bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapeseed Oil and Sunflower Oil Diets Enhance Platelet In Vitro Aggregation and Thromboxane Production in Healthy Men when Compared with Milk Fat or Habitual Diets
Authors: Mutanen Marja , Freese Riitta , Valsta Liisa M , Ahola Irma , Ahlström Antti 
Published: July 2018

SummaryIn this highly controlled trial, 26 normolipidemic men (average age 28 years, range 18 to 60) were fed a baseline diet high in milk fat (MF) (fat 36% of energy, saturates 19%, monounsaturates 11%, polyunsaturates 4%), followed by a diet high in sunflower oil (SO) (fat 38% of energy, saturates 13%, monounsaturates 10%, polyunsaturates 13%) and another diet high in low erucic-acid rapeseed oil (RO) (fat 38% of energy, saturates 12%, monounsaturates 16%, polyunsaturates 8%). All diets were mixed natural diets with the same cholesterol contents. The baseline milk fat diet was given for 14 days and the oil diets for 24 days in a blind cross-over design. The platelet in vitro aggregation (slope %/min) induced by 1, 2 and 3 pM ADP and collagen (25 pg/ml PRP) was highly significantly (p <0.001) increased after both oil diets when compared with the results from the milk fat diet. The aggregation pattern determined by threshold collagen concentration confirmed increased collagen sensitivity of the platelets after the rapeseed oil diet (p <0.001). The enhancement of platelet aggregation was associated with increased in vitro platelet thromboxane production after the oil diets vs. the milk fat diet (p <0.05 after the sunflower oil diet and p <0.001 after the rapeseed oil diet).
Report of Scientific and Standardization Subcommittee on Neonatal Hemostasis Diagnosis and Treatment of Neonatal Thrombosis
Authors: Schmidt Barbara , Andrew Maureen 
Published: July 2018

SummaryThrombotic disease in newborn infants is common and serious enough to require effective and safe intervention (1). Flowever, neonatal thrombosis is also sufficiently rare to prompt anecdotal observations rather than controlled clinical trials. While there is an abundance of case reports in the pediatric literature, there is a conspicuous paucity of well-designed studies to guide clinical decision-making (2).The Subcommittee on Neonatal Hemostasis of the Scientific and Standardization Committee recognizes the need for multicenter controlled clinical trials to determine the risks and benefits of different treatment modalities for neonatal thrombosis. Until such data becomes available, the following recommendations may assist clinicians in the management of newborn infants with thrombotic disease. These recommendations were endorsed by the Subcommittee after careful review of the literature and several consensus meetings.
Bacterial Expression of Biologically Active High Molecular Weight Kininogen Light Chain
Authors: Kunapuli Satya P , DeLa Cadena Raul A , Colman Robert W 
Published: July 2018

SummaryHuman high molecular weight kininogen (HK), a single chain plasma glycoprotein, serves as a cofactor in the contact system of blood coagulation. After cleavage by human plasma kallikrein, the nonapeptide bradykinin is released. The HK light chain (LC) contains coagulant activity, which requires both the ability to bind the contact system zymogens, prekallikrein and factor XI, and the ability to interact with negatively charged surfaces. Since bacterial expression might not be successful if carbohydrate was required for activity, we evaluated that possibility by incubating plasma HK with endoglycosydase F. Although the procedure removed detectable N-linked carbohydrate, no change in specific activity occurred. We then developed a bacterial expression system to produce recombinant HK LC. The cDNA coding for the HK LC was prepared by polymerase chain reaction (PCR), digested with restriction enzymes EcoRI and PstI, and introduced into the bacterial expression vector pKK223-3. E. coli harboring this recombinant plasmid (pSKl) expressed HK LC upon induction with isopropylthio-galactoside (IPTG). The recombinant protein (27 kDa), when transferred onto a PVDF membrane, was recognized by monospecific polyclonal anti-HK LC-antibodies. The recombinant HK LC was purified by heparin agarose affinity chromatography to homogeneity and found to have a specific activity of 28 coagulant units per mg protein, similar to the specific activity of the LC derived by proteolytic digestion of human plasma HK. We conclude: 1) The HK LC synthesized in bacteria is biologically active, and 2) the 40% carbohydrate content of the HK LC is not required for its cofactor activity.
The Effect of Suramin on Laboratory Tests of Coagulation
Authors: Horne McDonald K , Wilson Olga J , Cooper Michael , Gralnick Harvey R , Myers Charles E 
Published: July 2018

