bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombin-Hirudin Complex Formation, Thrombin-Antithrombin III Complex Formation, and Thrombin Generation after Intrinsic Activation of Plasma
Authors: Gallistl Siegfried , Muntean Wolfgang 
Published: July 2018

SummaryTo investigate the relative importance of direct inhibition of thrombin by complex formation and of inhibition of thrombin generation to the mechanisms by that unfractionated heparin (UH) and recombinant hirudin (rH) exert their anticoagulant effects, thrombin-antithrombin III complex (TAT) and thrombin-hirudin complex (THC) formation was compared with the generation of thrombin and prothrombin fragments 1 + 2 (F 1 + 2). Clotting was initiated by activation of citrated plasma in the absence or presence of UH or rH using partial thromboplastin, ellagic acid and calcium chloride. THC was determined by means of ELISA using specific antibodies to thrombin and rH.Activation of citrated plasma resulted in a sudden onset of thrombin generation after a lag phase of 2 min. Addition of 50 ng rH/ml plasma or 0.1 UH/ml plasma prolonged the clotting time to 3 min. While the peak of thrombin was only slightly decreased in hirudinized plasma, in heparinized plasma thrombin generation was significantly lower than in not anticoagulated plasma. This difference was more pronounced when the lag phase was prolonged to 5 min using 400 ng rH/ml plasma or 0.35 U UH/ml plasma. Using 1200 ng rH/ml or 0.65 U UH/ml to obtain a clotting time of 9 min only a small amount of thrombin could be detected in heparinized plasma, but hirudinized plasma still showed a high peak of thrombin. F 1 + 2 showed essentially the same pattern as thrombin. Prior to the onset of visible clot formation in all experiments using different concentrations of UH about the same values of TAT were observed. In contrast, when samples were anticoagulated with different amounts of rH, a dose dependent increase of THC was detected. When calculated from TAT and THC formation, much more thrombin was bound by rH than by AT III.Our experiments show that after intrinsic activation of plasma UH exerts its anticoagulant effect more by inhibiting thrombin generation, while rH suppresses thrombin generation to a much lesser extent but inhibits clotting more by direct inhibition of thrombin due to the formation of THC.
Structural Alterations in Fibrin Clots with Dextran
Authors: Muzaffar T. Z , Stalker A. L , Bryce W. A. J , Dhall D. P 
Published: July 2018

SummaryTheoretical reasoning underlying physicochemical measurement of opacity ratio of fibrin clots, i. e. the ratio of turbidity at 350 nm and 608 nm is given. From such considerations it is deduced that opacity ratio may be used to characterise clot morphology : opacity ratio will be inversely related to the size of inhomogeneities formed in the clot.A highly reproducible technique for the measurement of opacity ratio is described. Additions of small amounts of dextran to fibrinogen solution consistently decrease the opacity ratio of clots made subsequently. This decrease which indicates that the inhomogeneities forming in such fibrin clots are larger than control, is independent of the molecular weight of dextran, but is related to the logarithm of the final dextran concentration. Both thrombin and fibrinogen concentrations are also determinants of opacity ratio. Electron microscopy of fibrin clots made in the presence of dextran confirms that such clots have an altered morphology. Properties of clots in relationship to their structural morphology are discussed.
Studies on Activator Formation in Human Plasma with Streptokinase
Authors: Martin M ,   with the technical assistance of Frau R. Albrecht and Frau M. Altmaier
Published: July 2018

SummaryThe plasminogen-streptokinase complex called “activator” was present in diluted plasma in the form of a largely dissociated mixture. More than ⅞ of the streptokinase and plasminogen molecules were available for further activator formation.The activator is probably a dissociated complex of the formulaStreptokinase + Plasminogen ⇄ Activator.The fact that an increase in activator concentration by x times is obtained by multiplying either the streptokinase content by the factor y or the plasminogen concentration by the same factor y would point to a kinetic effect along the lines of the mass action law.
A Controlled Trial of Aspirin in Childhood Glomerular Disorders
Authors: Trygstad Carl W. , Bang Nils U. , Heldenreich Robert O. , Csiscko Barbara M. , Rodda Bruce 
Published: July 2018

SummaryA controlled, prospective, double-blind study of the effect of aspirin on the clinical course and renal function of 36 children with proliferative glomerulonephritis or the nephrotic syndrome was undertaken. Despite unequivocal evidence of suppression of platelet aggregation with aspirin treatment, there were no statistically significant changes in the clinical course or any of the laboratory parameters denoting activity of the chronic glomerular renal disorder. It would appear, therefore, that additional factors besides local platelet aggregation must be involved in the perpetuation of chronic childhood renal disease.
Do Coagulation Screening Tests Detect Increased Generation of Thrombin and Plasmin in Sick Newborn Infants?
Authors: Schmidt Barbara , Vegh Patsy , Johnston Marilyn , Andrew Maureen , Weitz Jeffrey 
Published: July 2018

