bluuebunny/crossref_metadata_2025 huggingface dataset:
Agglutination und Adhäsivität der Thrombozyten nach körperlicher Belastung
Authors: Breddin K , Hach W
Published: June 2018

Körperliche Belastung führte bei 7 gesunden Versuchspersonen zu einem Anstieg der Thrombozytenadhäsivität um 70,8% des Ausgangswertes (Mittelwert). Bei 10 Personen stieg nach der Belastung die Faktor-VIII-Aktivität im Mittel um 57% an. Es ist wahrscheinlich, daß es sich hierbei um die durch Adrenalin ausgelöste Aktivierung eines Plasmafaktors handelt, der mit dem von-Willebrand-Faktor identisch ist. Dieser »Adhäsivitätsfaktor« ist nicht identisch mit dem aktiven plättchenagglutinierenden Faktor, der sich im Plasma und im Serum von Patienten mit akuten Gefäßkrankheiten findet.

Nach körperlicher Belastung fand sich bei 22 von 23 Versuchspersonen kein Anstieg der Thrombozytenagglutination.

Die bisher verwendeten Methoden zur Messung der Plättchenadhäsivität zeigen sowohl Veränderungen der Haftneigung selbst als auch Änderungen der Aggregations- und Agglutinationstendenz an und sollten deshalb durch Verfahren ersetzt werden, die eine Unterscheidung zwischen diesen Mechanismen möglich machen.
Rapid Determination of Antifibrinolysin (Antiplasmin) in Plasma
Authors: Nanninga L. B , Guest M. M
Published: June 2018

A nephelometric assay of antifibrinolysin in plasma is described. This assay is based on the inhibition of fibrinogenolysis. An equation is derived to calculate the antifibrinolysin content. Only the activity of the rapid acting antifibrinolysin is obtained. The values for antifibrinolysin are given in mol/L based on a molecular weight 57.000 (1). All values are based (standardized) on the inhibition of fibrinolysin by crystalline soybean trypsin inhibitor.
A Serial Micro-Fibrinolysis Test and Its Use in Rats with Liver-Bypass
Authors: Wasantapruek S , von Kaulla K. N
Published: June 2018

A micro-euglobulin lysis test is described for serial testing in individual rats. With the method it was shown that the rat a) responds well with a fibrinolytic reaction to carbachol, b) that a liver-bypass in this animal produces a sustained fibrinolytic reaction which c) after subsiding can be re-established by carbachol and that d) the fibrinolytic phase in rats with liver-bypass lasts longer after preceding splenectomy and adrenalectomy.
Studies on the Mechanism of Interference by Fibrinogen Degradation Products (FDP) with the Platelet Function Role of Fibrinogen in the Platelet Atmosphere
Authors: Maria Kopeć , Budzyński A , Stachurska Jolanta , Węgrzynowicz Z , Kowalski E
Published: June 2018

1. Blood platelets can be aggregated by solutions of fibrinogen preparations of different origins. Fibrinogen degradation products (FDP) obtained by plasmin digestion do not aggregate platelets.

2. Preparations of FDP added to platelet suspension inhibit aggregation induced by fibrinogen,.

3. FDP when added to platelet suspensions, inhibit the release of adenine nucleotides induced by thrombin, connective tissue extract, kaolin or the contact factor.

4. Platelet suspensions pretreated with SKPL loose partly the ability to release adenine nucleotides after the action of inducing agents.

5. Washed platelet suspensions possess the capacity to adsorb fibrinogen and FDP, the latter being adsorbed in greater amounts and bound stronger than fibrinogen.

6. An attempt was undertaken to explain the observed phenomena on the basis of a general view on the molecular mechanism of platelet function.

It is postulated that fibrinogen is an integral part of the platelet surface and that it is one of the determinants of the platelet surface properties. Fibrinogen is necessary for platelet aggregation by ADP and for the adequate action of the agents which initiate metabolic changes and induce the release reaction. FDP act antagonistically to fibrinogen. They inhibit ADP aggregation as well as the access to the susceptible sites on. the surface of the platelet of the agents inducing release.
In Vitro Clumping of Human Platelets by Dextran
Authors: Dhall D. P , Matheson N. A
Published: June 2018

Platelet aggregation in vitro by dextrans of various molecular weights has been examined in platelet rich plasma and in suspensions of human platelets with a turbidi-metric method and microscopy. Addition of dextran to platelet rich plasma and platelet suspensions causes a biphasic effect on the optical density, consisting of an immediate decrease which seems independent of the molecular weight of the dextran and a delayed, time-dependent decrease influenced by it. Microscopically, platelet aggregation by dextran corresponds more closely to the delayed decrease. Aggregation of human platelets by dextran, for which stirring is necessary, is related to the final dextran concentration, is affected by the platelet population and is not spontaneously reversible. Platelet clumping by dextran is of particular interest since dextran has been shown to possess antithrombotic properties.
Distribution of Fibrinolytic and Proteolytic Enzymes in Subcellular Fractions of Human Granulocytes
Authors: Prokopowicz J
Published: June 2018

The Cohn and Hirsch method was applied for preparation of human granulocyte subfractions. It was found that specific granules contained about 50-60% of the total activity of acid phosphatase, alkaline and acid protease. The activities of fibrinolytic enzymes (plasminogen, activator of plasminogen and spontaneous fibrinolytic activity) were rather equally distributed in all subfractions.

