bluuebunny/crossref_metadata_2025 huggingface dataset:
von Willebrand Factor in Plasma and Urine of Men with Premature Coronary Artery Disease
Authors: Silveira Angela M V , Elgue Graciela , Hamsten Anders , Blombäck Margareta
Published: July 2018

Plasma and urine samples from 17 men who had suffered a myocardial infarction before the age of 45 years were quantitatively and qualitatively analyzed for von Willebrand factor antigen (vWF), and compared with samples obtained from controls. The levels of vWF in plasma and its characteristic multimeric composition in the patient samples were not different from those of the controls. However, when analyzed for lower molecular weight components, plasma samples from some patients contained more degraded material than those of the controls as indicated by the presence of an extra protein band of vWF related material having a molecular weight of about 200 kDa. The levels in urine of vWF and the molecular weight of the fragments excreted did not differ between patients and controls. A relative increase in excretion of lower molecular fragments was, however, observed in the patient group. In a second group of 97 consecutive post-infarction patients under the age of 45 years the extra 200 kDa vWF band was found in 46% of the patients, whereas it was not detected in control plasmas. Taken together these findings suggest that degraded forms of vWF occur in normal plasma and that a more extensive degradation may occur in patients with coronary atherosclerosis, which could account for the relative increase in the excretion of lower molecular weight fragments observed in these patients.
Sedimentation Behavior of Fibrinogen from Normal and Bleeder Swine
Authors: Cooper R. G , Cornell C. N , Muhrer M. E , Leimer K
Published: June 2018

The Missouri Bleeder Swine have prolonged bleeding time, low factor VIII levels, reduced platelet adhesion, and respond to plasma and serum transfusions in a manner similar to that of patients with von Willebrand’s disease. The swine disease is thus more similar to von Willebrand’s disease than to classical hemophilia. The present work demonstrates that the sedimentation behavior of fibrinogen from these bleeder swine is like that of normal swine and does not show the anomalous sedimentation pattern of fibrinogen from classical hemophiliacs.
The Estimation of Blood Platelet Survival
Authors: Murphy E. A , Francis M. E , Mustard J. F
Published: June 2018

The characteristics of experimental error in measurement of platelet radioactivity have been explored by blind replicate determinations on specimens taken on several days on each of three Walker hounds.

Analysis suggests that it is not unreasonable to suppose that error for each sample is normally distributed ; and while there is evidence that the variance is heterogeneous, no systematic relationship has been discovered between the mean and the standard deviation of the determinations on individual samples. Thus, since it would be impracticable for investigators to do replicate determinations as a routine, no improvement over simple unweighted least squares estimation on untransformed data suggests itself.
Variants of Haemophilia B
Authors: Elödi Susan , Puskás Éva
Published: June 2018

Variants of haemophilia B were examined by antibody-neutralization technique and by the ox brain thromboplastin time method. On the basis of the presence or absence of anomalous factor IX and of prothrombin time, four variants of haemophilia B were discerned. It is shown that the prolongation of prothrombin time, measured in our cases, cannot be attributed to an inhibitor in the patients’ plasma.
Cold Promoted Activation of Factor VII
Authors: Gjønnæss H
Published: June 2018

The activating principle (CPA) of the factor VII activation seen in plasmas of women taking oral contraceptives after overnight incubation of the plasmas at 0° C was investigated. The reaction was dependent on low temperature, and factor XII was indispensable. Concomitant with the activation of factor VII a 10–30 fold increase in TAME esterolytic activity was observed together with a near 100 per cent drop in plasma kininogen concentration. The results indicated that the activation of factor VII is linked to activation of the kallikrein system, and that the activator may be plasma kallikrein.
Tranexamic Acid in the Control of Spontaneous Bleeding in Severe Haemophilia
Authors: Rainsford S. G , Jouhar A. J , Hall Angela
Published: June 2018

A double-blind cross-over study of the prophylactic value of tranexamic acid (“Cyklokapron”), in a dose of 3.0 g per day, against spontaneous bleeding episodes in severe haemophilia was undertaken. Records of bleeding episodes were maintained during therapy in twenty boys with confirmed clinical severity, over two school terms. A significant reduction (p <0.05) in spontaneous bleeding episodes was attained with an associated lessening in the transfusion requirement of therapeutic material, and without obvious side effects. Recommendations are made for further investigations.
On the Complex Formation of Antithrombin III with Thrombin
Authors: Binder B
Published: June 2018

Based on gelfiltration studies, the part of AT III which becomes bound to thrombin during the process of in vitro blood coagulation was calculated to be about 40% of total AT III. Complexes consisting of one AT III and one thrombin molecule could not be detected while fractions corresponding to molecular weights of about 190,000 Dalton show AT III as well as thrombin activities. The AT III - thrombin complex in normal human serum consists, therefore, of either 2 AT III and 2 thrombin molecules or of one AT III and 4 thrombin molecules.
Behaviour of the Portal Clotting Time in Cats Following the Intraduodenal Administration of Heparin
Authors: Kokot Bogdan
Published: June 2018

This work makes an attempt to display the behaviour of portal clotting time after intraduodenal administration of heparin. The experiments were carried out in 20 cats, which were divided into two groups.

In the first stage of investigation the normal clotting time was determined in portal vein and caudal vena cava. Afterwards the same parameters were investigated after intraduodenal administration of heparin or saline solution.

