bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement by ADP of Thrombin-induced Aggregation in ADP-refractory Platelets
Authors: Simard-Duquesne Nicole 
Published: July 2018

SummaryIn ADP-refractory rat platelets, thrombin-induced aggregation is enhanced in the presence of ADP and inhibited in the absence of ADP. Two mechanisms are proposed for thrombin-induced platelet aggregation: one through ADP release which may become refractory, and a second mechanism in which thrombin acts synergistieally with ADP.
The Determination of Optimum Glycine Concentration for the Preparation of Human Fibrinogen at Ambient Temperatures
Authors: Silberstein Edward B. , Ingraham Samuel C. , Kereiakes James G. 
Published: July 2018

SummaryA glycine-precipitation method is presented allowing the preparation of human fibrinogen of high clottability and stability at ambient temperature (25 ± 3° C) with a minimum of specialized equipment. From barium sulfate adsorbed plasma, the optimum yield of clottable fibrinogen is found to occur with a 65% relative glycine saturation of plasma.
Plasminogen Depletion during Administration of Epsilon-aminocaproic Acid
Authors: Nibbelink D. W , Jacobsen C. D 
Published: July 2018

SummarySixteen patients with acute onset subarachnoid hemorrhage were treated with intravenous administration of epsilon-aminocaproic acid. This drug inhibits activation of plasminogen and, to some extent, the effect of plasmin as well. In this study a marked decrease in immunological quantities of plasminogen was observed. This depletion of plasminogen occurred without concommitant quantitative changes in platelets or fibrinogen. Hence, the antiftbrinolytic effect of epsilon-aminocaproic acid is not only through inhibition of plasminogen activation and of plasmin itself, but also through a marked reduction in plasminogen.
The Possible Role of Platelet Coagulant Activities in the Pathogenesis of Venous Thrombosis
Authors: Walsh Peter N 
Published: July 2018

SummaryRecent studies of the role of platelets in blood coagulation have shown that platelets can trigger intrinsic coagulation by two alternative pathways, protect platelet-associated active clotting factors from inactivation by plasma inhibitors and catalyze intrinsic coagulation reactions on the platelet surface to form fibrin. These platelet coagulant activities (i.e., contact product forming activity, collagen-induced coagulant activity, intrinsic factor-Xa forming activity and platelet factor 3 activity) were found to be increased in patients with deep vein thrombosis developing after hip surgery, in patients with established retinal vein thrombosis and in patients with established deep vein thrombosis. It is suggested that increases in platelet coagulant activities concerned with triggering and catalyzing intrinsic coagulation reactions may play a role in the pathogenesis of venous thrombosis.
The Effect of Dipyridamole and RA 233 on Human Platelet Function in Vitro
Authors: Rifkin Paul L. , Zucker Marjorie B. 
Published: July 2018

SummaryDipyridamole (Persantin) is reported to prolong platelet survival and inhibit embolism in patients with prosthetic heart valves, but its mechanism of action is unknown. Fifty jxM dipyridamole failed to reduce the high percentage of platelets retained when heparinized human blood was passed through a glass bead column, but prolonged the inhibition of retention caused by disturbing blood in vitro. Possibly the prostheses act like disturbance. Although RA 233 was as effective as dipyridamole in inhibiting the return of retention, it was less effective in preventing the uptake of adenosine into erythrocytes, and more active in inhibiting ADP-induced aggregation and release. Thus there is no simple relation between these drug effects.
Three Distinct Point Mutations in the Factor IX Gene of Three Japanese CRM+ Hemophilia B Patients (Factor IX BMNagoya 2, Factor IX Nagoya 3 and 4)
Authors: Hamaguchi Motohiro , Matsushita Tadashi , Tanimoto Mitsune , Tekahashi Isao , Yamamoto Kohji , Sugiura Isamu , Takamatsu Junki , Ogata Kanji , Kamiya Tadashi , Saito Hidehiko 
Published: July 2018