A significant rise of a total fibrinolytic activity was found during fractionation. The results suggest the existence of a fibrinolytic inhibitor in the granulocytes. This suggestion was substantiated by analysing dilution curves of the plasminogen activity in the granulocyte subfractions.

The inhibitor showed both “antiurokinase”, “antistreptokinase” and antiplasmin activity.

On the basis of experimental data it has been suggested that plasma plasminogen may be derived from the granulocytes.
Coagulation Factors and Components of the Fibrinolytic System in Lymph and Blood in Dogs
Authors: Leandoer L , Bergentz S.-E , Nilsson Inga Marie
Published: June 2018

Thoracic duct lymph of the dog was compared with blood regarding the concentration of various coagulation factors, coagulation properties, and components of the fibrinolytic system.

The recalcification time for lymph was almost twice as long as for blood. The quotients between the concentration of the coagulation factors in the lymph and blood varied considerably. For fibrinogen the lymph/blood concentration ratio was 1/3, for factor V 1/4, for factor VIII 1/4, for factor IX 2/3 and for P & P 1/2.

The fibrinolytic activity in the lymph was lower than in the blood and no split products were found in the lymph. The lymph/blood concentration ratio was 1/2 for plasminogen and 2/3 for the urokinase inhibitor activity.
In Vitro Studies on a Proteolytic Enzyme from Aspergillus Oryzae (Protease I)
Authors: Ogston D , Ogston C. M
Published: June 2018

1. Protease I was found to have potent fibrinolytic activity in concentrations which exceeded the blood inhibitory capacity when tested on fibrin plates and artificial thrombi.

2. Plasma inhibited the proteolytic activity of protease I to a greater extent than serum; serum had a greater inhibitory effect on protease I than on plasmin. Trasylol did not inhibit the proteolytic action of protease I.

3. Protease I caused the slow formation of fibrin in plasma in concentrations which did not produce fibrinogenolysis; this effect was seen in Al(OH)3-adsorbed plasma, and was not inhibited by heparin. Protease I also shortened the recalcified plasma clotting time.

4. The fibrinogenolytic action of protease I was more rapid than its fibrinolytic action both in the presence and absence of plasma inhibitors. No concentration of protease I lysed fibrin in plasma without prior destruction or conversion to fibrin of the surrounding plasma fibrinogen.

5. It is concluded from these in vitro studies that protease I does not have the properties necessary for a satisfactory thrombolytic agent.
Inactivation of Tissue Thromboplastin by Ultraviolet Irradiation
Authors: Åtland S , Hvatum M , Prydz H
Published: June 2018

Solutions of partially purified tissue thromboplastin have been irradiated with UV light of different wavelengths, and the resulting reduction in the procoagulant activity has been measured. The activity decreased as an exponential function of the dose. The action spectrum obtained was closely similar to the UV absorption spectrum of the thromboplastic preparations and had a maximum between 270-290 nm. The data suggested that the reduction in the procoagulant activity was caused by absorption of radiation energy in the protein part of the thromboplastic structure.
The Influence of Fats on Blood Coagulation and Fibrinolysis
Authors: Meuwissen O. J. A Th. , Hart H Ch. , Hemel-Rupert M. S. E van
Published: June 2018

A review of experiments described in the literature discloses a lack of agreement about the influence of nutritional fats on blood coagulation and fibrinolysis. The numerous pertinent studies yielded contradictory results even if identical techniques were used.

In our investigation, 17 normal subjects were given a breakfast containing 57 g saturated fats and one containing 54 g unsaturated fats. Before and 3 hrs after ingestion of the high-fat meal, blood was collected for determination of blood coagulation and fibrinolysis. There was no demonstrable difference between the two blood samples in terms of recalcification time of platelet-rich plasma in siliconized glass, euglobulin activity, fibrinolytic activity measured by lysis of plasminogen-poor and plasminogen-rich standard clots labelled with I131-fibrinogen, “activated fibrinolysis” (measuring the antiplasmin concentration) and the susceptibility to fibrinolysis of fibrin clots prepared in a standardized manner from fasting and hyperlipaemic plasma samples.

In 6 normal subjects the experiments were expanded to encompass breakfasts with 118 saturated and 117 g unsaturated fats. After these high-fat meals, too, there was no demonstrable difference in recalcification time and in the various parameters of fibrinolysis.

In order to establish whether atherosclerotic patients would show a different reaction to high-fat meals, the experiments were carried out also in 17 patients suffering from severe generalized atherosclerosis. These patients were given a low-fat breakfast, one with 57 g saturated fats and one with 54 g unsaturated fats. In this group, too, there were no demonstrable differences between the preprandial and postprandial data on blood coagulation and various parameters of fibrinolysis.
Hydrolysis of L-Histidine Methyl Ester
Authors: Cole E. R
Published: June 2018

The hydrolysis of L-histidine methyl ester (HME) by bovine thrombin preparations has been investigated. Activation of purified bovine prothrombin in 25% sodium citrate solution resulted in the simultaneous development of fibrinogen clotting activity and of TAME and HME esterase activities. Most of the HME esterase activity was identified with fibrinogen clotting activity on sequential chromatography of activated prothrombin on DEAE-cellulose and Amberlite CG-50 resin columns, although some HME esterase activity could be demonstrated in concentrates of the autoprothrombin C fraction. The optimum pH for HME hydrolysis by thrombin was found at 7.6 in phosphate and Tris buffered reactions. Tris buffer and other amines depress HME esterase activity of thrombin, while sodium cholate accelerates the reaction. The Michaelis constant, Km, was estimated to be 0.134 M at pH 7.6 in phosphate buffer and at 37° C.
Kinetic Aspects of the Interaction of Blood Clotting Enzymes
Authors: Hemker H. C , Veltkamp J. J , Loeliger E. A
Published: June 2018