It was shown that after intraduodenal administration of heparin the clotting time in portal vein in each case was prolongated, but in the caudal vena cava it remains normal. After intraduodenal administration of saline solution the clotting time in both portal vein and caudal vena cava was unchanged.

Conclusions. 1. In the performed experiments the heparin administered intraduodenally passes from the small intestine into the collection of the portal vein. 2. The lack of anticoagulative activity of the heparin given intraduodenally in the blood of the peripheral veins probably caused by a block present above the portal collection.
Role of Platelet Factor 3 in the Hypercoagulability Induced by Pregnancy and Oral Contraceptives
Authors: Renaud S , Gautheron P
Published: June 2018

As evaluated in a recording “coagulometer” the Stypven time of 16 to 19 days pregnant Holtzman rats was shorter than that of the controls solely in platelet-rich plasma but not in platelet-poor plasma collected in siliconized material when most of the platelets were removed by slow speed centrifugation (1000 G × 20 minutes). If the same blood was centrifuged at a higher speed (2000 G) the Stypven time was considerably shorter in the pregnant rats even if no platelets were left indicating that platelet factor 3 had been released in plasma during centrifugation.

Identical results were obtained in 10 women taking oral contraceptives as compared to 10 controls. Depending on whether blood was collected in siliconized glassware or not, and final determination performed in plastic or glass, the cephalin clotting time of oral contraceptives treated women was found to be longer, equal or shorter than this of the controls. When it was shorter, a comparable reduction in the Stypven time indicated that the shortening was probably due to “release” of platelet factor 3 in the platelet-poor plasma, in the course of its preparation.
Inhibition by Phenol and Phenolic Acids of Platelet Release Reaction
Authors: Molinas Felisa C.
Published: June 2018

It has been postulated that the high phenol and phenolic acids plasmatic levels found in patients with chronic renal failure are contributory factors in the abnormal platelet function described in these patients. This hypothesis was corroborated by “in vitro” studies showing the deleterious effect of these compounds on certain platelet function after pre-incubation of PRP with phenol and phenolic compounds. The present studies were conducted to determine the influence of phenolic compounds on platelet release reaction. It was found that phenol inhibited from 62.5 to 100% the effect of the aggregating agents thrombin, adrenaline and ADP on platelet 5-HT-14C release. The phenolic acids p-, m-, and o-HPAA inhibited from 36.35 to 94.8% adrenaline and ADP-induced platelet 5-HT-14C release. Adrenaline-induced platelet ADP release was inhibited from 27.45 to 38.10% by the phenolic compounds. These findings confirm the hypothesis that phenolic compounds interfere with platelet function through the inhibition of the release reaction.
Trial of Aspirin and RA 233 in Prevention of Post-operative Deep Vein Thrombosis
Authors: Wood Edward H. , Prentice Colin R.M. , McGrouther D. Angus , Sinclair John , McNicol George P.
Published: June 2018

Although the oral anticoagulants provide effective prophylaxis against postoperative deep vein thrombosis following fracture of neck of femur there is a need for an antithrombotic agent which needs less laboratory control and does not cause haemorrhagic complications. It has been suggested that drugs causing inhibition of platelet function may fulfil these requirements. A controlled trial was carried out in which aspirin, RA 233, or a combination of these drugs was compared with a placebo in the prevention of post-operative deep vein thrombosis. In thirty patients undergoing surgery for fractured neck of femur the incidence of post-operative calf vein thrombosis, as detected by 125I-fibrinogen scanning, was not significantly different between the untreated and treated groups.
Leucocytes and Thrombosis
Authors: Banks D.C , Mitchell J.R.A
Published: June 2018

When heparinised blood is rotated in a glass flask at 37°C. the white cell count falls and it has been shown that this is due to the adherence and aggregation of polymorphonuclear white cells on the wall of the flask. The masses formed bear a close structural resemblance to thrombi and the mechanisms involved in white cell loss during rotation may therefore increase our knowledge of the thrombotic process.
Chicken Fibrinogen and Human Fibrinogen
Authors: Ménaché Doris , Cesbron Nicole , Guillin Marie-Claude , Schlegel Nicole
Published: June 2018

In order to investigate the immunological features of chicken fibrinogen and to compare them with human fibrinogen, monospecific rabbit antichicken and antihuman fibrinogen antisera have been prepared. Both antisera agglutinated human tanned red cells coated with human fibrinogen. Inhibition of the reaction was obtained by prior incubation of rabbit antichicken fibrinogen antiserum with either human or chicken fibrinogen. Using precipitation reactions in agarose gels, precipitating antigen-antibody complexes were obtained between chicken fibrinogen and rabbit antihuman fibrinogen antiserum and vice versa only if the antisera were concentrated or if an increase in the sensitivity of the reaction was achieved using counter Immunoelectrophoresis. Cross absorption of rabbit antichicken fibrinogen antiserum with human fibrinogen did not abolish the precipitating reaction with chicken fibrinogen. In the same way, cross absorption of rabbit antihuman fibrinogen antiserum with chicken fibrinogen did not abolish the precipitating reaction with human fibrinogen.

These results indicate that chicken and human fibrinogen share common antigenic determinants; they also indicate additional antigenic determinants in both fibrinogens.
Antiheparin Activity of Human Serum and Platelet Factor 4
Authors: Sear C.H.J , Poller L , Path F.R.C
Published: June 2018

The antiheparin activity of normal serum has been studied by comparing the antiheparin activities of sera obtained from normal whole blood, platelet-rich plasma and platelet-’free’ plasma with a purified platelet extract during differential isoelectric precipitation and by gel filtration chromatography.

