bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction Of Stability Of Thromboplastin
Authors: Stevenson K J 
Published: July 2018

A new, rapid degradation method for predicting the stability of lyophilised extracts of tissue thromboplastin by accelerated oxygenation is described. This requires less time to complete and is more relevant to tissue thromboplastin age degradation than heat-accelerated methods previously advocated. Lipid oxidation is an important contributor to age-related change of thromboplastins. Although high teinperatures employed in heat degradation may increase oxidative processes in thromboplastin lipids, the protein component essential for procoagulant activity is also denatured.The practical application of the rapid oxygenation method as a technique for accelerated degradation of tissue thromboplastin reference preparations is described.
The Effect Of Different Activators And Thromboplastins On A Chromdgenic Aptt
Authors: Brandt J T , Triplett D A , Schaeffer J 
Published: July 2018

Four different activator/thromboplastin reagents (silica/rabbit brain cephalin, kaolin/ simian brain cephalin, ellagic acid/rabbit brain cephalin, and ellagic acid/bovine brain cephalin) were evaluated for use in a chromogenic activated partial thromboplastin time (APTT). Parallel determinations using the same reagents in a clotting APTT were made. Compared to the clotting APTT, the chromogenic APTT using ellagic acid activation showed much greater sensitivity to both in vivo and in vitro heparin. Silica activation in the chromogenic assay showed decreased sensitivity to in vivo and in vitro heparin compared to the clotting assay. The kaolin/simian brain cephalin reagent was relatively insensitive in both clotting and chromogenic assays. A significant difference between in vivo and in vitro heparin was noted with all of the reagents in both clotting and chromogenic assays.The chromogenic assays were more sensitive to the effect of vitamin K deficiency and coumadin administration than the corresponding clotting assays. Relative to the effect on the clotting APTT, the chromogenic assays were more sensitive to coumadin and vitamin K deficiency than to in vivo heparin.The results indicate that the chromogenic APTT is not equivalent to the clotting APTT. Distinct differences in sensitivity to heparin and coumadin exist between the two assay systems. There is a marked difference in response to different reagent systems in the chromogenic assay. These various effects need to be considered when designing chromogenic assays.
The Effects Of An Anticoagulant Phospholipase A2 On The Procoagulant Activity Of Phospholipids And Platelets
Authors: Cox A C 
Published: July 2018

Although phospholipids readily substitute for platelets in many in vitro blood coagulation tests, their participation in normal platelet procoagulant activity is uncertain. Phospholipase A2 (PLA2) from Naja nigricollis nigricollis venom, a known anticoagulant, blocked the enhancement of the rate of prothrombin conversion to thrombin by both phospholipids and platelets. The rate of inhibition of the phospholipid procoagulant activity by PLA2 was reduced by indomethacin, an inhibitor of PLA2. At concentrations of PLA2 which inhibited phospholipid procoagulant activity, conversion of purified prothrombin by factors Xa and Va without phospholipid was unaffected.Unactivated, washed platelets combined with coagulation factors II, Va and Xa initially produce thrombin at a slow rate before the platelets become activated but after this lag period the rate of thrombin generation increases. PLA2 added at the same time as the coagulation factors increased the lag period and decreased the rate of thrombin generation during and after the lag. Preincubation of platelets with PLA2 further decreased only the lag rate and this inhibition was partially blocked by 300 uM indomethacin. At a concentration of about one ng/ml, PLA2 reduced the post-lag thrombin generation rate of 3 × 10-9 platelets/ml in half but had no effect on platelet aggregation induced by thrombin, ADP or collagen.These results combined with the known specificity of PLA2 support the theory that phospholipids are involved in platelet procoagulant activity. Furthermore, the ineffectiveness of preincubating PLA2 with platelets on the post-lag procoagulant activity suggests that the phospholipids involved in this post-activation process become accessible during the lag period.
The Effects Of Platelets, Fibrinogen And Factor XIII In ‘Resonance-Thrombography’ (RTG)
Authors: Husar D , Hartert H 
Published: July 2018

