Factor V in Blood Coagulation in Vitro, and a Report of a Case of Factor-V Deficiency

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.

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“In vitro” correction of the severe factor V deficiency-related coagulopathy by a novel plasma-derived factor V concentrate

Haemophilia ◽

10.1111/hae.13465 ◽

2018 ◽

Vol 24 (4) ◽

pp. 648-656 ◽

Cited By ~ 10

Author(s):

C. Bulato ◽

C. Novembrino ◽

M. Boscolo Anzoletti ◽

L. Spiezia ◽

S. Gavasso ◽

...

Keyword(s):

Factor V ◽

Factor V Deficiency

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Antisense-based RNA therapy of factor V deficiency: in vitro and ex vivo rescue of a F5 deep-intronic splicing mutation

Blood ◽

10.1182/blood-2013-04-499657 ◽

2013 ◽

Vol 122 (23) ◽

pp. 3825-3831 ◽

Cited By ~ 10

Author(s):

Francesca Nuzzo ◽

Claudia Radu ◽

Marco Baralle ◽

Luca Spiezia ◽

Tilman M. Hackeng ◽

...

Keyword(s):

Ex Vivo ◽

Factor V ◽

Splicing Mutation ◽

Splicing Defect ◽

Factor V Deficiency ◽

Key Points ◽

Life Threatening

Key Points Homozygosity for the F5 c.1296+268A>G splicing mutation causes life-threatening factor V deficiency. Mutation-specific antisense molecules can correct this splicing defect and restore factor V synthesis in the patient’s megakaryocytes.

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Action of a Proteolytic Enzyme Inhibitor on Blood Coagulation in Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655028 ◽

1967 ◽

Vol 18 (01/02) ◽

pp. 190-197 ◽

Cited By ~ 2

Author(s):

B Blombäck ◽

Margareta Blombäck ◽

P Olsson

Keyword(s):

Blood Coagulation ◽

Proteolytic Enzyme ◽

Enzyme Inhibitor ◽

Factor V ◽

Generation System ◽

Antifibrinolytic Agents ◽

Coagulation Activity ◽

Serum Factors ◽

Proteolytic Enzyme Inhibitor

SummaryThe action of the kallikrein and trypsin inhibitor, Trasylol, has been studied in a three-stage thrombin generation system. It has been found that Trasylol inhibits one or several of the early reactions of blood coagulation. The inhibition of the early stages is dependent on the concentration of inhibitor, serum factors and factor VIII. The activation of factor V by tiger snake venom is not inhibited by Trasylol. The inhibition is most probably on one or several of the reactions preceding the factor V involved step.Some other known antifibrinolytic agents have also been tested for anti-coagulation activity.

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Identification of the first Alu-mediated large deletion involving the F5 gene in a compound heterozygous patient with severe factor V deficiency

Thrombosis and Haemostasis ◽

10.1160/th11-03-0149 ◽

2011 ◽

Vol 106 (08) ◽

pp. 296-303 ◽

Cited By ~ 4

Author(s):

Ilaria Guella ◽

Elvezia Maria Paraboschi ◽

Willem A. van Schalkwyk ◽

Rosanna Asselta ◽

Stefano Duga

Keyword(s):

Molecular Genetic ◽

Genetic Diagnosis ◽

Large Deletion ◽

Severe Bleeding ◽

Compound Heterozygous ◽

Factor V ◽

Large Gene ◽

Factor V Deficiency ◽

Heterozygous Patient

SummaryFactor V (FV) deficiency is a rare autosomal recessive haemorrhagic disorder associated with moderate to severe bleeding symptoms. Conventional mutational screening leads to a complete molecular genetic diagnosis only in about 80–90% of cases. Large gene rearrangements, which could explain at least part of the “missing alleles” have not been reported so far in FV-deficient patients. In this work, we investigated a family with hereditary FV deficiency, in which the proband is compound heterozygous for a 205-Kb deletion, involving the first seven exons of F5, and the entire selectin P, L, and E genes, and for a novel splicing mutation (IVS12+5G>A). The deletion breakpoints, determined by using a combination of semi-quantitative real-time PCR and long PCR assays, occurred within AluY repeat sequences, suggesting an Alu-mediated unequal homologous recombination as the mechanism responsible for the deletion. The in vitro characterisation of the IVS12+5G>A mutation demonstrated that this mutation causes the skipping of exon 12 and the activation of a cryptic splice site. Low levels of residual wild-type splicing were also detectable, in agreement with the notion that the complete absence of FV may be not compatible with life.