Application of enzyme kinetics to the results of thrombotest estimations in correlation with specific clotting factor estimations has led to the recognition of a protein moiety that occurs in plasma in vitamin K deficiency and acts as a competitive inhibitor of thrombin formation. A hypothesis is given by which the occurrence of this inhibitor is explained in terms of a biphasic synthesis of the vitamin K-dependent clotting factors.
Preparation and Standardization of a Stable AHF Plasma
Authors: Thelin G. M ,   Los Angeles, California
Published: June 2018

A stable, lyophilized AHF reference plasma has been prepared from pooled plasma from at least 50 normal healthy donors and standardized against a primary standard of fresh plasma from 20 healthy male donors aged 20 to 40. Average AHF potency of a typical lot is 98.8%, and moisture content is less than 0.5%. Under storage at -25° C, this AHF reference plasma is stable for at least 18 months. It has been used in several major coagulation laboratories, and has given consistently satisfactory and reproducible results in AHF assays.
Zum Mechanismus der Thrombozytenaggregation
Authors: Pfleiderer Th , Brossmer R
Published: June 2018

An normalen Thrombozyten im Plasmamilieu ist die aggregierende Wirkung von Dextransulfat und Lipidemulsionen an das Vorhandensein freier Kalziumionen gebunden. An mehrfach gewaschenen Plättchen im Puffermilieu sind jedoch beide Substanzen auch ohne Kalzium, d. h. bei Anwesenheit von 0,2% EDTA wirksam. Während EPL jegliche Wechselbeziehungen zwischen einer Lipidemulsion und Thrombozyten in Plasma verhindert, ist an mehrfach gewaschenen Plättchen eine solche Hemmung nicht mehr nachweisbar. Die Aggregation mehrfach gewaschener Plättchen in Puffermilieu läuft also bei Anwesenheit von negativen, zur Brückenbildung befähigten Makromolekülen oder von Lipiden weit unspezifischer ab als im Plasma. Bei positiv geladenen Makromolekülen zeigt sich kein Unterschied in der Aggregation gewaschener und nicht gewaschener Thrombozyten. Die an gewaschenen Plättchen erhobenen Befunde dürfen nicht ohne weiteres auf Thrombozyten im Plasmamilieu übertragen werden. Die »plasmatische Atmosphäre« könnte für die Regulation der Plättchen-klebrigkeit in vivo von Bedeutung sein.
Activity-pH Relationship and Michaelis Constants during Activation of Profibrinolysin and during Fibrinogenolysis
Authors: Nanninga L. B , Guest M. M
Published: June 2018

The pH dependence was investigated separately for the activation of Profibrinolysin by urokinase and for the breakdown of fibrinogen by fibrinolysin. The effects of concentration of the substrates, Profibrinolysin and fibrinogen, respectively, were investigated and Michaelis constants were estimated for both enzymatic reactions. The average concentration of Profibrinolysin in normal human plasma was found to be 1.4 × 10–6 M based on experiments with relatively pure Profibrinolysin.
Degradation of Fibrinogen by Proteolytic Enzymes
Authors: Sanchez-Avalos J , Miller S. P
Published: June 2018

Fibrinogen was subjected to enzymatic degradation by streptokinase-activated plasminogen (plasmin). There was a rapid split of the molecule into large polypeptide components. Four components were seen by electrophoresis in acrylamide gel. Two major components (D and E) were identified by Immunoelectrophoresis and immune diffusion. In addition, a minor component which arose from the slow component and is called D’ was seen.

Fibrin degradation yielded a slow component that was identical with the slow component of fibrinogen, but the fast component (E) of fibrin was different from that of fibrinogen.

Degradation of fibrinogen by trypsin, chymotrypsin and papain was not mediated through the plasminogen-plasmin system. The initial action of these enzymes yielded fragments which were immunologically identical and electrophoretically similar to those of plasmin, but subsequent action of chymotrypsin led to further degradation of the slow component, while the fast component was subsequently destroyed by papain.

The two main components (D and E) could be identified in the plasma and serum of patients suffering from fibrinolytic disorders. The components were immunologically identical with the components produced in vitro by proteolytic enzymes.
Studies on the Hypercoagulable State
Authors: Kropatkin M. L , Izak G
Published: June 2018

The intravenous injection of fibrinogen was associated with a prolonged hyperfibrinogenemia in the rabbit, out of proportion to the amount of fibrinogen administered. Factors V, II, VII and X activities were found to be elevated in the plasma simultaneously.

A similar pattern of changes was observed in the rabbit after the recovery period from thrombin-induced defibrination.

Based on the observations reported here, it was suggested that some fibrinogen or fibrin break-down products deliver the stimulatory message to the liver for increased fibrinogen production.

