A NEW MUCOPOLYSACCHARIDE FROM STICHPUS JAPONICUS(SEA CUCUMBER) AND ITS ANTICOAGULANT PRORETIES

1987 ◽  
Author(s):  
J Takamatsu ◽  
H Saito ◽  
T Kamiya ◽  
Y Muranaka ◽  
Y F Minami ◽  
...  
Keyword(s):  
Glucuronic Acid ◽  
Antithrombin Iii ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time ◽  
Similar Extent ◽  
Plasma Component ◽  
Platelet Factor ◽  
Antithrombin Activity ◽  
Significant Prolongation

A new mucopolysaccharide(FGAG) has been isolated from the cell wall of Stichopus japonicua. The molecular weight of FGAG is about 50,000. The component sugar of the FGAG are identified as galactosamine, glucuronic acid, fucose and sulfate with the molar ratioof 1:0.94:0.84:3.60,respectively. The anticoagulant effects of FGAG were studied. At low concentration(lμg/ml), FGAG completely inhibited the rabbit plateletaggregation induced by thrombin and prolonged thrombin time of not only human plasma but purified fibrinogen solution to a similar extent, suggesting that action of FGAG is not depend on plasma component(antithrombin III and/or Heparin c.ofactor II).After intravenous injection into rabbits(lmg/kg),significant prolongation of activated partial thromboplastin time(APTT) was observed. Although the in vivo antithrombin activity of the FGAG was weaker than that of heparin.it lasted longer than that of heparin and was not inhibited by platelet factor 4.These results suggested that FGAG is a new and unique mucopolysaccharide with antithrombin activity and may come into use for the treatment ofDiseminated Intravascular Coagulation.

STUDY OF THE PLASMA COMPONENT OF THE BLOOD AGGREGATION REGULATORY SYSTEM IN SUBJECTS IN THE EXPERIIMENT WITH 120-DAY ISOLATION INSIDE PRESSURIZED MODULE SIRIUS-19

2021 ◽  
Vol 55 (1) ◽  
pp. 59-62
Author(s):  
D.S. Kuzichkin ◽  
◽  
А.А. Markin ◽  
О.А. Zhuravleva ◽  
Z.А. Krivitsina ◽  
...  
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Regulatory System ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time ◽  
Plasma Samples ◽  
Plasma Component ◽  
Aggregation Parameters ◽  
Aggregation Control ◽  
D Dimer

Citrate plasma samples gathered 31 days prior to, on days 37, 63, 120 in and on days 7 and 14 after isolation (project Sirius-19) were analyzed for blood aggregation parameters including fibrinogen (FBG), D-dimer (DD), plasminogen (PG), antithrombin III (АТ3), protein C (PC) and α2-antiplasmin (AP), thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT). DD was lowered in all samples gathered during isolation. The complex of isolation factors combined with physical exercise reduced levels of fibrin formation and fibrinolysis. However, after isolation the procoagulent activity showed an increase manifested by elevated DD and reduced APTT. Appears that in the absence of insertion and reentry effects (redistribution of body fluids in microgravity) and high psychophysiological stresses it is the appropriate use of physical countermeasures that ensures plasma efficiency within the blood aggregation control system, and good body tolerance of the spaceflight factors.

Release of Platelet Factor 4 in Vivo during Intravascular Coagulation and in Thrombotic States

1968 ◽  
Vol 19 (03/04) ◽  
pp. 578-583 ◽  
Author(s):  
R Farbiszewski ◽  
S Niewiarowski ◽  
K Worowski ◽  
B Lipiński
Keyword(s):  
Coronary Thrombosis ◽  
Laboratory Diagnosis ◽  
Tolerance Test ◽  
Platelet Factor 4 ◽  
Thrombin Time ◽  
Significant Elevation ◽  
Platelet Factor ◽  
Thrombotic Diseases ◽  
Disseminated Intravascular Clotting

