bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clot Promoting Effect of Platelet-Vessel wall Interaction
Authors: Hornstra G. 
Published: May 2019

When a piece of vascular tissue (rat, rabbit) is incubated in plasma, clotting occurs. The presence of platelets accelle rates this clotting process. Inhibition of vascular prostacyclin (PGI2) production, either by drugs or by inducing arachidonic acid deficiency, causes the platelets to become activated by the vessel wall, resulting in platelet shape change and -aggregation and in a further enhancement of the coagulation response. Hirudin very actively inhibits both aggregation and clotting whereas ADP scavenging has only a weak effect. This indicates that the aggregation response, occurring upon plateletvessel wall interaction is for the greater part mediated by thrombin. Saturated fat feeding increases the clot promoting effect of the platelet-vessel wall interaction. This appeared not to be due to differences in the production of vascular PGI2 or platelet endoperoxides and thromboxanes (measured as malondialdehyde). These findings indicate that:1. Thrombin, locally generated upon the interaction between damaged vessel wall and blood constituents, contribute to arte rial thrombus formation;2. Prostacyclin regulates local thrombin formation viaits inhibiting effect on platelet activation;3. The existence of another, platelet bound affector is postulated.
Decreased Reactivity of Plasmin-Streptokinase Towards α-2-Antiplasmin
Authors: Cederholm-Williams S.A. , Lijnen H.R. , De Cock F. , Collen D. 
Published: May 2019

Plasmin (P) is very rapidly (rate constant 2 × 107 M-1s-1) inactivated by α-2-antiplasmin (A), and blocking of the lysine binding sites (LBS) of plasmin reduces this rate 50 fold (Eur. J. Blochen. 84, 573-578, 1978). Using purified reactants and the plasmin substrate D Val-Leu-Lys-pNA (S 2251) the influence of streptokinase (SK) on the reaction between P and A was examined. Addition of SK to P reduces the reaction rate with A in a sigmoidal fashion. Assuming the formation of a reversible bimolecular P:SK complex which is un-reactive towards A then the dissociation constant Kd of this complex is less than 10-9 M. The LBS of P does not play a role in this interaction since similar Kd values are found with modified P, lacking LBS and in the presence of 0.3 mM 6-aminohexanoic acid which blocks the LBS. The P:SK complex is only very slowly inhibited by A with a rate constant < 5 x 102 M-1s-1.It is concluded that the α-2-antiplasmin is less reactive towards the plasmin-strepto-kinase complex due to a modification of the active centre of plasmin rather than an effect upon the lysine binding sites.
Isolation and Partial Characterization of a Novel Circulating Antithrombin
Authors: Messmore Harry , Pervez Zaheer , Fareed Jawed 
Published: May 2019

We have previously reported on a novel circulating anticoagulant (Clin. Res. 22:396 A, 1974. Thromb. and Haem. 38:77, 1977 (abstr) in a 42 year old female who has had repeated episodes of life threatening hemorrhage since the age of 3. Our preliminary studies showed it to be a protein with some of the properties of a heparin activated antithrombin III. This report is on additional studies to further characterize the Inhibitor«The patient’s plasma was fractionated on Sephadex G-200, and the fraction showing immediate acting antithrombin activity was further purified on heparin-sepharose and conconavalin A-sepharose affinity columns. The patient’s inhibitor did not bind to heparin sepharose, and was thus separable from her antithrombin III. It did bind to conconavalin A, and was eluted from the conconavalin A with α - D (+) methylglucoside. It has very broad serine protease inhibitor activity, blocking the hydrolysis of synthetic chromogenic substrates by thrombin, factor Xa, plasmin and trypsin. It did not inhibit Reptilase.Immunochemical assays show it to be α1 antitrypsin. Isoelectric focusing shows it to he a variant of normal, with its isoelectric point being different from a normal control, and pure α1 antitrypsin (commercial, human).The total α1 antitrypsin level in this patient is about 50% of normal, and It has potent immediate acting antithrombin activity. It appears to be similar to a phenotype previously reported as Antithrombin Pittsburgh (Blood 51: 129, 1978).
Evidence of Abnormal Factor: VIII Related Protein in Diabetes Mellitus
Authors: Cacciola E. , Giustolisi R. , Lombardo T. , Musso R. , Russo M. , Sortino G. 
Published: May 2019