The possible relationship between these observations and hypercoagulable state has been discussed.
Radioimmunoassay of Fibrinogen and Its Proteolysis Products
Authors: Catt K. J , Hirsh J , Castelan D. J , Niall H. D , Tregear G. W
Published: June 2018

The solid-phase radioimmunoassay method has been applied to the measurement of fibrinogen. The method is extremely sensitive, being able to detect fibrinogen concentrations as low as 10 ng/ml. The immunoreactivity of fibrinogen proteolysis products differs from that of native fibrinogen, early proteolysis products showing enhanced immunoreactivity which decreases progressively with further digestion.
Kinetic Aspects of the Interaction of Blood-Clotting Enzymes
Authors: Hemker H. C , Muller A. D
Published: June 2018

PIVKA, the circulating anticoagulant protein found in vitamin K deficiency can, on kinetical grounds, be recognized as an analogue of factor X. The existence of analogues of other vitamin K-dependent clotting factors cannot be ruled out, but need not be assumed to explain the experimental results.
Immune Reactions of Human Blood Platelets
Authors: Mueller-Eckhardt Ch , Lüscher E. F
Published: June 2018

1. Provided they are coated with gammaglobulin, polystyrene latex particles induce in washed human blood platelets the release of adenine nucleotides, aggregation and the contraction of the formed aggregates. Albumin and fibrinogen are unable to replace gammaglobulin in this reaction. Particles with a diameter of about 0.8 μ proved most effective; larger ones were inactive.

2. The release of nucleotides is a fast process; it is impaired but not completely inhibited by the removal of Ca++-ions. Aggregation and contraction of the aggregates are absent without Ca++-ions.

3. Normal gammaglobulin by itself has scarcely an effect upon platelets and it fixes added hemolytic complement (C’) only to a negligible extent. After the adsorption to latex it acquires strong C’-fixing properties, and becomes more reactive towards platelets. Repeated adsorption of the same gammaglobulin preparation with latex did not change this behaviour, which therefore is due to a property of the gammaglobulin itself, and not of a preferentially adsorbed, C’-activating contaminant. Treatment at pH 4 of gammaglobulin before its adsorption onto latex simultaneously abolished its effects on platelets, and on C.

4. It must be concluded that the effect of opsonized latex particles upon blood platelets is unseparable from their C’activating capacity. On the other hand, the addition of C’ not only proved unnecessary; the presence of serum rather impaired the release of nucleotides by latex particles.
Evidence that Platelets May Continue to Circulate after Phagocytosis of Particles
Authors: Vegge T , Monn E , Hjort P. F
Published: June 2018

A suspension of thorium dioxide particles was injected intravenously into rabbits, and platelets were subsequently isolated from the peripheral blood for electron microscopical studies at intervals up to 48 hrs.

The injection provoked severe thrombocytopenia. Large numbers of particles adhered to the surface of circulating platelets, and many particles were phagocytosed, probably by invagination of the membrane. Gradually, the load of particles per platelet decreased, and the particles moved into the dense granules of the platelets.

We conclude that phagocytosis is not necessarily a lethal event, and platelets may continue to circulate with a heavy load of particles.
Nuclear Magnetic Resonance Studies of Fibrin Polymerization
Authors: Jędrychowski A
Published: June 2018

Fibrinogen clotting has been studied by means of the spin echo technique. Magnetic transversal T2 and longitudinal T1 relaxation times were measured during fibrin formation.

Human fibrinogen was clotted by means of thrombin, papain and reptilase, which were used in three different concentrations.

The time relations of T2 in the studied system reflect, among others, limitation of freedom of movement of molecules of fibrinogen in the process of formation of the fibrin clot. Distinct differences were found related to the concentration and type of enzyme used to clot fibrinogen.

Comparison of the results obtained by the spin echo technique with results of measurements of optical density and thromboelastographic measurements led to the conclusion that the study of relaxation times T1 and T2 provides new information relative to fibrin formation, mainly with reference to increasing rigidity of the fibrin network and binding of water in it. This information is significant in that it determines quantitatively the degree of limitation of movement of molecules in the fibrin clot and characterizes its functional value. This conclusion was confirmed by the thromboelastographic studies, which allowed correlation of the changes in T2 time with mechanical properties of the clot.
Fibrinolysis, Fibrinogen and Factor XIII in New Born Infants
Authors: Fisher Sh , Schwartz M , Gottlieb A , Yoseph N Ben , Shapiro S
Published: June 2018

Fibrinolysis and the last stage of clotting were examined in 20 healthy infants on days 1-4 after birth. Plasminogen was constantly at half its normal level: 1.2-1.4 u/ml. The euglobulin lysis was increased only on day 1 in 50% of the cases. The mean values on days 1 and 4 showed a statistically significant difference: 0.45 ± 0.20 and 0.14 ± 0.05 (t = 2.1 p < 0.05). Fibrinogen was low or low normal at birth (mean values: 230 ± 57 mg%) but increased significantly in the next days reaching a mean of 293 ± 41 mg% on day 4 (t = 3.6 ρ < 0.001). Factor XIII was normal in all cases. Increased fibrinolysis in day 1 is probably due to a high level of activator at birth and the low plasminogen and fibrinogen are probably a consequence of the physiological „immaturity” of the liver.
A New Method for Plasminogen Standardization
Authors: Gajewski J , Markus G
Published: June 2018