SummaryBackground: Disseminated intravascular coagulation (DIC) is usually diagnosed in sick infants who have prolonged clotting times, depletion of platelets and coagulation factors, and elevated levels of fibrin derivatives. However, the diagnostic accuracy of abnormal coagulation profiles in neonates at risk of DIC has been uncertain. Since DIC is characterized by activation of both the coagulation and fibrinolytic systems, the objective of this study was to determine whether coagulation screening tests correctly identify infants with biochemical evidence of increased thrombin and plasmin generation.Methods: Non-surgical patients in a tertiary care nursery who were sick enough to require an indwelling arterial catheter for monitoring purposes, were enrolled in a prospective cohort study. Blood samples for thrombin/antithrombin III (TAT) complexes and the plasmin-derived fibrinopeptide Bβ1-42 were drawn 36 to 72 h after birth from a free-flowing arterial line. Platelet counts, D-Dimer levels, plasma fibrinogen concentrations and prothrombin times, expressed as International Normalized Ratios or INR, were measured at the same time.Results: One hundred patients were studied. Fifty-seven infants had elevated levels of TAT (≥4 μg/l) and Bβ1-42 (≥4 nmol/l). The sensitivities of platelets <150 × 109/l, D-Dimer >500 ng/ml, fibrinogen <1.5 g/l, and INR >1.5 were 39%, 30%, 12%, and 11%, respectively. Corresponding specificities were 88%, 91%, 98%, and 95%.Conclusions: Abnormal coagulation screens in sick newborn infants strongly support a diagnosis of DIC. However, normal screens do not exclude activation of the coagulation and fibrinolytic systems.
Activation of Protein C and Its Distribution between Its Inhibitors, Protein C Inhibitor, α1-Antitrypsin and α2-Macroglobulin, in Patients with Disseminated intravascular Coagulation
Authors: Scully M F , Toh C H , Hoogendoorn H , Manuel R P , Nesheim M E , Solymoss S , Giles A R 
Published: July 2018

SummaryActivation and inactivation of protein C during the clinical course of disseminated intravascular coagulation (DIC) was studied in three patients by qualitative (Western blotting) and quantitative (ELISA) analysis and the intensity of procoagulant activity monitored by the measurement of thrombin and factor Xa antithrombin III complexes. In one patient, inhibitor complexes of APC with protein C inhibitor (PCI) and α1-antitrypsin (α1-AT) were observed and the latter predominated at presentation. Both disappeared during the development of remission but the loss of α1-AT complexes preceded PCI complexes which on Western blotting appeared to increase in intensity prior to disappearance. The two other patients bled to death from uncontrollable haemorrhage. In both cases, APC/inhibitor complexes with α2-macroglobulin (α2-M) in addition to PCI and αr-AT were detected and persisted until death. Although PCI appeared to be the primary inhibitor in all three cases, α1-antitrypsin and particularly α2-macroglobulin appeared to assume greater roles in the two fatal cases. These data are similar to previous findings in an experimental animal model of DIC that suggested that α2-macroglobulin and α1-antitrypsin become more important inhibitors of APC as the primary inhibitor PCI is consumed in the face of a sustained procoagulant challenge.
Comparative Effects of Enoxaparin and Heparin on Arterial and Venous Clot Lysis with Alteplase in Dogs
Authors: Stassen Jean-Marie , Rapold Hans J , Vanlinthout Ingrid , Collen Désiré 
Published: July 2018

