bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation Of Soluble Fibrin By Shear Rate
Authors: Puryear H A , Clark H G , Sellers J P 
Published: July 2018

The reaction of fibrinogen and thrombin has been carried out in a Couette-flow apparatus over a range of rates of shear from 0-150 s-1 and at pH’s from 6.4 - 6.8. A minimum is found in the rate of formation of insoluble fibrin at shear rates of 30-60 s-1 (well within the physiological range). The position of the minimum is determined by the concentration of reactants. Rate decreases of up to 50% have been observed. Hirudin quenching of thrombin activity shows that formation of fibrin monomer is unaffected by shear rate, hence the effect is due to changes in fibrin aggregation. The same sort of minimum has been observed when a solution of fibrin monomer is made to precipitate by altering pH and ionic strength in shear fields. The release of B-peptide as analyzed by HPLC appears to be less at the minimum.These results are interpreted as resulting from a lowering of the growth of fibrin particles at low shear rate and an increase in nucleation of particles at higher shear rates.
An Assessment Of An Amidolytic Assay For Factor VII In The Laboratory Control Of Oral Anticoagulants
Authors: Bodzenta A , Thomson Jean M , Latallo Z S 
Published: July 2018

An amidolytic assay for factor VII, modified from the method of Seligsohn et al (1978), has been compared with the results of the prothrombin time using British Comparative Thromboplastin, Thronbotest and a clotting assay for factor VII. In ‘long-term’ oral anticoagulant administration agreement with the conventional methods was good and better than in our previous study when amidolytic assays for factors II and X respectively were studied (Latallo et al 1981). The method appeared to be reasonably specific for factor VII.On the present evidence the chromogenic assay for factor VII offers a limited but apparently dependable guide to dosage but it is elaborate to perform and difficult to standardise. The main limiting factor for its routine application is the need to prepare a purified factor X extract.
Determination Of Thrombo Elastogram And Raby’S Transfer Test In Acute Myocardial Infarction
Authors: Rodzynek J J , Schoenfeld P L , Léautaud P , Martin T , Wettendorff P , Delcourt A 
Published: July 2018

Citrated whole blood thrombo elastogram (TEG) and its various parameters (r, k, am, IPT) and Raby’s transfer test (RTT) were performed in 52 healthy volunteers acting as normal controls (N), in 213 consecutive patients admitted in a general hospital for pathologies other than cardiac ischemia (group I), in 35 consecutive admissions for impending infarction without detectable myocardial necrosis (group II) and in 73 consecutive admissions for acute myocardial infarction, proved by EKG and specific enzyme determinations (group III).In conclusion: TEG is a poorly sensitive as well as poor specific indicator of unstable coronary insufficiency, with or without necrosis. RTT was found positive in 8.5% of unstable angina without demonstable myocardial necrosis, and in contrast in 94.5% of demonstrated acute myocardial infarction. Student’s test on mean values showed a highly significant difference (P<0.001). Further investigation is in progress to evaluate the usefulness of RTT for the early detection of myocardial necrosis.
Antithrombin III In Chronic Liver Diseases
Authors: Rak K , Boda Z , Misz M , Beck P 
Published: July 2018

One of the most constant abnormal laboratory results in chronic liver diseases is the low antithrombin III /AT-III/ acitivity measured in a properly sensitive system. Two functional assays have been used in our laboratory: /a/ coagulation test based on the progressive neutralization of thrombin with clotting time determinations in the presence of small amount of heparin and without it; results were expressed as plasma AT-III index or PAT-value, and /b/ amidolytic method on synthetic chromogenic substrate.Results of the last years can be summarized as follows: /1/ the measurement of AT-III in liver diseases/more than 300 cases, mostly cirrhosis/ is of diagnostic significance: a high index, hence a low AT-III activity, particularly in a system containing heparinized plasma is much more characteristic in cases of liver cirrhosis than results of other conventional clotting tests /prothrombin time, partial thromboplastin time, plasma fibrinogen and FDP level/; /2/ the observations may have theoretical importance, furnishing additional data on the pathophysiological role of AT-III and providing the first and strong evidence for the adverse effect of heparin in thrombin-antithrombin interaction. The level of this natural anticoagulant synthetized in liver may be reduced by increased consumption accompanying disseminated intravascular coagulation. Though it is not frequent, it must be taken into consideration, first of all in active chronic hepatitis.
AT-III Diagnostic And Prognostic Value In Hepatic Disease
Authors: Monreal M , Rodriguez R , Vañentin P , Monasterio J 
Published: July 2018

