A STUDY OF THE EARLY HAEMOSTATIC CHANGES FOLLOWING RUSSELL'S VIPER BITE IN HUMANS

1987 ◽  
Author(s):  
Than Than ◽  
Khin Ei Han ◽  
Hutton RA ◽  
Mvint Lwin ◽  
Tin Nu Swe ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Degradation Products ◽  
Early Stage ◽  
Coagulation Factor ◽  
Factor V ◽  
Thrombin Time ◽  
Factor X ◽  
Life Saving ◽  
Coagulation Factor Deficiency ◽  
Russell’S Viper

Amongst its many actions, Russell's viper (RV) venom activates factors X and V and enhances fibrinolysis, leading to defibrination which contributes to the clinical sequelae of RV bite. Early administration of antivenom may be life-saving, but not all of those bitten become sufficiently envenomed to require treatment. In an attempt to predict at an early stage those subjects who will progress to defibrination, we have serially monitored the haemostatic changes in 20 bite victims using the PT, APTT, thrombin time, platelet count, assays for factors X and V and fibrinogen and fibrin(ogen) degradation products (FDP).In five patients, no evidence of defibrination was seen at any time and none of these developed obvious clinical symptoms. In a further six subjects, slight prolongation of the PT (16-21/14s), APTT (39-51/38s) and thrombin time (16-25/14s) occurred concomitantly with a moderate fall in factor X (20-80%), factor V (30-66%) and fibrinogen (0.6-2.Og/1), but FDP never exceeded 40ug/ml. In the remaining nine subjects who all eventually defibrinated completely, moderate coagulation factor deficiency and thrombocytopenia developed as early as 1-2h after bite. The most pronounced and consistent changes were a rise in FDP to above 80ug/ml (80-640ug/ml) and a fall in factor V (2-50%), these results being obtained on admission, 1-12h after bite. We conclude that an FDP level of 80ug/ml or more is highly suggestive of impending defibrination and could be regarded as a criterion for commencing antivenom therapy.

Two parallel prothrombin activator systems in Australian rough-scaled snake, Tropidechis carinatus

2005 ◽  
Vol 93 (01) ◽  
pp. 40-47 ◽  
Author(s):  
Md. Abu Reza ◽  
Sanjay Swarup ◽  
Manjunatha Kini
Keyword(s):  
Blood Coagulation ◽  
Blood Clotting ◽  
Cdna Sequence ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Venom Gland ◽  
Factor X ◽  
Specific Expression ◽  
Life Saving ◽  
Sequence Encoding

SummaryIt is uncommon for similar pathways/systems to be involved in highly divergent functions within single organisms. Earlier, we have shown that trocarin D, a venom prothrombin activator, from the Australian rough-scaled snake Tropidechis carinatus, is structurally and functionally similar to the blood coagulation factor Xa (FXa). The presence of a haemostatic system in these snakes implies that they have two parallel prothrombin activating systems: one in the plasma, that participates in the life saving process of blood clotting and the other in their venom, where it acts as a toxin. Here, we report the complete cDNA sequence encoding the blood coagulation factor X (FX) from the liver of T. carinatus. Deduced T. carinatus FX sequence shows ~80% identity with trocarin D but ~50% identity with the mammalian FX. Our present study confirms the presence of two separate genes – one each for FX and trocarin D, that code for similar proteins in T. carinatus snake. These two genes have different expression sites and divergent uses suggesting that snake venom prothrombin activators have probably evolved by the duplication of the liver FX gene and subsequently marked for tissue-specific expression in the venom gland.

scholarly journals Coinheritance of Factor V (FV) Leiden enhances thrombin formation and is associated with a mild bleeding phenotype in patients homozygous for the FVII 9726+5G>A (FVII Lazio) mutation

Blood ◽  
2003 ◽  
Vol 102 (12) ◽  
pp. 4014-4020 ◽  
Author(s):  
Elisabetta Castoldi ◽  
José W. P. Govers-Riemslag ◽  
Mirko Pinotti ◽  
Debora Bindini ◽  
Guido Tans ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Clinical Phenotype ◽  
Activated Protein C ◽  
Coagulation Factor ◽  
Factor Vii ◽  
Factor V ◽  
Factor X ◽  
Fv Leiden ◽  
Fvii Deficiency ◽  
Thrombin Formation