Biochemical and functional properties of Factor VIII related protein (VIII:RP) have been studied in the plasma from two groups of diabetic patients with or without vascular complications compared to normal subjects.The Factor VIII related antigen (VIIIR:AG) was performed by Laurell’s electroimmunoassay (LA) and electrophoretic mobility (EM) by two dimensional crossed Immunoelectrophoresis (2 DC IE). Biophysical properties were evaluated by cryoprecipitation and concanavalin A (Con A) treatment at different concentrations. Biological functions were determined using the ristocetin cofactor (RiCoF ) assay on fixed-washed platelets and procongulant activity (F VIII:C).In diabetic patients, particularly in the ones at higher thrombogenic risk, the evaluation of VIII:C/VIIIR; AG and VIII:vWF/VIIIR;AG ratios showed a significant (P<0.001) increased VIIIR:AG with a higher co-ristocelin activity than the procoagulant one. Furthermore, biophysical and bio chemical modifications of diabetic Factor VIIIR;AG, mainly a lower EM on 2 DCIE, were found. These results suggest that the Factor VIIIR:AG abnormality, detectable in diabetic plasma, can be related with an abnormal glycoprotein biosynthesis.
Congenital Antithrombin III Deficiency in 3 Families (7 Affected Members).
Authors: Conard J. , Samama M. , Horellou H.H. , Cazenave B. , Griquer P. , Barsotti J. , Herreman G. , Godeau P. 
Published: May 2019

A congenital Antithrombin III (AT III) deficiency affecting 7 members of 3 families is reported.The first thrombo-embolic accidents were observed between the age of 22 and 35: they were spontaneous or occured after delivery or oral contraception. In one patient, a deep vein thrombosis was observed during heparin treatment. In 2 cases, recurrent pulmonary embolic episodes required vena cava ligation. No thromboembolic accident was observed during oral anticoagulation.AT III was measured by an amidolytic method and by the Mancini method on plasma and serum ; the antithrombin activity was determined on serum by the von Kaulla method. In 7 patients, a decreased AT III was found by all the methods performed. The AT III level was around 50% in patients treated or not by oral anticoagulants.One patient was studied during heparin treatment and then under oral anticoagulants: AT III levels were lower under heparin.
Heparin-Coated Surfaces that bind Antithrombin have Reduced Platelet Reactivity
Authors: Lindon J. , Brier-Russcll D. , Salane M. , Smith M. , Labarre B. , Dincer A. , Rosenberg R. , Merrill E. , Salzman E. 
Published: May 2019

Surfaces with heparin bound by covalent linkage react with platelets but are passivated by prior exposure to platelet free plasma (PFP), provided they are capable of adsorbing antithrombin III (AT). For example, heparin-agarose beads induce platelet adhesion and aggregation, which are reduced by preincubation of the beads with PFP, but PFP depleted of AT is not effective. The degree of passivation of the beads parallels their removal of AT from PFP. The beads are also passivated by a solution of purified AT.Furthermore heparin-polymethyl acrylate copolymers made by radical polymerization initiated by Ce4+ bind AT, as demonstrated by measurement of AT remaining in solution after adsorption or eluted from the surface after plasma incubation. On such a surface, AT is activated just as by heparin in solution, measured by the ability of heparinized beads to inactivate thrombin (S-2160 chromogenic tripeptide substrate assay) in the presence of AT and by lack of inactivation of thrombin with AT-poor plasma and return of inactivating effect when AT is added back.Aggregation of platelets by specific heparin fractions in solution appears to be an analogous phenomenon, which is inhibited by antithrombin.
The Formation of Fibrin Around Large Platelet Aggregates (PA’s) in Heparinized Platelet Plasma (PRP)
Authors: Wurzinger L.J. , Blasberg P. , Vehr H. 
Published: May 2019

In concavities on the surface of large PA’s (107-108 μm3) which were produced “spontaneously” or upon addition of ADP 10-6 M in a homogenous shear field in a Couette-type aggregometer (40 s-1), we observed the formation of a fibrin network within 5 mins after sampling. This fibrin network, which could be identified with fluorescent antibodies, formed despite anticoagulation with 7.5 II heparin/ml. The formation of this fibrin network was less pronounced and delayed when the heparin concentration was raised to 20 U/mL 50 U/ml completely suppressed the formation of the network. Concomitantly we found masses of degranulated and ballooned platelets around PA’s with fibrin formation. As we suspected secreted’PF 4 (Antiheparinfactor) being responsible for this phenomenon, we analysed the β-thromboglobulin (β-TC)in heparinized PRP, which is secreted along with PF 4.We found the formation of fibrin not so much correlated to the extent of platelet aggregation in the whole sample, but to the release of β-TG. The samples wherein fibrin was formed, were characterized by β-TG levels in plasma that amounted to up 5% of total platelet protein. In our view this explains the fact, that despite heparinization during extracoporeal circulation the local formation of fibrin-consolidated white thrombi and emboli is observed.
The Action of Calciparine in the Prevention of Premature Delivery
Authors: Eglin G. , GAUTIER G. , Maillet R. , Colette C. 
Published: May 2019