A method for the standardization of human plasminogen is proposed, based on the stoichiometric interaction between plasminogen and streptokinase, resulting in inhibition of proteolytic activity. Activation of a constant amount of plasminogen with increasing amounts of streptokinase yields linearly decreasing activities, as a function of streptokinase, with a sharp transition to a constant residual level. The point of transition corresponds to complete saturation of plasmin with streptokinase in a 1:1 molar ratio, and is therefore a measure of the amount of plasminogen present initially, in terms of streptokinase equivalents. The equivalence point is independent of the kind of protein substrate used, buffer, pH, length of digestion and, within limits, temperature. The method, therefore, is not subject to the variations commonly encountered in the usual determination based on specific activity measurements.
Assay of the Antifibrinolytic Activity in Human Plasma by Means of the Lysis Time Method
Authors: Ygge J , Berg W , Korsan-Bengtsen K
Published: June 2018

A one-stage lysis time method to determine the total antifibrinolytic activity of human plasma is described. Purified fibrinogen, thrombin, plasminogen, and urokinase were used in the test system. The necessity of using a high plasminogen concentration compared with the urokinase concentration is pointed out. The concentration of the reagents has to be carefully standardized.

A straight line will be obtained in a semi-logarithmic system when plasma dilutions are plotted against.

The validity of this relation is investigated when the concentrations of plasminogen, fibrinogen, and urokinase are varied. It is also shown that this relation is valied when the antifibrinolytic activity is increased postoperatively and after delivery.

The antifibrinolytic activity is expressed as a percentage of the activity of a standard plasma. The standard plasma does not change its antifibrinolytic activity during storage at —20° C for at least three months.

The error of the method is about 2%.

Finally, the present report includes an experiment, the result of which makes it probable that the main action of plasma tested in this one-stage lysis time system is an antiplasmin activity.
Initial Studies of a Potent Antiheparin Agent (Ubiquin®)
Authors: Goodsell E. B , Krause R. A , Kimura E. T
Published: June 2018

Ubiquin (oligo-3-(N-methylmorpholinium)-l,2-propylene oxide chloride) is a stable, water soluble, active heparin antagonist producing prompt neutralization when administered in a 1:1 ratio to rats and dogs. Initial studies indicate that it is devoid of any effect on coagulation per se; nor are there any obvious side effects manifested during the process of neutralization. The acute toxicity is less than that of other compounds in use: toluidine blue, protamine and hexadimethrine.
Absent Plasma Second Phase Platelet Aggregation Factor in a Patient with Hageman Trait
Authors: Okonkwo P , Post R , Sise H
Published: June 2018

A case is described of a patient with factor XII deficiency in whom the second phase of platelet aggregation was missing after addition of ADP to platelet rich plasma. There was very little aggregation on addition of epinephrine, collagen or thrombin. Clot retraction was absent, but all other platelet functions were normal and there was a very minor bleeding tendency. The defect was corrected by normal platelet poor plasma and was found to be due to a missing cofactor of platelet aggregation normally found in fraction 1–0. The defect could be distinguished from that seen in subjects ingesting aspirin as well as from the defect seen in patients with a long bleeding time, defective platelet aggregation with ADP, epinephrine and collagen at low concentrations, no correction by addition of normal platelet poor plasma, and a history of mild bleeding disorder. It is thought that this defect may exist in otherwise normal individuals and that attention in this case was called to it by the presence of the deficiency of factor XII. It could be conclusively shown that factor XII is not necessary for normal platelet aggregation.
Factor XII Defect and Hemorrhage Evidence for a New Type of Hereditary Hemostatic Disorder
Authors: Egeberg O
Published: June 2018

In some members of 4 Norwegian families, a slight to moderate bleeding tendency was found to be associated with a partial blood factor XII defect, the factor activity about half of average normal level. In keeping with the low factor XII, surface activation rate of factor VII in plasma was found significantly decreased.

The disorder seems to be transmitted as an autosomal intermediately dominant trait.

A high incidence of cerebral apoplexy was recorded in the patients, and the first cerebrovascular attack had in most affected patients occurred at a relatively early age.

In some of the patients attacks of localized edema, severe headache and abdominal pain, and different types of allergy remind of the problems of the demonstrated non-coagulation properties of factor XII.

The results are discussed.
New Families with Factor XII Deficiency
Authors: Egeberg O
Published: June 2018

Hereditary factor XII deficiency is reported in 2 unrelated Norwegian families.

Case 1 was a 50 year old female, who was investigated because of a subcutaneous hematoma of unexplained cause. She had bruised easily, but neither she nor members of her family had suffered from definite and marked bleeding tendency. In the last years she had had hemoptyses of unknown cause. Five years ago she had a slight cerebral vascular episode with temporary hemiparesis in extremities. A sister had died 46 year old in cerebral apoplexy. The parents were first cousins.

Case 2 was a 72 year old male. He had no definite history of bleeding tendency, neither had members of his family. He suffered from diabetes, hypertension and vascular encephalopathy. After the age of 67 he had several attacks of cerebral apoplexy with paresis of extremities, ataxia and parkinsonism.

Blood factor XII was for both case 1 and case 2 found lower than 1% of normal average, while other coagulation factors were in the main normal. A probable partial factor XII deficiency was demonstrated in some of the relatives of case 1 and case 2, consistent with the hypothesis that the principal patients were homozygous for their coagulation abnormality.

The study lends some support to a hypothesis that a factor XII defect might contribute to a hemostatic disorder, and especially to an increased risk for cerebral apoplexy.
Fibrinogen Recovery in Fibrinolytic Dogs
Authors: Dulock M. A , Kolmen S. N
Published: June 2018

Hypoprothrombinemic dogs with or without a superimposed hypofibrinogenemia were allowed to recover spontaneously or under the influence of vitamin K. The hypoprothrombinemic status was corrected more rapidly in K-treated animals irrespective of the fibrinogenemic status.