The mean values for the activity of PRP-serum and PFP-serum were 106% (S.D. 11) and 10% (S.D. 3) of untreated whole blood respectively. The activity of whole blood serum, PRP serum and whole blood serum plus platelet extract precipitated under identical physical conditions, i.e. pH 7.0, I =0.008, indicating that the activities of the three samples are probably associated with PF4. PF4 precipitated from human platelet extract at pH 4.0, but this is probably due to the difference in the two biochemical environments investigated, i.e. serum and platelet extract.

The gel filtration experiments revealed striking similarities between the major antiheparin activities of serum and platelet extract. At physiological pH and ionic strength both activities were associated with high molecular weight material, but at physiological pH and elevated ionic strength both activities behaved as much smaller entities of molecular weight between 25,000 and 30,000 daltons and it seems very likely that both activities are associated with the same molecule, i.e. PF4.
Fibrinocoagulopathy in Maturity Onset Diabetes Mellitus and Atherosclerosis
Authors: Banerjee R.N , Sahni A.L , Kumar Vijay
Published: June 2018

Immunofluorescent demonstrations of platelet-free fibrin deposit in the micro and macro-vascular lesions of maturity onset diabetes mellitus and atherosclerosis by earlier workers called for investigations of fibrino-coagulopathy in the two disorders. The present investigation included the determinations of plasma thrombin time (PTCT), fibrinogen concentration (FC), plasma fibrinogen half life (PFT ½) and plasma fibrinogen degradation product (FDP) in (i) the subjects of the two age-onset disorders and their consanguinous family members, and (ii) juvenile diabetes.

The assays were carried out by standard methods. 125Iodine labelled human fibrinogen was used for half life studies.

In a study of 525 subjects, very highly significant (p <0.001) reduction in PTCT, FC and PFT ½ with a very highly significant (p < 0.001) elevation of FDP were observed in the patients of the two age onset disorders. The results were normal in juvenile diabetes.

The study provides convincing evidence of a ‘state of slow consumptive fibrino-coagulopathy’ in the subjects and their siblings with the observed haemostatic defect likely being due to genetically determined Anti-thrombin III deficiency. This observation stimulates a unitary concept of a primary fibrinopathic vascular aetio-pathogenesis, with selective localisation in the macro and microvascular compartment being responsible for the clinical syndromes of ischaemic and metabolic alterations in athersclerosis and maturity onset diabetes mellitus respectively.
Fibrinoyltic Activity of Human Carcinomas
Authors: Peterson Hans-Inge , Petrusson Björn , Korsan-Bengtsen Kristoffer
Published: June 2018

The fibrinolytic activity of 25 human malignant tumour specimens was studied by a semi-quantitative histochemical method and by a plasminogen activator extraction procedure. A good accordance between the results obtained with the two methods was found. The advantages and disadvantages of the methods are discussed.
Studies on an Inhibitor of Plasminogen Activation in Human Serum
Authors: Hedner Ulla
Published: June 2018

A procedure is described for partial purification of an inhibitor of the activation of plasminogen by urokinase and streptokinase. The method involves specific adsorption of contammants, ion-exchange chromatography on DEAE-Sephadex, gel filtration on Sephadex G-200 and preparative electrophoresis. The inhibitor fraction contained no antiplasmin, no plasminogen, no α1-antitrypsin, no antithrombin-III and was shown not to be α2 M or inter-α-inhibitor. It contained traces of prothrombin and cerulo-plasmin. An antiserum against the inhibitor fraction capable of neutralising the inhibitor in serum was raised in rabbits.
Human Prothrombin: A New Method of Preparation from a Single Individual
Authors: Benarous Richard , Labie Dominique , Josso François
Published: June 2018

A simple method for purification of human prothrombin from ACT) plasma of one single individual is described. This method is based on three steps :

1. isolation of crude prothrombin complex by barium citrate adsorption;

2. first purification by hydroxyapatite chromatography;

3. further purification by DEAE Sephadex chromatography.

The final product was obtained with a good yield and exhibited less than 5 p. cent contamination. The human purified prothrombin obtained in this way displays :

– one single chain by SDS electrophoresis,

– a molecular weight of 75,000-80,000 daltons,

– a pi value pH 4.4 by electrofocusing,

– Alanine as थ terminal residue.

Amino-acid analysis is reported.
Congenital Hypoprothrombinemia in a Portuguese Family
Authors: Pina-Cabral J. M , Justiça Benvindo
Published: June 2018

A new case of congenital hypoprothrombinemia is described, in which the level of factor II in the propositus has been consistently near 1 per cent. Several specific assays of this factor have been used, including an immunochemical assay that rules out the presence of an abnormal molecule of prothrombin. The normal levels found for the other known coagulation factors, the lack of response to vit. K1 administration and the absence of a specific inhibitor, are all reasons to discard a secondary cause for this hypoprothrombinemia. Thromboplastin generation test was not only deficient, but it was also delayed. Serum composition was found responsible for this abnormality. The family pedigree of the propositus was compatible with autosomal recessive transmission of the disease.
The Measurement of Heparin
Authors: Denson K. W. E , Bonnar John
Published: June 2018