SummaryPlatelet factor 4 released from platelets into the circulating blood was determined using both the heparin thrombin time and paracoagulation methods. It has been found that thrombin injected intravenously into rabbits releases large amounts of this factor. Infusion of plasmin does not release this factor and this finding may be of importance for the differential diagnosis between disseminated intravascular clotting and primary fibrinolysis. PF4 is not released during the hyper coagulable condition induced by HgCl2 intoxication. Only small amounts of this factor are released after contact factor infusion.A significant elevation of extraplatelet PF4 was found in 23 patients with fresh coronary thrombosis and in 9 patients with thrombophlebitis and thromboembolic complications.The significance of the above findings for the pathogenesis, treatment and laboratory diagnosis of thrombotic diseases with particular reference to heparin tolerance test is discussed.

Effects of Heparin Oligosaccharides with High Affinity for Antithrombin III in Experimental Venous Thrombosis

1982 ◽  
Vol 47 (03) ◽  
pp. 244-248 ◽  
Author(s):  
D P Thomas ◽  
Rosemary E Merton ◽  
T W Barrowcliffe ◽  
L Thunberg ◽  
U Lindahl
Keyword(s):  
Antithrombin Iii ◽  
Specific Activity ◽  
High Specific Activity ◽  
Factor Xa ◽  
Blood Levels ◽  
Thrombin Time ◽  
High Affinity ◽  
Very High

SummaryThe in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.

scholarly journals On the interaction of rabbit antithrombin III with the luminal surface of the normal and deendothelialized rabbit thoracic aorta in vitro

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 878-886
Author(s):  
MW Hatton ◽  
SL Moar ◽  
M Richardson
Keyword(s):  
Thoracic Aorta ◽  
Antithrombin Iii ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Luminal Surface ◽  
High Affinity ◽  
Antithrombin Activity ◽  
Thrombin Antithrombin Iii Complex

Pure rabbit antithrombin III was isotope labeled (with 125I or 3H) by two different methods; neither procedure caused a loss of antithrombin activity although both methods affected the affinity of the protein for Sepharose-heparin. From segments from freshly excised rabbit aorta, the uptake of isotope-labeled antithrombin III by the endothelium was rapid and saturable, although relatively small compared to the uptake of thrombin; binding of 3H-antithrombin III to the endothelium resembled that of 125I-antithrombin III. Transendothelial passage of antithrombin III into the subendothelial layers (intima-media) was slow and progressive. Endothelium binding was not affected by pretreating the vessel with either heparin, thrombin, or glycosaminoglycan-specific enzymes. Endothelium-bound antithrombin III was not selectively displaced by either heparin or thrombin. In contrast, endothelium-bound thrombin was rapidly dislodged by antithrombin III as a thrombin- antithrombin III complex. The surface of the deendothelialized aorta (ie, subjected to a balloon catheter) bound antithrombin III avidly. Pretreatment of the deendothelialized vessel with glycosaminoglycan- specific enzymes, particularly heparitinase, decreased intima-media binding by up to 80%. 125I-antithrombin III, when bound to the deendothelialized vessel surface, was actively displaced by either heparin, thrombin, or by unlabeled antithrombin III. The relatively poor binding of antithrombin III compared with that of thrombin by the endothelium in vitro supports an earlier proposal (Lollar P, Owen WG: J Clin Invest 66:1222–1230, 1980) that thrombin bound to high-affinity sites, possibly pericellular proteoglycan, of the endothelium is inactivated by plasma antithrombin III in vivo. Such a situation probably holds for large arteries at least.

