Inhibition of Fibrin Monomer Polymerization by Lambda Myeloma Globulins

Blood ◽  
1972 ◽  
Vol 39 (2) ◽  
pp. 210-223 ◽  
Author(s):  
Morton Coleman ◽  
Edward M. Vigliano ◽  
Marc E. Weksler ◽  
Ralph L. Nachman
Keyword(s):  
Anticoagulant Activity ◽  
Enzymatic Digestion ◽  
Thrombin Time ◽  
Clot Retraction ◽  
Fibrin Polymerization ◽  
Myeloma Proteins ◽  
Fibrin Monomer ◽  
Low Concentrations ◽  
Polypeptide Chains

Abstract Blood obtained from seven patients with lambda type myeloma proteins showed evidence of gelatinous bulky clots, impaired clot retraction, and circulating anticoagulant activity associated with interference of fibrin monomer polymerization. Five patients had γG1 and two had γA1 myeloma proteins. The pathologic plasmas and isolated myeloma proteins had anticoagulant activity that prolonged both thrombin and reptilase times, that was not absorbed by BaSO4 or neutralized by protamine sulfate, and that resisted heating to 56°C for 10 min. Addition of excess calcium partially corrected the anticoagulant effect. The anticoagulant activity of the isolated whole myeloma proteins, the enzymatic fragments, and polypeptide chains was measured by a thrombin time assay and a spectophotometric system with fibrin monomer. Low concentrations of the isolated IgGL proteins inhibited fibrin polymerization. The IgAL proteins did not demonstrate this activity at low concentrations but were active at concentrations comparable to in vivo levels. F(ab')2 and Fab fragments produced from the IgG proteins by enzymatic digestion possessed full inhibitory activity of the native intact proteins. Fc fragments and isolated polypeptide chains did not display significant anticoagulant activity. The results suggest that the Fab sites of certain lambda myeloma proteins may bind to fibrin during clotting and fibrin polymerization.

The ultrastructure of fibrin prepared from fibrinogen ASAHI (γ 310 met→thr) and fibrinogen morioka (γ 275 arg→cys)

1992 ◽  
Vol 50 (2) ◽  
pp. 1090-1091
Author(s):  
J.P. DiOrio ◽  
K.R. Siebenlist ◽  
S. Terukina ◽  
K. Yamazumi ◽  
M. Matsuda ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Consensus Sequence ◽  
Three Dimensional ◽  
Thrombin Time ◽  
Fibrin Polymerization ◽  
Fiber Network ◽  
Fibrin Monomer ◽  
Covalently Linked ◽  
Polypeptide Chains

Fibrinogen is composed of three pairs of polypeptide chains, termed Aα, Bβ and γ, respectively, covalently linked at their amino termini by disulfide bonds. Fibrinogen is proteolytically activated to fibrin monomer by thrombin which cleaves two A (FPA) and two B (FPB) fibrinopeptides from the respective N-termini of Aα, Bβ chains, each exposing a different type of polymerization site [“A” or “B”]. Exposure of either site leads to fibrin monomer assembly to form two-stranded fibrils with subsequent lateral fibril association to a branched three-dimensional fiber network. Fibrinogen Asahi is a congenital fibrinogen variant [γ310 Met → Thr] characterized by posttraumatic bleeding, a prolonged thrombin time, and abnormal fibrin polymerization. Asn at γ308 on the variant γ chain is glycosylated due to formation of a consensus sequence for glycosylation [Asn-Gly-Thr] that is created by the γ 310 Thr substitution. Fibrinogen Morioka is another congenital fibrinogen variant [γ 275 Arg→Cys] also characterized by defective fibrin polymerization.

scholarly journals Anticoagulant Properties of a Green Algal Rhamnan-type Sulfated Polysaccharide and Its Low-molecular-weight Fragments Prepared by Mild Acid Degradation

Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 445 ◽  
Author(s):  
Xue Liu ◽  
Peng Du ◽  
Xiao Liu ◽  
Sujian Cao ◽  
Ling Qin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Anticoagulant Activity ◽  
Sulfated Polysaccharide ◽  
Low Molecular Weight ◽  
Thrombin Time ◽  
Acid Degradation ◽  
Molecular Weights ◽  
Green Algal

