bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombin-Antithrombin III and Plasm in-Antiplasmin Complexes as Indicators of in Vivo Activation of the Coagulation and/or Fibrinolytic Systems
Authors: Collen D. , Cock F.de 
Published: May 2019

Both the thrombin-antithrombin III and plasmin-antiplasmin complexes contain neoantigenic structures, not present in the parent molecules, to which non cross-reacting precipitating antibodies can be produced (Thromb.Res. 5, 577, 1974). This phenomenon has been used to develop immunochemical methods for the quantitation of these complexes in human blood (Thromb. Res 7, 235, 1975). Patients with in vivo activation of the coagulation and/or fibrinolytic systems consistently showed increased levels of enzyme-inhibitor complexes (Eur.J.Clin.Invest, in press, 1977). The circulatory half-life of these complexes was estimated to be several hours (0.5 to 0.75 days).On several occasions, increased plasmin-antiplasmin titers were observed in the presence of a normal screening hemostasis analysis, suggesting that these assays may be more sensitive indicators of in vivo activation of the coagulation-fibrinolytic systems that assays for fibrinogen degradation products.Studies to determine the clinical value of the measurement of these enzyme-inhibitor complexes as indicators of a prethrombotic state are in progress and will be reported.
Spontaneous Platelet Aggregation in Vivo
Authors: Hoak J.C. 
Published: May 2019

In recent years several new methods have been developed to quantitate the presence of platelet aggregates in whole blood. Included are techniques using an electronic particle analyzer after lysis of the RBC’s with saponin, fixation of platelet aggregates with dilute formalin, and measurement of changes in filtration pressure in systems where platelet aggregates obstruct the flow of blood across standardized filters.Using the formalin-fixation method (Lancet 2:294, 1974) to detect platelet aggregates we have found abnormal values in patients with transient ischemic attacks, acute myocardial infarction, acute peripheral arterial insufficiency, some patients with recurrent deep vein thrombosis, migraine, and certain types of ischemic retinopathy. Questions remain, however, as to whether the detected aggregates are definitely circulating aggregates or whether the technique selects out a population of abnormal platelets which behave differently upon exposure to formalin than to the normal platelets. While the current method appears to be satisfactory to delineate patients in whom platelet aggregates may be playing a primary or secondary role, additional information is required to provide a satisfactory explanation of the mechanisms involved if we are to achieve an optimal application of the technique.
Factor X Activation in Sodium Citrate
Authors: Aronson D.L. 
Published: May 2019

Early studies showed that partially purified prothrombin preparations generated thrombin in solutions of (NH4)2SO4 or sodium citrate. Milstone established that-the prothrombin activating enzyme Thrombokinase (Xa) would activate in (NH4)2SO4. More recent studies of the physiologic activation of Factor X have defined a role for both the intrinsic and extrinsic coagulation pathways. It has been proposed that the citrate activation of Factor X is independent of Factor VII or IX and results from the direct action of either thrombin or Xa on Factor X.When Factor X is incubated in sodium citrate there is a lag phase followed by the rapid generation of Factor Xa. This is followed by the degradation of Xa to a form which cannot interact with the cofactors of prothrombin conversion. If DFP is added during the phase of rapid X generation the reaction is inhibited. The addition of DFP prior to the activation has no effect.SBTI totally inhibits the activation of Factor X. Removal of residual Factor VII from the Factor X preparations prevents citrate activation and readdition of Factor VII restores this capability. Preincubation of the Factor VII in citrate does not effect the lag phase and the addition of Factor Xa to VII deficient Factor X has minimal effect.It is proposed that citrate activation of Factor X is Factor VII dependent but that the Factor VII must be activated by Factor Xa (or possibly thrombin). The inability of the degraded form of Xa to react with the cofactors may be due to the loss of the γ-carboxy glutamate containing portions of the molecule.
High Gene Frequency of Factor XI Deficiency in Ashkenazi Jews
Authors: Seligsohn Uri 
Published: May 2019