A method for the measurement of heparin utilising the potentiating effect of heparin on the action of anti-factor Xa is described. The effect on the assay of platelet contamination of plasma, the presence of fibrinogen degradation products and low levels of anti-factor Xa have been studied. The assay method has been compared with the calcium thrombin time method and a group of obstetrical patients have been studied using both methods.
Treatment of Tissue Thromboplastin Membranes with Phospholipase C
Authors: Bjørklid E , Otnæss A.-B , Storm E , Prydz H , Johansen B. V , Frøholm L. O
Published: June 2018

Tissue thromboplastin from human brain, partially purified by extraction with deoxycholate, gel chromatography and recombination of the protein (fraction A) and phospholipid (fraction B) fractions, was examined after treatment with phospholipase C (E.C. 3.1.4.3). Various morphological changes accompanied the loss in coagulation activity caused by the enzyme. All concentrically arranged vesicles (spherulites) disappeared. Instead, a large number of quite small vesicles and many big “blebs”, probably containing diglycerides, were seen. Fused membranes appeared after treatment with the enzyme. The phospholipid fraction (fraction B) showed similar structures as thromboplastin, but not quite the same morphological changes after enzyme treatment.

Phospholipase C treatment probably caused a splitting of the concentrically arranged tissue thromboplastin membranes, which spontaneously rearranged to form new vesicles or were fused to other membranes. The hydrophilic parts of the phospholipids are required for coagulation activity, either because they impart a certain ultrastructure to the membrane, or because they participate in the coagulation process in a more direct way, e.g. by forming complexes with factor VII or by binding factor VII through calcium bridges.
Platelet Factor 3 Activity in Washed Platelets
Authors: Renaud S , Gautheron P , Rosenstein H
Published: June 2018

Platelets collected with an EDTA solution and simply washed in an incomplete Tyrode’s presented clotting times in the recalcification (man and rat) and the Stypven (rat) tests that were practically identical to those of the PRP when slow speed centrifugation was used (800 G in man, 1000 G in rat). This was demonstrated, in 6 pools of 5 rats each and in 6 men, by comparing the clotting activity of the citrated platelet-rich plasma to that of the platelets washed and resuspended in the citrated platelet-poor plasma, for platelet counts ranging from 1 × 105 to 10 × 105/mm3. In contrast, centrifugation of platelets at 3000 G markedly affected these clotting activities, as was shown in an additional study comprising 6 pools of 3 rats.

Finally, the clotting activity of platelets totally disrupted by sonication appears to be identical quantitatively in both man and rats to that of the total phospholipids extracted from these platelets and separated from the other lipids by thin-layer chromatography and resuspended in plasma by sonication.
The in Vivo and in Vitro Effect of Antihistamines on Platelet Aggregation
Authors: Ungaro Peter C. , Beck Thomas M. , McCaa William M. , Hershgold Edward J.
Published: June 2018

The effect of antihistamines on platelet aggregation was studied by examining the platelet rich plasma of subjects taking three representative classes of these drugs, as well as by studying the effect of direct addition of antihistamine to platelet rich plasma. Inhibition of aggregation by in vitro addition was obtained only with drug concentrations much greater than would usually be found in vivo. Platelet aggregation was unimpaired in normal volunteers taking standard doses of antihistamines.
Soluble Fibrin Monomer Complexes, Plasma Fibrinolytic Activity and Aortic Wall
Authors: Wojewski A , Samochowiec L , Zajączkowski T , Szyszka K , Wojewska-Zajączkowska E , Abucewicz A
Published: June 2018

It has been stated that in prolonged CS2 intoxication of albino rats, the percentage of soluble fibrin monomer complexes in blood increases and there is a drop in plasma fibrinolytic activity. Simultaneous serotonin administration lowers the fibrinolytic activity to still greater extent. Prolonged CS2 intoxication does not alter the antiparacoagulating activity of the aorta. Deseril and cinarine administration elevates the aortic antiparacoagulating activity, while serotonin decreases it.
Reptilase-Induced Shortening of Coagulation Times in Normal and Hemophilic Individuals
Authors: Harder A. J , Stadelmann H , Straub P. W
Published: June 2018

In 5 normal volunteers infusion of small doses of Reptilase-def., a thrombin-like snake venom enzyme of Bothrops atrox, led to a transient shortening of the clotting time, which was significant when compared with a control group infused with glucose. In hemophilic individuals, clotting and recalcification times were also considerably shortened, the maximal effect in both groups occurring simultaneously with cryoprecipitability and positive paracoagulation phenomena. Whether this accelerating effect on blood coagulation is mediated by circulating soluble fibrin complexes, is not yet established. However, the clot-promoting action of Reptilase must predominantly be localized at the level of fibrinogen/fibrin conversion rather than in earlier phases of coagulation.
Adenine Nucleotide Metabolism of Human Platelets during Collagen-Induced Aggregation
Authors: Murakami M , Yoshino K , Takase M , Odake K
Published: June 2018

Changes in platelet adenine nucleotides during collagen-induced aggregation were estimated. Averaged values of ATP and ADP in intact platelets were 56.3 and 28.9 attomoles per platelet, respectively. After collagen-induced aggregation, intracellular ATP plus ADP was depleted to about half of that in intact platelets. The released ADP accounted for 13% of that in intact platelets.