Bleeding in Uremic Patients after Carbenicillin

1976 ◽  
Vol 36 (01) ◽  
pp. 115-126 ◽  
Author(s):  
K Andrassy ◽  
E Weischedel ◽  
E Ritz ◽  
T Andrassy
Keyword(s):  
Platelet Function ◽  
Antithrombin Iii ◽  
Serum Levels ◽  
Coagulation Factors ◽  
Coagulation System ◽  
Hemorrhagic Diathesis ◽  
Thrombin Time ◽  
Antithrombin Iii Activity

SummaryHemorrhagic diathesis was observed in patients with renal insufficiency after carbenicillin at serum levels > 300 μg/ml. Normal coagulation factors (F. I, II, V, VII, VIII, X), normal PTT, normal platelet counts, negative ethanol gelation test (fibrin monomers) were found as well as a prolongation of thromboplastin time (Quick), thrombin time, reptilase time and thrombin coagulase time. Platelet function was disturbed. In addition, the plasmatic system was involved: inhibition of fibrinogen-fibrin conversion (Belitser assay) and enhanced antithrombin III activity; in vivo the latter was ascribed to a heparin-like activity. In vitro, abnormal fibrinogen-fibrin conversion and a modified electrophoretic mobility of antithrombin III was seen: however an enhanced antithrombin III activity in vitro was not found with carbenicillin and various penicillin derivatives.This study demonstrates that carbenicillin, in addition to its known effect on platelet function, also disturbs the plasmatic coagulation system. This additional effect of carbenicillin is clinically important since protamin chloride effectively blocks bleeding without interfering with antibacterial activity.Both penicillin and penicillin derivatives have been shown to interfere with hemostasis and to cause clinically manifest hemorrhagic diathesis (Fleming and Fish 1947, Lurie et al. 1970a, b, McClure et al. 1970, Yudis et al. 1972, Demos 1971, Waisbren et al. 1971). Carbenicillin interferes with ADP-, collagen- or thrombin-induced platelet aggregation and with the release reaction both in vivo (McClure et al. 1970, Cazenave et al. 1973) and in vitro (McClure et al. 1970, Cazenave et al. 1973). In addition Lurie and colleagues (1970b) concluded that an inhibition of the conversion of fibrinogen to fibrin is involved although no experimental details were given. Later Brown and colleagues (1974) concluded that carbenicillin at usual dose levels “only affects the platelet component of hemostasis and has little effect on fibrin formation or other phases of coagulation in patients with normal renal function”.

Antithrombotic Effects of Synthetic Pentasaccharide with High Affinity for Plasma Antithrombin III in Non-Human Primates

1993 ◽  
Vol 70 (04) ◽  
pp. 631-635 ◽  
Author(s):  
Yves Cadroy ◽  
Stephen R Hanson ◽  
Laurence A Harker
Keyword(s):  
Antithrombin Iii ◽  
Thrombus Formation ◽  
Factor Xa ◽  
High Dose ◽  
Antithrombin Activity ◽  
Model Combining ◽  
Baboon Model ◽  
Dependent Inactivation ◽  
Antithrombotic Effects

SummaryThe pentasaccharide (PS) comprising the minimal heparin structure capable of binding with antithrombin III (ATIII) and exhibiting anti-factor Xa (anti-fXa) activity in plasma without producing detectable antithrombin activity, has been evaluated for its relative antithrombotic and antihemostatic effects in a baboon model combining both platelet-rich and fibrin-rich thrombosis. Thrombosis was produced in a two-component thrombogenic device incorporated into an exteriorized femoral arteriovenous (AV) shunt in baboons; the proximal component constituted a segment of collagen-coated tubing and induced platelet-rich arterial-type thrombus, while the distal component consisted of an expanded chamber producing static and disturbed flow and initiated fibrin-rich venous-type thrombosis. Thrombus formation was measured as the deposition of 111In-platelets and the accumulation of 125I-fibrin. PS was administered intravenously to maintain plasma anti-fXa activity at three different levels: a) low dose (LD) 0.3 ± 0.1 U/ml; b) intermediate dose (ID) 0.6 ± 0.1 U/ml; and c) high dose (HD) 5.6 ± 0.4 U/ml.In untreated Controls, thrombus formed rapidly, reaching a plateau by 40 min of 2.3 ± 0.2 × 109 platelets and 0.62 ± 0.04 mg fibrin deposited on the collagen segments, and 1.9 ±0.4 × 109 platelets and 3.3 ± 0.4 mg fibrin accumulated in the chambers. PS at HD abolished the formation of fibrin-rich thrombus in the chambers and decreased platelet-rich thrombus on collagen by half (p <0.01), while the ID reduced fibrin-rich thrombus in the chambers by about half (p <0.01) but had no effect on platelet-rich thrombus forming on the segments of collagen-coated tubing (p >0.5). Despite its lack of antithrombin activity, PS also decreased plasma fibrinopeptide A levels in a dose-response manner. However, PS had no effect on platelet hemostatic function in vivo, as measured by template bleeding time (BT) determinations (p >0.5). Despite the ability of PS-ATIII complex to inactivate soluble fXa, the complex lacked significant inhibitory activity for fXa immobilized to thrombus formed in vivo. Thus, PS-dependent inactivation of soluble fXa produces antithrombotic effects, primarily for venous-type thrombosis, that are equipotent to Standard heparin on a gravimetric basis, but more sparing of platelet hemostatic function.