SummaryThe antitrypanosomal drug suramin, which has recently been under investigation as a cancer chemotherapeutic agent, has previously been found to induce heparin-like anticoagulants in treated patients. In the currently reported work suramin is shown to have an additional anticoagulant activity that is due to direct effects of the drug on procoagulant proteins. The studies were conducted with pooled normal plasma treated in vitro with suramin and with plasma samples obtained from patients who had received the drug intravenously for 2 weeks. It is demonstrated that in plasma suramin inhibits factors V, VIII, IX, X, XI, and XII, while thrombin, prothrombin, and factor VII are unaffected. The inhibition of factor V is virtually irreversible, although the effect of suramin on the other factors is readily reversed by dilution.
Pharmacodynamic Properties of Long Lasting Butyryl Heparin Derivatives in the Rabbit
Authors: Saivin S , Caranobe C , Petitou M , Lormeau J C , Houin G , Boneu B 
Published: July 2018

SummaryThis paper reports on the pharmacodynamic properties of butyryl derivatives of unfractionated heparin (C4-UH) and of low molecular weight heparin (C4-CY 216) after bolus intravenous injection, constant infusion and subcutaneous administration to rabbits. The pharmacodynamic properties of the two butyryl derivatives were compared to those of the parent compounds, unfractionated heparin (UH) and low molecular weight heparin (CY 216). After bolus intravenous injection of increasing doses, the disposition of the butyryl derivatives were comparable to that of their parent compounds up to 3 mg kg-1. Over this dose, their clearances became 2 to 3 times lower. These long lasting properties were confirmed by constant intravenous infusion experiments. After subcutaneous administration, the bioavailability of C4-UH remained low (10%) at any dose while that of C4-CY 216 ranged from 42 to 120%. If these findings are confirmed in man, these new derivatives open the possibility of treating established deep vein thrombosis with only one daily injection of a butyryl derivative of low molecular weight heparin.
The Reversible Antithrombin Activity of Incubated Plasma
Authors: Gomperts E. D , Stavridis J. C , Mibashan R. S 
Published: July 2018

SummaryThe thrombin time of normal citrated plasma is progressively prolonged on incubation in open glass tubes at 37° C. The phenomenon is dependent on the temperature and duration of incubation, on the pH, and on the concentration of calcium ions present. Platelet-rich citrated plasma fails to exhibit augmented antithrombin activity when similarly incubated, and the addition of washed platelets to platelet-poor plasma inhibits this activity. The clot retarding action of incubated plasma against thrombin is also manifested against Arvin (Ancrod), but not against Reptilase-R. This thrombin time lenghening may be inhibited by incubation with anti-antithrombin III antiserum thus indicating that the phenomenon of thrombin time lengthening is consistent with enhanced activity of antithrombin III. It is unlikely that alterations in the activity of α2-macroglobulin, is important in the reduced thrombin-coagulability of incubated plasma. Interference with the polymerisation of fibrin monomers by the physicochemical changes may contribute to the observed phenomenon.
Enhancement of Platelet Sensitivity to ADP-Aggregation by Isometric Exercise in Arteriosclerotic Patients and its Prevention
Authors: Sano Tadahiro , Motomiya Takeshi , Yamazaki Hiroh , Shimamoto Takio 
Published: July 2018

SummaryA new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points:1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment.2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positive significant correlations between the values obtained by these three methods.3. It was proved to be highly reproducible and is thought to be useful clinically.By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement of platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise.
Factor VIII Inhibitor Associated with Chlorpromazine-Induced Hepatic Injury
Authors: Glazier Richard L , Crowell Edward B 
Published: July 2018

SummaryA 90-year-old man was given chlorpromazine for sedation and 2 weeks later developed cholestatic jaundice and subsequently a factor VIII inhibitor. His death 4 weeks after institution of chlorpromazine, from massive bleeding, coupled with the autopsy finding of intrahepatic cholestatic jaundice, suggests that both adverse reactions were due to the drug.
Fibrinolytic, Factor VIII and Pulse Rate Responses to Repeated Adrenaline Infusion Followed by Haemorrhage
Authors: Britton B. J , Giddings J. C , Brooks Lynne , Bloom A. L 
Published: July 2018