SummaryThe effects of Enoxaparin with a specific anti-thrombin (anti-IIa) activity of 32 U/mg and a specific anti-factor-XA (anti-Xa) activity of 96 U/mg, and of heparin with a specific anti-IIa and anti-Xa activity of 192 U/mg, on thrombolysis with alteplase (Actilyse®) were compared in a randomized blinded study using a combined arterial and venous thrombosis model in the dog. All dogs received an intravenous bolus of 5 mg/kg lysine-acetyl salicylate and 0.5 mg/kg alteplase over 60 min. Twenty-eight dogs were randomly assigned to seven treatment groups: placebo, Enoxaparin 1.5, 3 or 6 mg/kg, or heparin 0.5, 1 or 2 mg/kg, given as a 50% intravenous bolus and a 50% infusion over 2 h. Steady-state plasma levels ranged from 0.37 to 1.0 anti-IIa U/ml and 0.9 to 3.1 anti-Xa U/ml for Enoxaparin and from 0.4 to 2.3 anti-IIa U/ml and 0.42 to 3.2 anti-Xa U/ml for heparin. The activated thromboplastin time with 6 mg/kg Enoxaparin prolonged to 94 ± 19 s and with 2 mg/kg heparin to >150 s.The time to reflow was 120 ± 36 min with placebo, 19 ± 5 min with 6 mg/kg Enoxaparin (p = 0.03 vs control), and 22 ± 5 min with 2 mg/kg of heparin (p = 0.03 vs control). Arterial patency, expressed in min reflow during the 180 min observation period correlated significantly with the dose of anticoagulant given (r = 0.73, p = 0.003 for Enoxaparin and r = 0.61, p = 0.012 for heparin). When the dose of anticoagulant was expressed in anti-IIa U/kg, Enoxaparin was significantly more potent than heparin (patency times of 0.62 ± 0.15 and 0.21 ± 0.09 min per anti-IIa U/kg respectively, p = 0.04) but in terms of mg/kg or anti-Xa U/kg both anticoagulants were equipotent.Venous clot lysis also correlated significantly with the dose of anticoagulant given (r = 0.62, p = 0.011 for Enoxaparin and r = 0.76, p = 0.004 for heparin). When the dose of anticoagulant was expressed in anti-IIa U/kg Enoxaparin was equipotent to heparin, but in terms of mg/kg or anti-Xa U/kg heparin was more potent than Enoxaparin (6 ± 2% lysis per mg/kg Enoxaparin and 35 ± 9% lysis per mg/kg heparin, p= 0.001).In conclusion, Enoxaparin and heparin enhance arterial and venous clot lysis with alteplase differently; for arterial patency, potency correlates with anti-Xa activity whereas for venous clot lysis potency correlates with anti-IIa activity.
Familial High Plasminogen Activator Inhibitor with Hypofibrinolysis, a New Pathophysiologic Cause of Osteonecrosis?
Authors: Glueck C J , Glueck H I , Mieczkowski L , Tracy T , Speirs J , Stroop D 
Published: July 2018

SummaryIn a 29 year old white male with osteonecrosis of both hips and a shoulder, and in his family, we measured basal and stimulated (10 min cuff venous occlusion at 100 mgHg) fibrinolytic activity to determine whether low fibrinolytic activity might be heritable and etiologically associated with osteonecrosis. The proband’s basal tPA-Fx was low, 0.08 IU/ml (normal 0.11-1.94), tPA-Ag was normal (11.6 ng/ml), plasminogen activator inhibitor activity (PAI-Fx) was very high, 119 U/ml (normal 3.5-27), as was his plasminogen activator inhibitor antigen (PAI-Ag), 202 ng/ml (normal 3.2-37.1). The proband’s basal PAI-Fx (119) and PAI-Ag (202) were respectively 6 and 13 standard deviations greater than the mean PAI-Fx (17 ± 15 U/ml) and the mean PAI-Ag (25 ± 13 ng/ml) in 172 concomitantly studied hyperlipidemic men. Alpha-2 antiplasmin, fibrinogen, plasminogen and Lp(a) were normal. Despite lowering TG to 301 mg/dl, basal tPA-Fx remained low, 0.05; PAI-Fx and PAI-Ag remained very high (109 and 191). Following venous occlusion, stimulated tPA-Fx remained very low, 0.1 (normal 2.3-11.3), but tPA-Ag rose normally to 17 (normal 8.4-31.4); stimulated PAI-Fx and PAI-Ag were very high, 134 and 223, (normal PAI-Fx 3.6-24, PAI-Ag 12-96). Stimulated D-dimer was < the 10th percentile, 0.084 μg/ml. With such high PAI-Fx available to bind tPA, occlusionstimulated tPA-Fx could not rise, and fibrinolysis could not be initiated. Neither diseases nor drugs could explain the high PAI-Fx and PAI-Ag, low tPA-Fx, or osteonecrosis. The proband’s father, mother, and sister had very high basal PAI-Ag (240, 69, 66 ng/ml), high basal PAI-Fx (24, 24, 35 U/ml), and normal basal tPA-Fx (0.6, 1.0, and 0.2 IU/ml). Basal PAI-Ag, PAI-Fx, and tPA-Fx were normal in the proband’s son (13, 12, 0.3). The proband’s very high PAI-Fx and PAI-Ag appeared to be inherited, possibly as an autosomal dominant trait, producing hypofibrinolysis. We speculate that his osteonecrosis was caused by familial hypofibrinolysis mediated by high PAI, with subsequent inability to activate fibrinolysis, resulting in inadequate lysis of venous thrombi in bone, impaired bone venous circulation, and venous hypertension of bone characteristic of osteonecrosis.
Human Platelet Antigen 3 (HPA-3): Localization of the Determinant of the Alloantibody Leka (HPA-3a) to the C-Terminus of Platelet Glycoprotein IIb Heavy Chain and Contribution of O-Linked Carbohydrates
Authors: Djaffar Isabelle , Vilette Didier , Pidard Dominique , Wautier Jean-Luc , Rosa Jean-Philippe 
Published: July 2018