SummaryEnzymatic DNA amplification and complete sequence analysis were used to investigate human factor IX coding sequences in three CRM+ hemophilia B patients. In a patient with severe hemophilia B and a markedly prolonged ox-brain prothrombin time, a C to T transition in exon VI changed the codon for Argl80 to Trp (factor IX BMNagoya 2). This mutation would impair the cleavage by factor XIa required for activation of the zymogen. In a patient with mild hemophilia B, a G to A transition in exon VI changed the codon for Argl45 to His (factor IX Nagoya 3). This substitution also would be predicted to preclude the cleavage of factor IX by factor XIa at this peptide bond (Argl45-Alal46). Furthermore, this point mutation creates a new NlaIII restriction site which provides a quick and reliable method for carrier detection in the affected family members. A patient with severe hemophilia B (factor IX Nagoya 4) had a G to A transition in exon II changing the codon for Glu21 to Lys. This novel point mutation is assumed to impair the function of factor IX by disrupting the calcium binding of factor IX.
Dependence of Blood Clot Lysis on the Mode of Transport of Urokinase into the Clot - A Magnetic Resonance Imaging Study in Vitro
Authors: Blinc A , Planinšič G , Keber D , Jarh O , Lahajnar G , Zidansěk A , Demsar F 
Published: July 2018

SummaryMagnetic resonance imaging was employed to study the dependence of clot lysing patterns on two different modes of transport of urokinase into whole blood clots. In one group of clots (nonperfused clots, n1 = 10), access of urokinase to the fibrin network was possible by diffusion only, whereas in the other group (perfused clots, n2 = 10) bulk flow of plasma containing urokinase was instituted through occlusive clots by a pressure difference of 3 .7 kPa (37 cm H2O) across 3 cm long clots with a diameter of 4 mm. It was determined separately that this pressure difference resulted in a volume flow rate of 5.05 ± 2.4 × 10−2 ml/min through occlusive clots. Perfused clots diminished in size significantly in comparison to nonperfused ones already after 20 min (p <0.005). Linear regression analysis of two-dimensional clot sizes measured by MRI showed that the rate of lysis was more than 50-times faster in the perfused group in comparison to the nonperfused group. It was concluded that penetration of the thrombolytic agent into clots by perfusion is much more effective than by diffusion. Our results might have some implications for understanding the differences in lysis of arterial and venous thrombi.
Thrombolysis with an Escherichia coli-Produced Recombinant Plasminogen Activator (BM 06.022) in the Rabbit Model of Jugular Vein Thrombosis
Authors: Martin Ulrich , Fischer Stephan , Kohnert Ulrich , Opitz Ulrich , Rudolph Rainer , Sponer Gisbert , Stern Anne , Strein Klaus 
Published: July 2018

SummaryThe recombinant plasminogen activator BM 06.022 consists of the kringle 2 and the protease domains of human t-PA and is unglycosylated because of the expression in Escherichia coli The thrombolytic and pharmacokinetic properties as well as the hemostasis effects of BM 06.022 were investigated in the rabbit model of jugular vein thrombosis. The thrombi were 125I-fibrin labeled. Intravenous bolus injection of 50, 100, 200, and 400 kU/ kg BM 06.022 or 400, 800, and 1600 kU/kg alteplase over 15 s to six rabbits/dose produced a dose-dependent increase of thrombolysis determined 2 h post injection. The dose-response curve of BM 06.022 was located left compared with that of alteplase. The effective dose of 50% thrombolysis (ED50) obtained by half-logarithmic regression analysis was 163 kU/kg (=0.28 mg/kg) for BM 06.022 and 871 kU/kg (= 1.09 mg/kg) for alteplase. At equipotent doses (50% thrombolysis), the residual concentration of fibrinogen was 74.2% and 76.5%, that of plasminogen 66.7% and 69.4%, and that of α2-antiplasmin 47.3% and 46% for BM 06.022 and alteplase, respectively. Pharmacokinetic analysis for plasma activity at a dose of 400 kU/kg revealed a half-life of 18.9 ±1.5 min for BM 06.022, whereas alteplase was distributed with a half-life of 2.1 ± 0.1 min, accounting for 86.7 ± 1.9% of the total AUC, followed by a β-phase with a half-life of 13.8 ± 0.9 min. Plasma clearance of BM 06.022 was 4.7 ± 0.7 ml min-1 kg-1 compared with 20 ±1.2 ml min-1 kg-1 for alteplase. Due to its lower clearance rate, we conclude that BM 06.022 requires a 5.3-fold lower activity dose than alteplase to achieve an effect of 50% thrombolysis in rabbits. At equipotent doses, BM 06.022 is fibrin selective to the same degree as alteplase.
Functional Characterization of a Variant Factor XII (F XII Locarno) in a Cross Reacting Material Positive F XII Deficient Plasma
Authors: Wuillemin Walter A , Furlan Miha , Stricker Hans , Lämmle Bernhard 
Published: July 2018