In the study of the causes of premature delivery, interest in blood vessel-related mechanisms is related to platelet secretion of prostaglandin, whose activity on uterine muscle fiber is well established.The action of indometacine on this secretion of prostaglandin is used clinically but its lack of harmful effects on the fetus has not been shown, demanding great caution.Our clinical study of subcutaneous calcium heparin, with well known action on platelets, was undertaken in this framework. All threats of premature delivery from the 26th to 34th weeks, except in cases of cerclage, were considered in a double-blind study with 2 randomized groups. The first group was treated with Calciparine (7 500 IU b.i.d.) and beta-mimetics, the second group with a placebo (solvant) and beta-mimetics.Conclusions are based on prematurity in the 2 groups.
The Role of Platelets and Fibrin in Uteroplacental Arteries in Normal Human Pregancy
Authors: Sheppard B.I. , Bonnar J. 
Published: May 2019

In normal human pregnancy the uteroplacental vessels undergo extensive morphological adaptations to provide an increasing blood flow to the placenta. These involve platelets and fibrin adjacent to trophoblast invasion of spiral arteries.In early pregnancy, single layers of platelets or small thrombi are seen between trophoblast cells which form a pseudo-endothelium of the spiral arteries. In the media trophoblast cells and fibrin are present in an amorphous matrix which replaces the musculo-elastic component of the vessel. In late pregnancy these vascular changes extend into the myometrium, fibrin deposition is increased and mature mural thrombi are found.The fibrin deposition in uteroplacental arteries, is a physiological phenoncma of pregnancy. Fibrin may provide the dynamic structural support required in these vessels expanding to accommodate an increasing blood flow. Fibrin also enables the immediate collapse of the vessel following placental separation. Mural thrombosis in the arterial supplyprobably accounts for areas of ischemia and small placental infarcts found in normal pregnancy. Because of the large placental reserve, this minor degree of spiral artery occlusion does not appear to effect adversely the fetus.
The Evaluation of Hemostasis in Patients with Hepatic Cirrhosis
Authors: Stein Sidney F. , Harker Laurence A. 
Published: May 2019

The hemostatic defects in 36 patients with biopsy-proven hepatic cirrhosis have, been characterized kinetically using autologous 51Cr-thrombocytes (T), 131I-fibrinogen (F) and 125I-plasminogen (P). Mean concentrations (C) and survival times (S) of all three components were shortened significantly (see table), although the (ranges) were broad compared with the (values in normal subjects). FS was sometimes prolonged beyond normal values suggesting impaired hepatic catabolism.Thrombocytopenia was due to a combination of shortened S and increased splenic pooling that overwhelmed the two fold increase in production. Conversely, increased F production largely compensated for the shortened FS. PC was greatly decreased because both PS and P production were reduced. The mechanisms of destruction appear to be independent for each component since there was no correlation among TS, FS and PS, (r < 0.0156) and heparin therapy in 8 patients prolonged FS (p <0.01 ) without affecting TS (p > 0.9). (* x 10-3)
Management of Hemostase in Acute Liver Failure
Authors: Stemberger A. , Vogel G. , Fritsche H.M. , Fischer M. , Bottermann P. , Blümel G. 
Published: May 2019

In coma hepaticum perfusion with baboon liver in by-pass is a last remaining possibility. In order to maintain hemostase in the extra corporal circuit heparin was found to be necessary. This is of interest since clotting tests are prolonged and clotting factors like X,XIII and AT III are often based to zero values. AT III* was substituted with 250-500 AT III units every 3 hours resulting in 40-80 % of normal range and heparin was given in a dosage of 500-750 USPE hep./h resulting in 0.1-0.2 USPE hep./ml plasma. The therapy was monitored 4-8 times per day by chromogenic substrates. Further analysis of factor X, AT III heparin and hematocrit was performed in the arterial and venous part of the liver in by-pass. After blood passage there was a significant reduction of heparin; factor X,AT III and hematocrit showed constant values. With the controlled AT III substitution and minimal heparinization thrombus formation in the liver in bypass was never observed, hemostase was maintained, but the fate of the patients depended on liver regeneration.* kindly provided by Behringwerke and Kabi.
Effect of Indobufen (K 3920) A New Antiplatelet Agent After Oral Administration in Patients with Vascular Diseases
Authors: Coccheri S. , Fortunato G.C. 
Published: May 2019