Factor XI (fXI) deficiency has previously been reported mainly in Jews. Its frequency and ethnic distribution however, have not been determined. It was the purpose of this study to examine these questions.Since 1966, 78 patients with fXI deficiency have been observed. They belong to 36 unrelated families, all of whom are of Eastern European origin (Ashkenazim).Of 428 normal Ashkenazi Jewish subjects whose fXI levels were assayed, 1 subject had severe deficiency (3%), 35 partial deficiency (24 - 49%) and 392 had normal levels. The 95% confidence limits of the frequency of severe fXI deficient subjects in the total Ashkenazi Jewish population are 0.1 - 0.3%, and for partial deficient subjects 5.5 - 11%.Since severe as well as partial fXI deficient patients may not be diagnosed until profuse bleeding is presented following trauma, the observed high gene frequency warrants performing the appropriate tests in all Ashkenazi Jewish patients undergoing surgery.
Gel Filtration of 125I-fibrin and 131I-fibrinogen at 20°C and at 37°C
Authors: Krell W. , Mahn I. , Müller-Berqhaus G. 
Published: May 2019

Sepharose-6B columns were used to investigate the behaviour of urea-solu-bilized 125I-fibrin during gel filtration. Urea-solubilized 125I-fibrin was mixed with rabbit plasma containing 131I-fibrinogen. This mixture was gel-filtered at 20°C and 37°C. The elution medium was a TRIS-PO4 buffer, pH 7.4, containing EDTA, EACA and aprotinin. Results: 125I-fibrin was separated from 131I-fibrinogen at 20°C as well as at 37°C. Only 3% of the 131I-fibrinogen was eluted tcgether with fibrin at 20°C. At 37°C, however, no 131I-fibrinogen was eluted together with 125I-fibrin. At 370°C a mean of 90% of the applied 125I-fibrin was retained on the columns, whereas at 20°C a mean of 40% of the 125I-fibrin was retained. At both temperatures, 80-90% of the 131I-fibrinogen was eluted. From these experiments we con-clude:1. If 125I-fibrin is chromatographed on a TFIS-PO4 medium it partially precipitates on the column. 2. Fibrinogen and/or other plasma proteins are necessary to keep fibrin in solution. 3. Interactions between fibrinogen and fibrin are not maintained during gel filtration in a buffer medium, 4. Possibly formed complexes at 20°C do not exist at 37°C.(Supported by the Deutsche Forschungsgemeinschaft).
Intermediate Purity Factor VIII by the Thaw-Siphon Cryoprecipitate Procedure
Authors: Mason E.C. , Pepper D.S. 
Published: May 2019

The procedure begins with the separation of a 220 ml plasma donation into a plastic pack fitted with an internal siphon tube, which is an extension of the external tube connected to the satellite pack. The tube is arranged in an L-shaped configuration with one section aligned along the side edge of the pack, and the continuation along the bottom edge of the pack; the latter has perforations at regular intervals.The donation is frozen as a flat slab at -40°C, and is, subsequently, thawed in an upright position in a 3–5°C water bath, with continual siphoning of thawed phase into the attached satellite pack. This proceeds for 40-50 minutes, when the frozen mass has reduced to a matrix, 5-10 ml in volume, of essentially pure ice trapping the cryoprecipitate. Citrate saline is introduced to dissolve the cryoprecipitate.The procedure has been characterized by measurements of conductivity and protein, in eluant fractions, whilst investigation of the product for Factor VIIIC, total protein and fibrinogen, give respectively 150 u, 350 mg and 125 mg, i.e. 0.43u/mg protein.
Electron Microscopic Analysis of Subcellular Distribution and Translocation of Ca ION in Human Platelet
Authors: Kazama M. , Daimon T. , Nakamura K. , Matsuda J. , Naito I. , Abe T. 
Published: May 2019

For the analysis of the subcellular distribution of Ca ion in human platelet, the washed platelet suspension was fixed in the potassium antimonate-OsO4 method or in the potassium oxalate-glutaraldehyde method without post-fixation with OSO4. The STEM-images were observed with scanning image system fitted with the transmission electron microscope without electron staining.The dense deposition of antimonate or oxalate was found in plasmalemma, the membrane of open canalicular system, mitochondria, α-granules and dense bodies. It was revealed with the energy dispersive type electron probe x-ray microanalyzer system that the deposition of oxalate was exclusively composed of Ca.In the process of platelet aggregation with various agents, α-granules and dense bodies were expelled out together with Ca, which suggested the least role of these ion depositions in the aggregation and clot retraction. The translocation of antimonate deposits was not observed in the Verapamil-treated platelets even after the addition of aggregation agents. This phenomenon indicated that this drug inhibited the release of Ca from the Ca-storing organelles. The distribution of Ca was identical in the platelets of a case of thrombasthenia and the translocation of Ca was not observed with the addition of various aggregating agents.
Contact Activation of Plasma Prekallikrein and Fibrinolysis by Heparinoids and Heparin
Authors: Soulier J.P. 
Published: May 2019