SummaryThe role of catecholamines in the activation of coagulation and fibrinolysis following surgery remains controversial. In this study 5 dogs were infused with 1, 2, 3, 6, 9 and 12 μg kg–1 min–1 of adrenaline at twice weekly intervals and were then reexposed to 3 μg kg–1 min–1. Pulse rate and factor VIII increased after infusion of 1,2 and 3 μg kg–1 min–1 but thereafter there was a diminished response and no response on reexposure to 3 μg kg–1 min–1 although this was not significant in the case of pulse rate. Euglobulin lysis time shortened after each infusion of adrenaline and showed no development of tolerance. A control series of dogs infused with saline showed no similar changes.Both groups of animals were then bled to a blood pressure of 60 mm Hg for 60 minutes. Pulse rate and factor VIII did not change but euglobulin lysis time shortened in both groups. The results suggest that the activation pathways for changes in factor VIII and euglobulin lysis time induced by adrenaline are separate.
Pharmacokinetics of Full Length and Two-Domain Tissue Factor Pathway Inhibitor in Combination with Heparin in Rabbits
Authors: Bregengaard Claus , Nordfang Ole , Østergaard Per , Petersen Jens G L , Meyn Giorgio , Diness Viggo , Svendsen Ove , Hedner Ulla 
Published: July 2018

SummaryTissue factor pathway inhibitor (TFPI) is a feed back inhibitor of the initial activation of the extrinsic pathway of coagulation. In humans, injection of heparin results in a 2-6 fold increase in plasma TFPI and recent studies suggest that TFPI may be important for the anticoagulant activity of heparin. Full length (FL) TFPI, but not recombinant two-domain (2D) TFPI, has a poly cationic C-terminus showing very strong heparin binding. Therefore, we have investigated if heparin affects the pharmacokinetics of TFPI with and without this C-terminus.FL-TFPI (608 U/kg) and 2D-TFPI (337 U/kg) were injected intravenously in rabbits with and without simultaneous intravenous injections of low molecular weight heparin (450 anti-XaU/kg).Heparin decreased the volume of distribution and the clearance of FL-TFPI by a factor 10-15, whereas the pharmacokinetics of 2D-TFPI were unaffected by heparin. When heparin was administered 2 h following TFPI the recovery of FL-TFPI was similar to that found in the group receiving the two compounds simultaneously, suggesting that the releasable pool of FL-TFPI is removed very slowly in the absence of circulating heparin.
Platelet Aggregation on Extracellular Matrix: Effect of a Recombinant GPIb-Binding Fragment of von Willebrand Factor
Authors: Dardik R , Ruggeri Z M , Savion N , Gitel S , Martinowitz U , Chu V , Varon D 
Published: July 2018

SummaryPlatelets in whole blood incubated on extracellular matrix (ECM) produced by bovine corneal endothelial cells under oscillatory flow conditions demonstrate extensive aggregate formation. Since both platelet-subendothelium and platelet-platelet interactions are mediated by von Willebrand factor (vWF), we used this system to examine the effect of a recombinant GPIb-binding fragment of vWF (designated RG12986), comprising residues 445-733 of the native vWF subunit, on platelet reactivity with ECM. The seven cysteines present in the RG12986 fragment were reduced and alkylated in order to achieve a monomeric conformation. The recombinant vWF fragment binds to unstimulated platelets in the absence of exogenous modulators. When added to platelet-rich plasma, it inhibits ristocetin-induced platelet agglutination. Binding of 51Cr-labeled platelets in reconstituted whole blood to ECM was inhibited by RG12986 in a dose dependent and saturable manner, with IC50 of 4 μM and maximal inhibition (about 70%) at 6 μM. Scanning electron microscope (SEM) analysis showed that addition of RG12986 to whole blood significantly inhibited platelet aggregation on ECM. The extent of inhibition observed with RG12986 at a final concentration of 4 μM was similar to that obtained with the cell adhesion peptide RGDS at the concentration of 0.1 mM. The ability of the RG12986 fragment to inhibit platelet aggregation on ECM is in agreement with the concept that blockade of vWF-GPIb interaction may inhibit further events leading to activation of the glycoprotein IIb/IIIa (GPIIb/IIIa) complex and subsequent thrombus formation.
Some Relations Between Light Transmission Changes and Biochemical Parameters of Stored Platelet Packs
Authors: Järemo Petter , Edlund Bror , Berseus Olle , Kutti Jack 
Published: July 2018