The antiaggregating effect of a new butyric acid derivative, indobufen (K 3920), was investigated in 30 patients with vascular diseases. A between-patient study was performed by administering 50 mg b.i.d. or 100 mg b.i.d. for 14 days to 2 groups of patients. A series of platelet function and clotting parameters were recorded at the end of the treatment period, both 2 and 24 h after the last administration.A marked inhibition of platelet aggregation was observed in both groups, as shown from the significant changes in maximal amplitude, reaction time and slope of ADP- and collagen-induced aggregation wave.Similar results were observed at the Breddin test in both groups of patients and at all experimental times.Platelet adhesiveness was also reduced and circulating platelet aggregates were normalized in all patients who had abnormal basal values.A shortening of euglobulin lysis time was observed 2 h but not 24 h after administration of both doses.Tolerability was excellent.Indobufen appears to be a promising drug for treatment of vascular diseases where platelet aggregation is involved.
COllagen-induced Platelet Behaviour
Authors: Taylor Patricia M. , Heptinstall S. 
Published: May 2019

A comparison has been made of the extent to which collagen induces human platelets to aggregate (change in light absorbance) and to undergo the release reaction (release of 3H-serotonin) in heparinised platelet rich plasma which had been depleted of divalent cations by treating with Chelex 100 chelating resin (Ch.PRHP) and in Ch.PRHP to which different concentrations of CaCl2 or MgCl2 had been added.Platelet aggregation required extracellular Ca++; Mg++ could only support aggregation when Ca++ was also present. The release reaction occurred via Ca++-dependent and Ca++-independent pathways. The divalent cation requirement for Ca++-dependent release was the same as for aggregation.The extent to which platelets aggregated and were induced to undergo release varied with the concentration of extracellular Ca++ or Mg++. A plot of extent of aggregation or of release against concentration of Ca++ or Mg++ has an inverted ‘U’ shape. In any one experiment there was good correlation between extent of aggregation and of release.It is suggested that collagen induces a Ca++-independent release reaction that leads to aggregation and that Ca++-dependent release is a result of the platelets aggregating.
The Interaction of Platelets with Individual Components of the Blood Vessel Wall
Authors: MacIntyre D.E. , Bailey A.J. 
Published: May 2019

The aggregation of platelets by constituents (especially collagen) of the vessel wall is a basic event in haemostasis and perhaps in thrombosis and atherogenesis. Binding of platelets (without aggregation) in areas denuded of endothelium has also been seen. In this study, various constituents, identified in the vessel wall, have been isolated and their platelet reactivity examined. In particular, with the recognition of collagen polymorphism in the arterial wall, a number of different collagens have been examined. The results indicate that Types I nnd III collagens, as native-type fibrils, are both potent inducers of aggregation; both bind to platelets to aporox. the same degree. In contrast collagens Types IV and V, dialyzed against 0.02M Na2HPO4, or preincubated at 37° (procedures known to yield active fibrils with collagens I and III), failed to induce aggregation; little if any binding to platelets was detected. Disersions of lens capsule (containing Type IV in situ) were also inactive. However SLS-aggregates of these collagens did induce aggregation. These results emphasize that quaternary structure rather than specific type determines the ability of collagen to induce aggregation. They suggest the amorphous basement membrane collagens (IV and V) will not induce aggregation.Elastin and its associated microfibrillar element failed to aggregate platelets; little binding of platelets to either was observed.† Present address: Beth Israel Hospital, Boston, Mass., USA
The Mechanism of Activation of Human Coagulation Factor X
Authors: Mertens K. , Bertina R.M. 
Published: May 2019