Contact activation of plasma prekallikrein (PPK), using a tripeptide chromogenic substrate, and of surface mediated fibrinolysis using the euglobulin test (both tests insensitive to the anticoagulant effect of heparin and heparinoids) were studied. The following substances were tested : (1) Dextrans (different commercial therapeutic preparations) and dextran sulphate of different molecular weights. (2) Heparinoids such as: pentosane, mannuronate and galactose sulfuric polyester and liquoid. (3) Twelve different commercial therapeutic preparations of heparin.
Results: XII, PPK and HMWK are necessary for the full activation. Heparinoids have a strong activation capacity on PPK and fibrinolysis, dextran sulphate (500 000) being the most active as shown by Kluft. Dextran solutions as well as different brands of heparin have a slight but definite surface activation capacity (still unnoticed, being masked by the anticoagulant activity). This explains some side effects of heparinoids and why heparin is unable to prevent contact activation, in vitro and in vivo.
Detection of Circulating Platelet Aggregates in Thromboembolic Disease
Authors: Marie Lorène Scrobohaci , Petrilǎ Teodora , Constantinescu M. , Stadler Magdolna , Mihǎilǎ Doina , Pop I. , Popa D. 
Published: May 2019

Summary: The method of Wu and Hoak in det rmining circulating platelet aggregates in vivo was used.In different cardiac and vascular states, a low aggregation index is found: aorto-iliac occlusion (Leriche syndrome)- 38 csses(index X ± SD 0.52 ± 0.05 in comparison with normal subjects 0.91 ± 0.05); valvular diseasses (0.40±0.006); during extracorporeeal circulation - 14 cases (0.5±0.02l); thrombophlebitia-25 casea(0.84±0.065).After an antiaggaagation treatment (Dipiridamol) in 12 cases of aortoiliac occlusion the value of the aggregation index normalised(0.84±0.065) Experimenntlllly, 10 rabbits were perfused wi th thrombin soution (2 u./body woight k.); the lower values of the aggreeation index (0.91±0.085 brfore Emd 0.43±0.035 after the thromhin perfuaion) prove the fidelity of the method.The simplicity of the technique, the reproducti bili ty in experimental conditions and the normalisation of the valuwa after treatment prove the practical value in determining the circulating platelet aggregates.
Factor VIII and Ristocetin-Induced Aggregation in sickle Cell Disease
Authors: Mackie I.J. , Bull H. , walford D. , Brozovic M. 
Published: May 2019

Haemostatic variables were studied in 23 patients with sickle cell disease (SCD) who were followed over a year. Investigations included measurements of factor VIIIC, VIIIAg, antithrombin III biological and antigen levels, fibrinogen and platelet aggregation to ADP, collagen, porcine AHG and ristocetin. All eight SS patients in the steady state had normal levels of F VIIC and high levels of F VIIIAg with marked discordance between the two values (mean VIIIc: VIIIAg ratio 0.3). By contrast, 15 patients with 15 disease or S thalassaemia tended to show less Barked discordance between levels of F VIIIC and F VIIIAg (mean VIIIc VIIIAg 0.7). Patients in the steady state showed normal platelet aggregation to ADP, collagen and porcine AHG, but ristocetin induced aggregation was absent or œarkedly reduced. Platelet aggregation to ristocetin is absent in most individuals of Afro-Carribean origin and the ristocetin co-factor activity may be difficult to assess in this ethnic group.During crisis both factor VIIIc and factor VIIIAg were invariably high. Factor VIIIAg was studied using crossed Immunoelectrophoresis in 5 patients. In one patient two peaks were found and in the others the F VIIIAg had more anodal mobility than normal. These findings are suggestive of the presence of lower molecular weight fragments of factor VIIIAg and may account for the apparent very high levels as measured by Laurell rocket technique.
Prostacyclin can Replace Heparin for Haemodialysis in Dogs
Authors: Woods H.F. , Weston M.J. , Bunting S. , Moncada S. , Vane J.R. 
Published: May 2019