SummaryThe plasma of a healthy woman was found to contain half normal factor XII (FXII) antigen level (0.46 U/ml) without any FXII clotting activity (<0.01 U/ml). The variant FXII in this plasma, denoted as FXII Locarno, was partially characterized by immunological and functional studies on the proposita’s plasma. FXII Locarno is a single chain molecule with the same size (M
r = 80 kDa) as normal FXII. Isoelectric focusing suggested an excess of negative charge in the variant FXII as compared to normal FXII. In contrast to FXII in normal plasma, FXII Locarno was not proteolytically cleaved upon prolonged incubation of proposita’s plasma with dextran sulfate. Adsorption to kaolin was similar for both, abnormal and normal FXII. Incubation of the proposita’s plasma with dextran sulfate and exogenous plasma kallikrein showed normal cleavage of FXII Locarno outside of the tentative disulfide loop Cys340-Cys467, but only partial cleavage within this disulfide loop. Furthermore, plasma kallikrein-cleaved abnormal FXII showed neither amidolytic activity nor proteolytic activity against factor XI and plasma prekallikrein.These results suggest a structural alteration of FXII Locarno, affecting the plasma kallikrein cleavage site Arg353-Val354 and thus formation of activated FXII (a-FXIIa).
Changes in Haematological Indices, Blood Viscosity and Inhibitors of Coagulation during Treatment of Endometriosis with Danazol
Authors: Ford I , Li C , Cooke I D , Preston F E 
Published: July 2018

SummaryThe effects of treatment with danazol (600 mg daily) on haemostatic and haematological function were investigated in 18 pre-menopausal women with endometriosis. Blood samples were taken at 2 pre-treatment visits, at 6, 12 and 24 weeks on treatment, and at 6 weeks after discontinuation of the drug. Haemoglobin, red cell count, haematocrit and platelet count all rose significantly during treatment with danazol (p <0.01 vs. baseline). Plasma fibrinogen levels fell significantly (p <0.01), while whole blood viscosity increased during treatment and remained significantly elevated at follow-up. The prothrombin time shortened, but remained within normal limits, and there were no significant changes in factor VII:C, Vila, or fibrinopeptide A. No significant changes were found in platelet function. Plasma B-beta 15-42 increased significantly. Functional levels of protein C, protein S, and antithrombin III, all rose significantly, above the normal range, while C4b-binding protein levels fell. We conclude that the observed changes in coagulation inhibitors and fibrinolytic activity may be considered beneficial in the context of venous thromboembolism. The rheological effects, however, indicate a degree of caution in the use of the drug in individuals considered to be at risk from arterial cardiovascular disease.
Activation of Blood Coagulation after Abrupt or Stepwise Withdrawal of Oral Anticoagulants - A Prospective Study
Authors: Palareti G , Legnani C , Guazzaloca G , Frascaro M , Grauso F , De Rosa F , Fortunato G , Coccheri S 
Published: July 2018

SummaryThe occurrence of a “rebound hypercoagulable state” in patients after discontinuation of oral anticoagulants is still a matter of debate and no definite recommendation can be made on the best procedure for anticoagulant withdrawal. The present study investigated the changes in the levels of markers of activated blood coagulation in 32 patients (pts) in whom warfarin treatment (for venous thromboembolic disease) was randomly withdrawn abruptly (n = 17, group A) or gradually (n = 15, group B: ⅔ of initial dose the 1st week, ⅓ the 2nd weeks and nothing from the 3rd week on). Blood was sampled at baseline, once a week for the first three weeks and after 2 months. At the 1st week group A had significantly higher F1+2 and TAT values (p <0.001); at the 2nd week F1 + 2 levels remained higher (p <0.05) though INR values were not different from those of group B. After baseline, higher than normal F1+2 levels were recorded in 32/66 (48%) controls in group A vs 15/60 (25%) in group B (p <0.01); at the 2nd week, 10/17 (59%) patients in group A vs 1/15 (7%) in group B still had higher than normal F1+2 levels (p <0.01 ). The values of areas under curve (AUC) and maximum concentrations of all variables were not statistically different in the two groups; however, very high levels were observed in a few cases of group A. Thrombotic events (one DVT recurrence and one thrombophlebitis in a varicose vein) occurred in 2 pts of group A, both with high F1+2 and TAT AUC values. In conclusion, the present study shows that withdrawal of oral anticoagulants elicits low grade transient clotting activation, which is more intense and longer lasting after abrupt discontinuation. In single cases, however, such activation is particularly intense. It is possible that these cases are at greater risk of thrombotic complications.
Multicenter Evaluation of a Kit for Activated Protein C Resistance on Various Coagulation Instruments Using Plasmas from Healthy Individuals
Authors: Rosén S , Johansson K , Lindberg K , Dahlbäck B ,   (for the APC resistance study group)
Published: July 2018