AT-III activity has been evaluated in 675 patients with different kinds of hepatic disease.In 300 patients with hepatic chronic disease, AT-III levels showed a good correlation with prothrombin time as well as same diagnostic value. Survival in this group of patients was directly related to AT-III values.In 75 patients with acute liver disease, persistent low AT-III values correlated with clinical evolution of fulminans hepatitis.In 200 patients with cholestatic syndrome, evaluation of AT-III levels had no value for differential diagnosis of neither obstacle’s localization nor benign or neoplastic process.In 100 patients, suffering from cancer, without and with hepatic metastasis, AT-III values decreased in terminal states only.
Increased Anti-Xa Bioavailability Of Heparin By Jet Injection
Authors: Arleth D , Harenberg J , Mattes K , Zimmermann R 
Published: July 2018

To improve the standardisation and to diminish the time requirement of the subcutaneous (s.c.) application of low dose heparin a semiautomatic injection pistol was compared to the commonly used one way syringe.The precision of the injected amount of heparin was significantly higher by jet injection (VK 1% vs 4%). The time required for one injection was 110 sec by jet injection and 215 sec by the one way syringe including all preparation times.7500 USP heparin were injected into 10 volunteers by both techniques at weekly intervals randomly. The pharmacodynamic effects were controlled on the factor Ila activity (thrombin clotting time), aPTT and factor Xa activity (chromogenic substrate S2222) for 10 hrs by 12 blood samples. No differences were observed on the factor IIa activity and aPTT between the two injection techniques. The anti- Xa-activity of the heparin applicated by jet injection was significantly higher (maximal effect after 3 hrs: 0.24 vs 0.20 USP heparin/ml plasma, p < 0.01, area under the time related curve p < 0.01).The data indicate, that the bioavailability of heparin for factor Xa is even higher after the s.c. application by the jet injection method than after the one way syringe technique. These differences should be considered, when an improvement of the prophylaxis of thromboembolic diseases is discussed.
The Clinical Importance Of Heparin Assays In Plasma. Critical Aspects In Antixa Techniques
Authors: Giuliani R , Szwarcer E , Aquino E Martinez 
Published: July 2018

Different clotting assays for heparin measurement in plasma, based on AntiXa potentiating effect were studied, to determine the causes of variability in results in the currently used techniques. A modified 2 steps technique was also used (step I:0.1ml test plasma (PPP)+0.3ml buffer+0.1 mlXa.2' incubation at 37°C:step II: 0.1ml of step I mixtu- re+0.2ml of substrate plasma+CaCl 0.1ml. (Xa and VII-X defficitary bo vine plasma+cefalin: Thame, Oxon. Triz-Mal buffer,ionic strength 0.15, PH7.5 and CaCl 0.025M). Three modifications of the technique were used, varying test plasma treatment: a) using oxalated PPP, adsorbed with BaS04 b) like in a) plus heating it at 56°C 15'; c)using untreated plasma.Using a) assay (K dependant factors absent), straight regression lines and low variability of results was obtained, relating heparin concentrations to clotting times;usinga b) it was seen that heat diminishes AntiXa reactivity to hepa- riny using c)high variability in results was obtained. To show the difficulties in monitoring heparin in cases where Iox AntiXa concentrations, variable amounts of clotting factors and differents amounts of heparin might be present, a pool of normal plasmas, a normal plasma, and a cirrhotic one were compared, using the modified AntiXa assay in its 3 variations. Wide differences in results may be obtained while studying the cirrhotic plasma, using techniques that can vary AntiXa reactivity, or mask the real heparin in plasma, because of its variable content in K dependant factors.We did not find a way of clearing test plasma of K dependant factors when heparin is in it without altering heparin concentration or AntiXa reactivity.Thus, it is suggested, for clinical monitoring of the drug to use heated or untreated plasma, and to compare results with the same individuals plasma, studied under equal conditions, and not with a pool of normal plasmas, as common ly suggested.
Platelet Adhesion to Collagen Is Inhibited by Adenosine Diphosphate but Unaffected by Cell Shape
Authors: Meyer F A , Weisman Z , Frojmovic M M 
Published: July 2018