The method of ‘Resonance-Thrombography’ was invented by H. Hartert in 1970 and is now introduced as a screening test for various bleeding disorders. The RTG-curve mainly depends on the number of platelets as well as platelet-function, amount of fibrinogen and factor XIII.A successful theoretical approach to describe this depen- dancy is given by means of a one-dimensional, linearized model of apparatus and coagulation process. The experimental results and the simulated curves agree within the experimental errors. The model further provides the possibility to derive time-constants and cross-linking-factors for the fibrinogen-polymerisation and the interaction of platelets with fibrin.
Intensity Of Therapeutic Range And Mean Anticoagulant Dosage Prescribed: An International Study
Authors: Poller L , Taberner D A 
Published: July 2018

It has been suggested that anticoagulant dosage requirements vary in different parts of the world. An international survey on anticoagulant dosage involving over 500 laboratories was performed employing a questionnaire on the mean daily anticoagulant dosage of 20 stabilised patients. Replies received show a considerable variation in dosage between countries.In order to further investigate the influence of the intensity of the therapeutic range on local dosage differences, participants were asked to assess a lyophilised human coumarin plasma sample. Most agreed that the plasma was adequately anticoagulated. However, laboratories finding the plasma overdosed were prescribing a lower mean anticoagulant dosage than those laboratories finding the plasma underdosed. This suggests that some of the differences in dosage between laboratories may be accounted for by the varying intensities of the therapeutic ranges used in the different countries.
Development Of A Fully Automated Functional Fibrinogen Assay
Authors: Siefring G E , Wehrly J A 
Published: July 2018

A fully automated method for the determination of functional fibrinogen has been developed for the Du Pont ‘aca’. The basis of the assay is the measurement of turbidity formation upon the addition of thrombin to the test plasma. The method can measure fibrinogen in the plasma of patients on heparin therapy and provides a stat result in eight minutes.The assay of fibrinogen is accomplished in a two-stage sequence. First, clot enhancing agents and a heparin neutralizing compound are added. Thrombin is added in the second step to catalyze fibrin formation, the rate of turbidity change being proportional to the fibrinogen concentration. Optimization of the assay under ‘aca’ conditions was accomplished through the use of multivariate response surface analysis. The analytical performance of the method was judged to be acceptable based on precision, interference, and correlation studies. The range of the method is 40-1000 mg/dl fibrinogen. This ‘aca’ method represents the first fully automated determination of functional fibrinogen.
Fibrinogen In Liver Cirrhosis. Lack Of Correlation Between Soluble Fibrin Monomer Complexes And Fibrinopeptide A Levels
Authors: Coccheri S , Mannucci P M , Palareti G , Cattaneo M , Poggi M , Vigand S 
Published: July 2018

In this collaborative study we have investigated the coexistence of two different markers of fibrinogen to fibrin conversion in 19 patients with liver cirrhosis, confirmed with liver biopsy, and classified according to standardized criteria into 11 moderate and 8 severe cases. Sepharose gel filtration of plasma allowed separation of fibrinogen-like material (FLM) into high m.w. (HMWF), peak, and low m.w. (LMWF) fractions, quantitated as percent (w/w) of the total FLM eluted. FPA was assayed radioimmunologically.HMWF was markedly increased in the whole group of cirrhotics (av ± SD 10.4% ± 2.77) , and in both moderate and severe patients, vs controls (6.9% ± 1.39; n=16; p < 0.01 for each comparison). LMWF was moderately increased in patients (6.8% ± l.84) vs controls (5.3% ± 1.35; p < 0.05).FPA levels (controls: median (m) ng/ml 2.2; m confidence limits (mcl) 1.4-2.5; range (r) < 0.6 to 4.1) showed an increase in cirrhotics (m 2.8; mcl 2.64-3.35, r<0.6 to 94) but the difference was not statistically significant using a non-parametric test. However, in 6 out of 19 patients FPA values exceeded av ± 2 SD of controls (av ± SD 2.05 ± 1.15). No significant correlations were found between FPA and HMWF or LMWF levels.The lack of correlation between FPA and HMWF although possibly related to half-life differences, suggests that, besides thrombin effect, other mechanisms for excess formation and/or accumulation of HMWF, as dysproteinaemia, dys- fibrinogenaemia, or impaired clearance, should be considered.
Functional And Biochemical Studies On A Case Of Dysfibrinogenemia (Fibrinogen Genova)
Authors: Hassan H J , Orlando M , Mori P G , Tonini G , Casalbore P , Sarti A , Boeri E , Tentori L 
Published: July 2018