SummaryRecently a new hemostatic disorder has been described which appears to be an important risk factor for familial thromboembolism. The disorder is characterized by a poor anticoagulant response to activated Protein C (APC) and has been shown to be due to lack of an APC cofactor activity which is a property of factor V.A kit for determining the response of plasma samples towards addition of APC in an APTT-based assay - COATEST APC Resistance -has been evaluated on 35 coagulation instruments in a multicenter study involving 32 laboratories. A lyophilized normal plasma and identical plasma aliquots from 20 individuals, one of whom had a borderline resistance to APC, were analysed in each laboratory and the sensitivity of each plasma to APC was determined as the ratio between the clotting times obtained in the presence and absence of APC (APC ratio).The plasma from the individual with a borderline resistance to APC activity was correctly classified as the lowest responder in each laboratory, with an APC ratio in the range 1.6-2.4. In comparison, plasmas from individuals with a pronounced response to APC activity resulted in APC ratios above 3.4 in most cases. Interestingly, although the actual APT time for a plasma from a given individual showed a more than 10 s difference due to the type of instrumentation used, the variation in the APC ratio was limited. A similar discrimination was also obtained from evaluation of the actual prolongation of the clotting time in the presence of APC.The intra-laboratory coefficient of variation for the clotting times were on average 2.0% and 3.9% in the absence and presence of APC, respectively, indicating that the precision for the prolonged clotting times obtained in the presence of APC is sufficient to allow a safe assignment of the APC response. The APC ratio for the lyophilized normal plasma was 2.7 ± 0.2 (2 S.D.) illustrating a narrow distribution between instruments which shows the feasibility of including such plasma for assay validation. Altogether, the results indicate that all the coagulation instruments included in the study can be used for detection of individuals with resistance to APC activity through determination of the APC ratio or the prolongation time.
Results of a Multicenter Study Assessing the Status of Standardization of a Recombinant Thromboplastin for the Control of Oral Anticoagulant Therapy
Authors: Tripodi A , Chantarangkul V , Braga M , poller L , ten Cate J W , van den Besselaar A M H P , Mannucci P M 
Published: July 2018

SummaryAn international collaborative study involving 20 laboratories was undertaken to evaluate the status of standardization of a commerical recombinant thromboplastin. The results show that the reagent fulfills the WHO requirements for thromboplastin calibration against two International Reference Preparations (IRP) from different species, because there was a linear relationship of log-transformed prothrombin times as measured by the recombinant reagent and the two IRPs in normal individuals and patients stabilized on oral anticoagulants. The regression lines drawn through the patient data points passed through the normal data points in the majority of instances. The average ISI values for three different batches were close to unity. On the average, the ISI value calculated against BCT/253 (human, plain) was slightly smaller than that against RBT/79 (rabbit, plain). The between laboratory precision of calibration (CV = 5-6%) did not change whether BCT/253 or RBT/79 was used, whereas it was substantially improved when the calibrations of batches 2 and 3 were performed against batch 1, arbitrarily taken as standard (CV ≤ 1.7%). Statistical analysis to test for differences between slopes revealed no significant between-batch differences in 16 of 20 laboratories. However slight differences for the third batch (2.8% less than the average ISI value of batches 1 and 2) leave room for further improvement in the standardization of the reagent.
Potentiating Effect of Adenosine on Other Inhibitors of Platelet Aggregation
Authors: Murakami M. , Odake K. , Takase M. , Yoshino K. 
Published: July 2018

SummaryAdenosine was rapidly incorporated into human platelets, and the inhibitory effect of adenosine on platelet aggregation was correlated with the incorporation process. Adenosine potentiated the inhibitory action of other inhibitors, such as dipyridamole, prostaglandin E1 and Y-3642. The inhibition of aggregation was associated with the preservation of platelet adenine nucleotides and the prevention of ADP release. On the other hand, the radioactive adenine nucleotide pattern of platelets was not substantially affected by inhibitors. The relation of inhibition of aggregation with ADP release was discussed.
Activation of Hageman Factor by Cardiac Arrest
Authors: Latour J. G. , McKay D. G. , Parrish Mary H. 
Published: July 2018