Behavior of platelet adenine nucleotides during aggregation was divided into the following phases. At first, platelet ATP decreased without the release of nucleotides. The release of ADP occurred at the stage of rapid change of light transmission. Subsequently, the released ADP decomposed in parallel with the degradation of intracellular ADP. The radioactive ATP in platelets decreased during exposure to collagen, without appreciable release of radioactive nucleotides. The ATP released from disrupted platelets was rapidly metabolized in plasma.
The Effects of Salts and of Ionic Strength on the Hydrolysis of TAME (p-toluenesulfonyl-L-arginine methyl ester) by Thrombin and Thrombokinase
Authors: Roberts Phyllis S. , Fleming Patricia B.
Published: June 2018

The effects of varying concentrations of alkali chlorides (LiCl, NaCl, KC1, RbCl and CsCl), alkaline earth chlorides (BeCl2, MgCl2, CaCl2, SrCl2, and BaCl2), choline chloride and Tris,HCl (pH 8.0 at 37°) on the rates of hydrolysis of TAME by a purified preparation of human thrombin and of bovine thrombokinase were determined in 0.25 M Tris.HCl buffer, pH 8.0 at 37°. Each salt had its own individual effects on the reactions and these effects were completely different when thrombin instead of thrombokinase was used. Each salt, however, had the same qualitative effects on TAME hydrolysis by crude bovine thrombin as by purified human thrombin, but only minor effects on the hydrolysis of TAME by trypsin.

With the exception of LiCl, low concentrations of alkali chlorides had inhibitory and high concentrations had acceleratory effects on both the thrombin-TAME and the thrombokinase-TAME reactions. LiCl had no accelerating effects on either reaction and it was a stronger inhibitor of thrombokinase than of thrombin. In contrast to the alkali chlorides, the alkaline earth chlorides had no acceleratory effects but had inhibitory effects on both reactions. MgCl2, however, was an exception. It weakly accelerated the thrombokinase -TAME and weakly inhibited the thrombin -TAME reaction. When comparing 0.15 M concentrations of the salts (with the exception of BeCl2 which was the strongest inhibitor of both reactions), NaCl was the strongest inhibitor of the thrombin - TAME reaction, followed by CaCl2, but BaCl2 was the strongest inhibitor of the thrombokinase -TAME reaction, followed by KC1 and LiCl.

Choline chloride and Tris.HCl in concentrations up to 3 M had no significant effects on the rate of hydrolysis of TAME by either human or bovine thrombin. Increasing the ionic strength above 0.16 (lower values were not tested), therefore, may have no effect on this reaction, and all of the inhibitions and accelerations found in the presence of the alkali chlorides or the alkaline earth chlorides may be entirely due to the individual cations. On the other hand, increasing the ionic strength may produce a small inhibitory effect, as found in the presence of LiCl or MgCl2, and the lack of any effect in presence of even large concentrations of Tris.HCl or choline chloride may be due to a fortuitous balancing of the weak inhibitory effect of ionic strength by the weak acceleratory effect of the choline and Tris cations.

Choline chloride and Tris.HCl had no inhibitory effects but accelerated the thrombokinase -TAME reaction. Choline chloride was the strongest accelerator tested. Rates in the presence of 0.15 and 3 M choline chloride were respectively 204 and 601 % of the controls. Although the effects of ionic strength changes on this reaction could not be established, the data indicate that increasing the ionic strength has at most only a small effect, and the inhibitions and accelerations found are due primarily to the specific cations present.
Filipin as a Tool for the Study of Blood Coagulation Reactions
Authors: van der Plas P. M , Kraan L , Hemker H. C
Published: June 2018

The influence of polyene suspensions on blood coagulation was investigated. The following conclusions can be drawn :

1. Polyenes in suspension inhibit coagulation, the sequence of activity is in accordance with the lytic activity on micro - organisms and lipid mono- and bilayers.

2. Alteration of the molecule by means of hydrogenation of the conjugated system or irradiation in the presence of FMN diminish the lytic activity and inhibition of coagulation in the same sense.

3. The composition and amount of lipid are important for the magnitude of the inhibition.

4. The inhibition can be decreased by pre-incubation of the polyene with cholesterol. This can be explained by the formation of polyene-cholesterol complexes.

5. Polyenes do not inhibit the thrombin-fibrinogen-interaction in plasma.
A Double Blind Three Center Clinical Trial on the Short-Term Efficacy of 0-(β-Hydroxyethyl)-Rutosides in Patients with Post-Thrombotic Syndrome
Authors: de Jongste A B , Jonker J J C , Huisman M V , ten Cate J W , Azar A J
Published: June 2018

A multi-centre, double blind randomized clinical triatr was designed to assess the efficacy and safety of orally administered 0-(β-hydroxyethyl)-rutosides (HR) capsules in the treatment of L0L patients with post-thrombotic syndrome. Seventeen patients were excluded from the analysis for violation of the study protocol, 4l received HR capsules (I,200 mg/day) and 43 placebo.

Mean follow-up scores at the 4th and 8th week show that the HR patients displayed an improved state of tiredness as compared to the placebo's. The mean circumference of the calf for the HR group decreased from 390 (± 33) mm at visit one to 382 (± 33) mm at visit three, with a mean circumference reduction of 8.7 (± 8) mm, compared to a steady placebo circumference of 387 (± 31) mm at all 3 visits with a mean circumference reduction of only 2 mm (± 9). The estimated treatment effect at week 8 was −6.7 ffiffi, 95% confidence interval (−10.3, −3.0).

The mean circumference of the ankle, decreased from 243 (± 20) mm to 238 (± 20) mm at the 4th week, contrasted with a constant placebo circumference of.24l (± 22) mm at both visits. The estimated treatment effect at week 4 was-5.4 ffiffi, 95% confidence intenral (−10.2, −0.6). However, at week 8, the estimated treatment effect was only −3.4 mm; 95% corrfidence interval (−8.6, + 1.8).