The active sulfated polysaccharide from seaweed possesses important pharmaceutical and biomedical potential. In the study, Monostroma sulfated polysaccharide (MSP) was obtained from Monostroma angicava, and the low-molecular-weight fragments of MSP (MSP-Fs: MSP-F1–MSP-F6) were prepared by controlled acid degradation. The molecular weights of MSP and MSP-F1–MSP-F6 were 335 kDa, 240 kDa, 90 kDa, 40 kDa, 24 kDa, 12 kDa, and 6.8 kDa, respectively. The polysaccharides were sulfated rhamnans that consisted of →3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→ units with partial sulfation at C-2 of →3)-α-l-Rhap-(1→ and C-3 of →2)-α-l-Rhap-(1→. Anticoagulant properties in vitro of MSP and MSP-F1–MSP-F6 were evaluated by studying the activated partial thromboplastin time, thrombin time, and prothrombin time. Anticoagulant activities in vivo of MSP and MSP-F4 were further evaluated; their fibrin(ogen)olytic activities in vivo and thrombolytic properties in vitro were also assessed by D-dimer, fibrin degradation products, plasminogen activator inhibitior-1, and clot lytic rate assays. The results showed that MSP and MSP-F1–MSP-F4 with molecular weights of 24–240 kDa had strong anticoagulant activities. A decrease in the molecular weight of MSP-Fs was accompanied by a decrease in the anticoagulant activity, and higher anticoagulant activity requires a molecular weight of over 12 kDa. MSP and MSP-F4 possessed strong anticoagulant activities in vivo, as well as high fibrin(ogen)olytic and thrombolytic activities. MSP and MSP-F4 have potential as drug or helpful food supplements for human health.

A Comparison of Anticoagulation Activity of a Potent Heparin Preparation in Different Test

1979 ◽  
Author(s):  
A.S. Bhargava ◽  
J. Heinick ◽  
Chr. Schöbel ◽  
P. Günzel
Keyword(s):  
Blood Clotting ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Thrombin Time ◽  
Beagle Dogs ◽  
Clotting Time ◽  
Relative Potencies ◽  
Heparin Preparation

The anticoagulant effect of a new potent heparin preparation was compared with a commercially available heparin in vivo after intravenous application in beagle dogs. The anticoagulant activity was determined using thrombin time, activated partial thromboplastin time and whole blood clotting time after 5, 10 and 30 minutes of application. The relative potency of the new heparin preparation (Scherinq) was found to be 1.62 to 2.52 times higher than heparin used for comparison (150 USP units/mg, Dio-synth). The anticoagulant properties of both preparations were also studied in vitro using dog and human plasma. The relative potencies in vitro correlated well with those obtained in vivo. Further characterization with amidolytic method using chromogenic substrate for factor Xa and thrombin (S-2222 and S-2238 from KABI, Stockholm) showed that heparin (Schering) contains 243 to 378 USP units/raq depending upon the test systems used to assay the anticoagulation activity and in addition, proves the validity of the amidolytic method.

The Antithrombotic Effect of Borneol Related to Its Anticoagulant Property

2008 ◽  
Vol 36 (04) ◽  
pp. 719-727 ◽  
Author(s):  
Yan-Hong Li ◽  
Xiao-Ping Sun ◽  
Yin-Qing Zhang ◽  
Ning-Sheng Wang
Keyword(s):  
Platelet Aggregation ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Thrombin Time ◽  
Inhibitory Effects ◽  
Antithrombotic Activity ◽  
Coagulation Parameters ◽  
Venous Shunt

Borneol is consumed excessively in China and Southeast Asian countries particularly in combined formula for preventing cardiovascular disease, but few studies were conducted on its effects on thrombosis. In this study, the antithrombotic and antiplatelet activities of borneol were investigated on thrombosis in vivo and on platelet aggregation ex-vivo. In addition, the coagulation parameters and influence on fibrinolytic activity were also assessed. The results showed that borneol had concentration dependent inhibitory effects on arterio-venous shunt and venous thrombosis but no effect on ADP and AA-induced platelet aggregation. Meanwhile, borneol prolonged the coagulation parameters for prothrombin time (PT) and thrombin time (TT), but did not show any fibrinolytic activity. It suggested that the antithrombotic activity of borneol and its action in combined formula for preventing cardiovascular diseases might be due to anticoagulant activity rather than antiplatelet activity.

THE EFFECT OF THE VENOM OF THE ORIENTAL HORNET ON COAGULATION FACTORS

1987 ◽  
Author(s):  
A Kornberg ◽  
S Kaufman ◽  
L Silber ◽  
J Ishay
Keyword(s):  
Human Plasma ◽  
Degradation Products ◽  
Anticoagulant Activity ◽  
Coagulation Factors ◽  
Plasma Fibrinogen ◽  
Thrombin Time ◽  
Clotting Factors ◽  
Viii And Ix