Generation of a PGI2-Like Activity by Deendothelialized Rat Aorta

1979 ◽  
Vol 42 (03) ◽  
pp. 873-884 ◽  
Author(s):  
Chung-hsin Ts’ao ◽  
Charlotte M Holly ◽  
Margaret A Serieno ◽  
Theresa S Galluzzo
Keyword(s):  
Platelet Adhesion ◽  
Light Transmission ◽  
Rat Aorta ◽  
Activated Partial Thromboplastin Time ◽  
Collagen Fibrils ◽  
Thrombin Time ◽  
Platelet Aggregation Inhibitor ◽  
Inhibitor Activity ◽  
Platelet Factor ◽  
Aggregation Inhibitor

SummaryWe have tested a platelet aggregation inhibitor in the incubation fluid of deendothelialized fragments of the rat aorta and compared it with that of “intact” fragments. Some of the properties of the aortic inhibitor, and its effects on platelet adhesion to collagen fibrils, on platelet factor-3 (PF-3) availability, and on the activated partial thromboplastin time (APTT) and thrombin time (TT) were also evaluated in comparison with similar effects exerted by PGI2. We found that the incubation fluid of deendothelialized aortic samples contained inhibitor activity comparable with that of “intact” samples. The aortic inhibitor had similar properties to PGI2. The aortic inhibitor and PGI2 slightly inhibited light transmission changes of EDTA-PRP following exposure to collagen. However, scanning electron microscopy showed no appreciable difference in platelet adhesion to collagen fibrils. PGI2 and the aortic inhibitor inhibited Kaolin-induced PF-3 availability, but did not prolong the APTT or TT.

scholarly journals Effect of Angiography on Blood Coagulation

1977 ◽  
Author(s):  
W. H. Krause ◽  
A. Lang
Keyword(s):  
Contrast Media ◽  
Prothrombin Time ◽  
Antithrombin Iii ◽  
Degradation Products ◽  
Anticoagulant Activity ◽  
Thromboembolic Complication ◽  
Thrombin Time ◽  
Media Concentration

It is known, that angiographic contrast media have an anticoagulant activity in vitro. The purpose of the present study was, to investigate this effect in vivo. The catheter was introduced percutaneously according to Seldinger into the femoral artery. The prothrombin time, activated thromboplastin time (APTT), thrombin time, reptilase time, fibrinogen, plasminogen, antithrombin III, platelets, fibrin/fibrinogen degradation products (FDP), haematocrit and contrast media concentration were studied in a series of 50 patients before and following abdominal aorto-arteriographic procedures up to 6 hours. Thrombin time and reptilase time were prolonged significantly 30 and 60 minutes after angiography. There was a correlation between clotting tiies and contrast media concentrations. Prothrombin time, APTT, and platelet counts remained unchanged. Fibrinogen, plasminogen,and antithrombin III levels showed a significant reduction after 30 minutes. FDP concentrations were increased significantly up to 6 hours, there was no correlation between contrast media concentrations and split products. The results were corrected for contrast media dilution according to the haematocrit. No thromboembolic complication was observed. The results suggest that angiographic procedure may initiate an intravascular coagulation with an activation of the fibrinolytic system. In addition the contrast media showed an inhibition of fibrin polymerization in vivo.