Abstract We investigated the role of thrombophilic mutations as possible modifiers of the clinical phenotype in severe factor VII (FVII) deficiency. Among 7 patients homozygous for a cross-reacting material-negative (CRM-) FVII defect (9726+5G>A, FVII Lazio), the only asymptomatic individual carried FV Leiden. Differential modulation of FVII levels by intragenic polymorphisms was excluded by a FVII to factor X (FX) gene haplotype analysis. The coagulation efficiency in the FV Leiden carrier and a noncarrier was evaluated by measuring FXa, FVa, and thrombin generation after extrinsic activation of plasma in the absence and presence of activated protein C (APC). In both patients coagulation factor activation was much slower and resulted in significantly lower amounts of FXa and thrombin than in a normal control. However, more FXa and thrombin were formed in the plasma of the patient carrying FV Leiden than in the noncarrier, especially in the presence of APC. These results were confirmed in FV-FVII doubly deficient plasma reconstituted with purified normal FV or FV Leiden. The difference in thrombin generation between plasmas reconstituted with normal FV or FV Leiden gradually decreased at increasing FVII concentration. We conclude that coinheritance of FV Leiden increases thrombin formation and can improve the clinical phenotype in patients with severe FVII deficiency. (Blood. 2003;102:4014-4020)

Removal from Bovine Prothrombin of the Substrate for Russell’s Viper Venom

1969 ◽  
Vol 21 (02) ◽  
pp. 203-216 ◽  
Author(s):  
J. H Milstone ◽  
N Oulianoff
Keyword(s):  
Calcium Chloride ◽  
Barium Sulfate ◽  
Deae Cellulose ◽  
Factor V ◽  
Factor X ◽  
Bovine Plasma ◽  
Russell’S Viper ◽  
Repeated Passage ◽  
Almost All ◽  
Filter Cakes

SummaryBovine prothrombin was prepared by adsorption on barium sulfate. After elution, it was passed through thick filter-cakes of Standard Super-Cel, which removed some venom substrate (factor X). Almost all the remaining venom substrate was removed by repeated passage through columns of DEAE-cellulose. Finally, the ratio of venom substrate to prothrombin was considerably less than 1/1,000 that of plasma. The prothrombin was also poor in factor V. It yielded very little thrombin upon incubation with Russell’s viper venom, factor V, phospholipid and calcium chloride. However, inclusion of bovine plasma at a final dilution of 1/10,000 caused the mixture to produce thrombin rapidly. This system offers promise for the assay of venom substrate in plasma.Thrombokinase derived from bovine plasma was able, at 0.000071 mg/ml, to substitute for both the venom and its substrate in thrombin-producing systems. However, with this small amount of thrombokinase, phospholipid was indispensable. The system was sensitive to 0.00001 mg phospholipid/ml.With 1,000 times as much thrombokinase, prothrombin was activated without addition of accessory factors, in the presence of oxalate. Removal of venom substrate did not affect this response of prothrombin. Nor did removal of venom substrate from the prothrombin prevent its activation by crystallized trypsin in the presence of oxalate.

scholarly journals Activation of Bovine Blood Coagulation Factor V, A Prerequisite for it of Bind Both Prothrombin and Factor Xa.

1977 ◽  
Author(s):  
M.C. Guillin ◽  
A. Bezeaud ◽  
J.P. Freeman ◽  
C.M. Jackson
Keyword(s):  
Factor Xa ◽  
Coagulation Factor ◽  
Factor V ◽  
Factor Va ◽  
Bovine Plasma ◽  
Coagulation Factor V ◽  
Russell’S Viper ◽  
Blood Coagulation Factor V ◽  
Bovine Factor ◽  
Plasma Heparin

It is known that prior to bind bovine prothrombin and to become fully functional, bovine Factor V must itself be “activated” by either thrombin or an enzyme isolable from Russell’s viper venom. The purpose of this work was to determine if Factor V activation is also required in order for it to bind bovine Factor Xa.This has been investigated by measuring the binding of both “native” (unactivated) Factor V and Factor V activated by the Russell’s viper venom activating enzyme, to a column of agarose-bound Factor Xa. The experiments were also performed using diisopropylfluorophosphate (DFP) inhibited Factor Xa covalently bound to agarose. Both purified bovine Factor V (Va) and bovine plasma were used and gave the same results. In order to prevent initiation of clotting in bovine plasma, heparin wad added to the plasma to promote inactivation of Factor Xa by antithrombin III.The results indicate that Factor V activation is a prerequisite for it to bind Factor Xa ; Factor Va binds both Factor Xa and DFP inhibited Factor Xa, unmodified Factor V does not.These experiments suggest that Factor V may not participate in prothrombin activation at all, until after some thrombin has been formed. If this is so, an alternate pathway by which the first thrombin is generated must be considered and may be proposed to be simply that involving Factor Xa, phospholipid and Ca2+ alone.