SummaryThe effect of limited platelet activation, in the absence of aggregation, on the subsequent ability of rabbit platelets to adhere to collagen was studied in vitro. ADP at concentrations that initiate shape change (>0.01. μM) reduce platelet adhesion. Shape change per se however, was not responsible since the time-dependence of the effect of ADP on shape change and adhesion is different and ADP induces reduced adhesion even when shape change is prevented with PGE1 or fixatives. Platelets shape changed without ADP addition, e. g. by chilling or by low ethanol concentrations, display normal adhesion to collagenIt appears likely that upon binding to the platelet ADP induces a time-dependent alteration in the membrane, akin to refractoriness, that influences binding sites for collagen. The effect of ADP can be blocked by prior addition of AMP but not if the additions are reversed. The implications of the present findings for platelet adhesion studies are discussed.
Factor VIII : C and Factor VIII R: Ag in Argentine Hemorrhagic Fever
Authors: Molinas Felisa C , Maiztegui Julio I 
Published: July 2018

SummaryFactor VIII procoagulant activity (F VIII: C) and factor VIII related antigen (F VIII R: Ag) were investigated in 35 patients with Argentine hemorrhagic fever. Since the results obtained in the three clinical forms of the disease were not significantly different, they were tabulated altogether. F VIII: C was low in early stages of the disease but increased progressively in later days (days 5–6:0.54 ± 0.10 I.U./ml; days 13–14:0.95 ± 0.13 I.U./ml). In contrst, the levels of F VIII R: Ag were high all along the disease and they returned to normal values during the convalescence period (days 5–6; 2.58 ± 0.54 I.U./ml; day 30: 1.30 ± 0.14 I.U./ml). The levels of F VIII R: Ag were similar in samples drawn before (11 cases) or after (10 cases) the treatment with immune plasma infusion. Plasma samples from 12 patients were studied by two-dimensional immunelectrophoresis. The only abnormality found was increased height of the immune precipitation arc.
Prolonged Thromboprophylaxis Following Hip Replacement Surgery – Results of a Double-blind, Prospective, Randomised, Placebo-controlled Study with Dalteparin (Fragmin®)
Authors: Dahl O E , Andreassen G , Aspelin T , Müller C , Mathiesen P , Nyhus S , Abdelnoor M , Solhaug J-H , Arnesen H 
Published: July 2018

SummaryDiscontinuation of thromboprophylaxis a few days after surgery may unmask delayed hypercoagulability and contribute to late formation of deep venous thrombosis (DVT). To investigate whether thromboprophylaxis should be prolonged beyond the hospital stay, a prospective, double-blind randomised study was conducted in 308 patients. All patients received initial thromboprophylaxis with dalteparin, dextran and graded elastic stockings. On day 7, patients were randomised to receive dalteparin (Fragmin®) 5000IU once daily, or placebo, for 4 weeks. All patients were subjected to bilateral venography, perfusion ventilation scintigraphy and chest X-ray on days 7 and 35. Patients with venographically verified proximal DVT on day 7 were withdrawn from the randomised study to receive anticoagulant treatment. The overall prevalence of DVT on day 7 was 15.9%. On day 35, the prevalence of DVT was 31.7% in placebo-treated patients compared with 19.3% in dalteparin-treated patients (p = 0.034). The incidence of DVT from day 7 to day 35 was 25.8% in the placebo-treated group versus 11.8% in the dalteparin-treated group (p = 0.017). The incidence of symptomatic pulmonary embolism (PE) from day 7 to day 35 was 2.8% in the placebo-treated group compared with zero in the dalteparin-treated group. This included one patient who died from PE. No patients experienced serious complications related to the injections of dalteparin or placebo. This study shows that prolonged thromboprophylaxis with dalteparin, 5000 IU, once daily for 35 days significantly reduces the frequency of DVT and should be recommended for 5 weeks after hip replacement surgery.
In Vitro Clot Lysis as a Potential Indicator of Thrombus Resistance to Fibrinolysis – Study in Healthy Subjects and Correlation with Blood Fibrinolytic Parameters
Authors: Colucci Mario , Scopece Silvia , Gelato Antonio V , Dimonte Donato , Semeraro Nicola 
Published: July 2018