SummaryThe human platelet antigen (HPA) 3 system is expressed on GPIIb, one subunit of GPIIb-IIIa, the platelet fibrinogen receptor. It was recently shown that HPA-3 was associated with an Ile843/Ser polymorphism. To investigate further HPA-3 determinant structure, we localized an HPA-3a determinant, recognized by the alloantiserum Leka, within the last 29 amino acids of GPIIbα. This region encompasses the polymorphic Ile843, which, as expected, is substituted into Ser in Leka-negative individuals, as shown by DNA sequence after polymerase chain reaction on platelet RNA. In addition, contribution of glycosylation to the determinant structure was demonstrated since the Leka antigenicity was strongly decreased after specifically removing nonterminal O-linked sugars, but not terminal sialic acids. We have thus refined the localization of an HPA-3a determinant within the last 29 amino acids, including Ile843, of GPIIb heavy chain, and shown that the Leka HPA-3a determinant is dependent, in part, upon the serine-linked carbohydrates adjacent to Ile/Ser843.
Clinical Application Of Urokinase Treated Polymer For Antithrombogenic Medical Material
Authors: Ohshiro T , Kosaki G , Takaqi K 
Published: July 2018

Currently, there is an increasing need to develop better medical materials with high antithrom- bogenecity. Attempts have, in fact, been made to improve such materials by the following methods:
1) to develop a material compatible with tissue,
2) to coat a material with protein, 3) to immobilize an anticoagulant agent on the surface of a material, and 4) to immobilize a fibrinolytic enzyme on the surface. Amoung these methods, the last is intriguing.In this series, we devised the antithrombogenic medical materials for intravenous catheterization, vascular suture and lymph-drainage, based on the fundamental examination. Urokinase was coupled to the surface of polymer by peptide linking. Material was disinfected by EOG.The results are as follows: 1)This material has 5-10 u. of urokinase activity per cm2. 2)The activity was influenced by the procedure of EOG disinfection. 3)The activity decreased after the repeated fibrinolysis test to 20%. 4) Urokinase treated evatate-tube for intravenous catheterization was used in 26 patients and almost no throbei adhered to tube. 5)Urokinase treated nylon-filament for vessel suture was in 10 patients and two suffered from reocclusion. 6)Urokinase treated nylon-thread for lymph-drainage was in 10 patients and some of them had the effective clinical course. 7) These materials maintained the almost 10% of initial fibrinolytic activity after clinical application.
Hemostatic Defects In Acute Leukemias: Special Investigations Including Agarose-Gel-Filtration Of Plasma Samples
Authors: Asbeck F , Schmitz-Huebner U , Kirchhof B , Zimmermann E , van de Loo J 
Published: July 2018

22 patients with acute leukemias were investigated before and during cytostatic polychemotherapy. The mean decrease of peripheral leukocytes was 38 000/mm3 within the first 3 days of treatment. The bleeding tendency could be attributed to thrombocytopenia and one or more of the following mechanisms.1) Only in febrile patients the development of a PIC could be shown: increase of fibrinogen and soluble fibrin; decrease of prothrombin (E.C.-activation, chrom. substrate), F. V, F. VIII, and antithrombin III (chrom. substrate, immunological). In these patients, no consumption of antiplasmin was demonstrable.2) Non-febrile patients did not develop a PIC during the cytostatic treatment. 3) In some patients an isolated fibrinolysis could be shown already before treatment: increase of soluble fibrin and FDP; marked decrease of fibrinogen, antiplasmin, and F. XIII, which were correlated with the amount of cytoreduction. In these patients, there was no consumption of AT III.4) Asparaginase produced the well-known defect in protein synthesis. No further influence of either cytostatic therapy or different cytological classifications of the blasts could be demonstrated.
Streptokinase and Urokinase Activation of Human, Chimpanzee and Baboon Plasminogen
Authors: McKee P. A , Lemmon W. B , Hampton J. W 
Published: July 2018