Characterization Of The In Vitro “Factor VIII Bypassing Activity”

1981 ◽  
Author(s):  
D L Aronson ◽  
J Bagley
Keyword(s):  
Factor Viii ◽  
Early Stage ◽  
Deae Cellulose ◽  
Factor Ix ◽  
Factor Xii ◽  
Factor V ◽  
Factor X ◽  
Hemostatic Effect ◽  
Prolonged Aptt

The in vitro correction of the prolonged APTT of hemophilic plasma has been ascribed to an uncharacterized entity “Factor VIII Bypassing Activity.” Such products also correct the prolonged APTT plasma deficient in Factor IX, Factor X and Factor XII, but not of Factor V deficient plasma. Correction of the APTT in Factor VIII deficient plasma by early stage coagulants such as Factor XIIa, Kallikrein and Factor IXa is minimal. These results indicate that this in vitro activity acts at the level of either the activation of Factor X or the activation of prothrombin.A coagulant has been prepared from serum by barium precipitation, heparin-agarose, DEAE cellulose and high pressure liquid chromatography (HPLC). The in vitro coagulant properties are similar to “activated” prothrombin complex (Autoplex) and the biologic and chemical properties are identical to activated Factor X.Infusion of the partially purified serum coagulant into normal dogs was well tolerated and, in contrast to Factor IX concentrates, gave no signs of DIC. Infusion into bleeding hemophilic dogs had no hemostatic effect. It is concluded that a major portion of the in vitro potency of activated prothrombin concentrates is due to activated Factor X, a material which when infused has no in vivo hemostatic effect.Acknowledgments - The authors gratefully acknowledge the studies of Dr. Henry Kingdon in hemophilic dogs.

A Review of Coagulation Abnormalities of Autoimmune Acquired Factor V Deficiency with a Focus on Japan

2021 ◽  
Author(s):  
Akitada Ichinose ◽  
Tsukasa Osaki ◽  
Masayoshi Souri
Keyword(s):  
Coagulation Factor ◽  
Nationwide Survey ◽  
Autoimmune Disorder ◽  
Antibody Detection ◽  
Extensive Literature ◽  
Factor V ◽  
Bleeding Tendency ◽  
Factor X ◽  
Timely Initiation ◽  
Fv Antibody

AbstractCoagulation factor V (or FV for the purpose of medical safety) is an essential cofactor of coagulation factor X in the common pathway of coagulation; severe FV deficiency leads to a bleeding tendency. Although both congenital and acquired FV deficiencies are widely recognized, FV deficiency also presents as an autoimmune disorder. A nationwide survey on autoimmune coagulation factor deficiencies (AiCFDs) conducted in Japan by our Japanese Collaborative Research Group identified 24 new patients with autoimmune FV deficiency (AiFVD) in the past 5 years. Furthermore, our extensive literature search confirmed that 177 AiFVD cases have been reported in previous articles published from Japan. Patients with AiFVD in Japan were predominantly men, with age similar to those with other AiCFDs. AiFVD was confirmed as a relatively mild type of bleeding diathesis, associated with lower mortality rate than that for AiFVD and other AiCFDs reported in previous studies. Patients with AiFVD had variable FV inhibitor titers and both neutralizing anti-FV autoantibodies and nonneutralizing counterparts. Although spontaneous resolution occurs in some patients, timely initiation of hemostatic and immunosuppressive therapies helps arrest the bleeding and eliminate anti-FV antibodies, resulting in a high cumulative recovery rate. Immunological anti-FV antibody detection is recommended to avoid missing AiFVD cases for the presence of nonneutralizing anti-FV autoantibodies. Further investigation is necessary to clarify the long-term prognosis and optimal management of AiFVD.