In conclusion, HR capsules may show an improvement in the clinical symptoms and may show a mean circumference reduction of the calf and ankle at the 8th week, in patients with postthrombotic syndrome.
Blood Collection in Strong Acidic Citrate Anticoagulant Used in a Study of Dietary Influence on Basal tPA Activity
Authors: Rånby Mats , Sundell I Birgitta , Nilsson Torbjörn K
Published: June 2018

Tissue plasminogen activator (tPA) activity in blood and blood plasma has been difficult to determine because it is unstable, especially in subjects with high levels of plasminogen activator inhibitor type 1 (PAI-1). We have attempted to stabilize the tPA activity by collecting 9 volumes of blood in 1 volume acidic citrate buffer which immediately lowers the pH of the blood. At final blood pH of 4.9 to 6.3, consistent and high tPA activity levels were found. One acidic citrate buffer composition, 0.5 mol/1 citrate buffer pH 4.0, resulted in final blood pH 5.5, tPA half-life of 10 days and an acceptably low degree of haemolysis. This anticoagulant composition was selected for more extensive evaluation and was used to collect blood plasma samples from 29 volunteers in the morning after a 10-minute bed rest. Basal tPA activity, mean and SD, was 0.47 ±0.21 IU/ml. After donating of the first blood sample, 10 of the volunteers entered into a 24-hour fast after which they donated a second sample. During the fast, the basal tPA activity increased from 0.34 ±0.21 to 0.47 ±0.23 IU/ml (p = 0.05) and the PAI-1 activity decreased from 11.4±11.6 to 6.3±8.9 U/ml (p = 0.04).
The Absorption, Clearance and Metabolic Fate of Dermatan Sulphate Administered to Man - Studies Using a Radioiodinated Derivative
Authors: Dawes J , Hodson B A , Pepper D S
Published: June 2018

An iodinated derivative of dermatan sulphate was administered by the intravenous, subcutaneous and oral routes to healthy human volunteers in conjunction with unlabelled dermatan sulphate. Following intravenous injection clearance of radiolabel and concentration as measured by competitive binding assay were highly correlated and displayed complex kinetics which were not dose-dependent. Intact 125I-dermatan sulphate was absorbed following both subcutaneous and oral administration, though there appeared to be selective uptake by the gut of a subfraction comprising the smaller or less sulphated molecules. The intact material was subsequently excreted unchanged in the urine. Degradation products of dermatan sulphate were not detected by either gel filtration or affinity chromatography on Polybrene-Sepharose at any time in either plasma or urine, indicating that administered dermatan sulphate is not catabolised by man.
Absent Platelet Aggregation with Normal Fibrinogen Binding in Basset Hound Hereditary Thrombopathy
Authors: Patterson Wayne R , Estry Douglas W , Schwartz Kenneth A , Borchert Ronald D , Bell Thomas G
Published: June 2018

Platelets from dogs with Basset Hound Hereditary Thrombopathy (BHT) initially displayed a thrombasthenia-like aggregation defect but have been shown to have normal amounts of platelet membrane glycoproteins lib and Ilia (GPIIb-IIIa), and therefore are more accurately described as thrombopathic. The presence of normal quantities of GPIIb-IIIa, however, did not rule out the possibility of a functionally abnormal glycoprotein complex which would be unable to bind radio-labeled fibrinogen. Therefore, fibrinogen binding in BHT platelets was evaluated. Platelets from BHT and normal dogs were activated with 1 × 10−5 M ADP in the presence of 125I-fibrinogen and the surface-bound radioactivity was quantitated. The amount of fibrinogen bound by BHT dog platelets was not significantly different than that bound by normal dog platelets. Platelets from dogs with BHT bound 30,282 ± 3,133 and normal dog platelets bound 31,664 ± 2,772 molecules of fibrinogen per platelet. The quantitatively normal GPIIb-IIIa complex binds fibrinogen in normal amounts and does not seem to represent the abnormality responsible for the aggregation defect in BHT platelets. Therefore, other factors central to normal platelet function and related to platelet aggregation must be considered.
Determinants of the Formation and Activity of Factor V-phospholipid Complexes II. Molecular Properties of the Complexes
Authors: Kandall Carol L , Shohet Stephen B , Akinbami T. K , Colman Robert W
Published: July 2018

The stability, buoyancy, and intrinsic activity of factor V-phospholipid complexes were investigated.

The decay of factor V activity in the absence of phospholipid followed first order kinetics; however, in the presence of several phospholipids a biphasic decay curve was observed. The addition of phosphatidylethanolamine to factor V produced only a small loss of activity in the first 2 minutes but decreased the subsequent rate of inactivation fourfold. A PE-factor V complex with a low bouyant density was separated from uncomplexed factor V by sucrose density ultracentrifugation. The association constant for this complex was 5 × 106 M-1 with approximately 2 moles of factor V bound per mole of lipid micelle. The isolated complex was capable of increasing prothrombin conversion 10-fold without additional phospholipid. A still lighter complex increased the rate of prothrombin conversion 18-fold.

Phosphatidyl serine produced a concentration-dependent loss of up to 95% of the factor V activity in the first 2 minutes. After ultracentrifugation on a sucrose density gradient, a PS-factor V complex of increased density was detected. This complex failed to accelerate prothrombin conversion in the intrinsic two-stage assay.