SummaryThe induction of cardiac arrest in rabbits for a period of 3min, followed by reestablishment for the circulation, resulted in a 27 % decrease in circulating Hageman factor. The maximum depletion occurred within 30 to 60 min and normal levels were restored by 4 h. Anti-contact product activity remained unchanged. Circulating platelets dropped by 17 % and small arterial thrombi were found predominantly in the lungs. It is concluded that cardiac arrest followed by re-circulation of the blood causes activation of Hageman factor. The proximate mechanism of this activation in experimental generalized anoxemia remains to be determined. Administration of a potent glucocorticoid prior to cardiac arrest markedly inhibited activation of the clotting mechanism.
Measurement of Fibrin Proteolysis In Vivo by a Radioactive Fibrin-Millipore Tube Technique
Authors: Cihak R. W , Shaw S. T 
Published: July 2018

SummaryMillipore tubes containing radioactive fibrin can be used to measure fibrin proteolysis. Experiments described herein indicate that loss of soluble radioactivity from fibrin- containing tubes during in vivo incubation can be used to measure relative rates of lytic activity at specific locations within an organism under various conditions.Preparation of urea-insoluble 125I-fibrin and its apparent purity and uniformity of label have been described. This preparation has been shown to be stable over a period of several months, when properly stored, in its response to protease activity and lack of spontaneous degradation. Contained within Millipore tubes, the fibrin is protected from direct cellular attack while it is susceptible to enzymes from the environment which can enter the porous chambers. Enzymatic degradation of fibrin releases diffusible radioiodinated peptides from the tubes. Thus, determination of fibrin-tube radioactivity before and following in vivo incubation may be used as a measurement of proteolytic rate within the organism.
Clot Lysis in a Perfusion System
Authors: Bouvier C. A , Gruendlinger J , Berthoud S 
Published: July 2018

SummaryMost information on clot lysis is derived from in vitro methods whereby various components of the clotting and fibrinolytic systems are mixed before an actual clot is formed. This situation bears little relationship to thrombolysis in vivo. Therefore several techniques have been recently proposed, in which pre-formed clots are exposed to the effects of active agents by contact and diffusion rather than by intimate mixing prior to clotting. We describe an apparatus whereby a perfusion is delivered at controlled rates to clots of standard size and volume formed in calibrated tubes. The composition of the clots can be varied as well as the rate of perfusion and the content of perfusate. The surface of contact between the fluid and the fibrin gel is kept constant throughout and the clot-perfusate relationship is as close as possible to the in vivo situation during thrombolytic therapy. Under these conditions clot lysis by Streptokinase appears as a linear function of time, and the rate of lysis is directly related to kinase concentration. Since the clot intrinsic plasminogen-proactivator content is sufficient to ensure lysis, the lysis time finally depends upon the rate of diffusion of the kinase into the gel. Inhibition obtained with various amounts of E-aminocaproic acid incorporated to the clots or added to the perfusion fluid also suggests that diffusion problems are of major importance in physiological and therapeutic thrombolysis.
Human Antihemophilic Factor (AHF) Purification A Comparison of Two Procedures
Authors: Hurt J. P , Wagner R. H , Brinkhous K. M 
Published: July 2018

SummaryA method is described for the precipitation from plasma of a human AHF fraction (Fraction AA) with beta alanine. The Fraction AA is further purified by reprecipitation with beta alanine or by adsorption with Florigel or bentonite. Reprecipitation with beta alanine is a convenient step as no additional equipment or reagents are required for the second precipitation. All reagents can be rendered sterile and free of pyrogens. When the precipitates are quantitatively dissolved, the yields are greater than 70% and purification ranges from 300-600 times. The adsorption procedure also has advantages. Adsorption adds only 45 minutes to a 6 hour fractionation. AHF recovery is as high as 70% with a purification of 3,000 to 5,000 times.
Some Effects of Fibrinogen Degradation Products (FDP) on Blood Platelets
Authors: Jerushalmy Z , Zucker M. B 
Published: July 2018

Summary“Early” fibrinogen degradation products are more potent inhibitors of thrombin-induced clotting than “late” products and also interfere with the ability of thrombin to release serotonin from platelets. “Early” and “intermediate” FDP cause moderate inhibition of platelet aggregation induced by adenosine diphosphate or connective tissue particles. Serotonin release by connective tissue particles is probably not inhibited by FDP.