Hypofibrinogenemic dogs, irrespective of supplemental vitamin K, showed a biphasic rate of recovery. The initial phase was accelerated when vitamin K was administered, the second phase was not altered by vitamin therapy.

It is suggested that vitamin K influence fibrinogen recovery in a manner analogous to its influence on prothrombin recovery; namely, “finalization” of precursor protein and accelerated release of the protein into the circulating fluid compartments.
Protection by Catatoxic Steroids against Phenindione Overdosage*
Authors: Selye H
Published: June 2018

In rats the severe and often fatal hemorrhagic diathesis induced by phenindione overdosage can be prevented by various catatoxic steroids such as ethylestrenol, SC-11927, spironolactone, norbolethone and oxandrolone. Conversely, steroids previously shown to possess no catatoxic potency in other test systems offer little or no protection against phenindione intoxication.
Inhibition of Platelet Aggregation by Dialysable Fibrinogen Degradation Products (FDP)
Authors: Stachurska Jolanta , Latałło Z , Kopeć Maria
Published: June 2018

During prolonged proteolysis of fibrinogen by plasmin dialysable, low molecular fragments accumulate which inhibit platelet aggregation induced by thrombin, ADP, adrenaline and noradrenaline. These fragments isolated by dialysis were separated on sephadex G-25 column. The active component has probably a molecular weight lower than 5,000 and does not contain aromatic amino acids.
Platelet Reactions and Immune Processes
Authors: Jobin F , Tremblay France , Morissette M
Published: June 2018

We have studied the effect of chymotrypsin substrates and inhibitors on the aggregation of human platelets by collagen, latex, and epinephrine :

1. We have found that platelet aggregation was inhibited by most chymotrypsin substrates and inhibitors which we studied.

2. In general, there was a positive correlation between the effectiveness of the compounds as chymotrypsin substrates or inhibitors on one hand, and as platelet aggregation inhibitors on the other hand. However aromatic amino acid derivatives acetylated on the α-amine group were much less effective with platelets than they are with chymotrypsin.

3. Chymotrypsin substrates and inhibitors also inhibit the anaphylactic release of histamine. The view is presented that the platelet release reaction and the mast cell release reaction have several common biological and biochemical features.

4. The possible role of platelet esterases in platelet thrombogenetic reactions is discussed in the light of the present knowledge of the role of cell bound esterase in several inflammatory or immune cellular processes.
Amino Acid Transport into Human Platelets and Subsequent Incorporation into Protein
Authors: Cooper I. A , Firkin B. G
Published: June 2018

Human platelets are known to contain various protein components. Among them are fibrinogen and other soluble proteins. The origin of such proteins has not been clear.

Studies were designed to demonstrate the ability of the platelet to incorporate amino acids and subsequently utilise these for de novo protein synthesis.

Seven different 14C labelled amino acids were used, cysteine, lysine, serine, glutamic acid, proline, valine und leucine.

Active incorporation into platelets of all these amino acids was demonstrated with some evidence for incorporation of cysteine, lysine and serine into the fibrinogen and soluble protein.
The Effect of Adenosine Monophosphate, Arcaine and Anti-Inflammatory Agents on Thrombosis and Platelet Function in Rabbits
Authors: Peterson Jane , Zucker Marjorie B.
Published: June 2018

Thrombi were produced by exposing femoral veins of rabbits to sodium morrhuate followed by partial ligation. The incidence of occlusive thrombosis in 30 min was 95% in animals with or without the infusion of 50-60 ml isotonic saline/kg body weight in 1½–2½ hrs. Comparable infusion of 0.04 M adenosine monophosphate reduced the incidence to 53% (p < 0.01). Arcaine was ineffective even at a toxic concentration. Injection of up to 180 mg phenylbutazone, 25 mg sodium salicylate, or 8.5 mg acetylsalicylic acid (ASA) per kg did not affect the incidence of occlusive thrombosis, but from 15 to 100 mg ASA per kg reduced the incidence to 46% (p < 0.01). Suspensions of connective tissue or collagen particles caused somewhat greater release of platelet-bound 14C-serotonin in heparinized than in citrated, platelet-rich rabbit plasma, and ASA more readily inhibited connective tissue- or collagen-induced aggregation in the latter. With varying connective tissue concentrations, this drug caused a constant reduction in the amount of 14C-serotonin released from the platelets in citrated, platelet-rich rabbit plasma, whereas considerably greater inhibition was observed in many samples of citrated, platelet-rich human plasma.
Quantitative Determination of Plasminogen
Authors: Bruhn H. D , Müller L , Duckert F
Published: June 2018

A modification of the caseinolytic assay for plasminogen is described. This assay system is characterized by the following features :

1. Urokinase is used as activator achieving a complete activation of the plasminogen whereas with streptokinase caseinolytically inactive plasminogen-activator complexes are formed.

2. All incubation times are reduced to the minimum which is still compatible with accuracy.

3. Results are expressed in percent of a standard of ten normal plasmas.

4. In this two-stage assay-system (activation of plasminogen to plasmin, digestion of casein by plasmin) both stages proceed simultaneously in the same system, thus the plasmin formed is stabilized “in statu nascendi” by the casein.