SummaryIn the present work a computerised method for continuous monitoring of light transmission through platelet packs was evaluated. One series (Series 1) of 50 platelet concentrates was studied over a 5-day period, and thereafter the pH, extracellular lactate dehydrogenase (LDH) and platelet factor 4 (PF4) in the concentrates were determined. A second series (Series 2) of 52 concentrates was also monitored over 5 days, and thereafter the pH, extracellular LDH and intracellular concentrations of ATP, ADP and AMP were determined. 11 and 14 of the concentrates of Series 1 and 2, respectively, demonstrated long lasting transmission increases (≥ 3.0 days). In the total of 102 platelet concentrates 34 were observed to have late (<1.0 day) or no transmission increase. It is concluded, that the present optical method identifies both a group of platelet concentrates having long lasting transmission increases and a group consisting of platelet concentrates having late or no transmission increase. Compared to the latter concentrates preparations with long lasting transmission changes demonstrated significant biochemical alterations. These observations could be applicable in the quality control of platelet concentrates.
Prothrombin Activation Fragment 1 + 2 and Thrombin Antithrombin III Complexes in Patients with Angina Pectoris: Relation to the Presence and Severity of Coronary Atherosclerosis
Authors: Kienast J , Thompson S G , Raskino C , Pelzer H , Fechtrup C , Ostermann H , Loo J van de 
Published: July 2018

SummaryPlasma levels of the prothrombin activation fragment 1 + 2 (F 1 + 2) and of thrombin antithrombin III complexes (TAT) were determined in 225 patients with angina pectoris undergoing coronary angiography. Oral anticoagulant therapy was associated with a marked reduction in mean Fl + 2 (0.63 vs 1.62 nmol/l, p <0.0001) and TAT levels (1.65 vs 2.23 μg/1, p <0.0001). Omitting patients on oral anticoagulants, TAT values showed a positive association with patients’ age (r = 0.18; p = 0.01) and were slightly higher in patients with a history of myocardial infarction than in those without (2.47 vs 2.11 <g/l; p = 0.06). Both Fl + 2 and TAT levels were increased in patients with angiographically verified coronary atherosclerosis as compared to patients with angina and angiographically normal coronaries (Fl + 2: 1.76 vs 1.36 nmol/1, TAT: 2.35 vs 2.00 μg/1; p-values after adjusting for age, sex and past history of myocardial infarction 0.06 and 0.11 respectively). However, no graded relationship between Fl + 2 or TAT values and severity of atherosclerosis was observed. This study provides suggestive evidence that a procoagulant state exists in patients with angina pectoris and coronary atherosclerosis. Its relevance in predicting coronary ischaemic events needs to be studied prospectively.
Enhanced Prothrombin and lntrinsic Factor X Activation on Blood Platelets from Diabetic Patients
Authors: Lupu Cristina , Calb Maria , Lonescu Mihaela , Lupu Florea 
Published: July 2018

SummaryThe present work was conducted to bring information about the enhanced procoagulant activity of blood platelets in diabetes mellitus, as compared to normal control platelets. The inquiry was performed on platelets from either human patients or hamsters with streptozotocin-induced diabetes. The experiments comprised functional assays of factor Xa and thrombin generation in the presence of normal or diabetic platelets, using saturating amounts of coagulation factors. The prothrombinasic and tenasic complexes activation was measured by using discontinuous amidolytic tests with chromogenic substrates (S-2238 for FXa and S-2222 for thrombin). The results showed that, in contrast to the low prothrombin and factor X converting activity of normal platelets, the thrombin and FXa generation on diabetic platelets was increased by 3-7 times for either humans or hamsters. These findings may be relevant for the pathogenesis of thrombotic complications known to occur in diabetes mellitus.
Haemostatic Variables and Menopausal Status: Influence of Hormone Replacement Therapy
Authors: Scarabin Pierre-Yves , Plu-Bureau Geneviève , Bara Lucienne , Bonithon-Kopp Claire , Guize Louis , Samama Meyer M 
Published: July 2018