The extract from the venom sac of Vespa orientalis (VSE) inactivates exogenous and endogenous thromboplastin (Joshua and Ishay, Toxicon, 13:11-20,1975). The prolongation of both prothrombin time (PT) and recalcification time suggests inactivation of other factors. The aim of the present study is to investigate the effect of VSE on clotting factors. A lyophilized VSE with protein concentration of 5 mg/ml was used. Studies were performed in vitro with human plasma and in vivo in cats. Routine methods were employed for the assay of PT, activated tissue thromboplastin (APTT), thrombin time (TT), fibrinogen degradation products (FDP), fibrinogen and factors V,VII,VIII,IX,X. Human plasma was incubated with various concentrations of VSE (0,1,5,10,50,100 μg/ml) for 60 min and for various incubation times (0,5,15,30,+ 60,90,120 min) with 50 μg/ml VSE (n=8). 1 μg/ml VSE prolonged PT from 13.5 to 16 sec (p<0.05) and APTT from 62 to 180 sec. PT was maximal (17.7 sec) with 10 μg/ml and APTT (442 sec) with 50 μg/ml VSE. Factors V,VII,X decreased gradually from 94-105% to 11%,11% and 29% with 100 μg/ml VSE and VIII and IX to 1% even with 1 μg/ml VSE. After 5 min with constant concentration of VSE (50 μg/ml) PT was 14.9 sec (normal 13 sec) and APTT 165 sec (normal 54 sec). Both were maximal (17.5 and 298 sec) after 60 min. Factors VII and X decreased to 13% and 32% and VIII and IX to >1% after 60 min of incubation. Injection of 5 mg/kg VSE to cats (n=6-8) resulted in prolongation of PT from 9.4 to 11.2 sec and of APTT from 19.5 to 63 sec after 5 min. Both were maximal after 90 min (12.3 and 127 sec). Factors V,VII and X decreased from 100% to 7.6%, 13% and 37% and VIII and IX to 1% after 10 min. In all experiments TT and plasma fibrinogen were not affected and FDP were normal. Heating of VSE for 5 min at 80°C abolished completely the anticoagulant activity but dialysis for 24 hr at 4°C had no effect on it. The activity was eluted on Sephadex-25 both in void and post void volumes. The results show that VSE has a potent anticoagulant activity against various factors. Factors VIII and IX are markedly decreased. The effect on V, VII and X is moderate. Plasma fibrinogen is not affected. The nature and clinical significance of the anticoagulant activity merit further investigation.

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.

Role of exosite binding modulators in the inhibition of Fxa by TFPI

2016 ◽  
Vol 115 (03) ◽  
pp. 580-590 ◽  
Author(s):  
Alexandra Heinzmann ◽  
Tilman M. Hackeng ◽  
Rudolf Hartmann ◽  
Friedrich Scheiflinger ◽  
Michael Dockal ◽  
...  
Keyword(s):  
Plasma Proteins ◽  
Tissue Factor Pathway Inhibitor ◽  
Anticoagulant Activity ◽  
Protein S ◽  
Low Concentrations ◽  
Tissue Factor Pathway ◽  
Coagulation Pathway ◽  
Prothrombin Activation

SummaryTissue factor pathway inhibitor (TFPI) down-regulates the extrinsic coagulation pathway by inhibiting FXa and FVIIa. Both TFPI and FXa interact with several plasma proteins (e. g. prothrombin, FV/FVa, protein S) and non-proteinaceous compounds (e. g. phospholipids, heparin). It was our aim to investigate effects of ligands that bind to FXa and TFPI on FXa inhibition by full-length TFPI (designated TFPI) and truncated TFPI (TFPI1-150). Inhibition of FXa by TFPI and TFPI1-150 and effects of phospholipids, heparin, prothrombin, FV, FVa, and protein S thereon was quantified from progress curves of conversion of the FXa-specific chromogenic substrate CS11-(65). Low concentrations negatively charged phospholipids (~10 μM) already maximally stimulated (up to 5- to 6-fold) FXa inhibition by TFPI. Unfractionated heparin at concentrations (0.2–1 U/ml) enhanced FXa inhibition by TFPI ~8-fold, but impaired inhibition at concentrations > 1 U/ml. Physiological protein S and FV concentrations both enhanced FXa inhibition by TFPI 2- to 3-fold. In contrast, thrombin-activated FV (FVa) impaired the ability of TFPI to inhibit FXa. FXa inhibition by TFPI1–150 was not affected by FV, FVa, protein S, phospholipids and heparin. TFPI potently inhibited FXa-catalysed prothrombin activation in the absence of FVa, but hardly inhibited prothrombin activation in the presence of thrombin-activated FVa. In conclusion, physiological concentrations TFPI (0.25–0.5 nM TFPI) inhibit FXa with a t1/2 between 3–15 minutes. Direct FXa inhibition by TFPI is modulated by physiological concentrations prothrombin, FV, FVa, protein S, phospholipids and heparin indicating the importance of these modulators for the in vivo anticoagulant activity of TFPI.