Prostacyclin, produced by vascular endothelium, is the most potent inhibitor of platelet aggregation known to man. To assess its effects on platelets during dialysis ten greyhounds were dialysed for 90 minutes with cuprophan coils. At the end of dialysis arterial platelet counts (% of initial value) were significantly higher in the five dogs in which prostacyclin had been infused (115.7 ± 8.6) than in the animals in which heparin alone had been used (77.8 ± 16.8, < 0.05). Prostacyclin reduced the extraction of platelets by the dialyser. The screen filtration pressure, a measurement of platelet aggregates in blood leaving the dialyser, remained unelevated in the prostacyclin treated animals (80 ± 11.3 mm Hg) but rose significantly in those infused with heparin alone (249 ± 57 mm Hg, < 0.02). In another five dogs infused with prostacyclin but no heparin, dialysis did not reduce platelet count, elevate the screen filtration pressure or alter the overall clotting tests.Thus prostacyclin enables haemodialysis to be carried out without the undesired effects on platelets and haemostasis that are associated with the use of heparin.
The Use of Prostacyclin [PGI2) During Charcoal Haemoperfusion
Authors: Woods H.F. , Weston M.J. , Bunting S. , Moncada S. , Vane J.R. 
Published: May 2019

Although charcoal haemoperfusion has been used in the treatment of hepatic and renal failure and of drug and other intoxications, its potential has been limited by thrombocytopenia and other effects on platelet function. To try to improve blood-compatibility of charcoal haemoperfusion we infused PGI2, the most potent platelet inhibitor known to man, in addition to heparin during charcoal haemoperfusion carried out for 120 minutes in healthy dogs. With PGI2; platelet counts fell toonly 86 ί 2.3% of initial compared to 17 ± 3.7% when heparin alone was used. PGI2 prevented any rise in screen filtration pressuring during charcoal haemoperfusion (a measure of platelet aggregate formation) whereas with heparin alone the screen filtration pressure quadrupled. During charcoal haemoperfusion with heparin only the plasma fibrinogen levels fell to 54 ± 4% of initial but with heparin plus PGI2 the plasma fibrinogen levels were maintained at 92 ± 3.8%. Furthermore the use of PGI2 prolonged the activity of heparin as measured by thrombin clotting time during charcoal haemoperfusion.This dramatic improvement in biocompatibility during charcoal haemoperfusion when PGI2 is used may allow more satisfactory assessment of its use for detoxification.
The Influence of Pregnancy upon Blood Coagulation and Plasma Fibrinolytic Enzyme Function
Authors: Fletcher A.P. , Alkjaersig N.K. , Burstein R. 
Published: May 2019

Fibrinogen catabolism has been studied in 27 patients from early pregnancy through delivery by plasma fibrinogen chromatography. This technique quantifies in plasma, the concentration of high molecular weight fibrino(ogen) complexes (HMWFC), reflecting the rate of fibrin formation in vivo, native fibrinogen and derivatives of fibrinogen smaller than the native molecule (Fragment X) resulting from the actions of the enzyme plasmin on fibrinogen; this reflects the rate of fibrinogenolysis. During the second gestational month plasma HMWFC concentration was elevated 2-3 fold over control values, increased with gestational age being 5 fold elevated at delivery. Fragment X was mildly elevated throughout pregnancy.These results demonstrate that intravascular fibrin deposition, presumably involving the uteroplacental circulation is the earliest and most persistent alteration in blood coagulation function noted during pregnancy. Further, the significant increase in fibrin deposition occurring during pregnancy is accompanied by a significant increase in compensatory fibrinolysis.
The Assay of Factor VII in its Native and Activated Forms
Authors: Snape T.J. , Griffiths D. 
Published: May 2019

The preparation and use for factor VII assay of an artificial human factor VII-deficient substrate plasma is reported. Results of factor VII assays carried out using this plasma as substrate were closely comparable with values obtained using congenitally deficient plasma.Neither of these assay systems distinguishes between factor VII in its native and activated forms. The activation state of factor VII in plasma and in a therapeutic factor VII concentrate has been investigated using an amidolytic assay (Seligsohn et al, 1978, Blood, 52, 978) and also by a method involving conventional assay before and after incubation with heparin (Godal et al, 1974, Thromb. Res., 5, 773). The results suggest that factor VII in the concentrate is unactivated and is stable with respect to attempts to activate it by cold activation in the presence of contact activators.
The Interaction of Human Factor VII and Tissue Factor, and the Effect of DFP.
Authors: Østerud B. , Bjørklid E. , Brown S.F. 
Published: May 2019