Except at very high concentrations, phosphatidylcholine did not alter the kinetics of inactivation of factor V. A factor V-phosphatidylcholine complex could not be detected after ultracentrifugation.

When added to factor V, cardiolipin (200 μg/ml), produced a rapid 50% decline in activity with a subsequent three-fold increase in the rate of inactivation. No activity was recovered after ultracentrifugation of factor V in the presence of cardiolipin.

Saturated phosphatidylethanolamine produced a concentration dependent initial loss of activity, but only a minimal increase in the subsequent rate of inactivation. At 200 μg/ml almost no light complex was detected after ultracentrifugation, but at 800 μg/ml a light complex was observed. This behavior corresponds to the ability of saturated phosphatidylethanolamine to accelerate prothrombin conversion only at very high concentrations.

Thus, phospholipids combine with factor V to form complexes which differ in their ability to accelerate prothrombin conversion. The most active species are stable lipoprotein complexes of lower buoyant density than factor V.
Studies on PIVKA-X
Authors: Gaudernack Gustav , Prydz Hans
Published: July 2018

The incorporation of 14C-glucosamine and 3H-leucine into PIVKA-X and factor X has been studied in Macaca mulatta by means of a monospecific precipitating antiserum. No difference in the incorporation into PIVKA-X and factor X was found.

The half-lives of PIVKA-X and factor X were similar (about 30-35 h and 27-31 h respectively) indicating that the vitamin K-induced modifications did not alter the survival of protein.

A Russell’s-viper venom/cephalin test system for factor X was more sensitive to inhibition by PIVKA-X than was a tissue thromboplastin-based system.
Serial Changes in the Coagulation System Following Clotting Factor Concentrate Infusion
Authors: Preston F. E , Winfield D. A , Malia R. G , Blackburn E. K
Published: July 2018

Various parameters of the coagulation system have been monitored in patients with Christmas disease following the infusion of clotting factor concentrates. Significant reduction of clotting factor VIII and serum antithrombin III were observed in each of the five studies, whilst the plasma fibrinogen level fell in four subjects. The induced abnormalities were shortlived and there were no clinical sequelae. Further studies are required to assess the effects of similar concentrates in patients with liver disease.
Effects of Experimental Coronary Thrombosis upon Regional and Systemic Plasma Chromatographic Patterns
Authors: Chowdhury Parimal , Moschos Christos B
Published: July 2018

An evaluation of changes in the plasma chromatographic pattern was carried out in dogs with experimental coronary thrombosis. Sequential samples were taken simultaneously from the aorta and coronary sinus over a two, four and twenty-four hour period. In addition to gel-chromatography, immunodiffusion and electrophoresis were also employed to identify the protein components of the elution fractions. The results showed that there was a shift of the normal chromatographic pattern to the left from the control within two hours following thrombotic occlusion of the coronary artery and it was maintained over a twenty-four hour period. The shift to the left was presumably due to the earlier elution of the heavy molecular weight components forming as a result of the thrombotic process. The early appearance of the altered chromatographic pattern constitutes an important advantage worthy of further exploration for possible diagnostic application in the human subject.
Assessment of Different Mathematical Models for Calculating and Expressing the Results of Coagulation Test Procedures
Authors: Kahan J , Norén I
Published: July 2018

Coagulation activity, expressed as percentage of normal and as clotting time ratio, was estimated in 220 specimens from patients on long-term anticoagulant treatment by 3 different coagulation test procedures, i.e. Thrombotest, Simplastin-A and Normotest. The estimates were calculated from the same determinations.

The distribution of percentage values showed a fairly pronounced deviation from normality. After logarithmic transformation, the distribution was normalized, the regression lines between Thrombotest and other tests became parallel, and that between PIVKA-insensitive systems was shifted to a 45° line. Logarithmic transformation also stabilized the residual variance. These features make percentage values accessible for treatment according to the standard methods of bioassay statistics.

Attempts to normalize the distribution of ratio values by various transformations were unsuccessful. Formal analysis of data revealed a variation in the proportionality of ratio values with the level of estimated coagulation defect. This may restrict the usefulness of the ratio approach. Logarithmic transformation partly reduced the discrepancy.
Standard for Human Thrombin
Authors: Robertson I , Gaffney P. J , Bangham D. R
Published: July 2018

Ten laboratories took part in an international study of the proposed standard for human thrombin. A freeze-dried preparation (coded 70/157) was shown, using clotting time tests, to be suitable to serve as a standard for the assay of human and bovine thrombin preparations. The study shows that assay variation within laboratories was much less than between laboratories. The preparation was stable, having a negligible estimated loss of potency after ten years under the recommended storage conditions (—20° C in the dark).

Each ampoule of the standard was assigned a potency of 100 units of thrombin activity, and one unit was defined as the activity contained in 0.0853 mg of the freeze-dried preparation.