The Relationship between Antithrombin III, Progressive Antithrombin Activity and Anti Xa Activity in Plasma

1975 ◽  
Author(s):  
Katherine Whigham ◽  
P. W. Howie ◽  
C. D. Forbes ◽  
C. R. M. Prentice
Keyword(s):  
Antithrombin Iii ◽  
Factor Xa ◽  
Normal Subjects ◽  
Strong Positive Correlation ◽  
Positive Correlation ◽  
Antithrombin Activity ◽  
Α2 Macroglobulin ◽  
Immunological Assays ◽  
The Relationship

In 30 normal subjects, progressive antithrombin activity, as measured by the rate of thrombin neutralisation in ancrod-defibrinated plasma, was compared with antithrombin III, as measured by radial immunodiffusion. No significant correlation was found between the two methods of antithrombin measurement (r = —0.101). Similarly, no correlation was found between progressive antithrombin activity and immunological measurements of α2 macroglobulin and α1 antitrypsin. These results were not changed by using thrombin purified by Amberlite 1RC50 chromatography in place of commercial thrombin in the clotting test. There was, however, a strong positive correlation between the measurements of progressive antithrombin activity using the commercial and purified forms of thrombin (r = 0.78, p < 0.001). In contrast, there was a positive correlation between antithrombin III and anti-factor Xa activity in plasma (r = 0.48, p < 0.01). There was no correlation between plasma anti Xa activity and α2 macroglobulin or α1 antitrypsin.These results suggest that plasma antithrombin activity is a measure of the activities of several plasma proteins and that antithrombin III may not be the major determinant of antithrombin activity. There is little evidence that immunological assays of antithrombin III reflect total thrombin inhibitory capacity as measured by the biological assay. Caution must be exercised in extrapolating from immunological measurements of antithrombin III to antithrombin activity in-vivo.

scholarly journals Antiplatelet and Anticoagulant Activities of Angelica shikokiana Extract and Its Isolated Compounds

2016 ◽  
Vol 23 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Amira Mira ◽  
Wael Alkhiary ◽  
Kuniyoshi Shimizu
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Cardiovascular Diseases ◽  
Medicinal Plant ◽  
Partial Thromboplastin Time ◽  
Aerial Part ◽  
Methanol Extract ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time ◽  
Significant Prolongation

Angelica shikokiana is a Japanese medicinal plant that is used traditionally in several ailments of cardiovascular diseases. However, there is no report regarding its anticoagulant or antiplatelet activities. So this study was designed to screen for such activities (anticoagulant by prothrombin time [PT], activated partial thromboplastin time, and thrombin time assays and antiplatelet activities against adenosine 5′-diphosphate [ADP] and arachidonic acid-induced platelet aggregations) for the methanol extract of the aerial part ( Angelica methanol extract [AME]), its isolated coumarins, flavonoids, and flavonoid metabolites. The AME had potent anticoagulant and antiplatelet activities, and the flavonoid compounds were evidenced to be responsible for such activities. Among coumarins compounds, hyuganin C showed significant prolongation of only PT, while other coumarins were inactive. Similarly, hyuganin C and bergapten were the only active coumarins against ADP-induced platelet aggregation. Compared to the parent compounds, colonic metabolites of the flavonoids had similar anticoagulant and antiplatelet activities, while glucuronides showed sharp decreases in all studied activities. This is the first report showing that the medicinal plant A shikokiana has potent antiplatelet and anticoagulant activities.

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