SummaryUsing an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in 103 healthy donors. 125I-fibrin labelled blood clots were submersed in autologous plasma, supplemented with 500 ng/ml of rt-PA or solvent, and the degree of lysis was determined after 3 h of incubation at 37° C. Baseline plasma levels of t-PA, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-anti-plasmin, fibrinogen, lipoprotein (a), thrombomodulin and von Willebrand factor as well as platelet and leukocyte count and clot retraction were also determined in each donor. rt-PA-induced clot lysis varied over a wide range (28-75%) and was significantly related to endogenous t-PA, PAI-1, plasminogen (p <0.001) and age (p <0.01). Multivariate analysis indicated that both PAI-1 antigen and plasminogen independently predicted low response to rt-PA. Surprisingly, however, not only PAI-1 but also plasminogen was negatively correlated with rt-PA-ginduced clot lysis. The observation that neutralization of PAI-1 by specific antibodies, both in plasma and within the clot, did not potentiate clot lysis indicates that the inhibitor, including the platelet-derived form, is insufficient to attenuate the thrombolytic activity of a pharmacological concentration of rt-PA and that its elevation, similarly to the elevation of plasminogen, is not the cause of clot resistance but rather a coincident finding. It is concluded that the in vitro response of blood clots to rt-PA is poorly influenced by the physiological variations of the examined parameters and that factors other than those evaluated in this study interfere with clot dissolution by rt-PA. In vitro clot lysis test might help to identify patients who may be resistant to thrombolytic therapy.
Erythropoietin Potentiates Thrombus Development in a Canine Arterio-Venous Shunt Model
Authors: Wolf Roman F , Gilmore Laura S , Friese Paul , Downs Tamyra , Burstein Samuel A , Dale George L 
Published: July 2018

SummaryErythropoietin (EPO) has been previously shown to affect platelet as well as red cell production. In addition, recent studies demonstrated that platelets from EPO-treated dogs are hyperreactive towards thrombin when compared to age-matched, control platelets. This report extends these observations by quantitating the thrombogenic potential of EPO in dogs. Dogs with arterio-venous (A-V) shunts received 100 U EPO/kg/day for 6 days, and thrombogenicity was serially monitored by insertion of a thrombotic surface into the A-V shunt. The resulting experimental thrombi were analyzed for platelet and erythrocyte content after formalin-fixation and chymotrypsin digestion, a technique which allows non-isotopic quantitation of cellular components. By day 5 of EPO-administration all animals demonstrated a significant increase in platelet and red cell content of the experimental thrombi; the average increase in platelet number was 2.94 ±0.12 fold (mean ± 1 SE; n = 3; p = 0.006) above baseline while that for red cells was 2.46 ±0.18 fold above baseline (p = 0.023). After cessation of EPO, thrombogenicity returned to normal. During EPO-treatment, the percentage of thiazole orange-positive (TO+) platelets increased significantly to 17.2 ± 1.6% (mean ± 1 SE; n = 3) on day 5 compared to a pre-treatment level of 8.5 ± 0.9% (p = 0.029). Although the percentage of TO+ erythrocytes also increased during the short course of EPO administration, the change was not significant. Despite the increases in TO+ cells, total platelet and erythrocyte counts did not change significantly within the time frame of these experiments. Fibrin/fibrinogen content of the experimental thrombi was unaltered with EPO-treatment. These data demonstrate that human EPO is pro-thrombotic in dogs and, in conjunction with earlier studies, suggest that hyperreactive platelets may be responsible for the potentiated thrombogenicity.
Factor XIII Deficiency due to a Leu660Pro Mutation in the Factor XIII Subunit-a Gene in Three Unrelated Palestinian Arab Families
Authors: Inbal Aida , Yee Vivien C , Kornbrot Nurit , Zivelin Ariella , Brenner Benjamin , Seligsohn Uri 
Published: July 2018