It was agreed by the participants in the study and by the International Committee on Thrombosis and Haemostasis (Vienna, 1973) that the thrombin preparation coded 70/157 is suitable to serve as an international standard for human thrombin.
Calcium Ionophore A23187 (Eli Lilly)
Authors: Mürer Erik H , Stewart Gwendolyn J , Rausch Michael A , Day H. James
Published: July 2018

The addition of 0.1 μM ionophore A23187 to washed platelets incubated in citrated saline caused massive release of stored serotonin accompanied by intracellular accumulation of inosine monophosphate, but produced no detectable influx of externally added calcium or abnormal structural alterations. With increasing ionophore concentration there was a significant influx of calcium and a drastic alteration in the platelet ultrastructure. The increase in ionophore concentration was accompanied by the conversion of the major part of metabolic adenine nucleotides to inosine monophosphate and an almost complete blockage of further conversion to inosine and hypoxanthine. The metabolic changes were accentuated by the addition of calcium at concentrations less than 1/10 of the citrate concentration. In the presence of Ca++, or when citrate was omitted, there was a substantial leakage of cytoplasmic material, which at times suggested complete exchangeability between cytoplasm and extracellular medium. Our findings are consistent with the hypothesis that the platelet release reaction is triggered by intracellularly bound calcium. They also suggest that the application of high ionophore concentration has a toxicologic rather than a physiologic effect on platelets, and that a weak chelator added during incubation with the ionophore can in the absence of divalent cations prevent cell destruction, but not the toxic effect on cell metabolism.
Derivation and Validation of a Prediction Model for Risk Stratification of Post-Thrombotic Syndrome in Elderly Patients with a First Deep Vein Thrombosis
Authors: Méan Marie , Limacher Andreas , Alatri Adriano , Aujesky Drahomir , Mazzolai Lucia
Published: June 2018

Background Not all patients carry the same risk of developing a post-thrombotic syndrome (PTS), we therefore aimed to derive a prediction rule for risk stratification of PTS in patients with deep vein thrombosis (DVT).

Methods Our derivation sample included 276 patients with a first acute symptomatic lower limb DVT enrolled in a prospective cohort. We derived our prediction rule using regression analysis, with the occurrence of PTS within 24 months of a DVT based on the Villalta score as outcome, and 11 candidate variables as predictors. We used bootstrapping methods for internal validation.

Results Overall, 161 patients (58.3%) developed a PTS within 24 months of a DVT. Our prediction rule was based on five predictors (age ≥ 75 years, prior varicose vein surgery, multi-level thrombosis, concomitant antiplatelet/non-steroidal anti-inflammatory drug therapy and the number of leg symptoms and signs). Overall, 16.3, 31.2 and 52.5% of patients were classified as low- (score, 0–3), moderate (score, 4–5) and high-risk (score, ≥ 6), for developing a PTS. Within 24 months of the index DVT, 24.4% of the patients in the low-risk category developed a PTS, 38.4% in the moderate and 80.7% in the high-risk category. The prediction model showed good predictive accuracy (area under the curve, 0.77; 95% confidence interval, 0.71–0.82, calibration slope, 0.90 and Brier score, 0.20).

Conclusion This easy-to-use clinical prediction rule accurately identifies patients with DVT who are at high risk of developing PTS within 24 months who could potentially benefit from special educational or therapeutic measures to limit the risk of PTS.
Haematopoietic Stem Cell Transplantation in Children Shifts the Coagulation System towards a Pro-Coagulant State
Authors: Långström Satu , Koskenvuo Minna , Huttunen Pasi , Lassila Riitta , Taskinen Mervi , Ranta Susanna , Heikinheimo Markku , Mäkipernaa Anne
Published: June 2018

Coagulation system is disturbed by several mechanisms after allogeneic haematopoietic stem cell transplantation (HSCT). We evaluated the effect of HSCT on coagulation system by various conventional and investigational methods in 30 children and adolescents who received HSCT due to haematological malignancies. Pro-thrombin fragment 1 + 2, a specific measure of thrombin generation, and von Willebrand factor, a measure of endothelial activation, increased after conditioning treatment, and remained elevated until 3 months after HSCT (p < 0.05 for all comparisons to pre-conditioning treatment). D-dimer, a measure of fibrin turnover, was elevated from the second week onwards until 4 weeks after HSCT (p < 0.05). Endogenous thrombin potential was increased after conditioning, and at 2 weeks after HSCT (p < 0.05). Furthermore, the activities of acute phase reactants fibrinogen and coagulation factor VIII were increased (p < 0.05 for all comparisons to pre-conditioning treatment) from the first week onwards up to 3 weeks and 3 months after HSCT, respectively. Taken together, paediatric patients receiving HSCT demonstrate distinct and prolonged variations in the coagulation system towards a pro-coagulant state. This shift is of importance when estimating the risk of haemostatic and thrombotic complications in these children.
High performance Ge0.89Sn0.11 photodiodes for low-cost shortwave infrared imaging
Authors: Tran Huong , Pham Thach , Du Wei , Zhang Yang , Grant Perry C. , Grant Joshua M. , Sun Greg , Soref Richard A. , Margetis Joe , Tolle John , Li Baohua , Mortazavi Mansour , Yu Shui-Qing
Published: July 2018

Low-cost shortwave infrared detectors have great potential for emerging civilian night-vision applications. This paper reports the characteristics of Ge0.89Sn0.11 photodiodes monolithically grown on a Si substrate that holds great promise for those applications. At room temperature, the 500 μm diameter active area device demonstrated a longwave cutoff of 2.65 μm and a responsivity of 0.32 A/W at 2 μm, which corresponds to an external quantum efficiency of 20% without any contribution from the Ge buffer layer. The measured peak specific detectivity at 300 K and 77 K is 1.7 × 109 Jones and 4.3 × 109 Jones, respectively. The specific detectivity at 77 K is only one-order-of-magnitude lower than that of the market dominating extended-InGaAs photodiode. The detailed device analysis indicated that the 700-nm thick fully relaxed high-quality GeSn absorbing layer and the modified depletion region lead to the above-mentioned device performance.