When partially purified F.VII (absolutely free of F.X) was incubated with tissue factor (T.F.) and Ca++, a product was formed that over time increased its potency to clot F.VIII d.p. (58 sec at 0 min and 32 sec C.T. at 5 min incubation time). The effects of monospecific antibodies to F.VII and the apo-protein of T.F. were tested on these products. Thus, when anti-F.VII was added to a 10 min incubation mixture of F.VII, T.F. and Ca++, the clotting time increased from 32 sec to 125 sec. However, adding anti-T.F. to an identical 10 min incubation mixture had no effect on this mixture’s ability to clot F.VIII d.p.. Anti-T.F. allowed to react with T.F. prior to incubation with F.VII and Ca++, abolished the formation of a F.X. activator.DFP neutralized purified human F.VII and F.VII in human plasma. The inhibition was relatively slow. However, when F.VII had been preincubatcd with T.F. and Ca++, the neutralization of F.VII activity by 2 mM DFP occurred rapidly. We conclude that there is a time consuming reaction between F.VII and T.F. resulting in a product of F.VII that apparently no longer needs T.F for its activation of F.Y.
Immunchemical Investigation on Antithrombin III/AT-III/in Presence of Heparin
Authors: Bánuergyi D. , Sas G. 
Published: May 2019

Various components of AT-III car, be differentiated by crossed ioununo-eleetrophoresis in the presence of heparin as we described previously / Sas et al. 1975 /. The migration of heparin is discontinuous in this original method, i.e. at the end of the electrophoresis the plate does not contain heparin at all. This fact rises the possibility pf the artefactual nature of these AT-III components. To exclude this effect we introduced a modification using double plates incorporated with heparin. The second plate was used as a heparin “reservoir”. By this modification we obtained constant heparin flow in the course of electrophoresis. We found four different AT-III components in normal plasma comparing with three AT-III eomportints of the original method.Investigating heparins originated from different sources we found a higher mobility of AT-III in the pnsenee of mucous heparin than that of lung heparin. This observation corresponds well with the results obtamed by heparin-agarose affinity chromatography.
Drug Treatment in the Prevention of Coronary Artery Disease
Authors: Mitchell J.R.A. 
Published: May 2019

The disappointing performance of anticoagulants in the prophylaxis of coronary heart disease led to the realisation that components other than fibrin play a major part in the structure of arterial thrombi. Attention has therefore been focussed on the possible role of agents which modify platelet behaviour. Novel agents which alter thromboxane synthesis will not be available for large-scale clinical trials for some years, so the present trials are assessing the value of platelet-modifying agents which are already in use for other purposes. The implications of the Antura-Reinfarction study and the role of aspirin and persantin will be discussed.Attention will also be drawn to the importance of using valid end-points to assess potential anti-thrombotic regimes in coronary disease. The differential implications of using infarction, sudden death, pump failure, dysrhythmias and re-infarction as end-points in trials will be described.
Structure of the Antithrombin III-Binding site in Heparin
Authors: Lindahl U. , Bäckström G. , Höök N. , Riesenfeld J. , Thunberg L. , Fransson L.-A. , Linker A. 
Published: May 2019

Fragments with high affinity for antithrombin III (AT), composed of 12 to 16 monosaccharide units, were isolated from heparin after partial chemical or enzymatic depolymerization of the polysaccharide. Analysis of such fragments based on identification ot deamination products suggested that nonsulfated L-iduronic acid (a minor constituent) is essential for the anticoagulant activity of heparin. The location of this unit in the AT-binding sequence was determined by periodate oxidation. Furthermore, an N-sulfate group essential for activity was located by structural analysis of partially N-desulfated fragments retaining high affinity for AT. It is proposed that the AT-hinding sequence in heparin has a variable structure containing certain nonvanable regions. A tentative structure for this sequence is presented, with indication of identified constant and variable regions.(Supported by grant No. 2309 from the Swedish Medical Research Council).