SummaryLarge cohort studies have shown that postmenopausal estrogen use was associated with a reduction in the risk of coronary heart disease, This putative beneficial effect of hormone replacement therapy (HRT) may be partly mediated through changes in clotting factors and fibrinolytic system. We have measured haemostatic variables in 293 consecutive healthy women aged 45-54 years who attended a health check-up centre in Paris (IPC). Premenopausal women taking hormonal therapy were excluded (n = 34). Most women using HRT were given 17-β estradiol in combination with progestin. Mean levels (m ± sd) of plasma fibrinogen, factor VII coagulant activity and plasminogen activator inhibitor (PAI) were significantly higher in postmenopausal women not taking HRT (n = 99) than in premenopausal women (n = 139) within the same decade (319 ± 52 mg/dl vs 304 ± 60 mg/dl, 107 ± 17% vs 96 ± 16%, 9.73 ± 5.71 U/ml vs 7.61 ± 4.36 U/ml respectively). Allowance for main cardiovascular risk factors made no substantial differences to the results, although the effect of the menopause on fibrinogen was no longer significant. HRT (n = 21) significantly reversed the menopause-related changes in factor VII (94 ± 15%), even after adjustment for confounding factors. The same trend in both fibrinogen (294 ± 46 mg/dl) and PAI (8.22 ± 5.51 U/ml) was observed. Similar results were found in women using oral or percutaneous estrogen. Our findings suggest that 17-β estradiol in combination with progestins may protect against an increased thrombotic tendency in postmenopausal women. Randomized clinical trials are urgently needed for a better understanding of HRT effect on atherothrombotic process.
A Compound Heterozygous Protein C Deficiency with a Single Nucleotide G Deletion Encoding Gly-381 and an Amino Acid Substitution of Lys for Gla-26
Authors: Ido Masaru , Ohiwa Michiaki , Hayashi Tatsuya , Nishioka Junji , Hatada Tsuyoshi , Watanabe Yasuyuki , Wada Hideo , Shirakawa Shigeru , Suzuki Koji 
Published: July 2018

SummaryWe report genetic abnormalities of protein C gene in a male infant who developed neonatal purpura fulminans. DNA-sequence analysis of all exons in protein C gene in this family revealed two mutations. The first abnormality, derived from the mother, was a deletion of one of four consecutive G at nucleotide number 10758 in exon IX which would result in a frame shift mutation and completely change amino acid sequence from Gly381 in the carboxyl-terminal region of protein C. The second abnormality, derived from the father, was a single nucleotide mutation from G to A in the codon (GAG to AAG) at nucleotide number 2977 in exon III, which would result in a substitution of Lys for γ-carboxyglutamic acid (Gla)26. This change would be responsible for the reduced immunological protein C levels of the patient and the father, estimated by a monoclonal antibody which recognizes the Gla-domain in a Ca2+-dependent manner (3.8% and 57%, respectively). Partially purified abnormal protein C from the father’s plasma showed a normal amidolytic activity and a change in the electrophoretic mobility. We detected the above mutations in his family members using two methods; one was a creation of new restriction enzyme sites using mutagenic primers and the other was single nucleotide primer extension. Both methods are rapid and useful for the diagnosis of prenatal protein C abnormalities.
The Routine Measurement of Platelet Size Using Sodium Citrate Alone as the Anticoagulant
Authors: Bath P M W 
Published: July 2018

SummaryMean platelet volume (MPV), a measure of platelet size, is becoming recognised as an important marker of platelet function. However, platelets swell in edetic acid (EDTA), the Standard haematology anticoagulant, in a time-dependent manner making such measurements potentially unreliable. The effect of incubation time on MPV, and platelet distribution width (PDW), as measured in EDTA, low (1:9 volume/volume with blood) or high (1:4 v/v with blood) concentration sodium citrate was studied. MPV measured in high concentration sodium citrate did not change with time in contrast to MPV measured in either low concentration sodium citrate or EDTA which both increased in an inverse exponential fashion. MPV and PDW, measured in high concentration sodium citrate, had similar within-assay and between-assay coefficients of Variation as other platelet, red cell and white cell haematology variables measured in EDTA: MPV 1.4%, 2.1%; PDW 1.4%, 1.5%; MCV 0.4%, 0.7%; PC 3.1%, 6.1%; WCC 1.5%, 7.3%; Hb 2.1%, 2.4% respectively. MPV measured in EDTA and corrected for incubation time approximated to, but was higher than, the MPV measured in high concentration sodium citrate. PDW correlated inversely with platelet count (r = <0.415, 2p <0.001). MPV may be measured in sodium citrate (at 1:4 v/v with blood) alone with a better accuracy and reproducibility than similar measurements made in EDTA. Furthermore, such measurements are not influenced by incubation time, unlike for EDTA.