Heme arginate: effects on hemostasis

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 625-628 ◽  
Author(s):  
L Volin ◽  
V Rasi ◽  
E Vahtera ◽  
R Tenhunen
Keyword(s):  
Side Effects ◽  
Animal Studies ◽  
Degradation Products ◽  
Coagulation Factor ◽  
Clinical Use ◽  
Factor X ◽  
Degradation Rates ◽  
Heme Arginate ◽  
Acute Porphyrias ◽  
Coagulation And Fibrinolysis

Abstract Hematin, the drug used for acute porphyric attacks, has been shown to cause disturbances in hemostasis, mainly because of its degradation products. Lately a new heme compound, heme arginate, has been developed for the treatment of porphyrias. In experimental animal studies as well as in clinical use it has proved to be well tolerated. To find out whether heme arginate has any effects on hemostasis we have studied a number of parameters of coagulation and fibrinolysis after a heme arginate infusion in seven healthy volunteers. All parameters studied remained practically unchanged except the coagulation factor X, which showed a transient, insignificant decrease during the maximal heme concentration. We believe that the lack of side effects is due to a better stability of heme arginate, the degradation rates being 1% for heme arginate and 61% for hematin in four hours. Our data favor the use of heme arginate in acute porphyrias as well as in other deficiency states of heme.

Acquired factor V inhibitor associated with life-threatening bleeding and a mixing test result that indicated coagulation factor deficiency

Hematology ◽  
2013 ◽  
Vol 18 (5) ◽  
pp. 300-304 ◽  
Author(s):  
Masahiro Ashizawa ◽  
Shun-ichi Kimura ◽  
Hidenori Wada ◽  
Kana Sakamoto ◽  
Miki Sato ◽  
...  
Keyword(s):  
Coagulation Factor ◽  
Factor V ◽  
Factor Deficiency ◽  
Life Threatening ◽  
Coagulation Factor Deficiency ◽  
Test Result

Phosphorothioate Oligonucleotides Inhibit the Intrinsic Tenase Complex

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1617-1625
Author(s):  
John P. Sheehan ◽  
Hao-Chang Lan
Keyword(s):  
Plasma Concentrations ◽  
Coagulation Factor ◽  
Intercellular Adhesion Molecule ◽  
Specific Factor ◽  
Thrombin Time ◽  
Factor X ◽  
Contact Activation ◽  
Intercellular Adhesion Molecule 1 ◽  
Phosphorothioate Oligonucleotide

Systemic administration of ISIS 2302, a 20-mer antisense phosphorothioate oligonucleotide targeting human intercellular adhesion molecule-1 mRNA, causes prolongation of plasma clotting times in both monkey and human studies. The anticoagulant effects of ISIS 2302 were investigated with both in vitro coagulation assays in human plasma and purified enzyme systems. At high oligonucleotide plasma concentrations (>100 μg/mL), prolongation of the prothrombin and thrombin times was observed. In a thrombin time assay using purified components, high concentrations of ISIS 2302 inhibited thrombin clotting activity both by stimulating inhibition by heparin cofactor II and directly competing with fibrinogen for binding to anion binding exosite I. In contrast, low concentrations of ISIS 2302 (<100 μg/mL) showed a selective, linear prolongation of the activated partial thromboplastin time (PTT). The rate limiting effect of 50 μg/mL ISIS 2302, which prolonged the PTT to 1.5 times control, was identified by sequential modification of the clotting assay. Delaying addition of oligonucleotide until after contact activation failed to correct prolongation of the PTT. The calcium-dependent steps of the intrinsic pathway were individually assessed by adding sufficient activated coagulation factor to correct the PTT in plasma deficient in that specific factor. Addition of factor XIa, IXa, VIIIa, or Va failed to correct the PTT in the presence of ISIS 2302. In contrast, 0.2 nmol/L factor Xa corrected prolongation of the PTT in factor X–deficient plasma with or without oligonucleotide present. ISIS 2302 (50 μg/mL) did not prolong a modified Russel viper venom time, suggesting no significant inhibition of prothrombinase. Thus, 50 μg/mL ISIS 2302 prolonged the PTT by selectively inhibiting intrinsic tenase activity. ISIS 2302 showed partial inhibition of intrinsic tenase activity (to approximately 35% of control) at clinically relevant oligonucleotide concentrations in a chromogenic assay. This activity was oligonucleotide sequence–independent but required the phosphorothioate backbone, suggesting that inhibition of intrinsic tenase is a general property of this class of oligonucleotides. These results are relevant to both the therapeutic use of phosphorothioate oligonucleotides and the potential design of inhibitors of the intrinsic tenase complex, a novel target for anticoagulation. © 1998 by The American Society of Hematology.

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