SummaryHuman, chimpanzee and baboon plasminogens, in that order, were found to be decreasingly susceptible to streptokinase (SK) activation. The relative activation of the three primate plasminogens remained the same when species specific fibrin or casein was used as substrate and when the following conditions were varied: 1. SK concentration; 2. plasminogen concentration; and 3. length of incubation of the SK-plasminogen-substrate reaction mixture. Under the same conditions, the three primate plasminogens were readily activated by human urokinase (UK) and no consistent order of activation by UK was observed. Our findings suggest that the site on plasminogen which interacts with SK has undergone changes during evolution whereas the site at which UK activates each of the three plasminogens has changed little. It remains obscure whether the susceptibility of primate plasminogen to SK activation is a specifically selected genetic trait or is simply a laboratory indication of structural changes in the plasminogen molecule that have occurred for other reasons.
Effects of Chemical Compounds upon Current Induced Thrombosis in Rat Mesenteric Vessels
Authors: Aaron R. K , Srinivasan S , Burrowbs B , Sawyer P. N 
Published: July 2018

SummaryFrom previous work in our laboratories, there is a large amount of evidence for an electrochemical mechanism of thrombosis. The blood vessel wall and blood cells are negatively charged under normal conditions. Antithrombogenic drugs increase their negative charge densities while thrombogenic drugs have the opposite effect. Injury makes the blood vessel wall less negatively charged or even positively charged. There is a relation between vascular injury currents and thrombosis. In the present study, the effect of certain chemical agents upon in situ thrombosis in rat mesoappendix vessels, produced by an applied electric current of the sign and magnitude of physiological injury currents, is examined. Compounds such as polyquarternary, with basic groups enhance thrombosis while compounds such as heparin with acidic groups inhibit thrombosis.
Effect of Adrenaline on Thrombosthenin
Authors: Levy-Toledano S , Caen J ,   with the technical assistance of Eva Bodevin
Published: July 2018

SummaryIt has been found that adrenaline protects the two activities of thrombosthenin from inhibition by NEM if added before or with NEM but not if added after.The α-blockers of epinephrine, phentolamine, abolishes the protective effect of adrenaline when it is added before adrenaline. We find the same results with noradrenaline but not with 5-hydroxytryptamine.A parallemism exists between the effect of adrenaline on thrombosthenin and clot retraction, but not on platelet aggregation. This shows possibly that the activities of thrombosthenin are directly linked to clot retraction, but in platelet aggregation it seems that thrombosthenin is necessary but not sufficient.
Kombinierter AHG- und PTA-Mangel
Authors: Schulz K , Nowotny P , Schmutzler R , Duckert F 
Published: July 2018

ZusammenfassungEs wird über die Kombination eines Faktor-VIII- und Faktor-XI-Mangels bei einem Patienten mit schwerer Blutungsneigung berichtet. Die Schwierigkeiten der Differentialdiagnose werden aufgezeigt und ähnliche Fälle in der Literatur diskutiert.
Purification of Antihemophilic Factor (Factor VIII) by Amino Acid Precipitation*
Authors: Wagner Robert H , McLester William D , Smith Marion , Brinkhous K. M 
Published: July 2018

Summary1. The use of several amino acids, glycine, alpha-aminobutyric acid, alanine, beta-alanine, and gamma-aminobutyric acid, as plasma protein precipitants is described.2. A specific procedure is detailed for the preparation of canine antihemophilic factor (AHF, Factor VIII) in which glycine, beta-alanine, and gammaaminobutyric acid serve as the protein precipitants.3. Preliminary results are reported for the precipitation of bovine and human AHF with amino acids.
Preservation of Morphological Integrity and Clot Retraction Activity of Human Platelets After Freezing
Authors: Djerassi Isaac , Roy Albert , Alvarado Jorge ,   With the technical assistence of TERESITA DACEY
Published: July 2018

SummaryHuman platelets frozen at −195° C (liquid nitrogen) retain their morphological integrity and ability to promote clot retraction when 5% dimethyl-sulfoxide and 5% dextrose are added to the suspending plasma medium. Slow freezing was more effective than direct immersion in the liquid nitrogen. Although similar results may be achieved with dimethylsulfoxide alone with rigidly controlled freezing rates, the addition of sugars may permit freezing under less critical conditions.Dimethylsulfoxyd und 5% Dextrose dem Plasmamilieu hinzugefügt werden. Das langsame Einfrieren ist effektiver als das direkte Eintauchen in flüssigen Stickstoff. Obschon ähnliche Resultate mit Dimethylsulfoxyd allein unter exakter Kontrolle der Einfrierungsgeschwindig-keit erreicht werden können, erlaubt die Zugabe von Dextrose ein Einfrieren unter weniger kritischen Bedingungen.