During the coagulation process factor X is converted to a serine protease, factor Xa. The present study concerns the molecular events which occur during the activation of human factor X by Russell’s viper venom and by the purified proteins of the extrinsic and intrinsic activator. Conversion of factor X was detected by amidolytic assays and SDS/polyacrylamide-gel electrophoresis.The results show that all activators convert factor X (MW 72,000) to an active form. In the presence of phospholipid the initially formed factor Xa (MW 54,000) complicates the further sequence of reactions by catalysing a) the conversion of factor Xa to a second active form (MW 50,000), b) the conversion of factor X to an inactive product (MW 59,000) by splitting off a peptide containing the active site serine, and c) the further degradation of the 50,000 and 59,000 components to a smaller component (MW 40,000).Comparison of these data with those reported for bovine factor X suggests that the mechanism of activation of human factor X is more complicated. The inactivation of both factor Xa and factor X by product factor Xa might be considered as important regulatory principles.
Three Types of Hereditary Antiterombin III Deficiency
Authors: Nagy I. , Losonczy H. 
Published: May 2019

The authors detected in the last seven years 15 patients with hereditary antithrombin III/AT III/ abnormality. All of them had typical clinical signs of recurrent arterious and venous thromboembolie. The abnormality inherited as an autosomal trait. Three types of the abnormality could be observed. In Type I both quantity and function of AT III were extremely decreased. In type II AT III is normal in quantity but abnormal in function. In Type III AT III is quantitatively normal and also its function seems normal as far as its basic activity is concerned /activity measured in absence of heparin/, but its abnormality becomes manifest in the presence of heparin in vitro/and also in vivo/. 5 of the patients belonged to Type I, 4 to Type II and 6 to Type III. In 60 examined family members of the 15 patients an abnormal AT III could be observed in 44, clinical signs in 23.The examination of AT III activity in the presence of a given amount of heparin ia of great importance in recognition of the different types of antithrombin III abnormalities.
Detection of Activated Platelets and the Evaluation of Anti Platelet Drugs
Authors: Tsukada T. , Ito T. 
Published: May 2019

Usefulness of examinations such as the assay of plasma beta-thromboglobulin(BTG) plasma platelet factor 4 or platelet survival is stressed for the detection of activated platelets in vivo. To determine whether changes of platelet nucleotide contents is useful indicator detecting the presence of activated platelets, platelet nucleotide contents were measured by high pressure liquid chromatography simultaneously with plasma ETC in diabetics with various vascular complications. Only 40/84 cases demonstrated both normal nucleotides(ATP 4±0.2 (SEM), ADP 2.6±0.2, GTP 0.4±0.04 μ moles/1011 plts.) and normal BTG levels( less than 50 ng/ml). 6/15 cases with elevated BTG showed decrease in nucleotides (ATP 1.5±0.4, ADP 1±0.1, CTP 0.2±0.04). 29/69 patients with normal plasma BTG demonstrated significant decrease of nucleotides (ATP 2±0.2, ADP 1.2±0.1, GTP 0.3±0.03). These abnormal nucleotide contents and/or BTG levels have returned to normal range within one month after daily administration of 750 mg aspirin and 150 mg dipyridamole. Without anti-platelet therapy, these abnormal values have continued for several months.Simultaneous measurement of platelet nucleotide and plasma BTG is an excellent indicator detecting the activated platelets in vivo and demonstrating the effectiveness of antl-platelet drugs.
Ex Vivo Effects of Acetylsalicylic Acid, Sulfinpyrazone and Dipyridamole on Platelet Adhesion and Thrombus Formation in Flowing Native and Anticoagulated Blood
Authors: Baumgartner H. R. 
Published: May 2019

Potential platelet inhibitors are usually tested ex vivo by investigating platelet function in vitro after drug ingestion and subsequent blood collection into citrate. The purpose of the present study was to determine whether and how citrate anticoagulation interferes with possible drug actions in rabbits. Platelet adhesion and thrombus formation on subendothelium were compared after perfusion at 1300 sec-1 wall shear rate of native blood and of blood anticoagulated with citrate, heparin or heparin plus citrate.
Results. 15 mM citrate in plasma caused significant reduction of aggregation, thrombus volume and thrombus height; adhesion was concomitantly increased. Heparin (500 U/kg) had no effect on adhesion and thrombus dimensions. Treatment of rabbits with acetylsalicylic acid or sulfinpyrazone (2x100 µmol/kg) caused a significant reduction of thrombus volume and thrombus height in the presence of citrate. However, no drug effects were observed after perfusion of native or heparinized blood of the same rabbits. Equimolar doses of dipyridamole were always without effect.
Conclusion. Low citrate concentrations (1) inhibit thrombus growth, (2) enhance thrombus breakdown,(3) secondarily increase adhesion and (4) strongly enhance a possible inhibitory effect of acetylsalicylic acid and sulfinpyrazone on thrombus growth and/or breakdown.