5. Several conditions (stability of plasminogen in frozen plasma, use of anticoagulants, reproducibility) are defined.
A Fixation-Shadowing Technique for Electron Microscopic Visualization of Platelets, Subcellular Material, and Fibrin
Authors: Stewart G. J
Published: June 2018

Plasma components were visualized in three-dimensional detail by a method which depends on attaching plasma components, including platelets and fibrin, to a siliconized surface where they can be fixed, dehydrated and shadowed. Citrated PRP and blood contained a mixed population of discoid and dendritic platelets. Discoid platelets were thin with gently changing elevations and depressions on their surfaces. Dendritic platelets exhibited a random number and arrangement of dendritis. The “bodies” of dendritic platelets appeared to be thicker than discoid platelets. After thrombin action, the “bodies” from which dendrites radiated resembled various irregularly shaped geometric forms whose thickness was approximately equal to their width. Continued thrombin action caused disintegration of platelet membranes.

Fibrinogen could not be resolved. However, after thrombin action, extensive polymerization of fibrin monomers into protofibrils about 130 Å wide was observed well before appreciable lateral or vertical polymerization had occurred. Later, large strands with frequent points of Y-type branching were common.

The method has clinical potential since the entire procedure is simple and can be completed in less than an hour.
Changes in the Ultrastructure and Number of Platelets Induced by an Adrenochrome Complex
Authors: Stewart G. J
Published: June 2018

Adrenochrome semicarbazone injected intramuscularly into apparently healthy human volunteers resulted in a decrease in the number of circulating platelets after 30 min. The decrease ranged from 9 to 44% with an average of 24%. The platelet count returned to near normal by 60 min. A similar concentration had no effect in vitro. The sodium salicylate carrier used to solubilize the adrenochrome complex had no effect on platelet numbers in vivo or in vitro.

Blood taken 30 min post injection and prepared by a fixation-shadow cast technique contained many disintegrating platelets and a high concentration of membrane fragments and free organelles. Thin sections of platelets revealed extensive intracellular alteration, but physically intact limiting membranes. Many free vesicles of various sizes and shapes and a few free mitochondria were shown in cross section.

Two major metabolites isolated from human urine after adrenochrome semicarbazone injection caused platelet disruption when added to citrated PRP in vitro. The disruption was reflected by a decrease in the number of platelets and by the electron microscopic appearance of fixed-shadow cast preparations.

It is suggested that the sequence of events observed in this study may represent, greatly exaggerated, a process which occurs in the body constantly as a small amount of epinephrine seems to be metabolized through an adrenochrome pathway.
Prostaglandins and Platelet Aggregation in Vivo
Authors: Kloeze J
Published: June 2018

Prostaglandins E1 and ω-homo-E1 which were shown previously to inhibit adenosine diphosphate (ADP)-induced platelet aggregation in vitro have now been found to inhibit this process also in vivo. Both prostaglandins inhibit transient thrombocytopenia induced by intravenous injection of ADP; PGE1 increases also the LD 50 of ADP when injected in high amounts into young rats. In both cases platelet aggregation in vivo is the primary cause of the phenomena observed.

The symptoms observed on overdosing ADP by intravenous injection are unconsciousness within 10-20 sec after completion of the injection immediately followed by respiratory arrest and eventual death of the animal, generally within 10 min. It seems that blocking of the supply of blood to the brain by platelet thrombi, which on histological examination were found to occlude blood vessels in different organs, is the most important causative factor of the symptoms observed.
Laboratory Control of Oral Anticoagulants
Authors: Loeliger E. A , Meuwisse-Braun J. B , Muis H , Buitendijk F. J. J , Veltkamp J. J , Hemker H. C
Published: June 2018

The therapeutic range in oral anticoagulation, which is defined as the range of hypocoagulability resulting in optimal thrombosis prophylaxis and an acceptable bleeding tendency, is monitored by assay procedures of which the majority are modifications of Quick’s original prothrombin time test. With respect to individual patients on stabilized anticoagulation, the different modifications commonly used give the same information, the reliability depending more on the accuracy than on the sensitivity of the tests. The results do not appear to be comparable in terms of conventional reference curves or prolongation ratios of the coagulation times found, but on the basis of painstakingly defined normal and patient plasma, the mean of the factor II and factor X activity present in patients’ plasma proved to be a useful common denominator. In terms of this common denominator, the therapeutic range to be aimed at lies between (8 to) 10 and 20(to 25)percent.
Coagulation Findings in Rats with Experimental Hypersplenism and Their Changes after Splenectomy and after Administration of Adrenaline
Authors: Pudlák P , Farská I , Brabec V , Pospíšilová V
Published: June 2018

1. The following coagulation changes were found in rats with experimental hypersplenism: a mild prolongation of the recalcification time, shortened times in Quick’s test, a lowered activity in plasma thrombin time and shortened times in the partial thromboplastin test. Concentrations of factor II, V, VII (+X), VIII and X did not differ from those of normal control rats.

2. The administration of adrenaline to hypersplenic rats induced the correction of the partial thromboplastin test, Quick’s test and plasma thrombin time to normal values. Concentrations of coagulation factors were not significantly changed. An increase was found in factor V.

3. Splenectomy performed in hypersplenic rats was followed by a shortened recalcification time, a prolongation of the partial thromboplastin test and of the test with partial thromboplastin and kaolin. A prolongation was also observed in Quick’s test. Complete correction of plasma thrombin time was not observed. The concentration of factor VII increased.