SummaryIn this report we describe the molecular basis of FXIII a-subunit deficiency in three unrelated Palestinian Arab families. In three patients representing each family two substitutions were identified in exon 14 on both alleles: C to G change resulting in a Gln651Glu substitution (a previously described polymorphism) and a T to C transition causing Leu660Pro substitution. The latter is a new mutation which creates a restriction site for FnuDII enzyme. Restriction analysis performed in members of the three families clearly distinguished between severely affected patients, obligate carriers and unaffected subjects. A population survey failed to detect the mutation among 250 Jewish individuals but did detect two heterozygotes among 300 Arabs suggesting a 0.0033 frequency for the Pro660 allele in this population. In two out of the three families the Pro660 allele was linked to allele 5 of the 5’ short tandem repeat polymorphism within the FXIII a-subunit gene suggesting that the mutation might have occurred at least twice. cDNA obtained from mRNA isolated from patients’ platelets and monocytes appeared similar in size to that of normal control indicating that the Leu660Pro mutation does not affect mRNA synthesis. Computer modeling based on cristallographic studies of the a-subunit of factor XIII predicted that the mutant protein is expected to misfold into a structure which is either unstable or susceptible to degradation.
The Stability of Factor VIII in Heparinized Plasma
Authors: Krachmalnicoff A , Thomas D P 
Published: July 2018

SummaryWe studied the stability for 24 hr of factor VIII: C and factor Vm C:Ag in plasma collected in citrate, EDTA or heparin, and confirmed the previously reported two-phase decay of factor VIII:C in plasma when calcium ions have been chelated. We observed that plasma factor VIII:C is remarkably stable at 22° C (±2°) when normal calcium ion concentrations are maintained. The loss of activity of factor VIII:C between one and 24 hr after blood collection was on average only 0.5% per hr for heparinized plasma. There was also an apparent loss of factor VIII C:Ag in plasma where calcium ions had been removed, compared with factor VIII C:Ag in heparinized plasma. However, a comparison of one-site and two-site assays suggested that calcium chelating agents may lead to factor VIII C:Ag levels being under-estimated when one-site fluid-phase assays are employed.To confirm the action of calcium ions in maintaining factor VIII:C stability, we carried out a series of experiments where calcium chloride was added four hr after blood collection to plasma anticoagulated by a mixture of citrate plus heparin; we observed total recovery of factor VIII:C activity within four hr.The stability of factor VIII:C, even at room temperature, in the presence of physiological calcium ion concentrations has implications for manufacturers of factor VIH concentrates and cryo-precipitates.
Direct Analysis of Plasma Fibrinogen-Derived Fibrinopeptides by High Performance Liquid Chromatography: Investigation of Aα-Chain N-Terminal Heterogeneity
Authors: Southan Christopher , Thompson Elizabeth , Lane David A 
Published: July 2018

SummaryFibrinopeptide A (FPA), released from the fibrinogen Aa-chain by thrombin, can be resolved by high-performance liquid chromatography (HPLC) into three forms, the intact peptide (A), a modified peptide phosphorylated at the serine in position 3 (AP), and an N-terminally degraded form (AY). A new method has been developed, using HPLC, that allows direct measurement of the proportions of AP, A, and AY released by thrombin from fibrinogen in plasma samples of 200 ul or less. The method was used to examine variations in the proportions of AP and AY expressed as a % of total FPA in a number of patient and control groups. The mean percentages of AP and AY of plasma fibrinogen were found to be 21.7 and 14.2%, respectively, in normal laboratory controls. In older, apparently normal, individuals these figures were 27.0 and 15.5%, respectively. Cord plasma exhibited very high AP and slightly reduced AY levels (41.6 and 12.4%, respectively) compared with normal adults. Patients with liver failure had low AP levels and high AY levels (11.6 and 21.1%, respectively). Patients, recovering from major surgery or acute thrombotic stroke showed an acute-phase rise in fibrinogen level that was accompanied by an increase in AP and variable reduction in AY. Incubation of heparinized whole blood for 8 days in vitro demonstrated a gradual decrease in the proportion of AP and increase in AY of plasma fibrinogen. These results provide some support for the idea that an increased “aging” of fibrinogen in the circulation may result in a decrease in the AP content of fibrinogen accompanied by a more variable increase in AY.
A mean field view of the landscape of two-layer neural networks
Authors: Mei Song , Montanari Andrea , Nguyen Phan-Minh 
Published: July 2018

Significance
Multilayer neural networks have proven extremely successful in a variety of tasks, from image classification to robotics. However, the reasons for this practical success and its precise domain of applicability are unknown. Learning a neural network from data requires solving a complex optimization problem with millions of variables. This is done by stochastic gradient descent (SGD) algorithms. We study the case of two-layer networks and derive a compact description of the SGD dynamics in terms of a limiting partial differential equation. Among other consequences, this shows that SGD dynamics does not become more complex when the network size increases.