Fibrinogen Genova was recognized in an Italian family. The propositus had no bleeding tendency and diagnosis was performed on the basis of prolonged prothrombin, thrombin and reptilase times of plasma, associated with normal fibrinogen levels. The purified fibrinogen showed an inhibitory effect on the clotting times of the normal one.Functional studies performed on purified fibrinogen revealed that the clottability was reduced (74%, normal 88-94%) and the thrombin polymerization curve was abnormal due to a delayed fibrin monomers aggregation. The fibrino- peptides release was normal.Analysis of plasmic derivatives carried out by both SDS gel electrophoresis (5 and 9%) and immunological methods showed some differences compared with normal fibrinogen. The fibrinogen chains were studied on isoelectric focusing slabs and SDS gel electrophoresis. Preliminary results did not reveal any difference with normal.
Fibrinogen Binding Is Independent of an Increase in Intracellular Calcium Concentration in Thrombin Degranulated Platelets
Authors: Pulcinelli Fabio M , Daniel James L , Riondino Silvia , Gazzaniga Pier Paolo , Salganicoff Leon 
Published: July 2018

SummaryIn a suspension of thrombin degranulated platelets (TDP), ADP and epinephrine can induce platelet aggregation, whereas the synthetic agonist of the thromboxane/endoperoxide receptor U46619 causes only shape change. However, U46619 can enhance platelet aggregation induced by ADP and epinephrine. In this paper, we have measured fibrinogen binding in relation to phospholipase C(PLC) activation and calcium mobilization in TDP activated by ADP, epinephrine and U46619.ADP caused fibrinogen binding in TDP but neither activated PLC nor caused a calcium mobilization. The requirement for ADP in inducing exposure of fibrinogen binding sites was not absolute since the combination of epinephrine and U46619 produced an increase in fibrinogen binding. U46619 caused significant PLC activation and cytosolic calcium release but not fibrinogen binding. These results suggest that in TDP the exposure of fibrinogen binding sites, after agonist activation, is independent of both PLC activation and calcium mobilization.
Estrogens Reduce Plasma Histidine-rich Glycoprotein (HRG) Levels in a Dose-dependent Way
Authors: Hennis B C , Boomsma D I , Fijnvandraat K , Leuven J A Gevers , Peters M , Kluft C 
Published: July 2018

SummaryPlasma levels of histidine-rich glycoprotein (HRG) were investigated in three groups of women receiving a different dose of estrogens. First, the effect of low-dose estrogen was studied in a group of 83 postmenopausal women who were treated with 0.625 mg conjugated estrogens (CE). No significant change from baseline levels was found at the end of cycle 3 and cycle 13. Secondly, in 15 mothers and 23 daughters using oral contraceptives (OC) containing 30-50 fig ethinyl estradiol (EE) daily the mean HRG level was 14% and 24% lower than in a group of 144 mothers and 134 daughters not taking oral contraceptives, respectively (p < 0.05). Finally, in 11 excessively tall prepuberal girls who received 300 μg EE daily to reduce their final height the mean plasma HRG levels were decreased by 68% (p < 0.005). The effect of proges- togens administered during low-dose and high-dose estrogen therapy appeared to be minor.The results from these three studies indicate that estrogens reduce plasma HRG levels in a dose-dependent way.
Targeting Platelets Containing Electro-encapsulated lloprost to Balloon Injured Aorta in Rats
Authors: Crawford N , Chajara A , Pfliegler G , Gamal B EI , Brewer L , Capron L 
Published: July 2018

