ◽  
pp. 84-95
Author(s):  
Patience O. Obi ◽  
Jennifer E. Kent ◽  
Maya M. Jeyaraman ◽  
Nicole Askin ◽  
Taiana M. Pierdoná ◽  
...  
Keyword(s):  
Systematic Review ◽  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Grey Literature ◽  
Specific Treatment ◽  
Therapeutic Effects ◽  
Management Options ◽  
Paracrine Signalling

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.

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