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Effects of fibrinolytic agents and heparin on blood coagulation in dogs

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1964.207.5.1049 ◽

1964 ◽

Vol 207 (5) ◽

pp. 1049-1052 ◽

Cited By ~ 8

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.

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FactorV C1149G and 5609–10INSCGTGGTT causing factor V deficiency: Molecular characterization by in-vitro expression

Thrombosis and Haemostasis ◽

10.1160/th07-01-0041 ◽

2007 ◽

Vol 98 (09) ◽

pp. 683-685 ◽

Cited By ~ 3

Author(s):

Qiu-Lan Ding ◽

Qi-Hua Fu ◽

Xiao-Hong Cai ◽

Xue-Feng Wang ◽

Hong-Li Wang

Keyword(s):

Molecular Characterization ◽

Factor V ◽

In Vitro Expression ◽

Factor V Deficiency

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

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615117 ◽

1998 ◽

Vol 79 (05) ◽

pp. 1041-1047 ◽

Cited By ~ 20

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.

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Dermatan Sulfate and LMW Heparin Enhance the Anticoagulant Action of Activated Protein C

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614856 ◽

1999 ◽

Vol 82 (11) ◽

pp. 1462-1468 ◽

Cited By ~ 22

Author(s):

José Fernández ◽

Jari Petäjä ◽

John Griffin

Keyword(s):

Molecular Weight ◽

Unfractionated Heparin ◽

Protein C ◽

Dermatan Sulfate ◽

Anticoagulant Activity ◽

Activated Protein C ◽

Factor V ◽

Factor Va ◽

Anticoagulant Action

SummaryUnfractionated heparin potentiates the anticoagulant action of activated protein C (APC) through several mechanisms, including the recently described enhancement of proteolytic inactivation of factor V. Possible anticoagulant synergism between APC and physiologic glycosaminoglycans, pharmacologic low molecular weight heparins (LMWHs), and other heparin derivatives was studied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs showed differing abilities to promote APC activity, and the molecular weight of LMWHs correlated with enhancement of APC activity. Degree of sulfation of the glycosaminoglycans influenced APC enhancement. However, because dextran sulfates did not potentiate APC action, the presence of sulfate groups per se on a polysaccharide is not sufficient for APC enhancement. As previously for unfractionated heparin, APC anticoagulant activity was enhanced by glycosaminoglycans when factor V but not factor Va was the substrate. Thus, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that could be of physiologic and pharmacologic significance.

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Self-Damping Mechanism in Blood Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647672 ◽

1974 ◽

Vol 32 (01) ◽

pp. 057-064 ◽

Cited By ~ 3

Author(s):

Y Nemerson ◽

S.A Silverberg ◽

J Jesty

Keyword(s):

Tissue Factor ◽

Blood Coagulation ◽

Calcium Ions ◽

Control Mechanism ◽

Factor Vii ◽

Damping Factor ◽

Factor V ◽

Factor X ◽

Extrinsic Pathway ◽

Two Systems

SummaryTwo reactions of the extrinsic pathway of coagulation, the activations of Factor X and prothrombin, have been studied in purified systems and shown to be self-damping. Factor X was activated by the tissue factor - Factor VII complex, and prothrombin by two systems: the coagulant protein of Taipan venom, and the physiological complex of activated Factor X, Factor V, lipid, and calcium ions. In each case the yield of enzyme, activated Factor X or thrombin, is a function of the concentration of activator. These and other observations are considered as a basis for a control mechanism in coagulation.

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