SummaryDrugs can be electro-encapsulated within platelets and targeted to damaged blood vessels by exploiting the platelet’s natural haemostatic properties to adhere to collagen and other vessel wall constituents revealed by injury. A rat aorta balloon angioplasty model has been used to study the effect on platelet deposition of giving iloprost loaded platelets i.v. during the balloon injury. After labelling the circulating platelets with 111-Indium before balloon injury, time course studies showed maximum platelet deposition on the injured aorta occurred at about 1 h post-injury and the deposition remained stable over the next 2-3 h. When iloprost-loaded platelets were given i.v. during injury and the circulating platelet pool labelled with 111-Indium 30 min later, platelet deposition, measured at 2 h postinjury, was substantially and significantly reduced compared with control platelet treatment. Some antiproliferative effects of iloprost-loaded platelets given i.v. during injury have also been observed. Whereas the incorporation of [3H]-thymidine into aorta intima-media DNA at 3 days post injury was 62-fold higher in balloon injured rats than in control sham operated rats, thymidine incorporation into intima/media of rats which had received iloprost loaded platelets during injury was reduced as compared with rats subjected only to the injury procedure. The reduction was only of near significance, however, but at 14 days after injury the total DNA content of the aorta intima/media of rats given iloprost loaded platelets during injury was significantly reduced. Although iloprost loaded platelets can clearly inhibit excessive platelet deposition, other encapsulated agents may have greater anti-proliferative effects. These studies have shown that drug loaded platelets can be targeted to injured arteries, where they may be retained as depots for local release. We believe this novel drug delivery protocol may have therapeutic potential in reducing the incidence of occlusion and restenosis after angioplasty and thrombolysis treatment. Electro-encapsulation of drugs into platelets is a simple procedure and, using autologous and fully biocompatible and biodegradable platelets as delivery vehicles, might overcome some of the immunological and toxicological problems which have been encountered with other delivery vectors such as liposomes, microbeads, synthetic microcapsules and antibodies.
Diagnosis of Subtype 2B von Willebrand Disease in a Patient with 2A Phenotype of Plasma von Willebrand Factor
Authors: Gaucher Christine , de Romeuf Christophe , Rauïs-Morret Michéle , Corazza Francis , Fondu Pierre , Mazurier Claudine 
Published: July 2018

SummaryType 2A of von Willebrand disease refers to qualitative variants with decreased platelet dependent function that is associated with the absence of high molecular weight forms of von Willebrand factor (vWF) multimers. Type 2B refers to qualitative variants with increased affinity for platelet glycoprotein lb. In this report we describe the study of a patient who has been previously diagnosed as having subtype 2A von Willebrand disease (vWD), because she had no heightened ristocetin-induced platelet aggregation, no large and intermediate molecular weight von Willebrand factor (vWF) multimers in plasma, and no increase in plasma vWF capacity to bind to normal platelets in the presence of low ristocetin concentrations. The DNA sequencing of the 3’ part of the exon 28 of the vWF gene where most of the subtype 2A mutations have already been identified, did not detect any nucleotide change. At variance, a G to A transition changing the encoded amino acid residue from Val 553 to Met in mature vWF, was found in the 5’ part of this exon. This mutation which has already been found in several unrelated families with 2B vWD and the increased binding of the patient platelet vWF on normal platelets in the presence of low ristocetin concentrations provide evidence for subtype 2B vWD. This study thus illustrates the importance of the molecular characterization of patients in the correct diagnosis and classification of type 2 vWD.
Genetic Determinants of Plasma Factor VII Activity in the Japanese
Authors: Kario Kazuomi , Narita Naoko , Matsuo Takefumi , Kayaba Kazunori , Tsutsumi Akisumi , Matsuo Masafumi , Miyata Toshiyuki , Shimada Kazuyuki 
Published: July 2018