The effects of parathyroid hormone on osteoblast-like cells from embryonic chick calvaria

1985 ◽  
Vol 108 (2) ◽  
pp. 217-223 ◽  
Author(s):  
A. K. Hall ◽  
I. R. Dickson
Keyword(s):  
Alkaline Phosphatase ◽  
Parathyroid Hormone ◽  
Bone Cells ◽  
Primary Cultures ◽  
Enzymatic Digestion ◽  
Bone Cell ◽  
Prostaglandin E ◽  
Embryonic Chick ◽  
Low Concentrations

Abstract. A bone cell fraction was isolated from 16 day old embryonic chick calvaria using a sequential enzymatic digestion procedure. The fraction contained cells, of an osteoblast-like character, which responded to parathyroid hormone (PTH) and prostaglandin E2, but not to calcitonin, in terms of increased production of cyclic AMP. Primary cultures of cells maintained their responsiveness to PTH for at least 2 weeks after reaching confluence. Production of alkaline phosphatase by the bone cells was inhibited when 1,25(OH)2 vitamin D3 was added to cultures at concentrations of 10−8 m or greater. When cells were cultured in the presence of PTH a biphasic effect was observed; alkaline phosphatase levels were stimulated at low concentrations of this hormone but were decreased at higher concentrations. The latter finding appears consistent with observations that PTH can in vivo exert either anabolic or catabolic effects on bone, depending upon the circulating level of hormone present.

Construction and functional evaluation of hirudin derivatives with low bleeding risk

2008 ◽  
Vol 99 (02) ◽  
pp. 324-330 ◽  
Author(s):  
Bin Yuan ◽  
Chunna Dong ◽  
Hongyang Yu ◽  
Lisheng Wang ◽  
Chuanling Zhang ◽  
...  
Keyword(s):  
Anticoagulant Activity ◽  
Vena Cava ◽  
Coagulation Factor ◽  
Bleeding Risk ◽  
Coagulation System ◽  
Bleeding Complications ◽  
Functional Evaluation ◽  
Thrombin Time ◽  
N Terminus

SummaryThe purpose of this study was to design and evaluate hirudin (HIR) derivatives with low bleeding risk. In these derivatives, the factor (F) XIa, FXa, and thrombin recognition peptides (EPR, GVYAR, and LGPR, respectively) were linked to the N-terminus of HIR. The intact derivatives have no anticoagulant activity because of the extension of the N-terminus of HIR. After cleavage by the corresponding coagulation factor that occurs on the activation of the coagulation system and in the presence of the thrombus, its activity is released. This limited the anticoagulant activity of these derivatives to the vicinity of the thrombus, and as a result, systemic bleeding complications were avoided. The definite antithrombotic effect and low bleeding parameters of these derivatives were investigated in rat carotid artery and inferior vena cava thrombosis models. In both models, the three derivatives showed significant antithrombotic effects, indicating that anticoagulant activity could be successfully released in vivo. Moreover, the bleeding parameters of these derivatives were lower than that of HIR as indicated by the values of activated partial thromboplastin time (APTT) and thrombin time (TT). To further assess the safety of these derivatives, bleeding time was measured in a mouse tail-cut model. Although the derivatives had obvious effects on bleeding at a dose of 6 mg/kg, the effect of these derivatives on bleeding was significantly weaker than that of HIR at a dose of 1.5 mg/kg. Thus, the benefit-to-risk profiles of the derivatives were superior to that of HIR.

scholarly journals Isolation and Characterization of a Heparin-Like Compound with Potent Anticoagulant and Fibrinolytic Activity from the Clam Coelomactra antiquata

Marine Drugs ◽  
2019 ◽  
Vol 18 (1) ◽  
pp. 6 ◽  
Author(s):  
ZhenXing Du ◽  
XueJing Jia ◽  
Jing Chen ◽  
SiYi Zhou ◽  
JianPing Chen ◽  
...  
Keyword(s):  
Fibrinolytic Activity ◽  
High Performance ◽  
Anticoagulant Activity ◽  
Resonance Spectroscopy ◽  
Thrombin Time ◽  
Sulfated Glycosaminoglycan ◽  
Isolation And Characterization

Heparin from mollusks with unique sulfated glycosaminoglycan exhibits strong anti-thrombotic activities. This study reports on a purified heparinoid from Coelomactra antiquata, which shows potent anticoagulant and fibrinolytic abilities. Its structure was characterized by infrared spectroscopy, high-performance liquid chromatography, and one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy. Its fibrinolytic activity was determined in vitro and in vivo. Its anticoagulant activity was determined by activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicated that clam heparinoid was a homogeneous glycosaminoglycan with a molecular weight of 30.99 kDa, mainly composed of →4)-α-IdoA2S-(1→4)-α-GlcNS3S6S (or GlcNS6S)-(1→4)-β-GlcA-(1→4)-α-GlcNS6S (or GlcNAC)-(1→. Furthermore, this heparinoid showed a highly anticoagulant titer and fibrinolytic value of 149.63 IU/mg and 1.96 IU/mg, respectively. In summary, clam heparinoid shows great potential for application in the clinic and antithrombotic drugs industry.

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