4. The administration of adrenaline to splenectomized rats with experimental hypersplenism did not induce any significant changes with the exception of a corrected plasma thrombin time and a decreased concentration of factor VIII.

5. A different reaction of factor VIII to adrenaline in normal and hypersplenic rats is pointed out.
A Machine for the Determination of the Whole Blood Clotting Time
Authors: Watt D. L
Published: June 2018

The whole blood clotting time in glass tubes is widely used for the control of heparin therapy. In the investigation of coagulation disorders the whole blood clotting time is commonly done both in glass tubes and in tubes with non-wettable surfaces.

This presentation concerns the development of a portable mechanical device, the Coagulation Timer, to perform this test. The end point is measured automatically by a photo-electric mechanism. Only a few minutes are required to draw blood and place samples in the machine, which may then be left unattended.

Data are presented to show that results obtained using glass tubes in the Coagulation Timer correlate well with those of a technician using a modification of the Lee White method. Further data are presented establishing the normal range for the whole blood clotting time using polystyrene tubes in the Coagulation Timer.
The Treatment of Patients with Factor-V Deficiency
Authors: Rush B , Ellis H
Published: June 2018

Two patients with congenital factor-V deficiency and a third with a combined deficiency of factor V and factor VIII are described. Under cover of fresh frozen plasma, tooth extractions were performed on two of these patients and spontaneous bleeding arrested.

It is concluded that the achievement of a blood level of factor V of 20 per cent once daily is sufficient to assure adequate haemostasis. A low recovery of factor V activity in the plasma following infusion was found. However, in spite of this, adequate blood levels were easily attained due to the excellent preservation of factor V activity in the stored fresh frozen plasma.
Platelet Function in Congenital Afibrinogenemia
Authors: Gugler E , Lüscher E. F
Published: June 2018

Platelet functions have been studied in relation to hemostasis in two patients with congenital afibrinogenemia.

Neither in the plasma nor in the aqueous platelet extracts of these patients was fibrinogen detectable by immunoelectrophoresis or with the aid of the Ouchterlony technique. ADP-induced platelet aggregation, adhesion to connective tissue particles, viscous metamorphosis under the influence of thrombin, clot retraction activity of the platelets, as well as their factor 3 activity were all found normal. Abnormal was the behaviour of the patient’s platelets on glass surfaces : they were unable to adhere to glass and the typical spreading on such surfaces was equally missing. This defect was normalized in vitro by the addition of small amounts of fibrinogen and correspondingly the patients platelets showed normal adhesiveness after fibrinogen transfusions. Normal platelets, suspended in afibrinogénémie plasma lost their adhesiveness toward glass surfaces.

After transfusion of Cohn fraction I the prolonged bleeding time of the patients was normal and the clinical improvement presisted for a period of about 3 weeks, this inspite of the fact, that no fibrinogen was detectable by the usual methods 10 days after the transfusion.

The significance of these results as well as their implications for the role of fibrinogen in hemostasis are discussed.
Observations on Factor VIII (Antihaemophilic A Factor) Stability in Rabbit and Rat Plasma Estimation of Factor VIII in Rat Blood by a New Method
Authors: Nilsson D , Waaler B. A
Published: June 2018

1. Factor VIII activity of rat and rabbit plasma can be measured with a modification of the thromboplastin generation test.

2. Using this method it can be shown that factor VIII activity is unstable on storage and on repeated freezings and thawings in oxalated plasma from the two animal species. The factor VIII activity is especially unstable in oxalated rat plasma, from which it disappears almost completely by four or more repeated freezings and thawings.

3. A rat oxalated plasma, which had been frozen and thawed ten times, could be used as a factor VIII-free reagent in a simple one-stage test system for measurements of this factor in rat or rabbit plasma.

4. The method developed may be used with rat tail capillary blood as test material, making repeated observations on rats possible. The use of the method is discussed.
Resistance to activated protein C, the FV: Q506 allele, and venous thrombosis
Authors: Hillarp A. , Rosen S. , Zöller B. , Dahlbäck B.
Published: June 2018

Vitamin K-dependent protein C is an important regulator of blood coagulation. After its activation on the endothelial cell surface by thrombin bound to thrombomodulin, it cleaves and inactivates procoagulant cofactors Va and Villa, protein S and intact factor V working as cofactors. Until recently, genetic defects of protein C or protein S were, together with antithrombin III deficiency, the established major causes of familial venous thromboembolism, but they were found in fewer than 5-10% of patients with thrombosis. In 1993, inherited resistance to activated protein C (APC) was described as a major risk factor for venous thrombosis. It is found in up to 60% of patients with venous thrombosis. In more than 90% of cases, the molecular background for the APC resistance is a single point mutation in the factor V gene, which predicts substitution of an arginine (R) at position 506 by a glutamine (Q). Mutated factor V (FV: Q506) is activated by thrombin or factor Xa in normal way, but impaired inactivation of mutated factor Va by APC results in life-long hypercoagulability. The prevalence of the FV:Q506 allele in the general population of Western countries varies between 2 and 15%, whereas it is not found in several other populations with different ethnic backgrounds. Owing to the high prevalence of FV:Q506 in Western populations, it occasionally occurs in patients with deficiency of protein S, protein C, or antithrombin III. Individuals with combined defects suffer more severely from thrombosis, and often at a younger age, than those with single defects, suggesting severe thrombophilia to be a multigenetic disease.