SummaryWe investigated the frequency of the factor VII Gln353 (FVII Gln353) allele in Japan, where coronary artery disease is much less common and factor VII coagulant activity (FVIIc) is lower than in Western countries. Japanese males (n = 144) aged 40-59 years living in 2 different districts were studied, and the FVIIc and activated factor VII (FVIIa) levels were measured with human (FVIIa Hum) and bovine soluble tissue factor (FVIIa Bov). The frequency of the FVII Gln353 allele in the 2 districts was 0.026 and 0.052 (combined: 0.034), which was about one third of that in a European population. Thus, the lower FVIIc level in Japanese is not due to the effect of FVII Gln353 allele. Ten individuals with the Gln353 allele showed a 39% decrease of FVIIa Hum levels and a 29 % decrease of the FVIIa Bov level compared with 134 individuals homozygous for the FVII Arg353 allele. These decreases of FVIIa were greater than the decrease of FVIIc (17%), suggesting that FVII Gln353 may be difficult to activate in vivo. The marked decrease of FVIIa levels in individuals with the FVII Gln353 allele suggests that they are genetically protected against cardiovascular disease irrespective of ethnic background, by virtue of their decreased FVIIa level.
Genetic Determination of Coagulation Factor VIIc Levels among Healthy Middle-aged Women
Authors: Meilahn Elaine , Ferrell Robert , Kiss Joseph , Temple Anne , Green Fiona , Humphries Steve , Kuller Lewis 
Published: July 2018

SummaryA recent study (1) reported variation among men in clotting factor Vile levels is associated with a genetic polymorphism detected by the restriction enzyme Msp I. The present study determined the Msp I genotype (Arg353, Gln353 alleles) for 189 women (mean age 53) who were subjects in the Healthy Women Study, a population study of CHD risk factor change at menopause. Women with the Arg/Arg genotype (n = 147) had an 16% higher (geometric) mean FVIIc level than those with the Arg/Gln (n = 41) genotype (1.21 vs 1.04 U/ml, p<0.01), while the one subject with the Gln/Gln genotype had an FVIIc level of 1.00 U/ml. These results are consistent with those previously found in healthy men (1). In addition, women carrying the Gin allele did not exhibit the elevation in FVIIc with menopause and use of hormone therapy found among those with the Arg allele, suggesting that genotype may modify the observed rise in factor Vile at menopause. Possibly because of the small sample size this interaction did not reach conventional levels of statistical significance. Results of multiple linear regression analyses controlling for age, hormone use, obesity, (In) triglyceride levels, and family history of CHD found FVIIc levels to be significantly (p<0.001) related to genotype. Thus, genotype appears to be a major determinant of FVIIc levels among women.
Growth Hormone Deficiency Impairs Blood Clotting and Reduces Factor VII Coagulant Activity in Rat
Authors: Sävendahl L S G , Grankvist K , Engström K G 
Published: July 2018

SummaryTo investigate pituitary effects on the vitamin K-dependent coagulation factors, female rats were hypophysectomized (hypox) and treated with growth hormone (GH), cortisone, thyroxine, vitamin K, or saline. After 11 days of treatment, the prothrombin time, platelet count, and factors II, VII, IX, and X were determined. The prothrombin time was 52.9 ± 1.2% for control rats and 39.1 ± 0.8% for hypox rats (mean ± SEM; p<0.001). All factors decreased after hypophysectomy, reaching significance for factor VII (from 264 ± 23% to 131 ± 9%; p <0.001) and factor IX (from 28.4 ± 2.2% to 17.1 ± 2.5%; p<0.01) while the platelet count was unaffected. When hypox rats were treated with GH, the prothrombin time increased to 50.9 ± 1.0% (p <0.001) and factor VII to 299 ± 10% (p<0.001). Factor II, IX, and X were slightly increased after GH substitution but not after cortisone, thyroxine, or vitamin K treatment. To summarize, GH is of importance for normal hemostasis in the female rat.
Thromboplastic Activity of Split Products of Phosphatidyl Ethanolamine
Authors: Slotta Karl H. , Deutsch Erwin 
Published: July 2018

SummaryPure synthetic L-α-(dioleoyl) PE is inactive as a platelet substitute in the thromboplastin generation test, even when in a stable suspension. Under humid conditions it is partly hydrolyzed. Among the split products lyso PE and phosphoryl ethanolamine were identified. The resulting mixture has thromboplastin generating activity. This thromboplastin is formed slowly, but it is stable over longer periods of time than thromboplastins formed from PS + PC or PS + PE mixtures, which are rapidly generated and lose activity faster.