bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Blood Coagulation Factor V
Authors: Kahn M. J. P , Hemker H. C
Published: June 2018

The interaction between stearates and coagulation factors consists of adsorption of the factors and partial activation resulting in thrombin formation. Factors V and XI are most readily adsorbed, closely followed by factor X.

Activation is seen most clearly with low concentrations of the adsorbant. It can be inhibited by omission of Ca++ ions and addition of hirudin, thus it involves most probably the generation of thrombin. No thrombin is found in the reaction mixture due to the strong adsorption of thrombin on stearates. The effects of activation are small compared to the effect of adsorption time, pH, temperature and hirudin.

Activity of factor V can be demonstrated in the adsorbed state but the factor cannot be eluted. Factor X shows no activity when adsorbed, but can be eluted from the powder. This suggests that the biological activity of factor V resides in a hydro-phylic part of the molecule, whereas the active centre of factor X probably is hidden but not destroyed by hydrophobic surfaces. The implications of these findings for the concept of prothrombinase formation on phospholipids are discussed.
Thrombosthenin - Electron Microscopical Studies on Its Localization in Human Blood Platelets and Some Properties of Its Subunits
Authors: Bettex-Galland M , Lüscher E. F , Weibel E. R
Published: June 2018

1. Thrombosthenin A, the actin-like component of the contractile protein of blood platelets, was prepared in its monomeric or globular form and compared by gel electrophoresis with actin from rabbit striated muscle. Both proteins migrate at the same speed.

The ultrastructure of the fibrillar form of thrombosthenin A was studied by negative contrast technique in the electron microscope. The pictures reveal a helicoidal, double-stranded, beaded structure similar to the fibrillar form of muscle actin. From measurements of periodicity it was concluded that the protein unit must have a diameter of approximately 35 Å.

2. The structure of thrombosthenin in its superprecipitated form, also on negative contrast pictures, shows the presence of the fibrillar form of thrombosthenin A and of large, spindle-like aggregates of thrombosthenin M.

3. Thrombosthenin in the precipitated and superprecipitated form was fixed and examined on ultra-thin sections. The precipitate is built up of fine, evenly distributed strands due mainly to the presence of the fibrillar form of thrombosthenin A; the super-precipitate shows an obvious contraction of the protein material made up of thin filaments of thrombosthenin A and spindle-like, well contrasted large needles of thrombosthenin M.

4. Glycerol-extracted normal, human platelets were exposed to conditions favoring precipitation and superprecipitation of thrombosthenin : it was possible to localize the contractile material in the platelet cytoplasm on the basis of its characteristic structure in the contracted state.

5. Normal platelets were fixed and examined by means of electron microscopy: the complex structure of the marginal region is described and possible relationships between its structure and the contractile protein are discussed.
Platelet Reactions and Immune Processes
Authors: Jobin F , Tremblay F
Published: June 2018

We have studied the interaction between gammaglobulin, complement and several surfaces, in view of gaining a better insight into the molecular mechanisms of the platelet-surface interaction :

1. Glass, polystyrene latex, carbon, kaolin and celite particles are known platelet-activating surfaces. All these surfaces activated complement when coated with gammaglobulin. Collagen however did not show complement fixing ability.

2. Bentonite and betamethasone acetate particles also fixed complement when coated with gammaglobulin.

3. The mechanism of complement fixation induced by these various surface-gammaglobulin complexes was found to be very similar to the reactions induced when immune complexes fix complement.

4. The diverse mechanisms of activation of IgG molecules and the various biological and immunochemical properties of activated IgG are reviewed and discussed.

5. The view is presented that many non-immune as well as immune activators of platelet reactions have in common the ability to activate complement; the possible significance of this property and the role of IgG activation in the induction of platelet reactions are discussed.
A Simple Test for Measuring Platelet Aggregation
Authors: Holdrinet A , Ewals M , Haanen C
Published: June 2018

A simple method of measuring platelet aggregation is described which is suitable as a screening test in studies of haemostasis. This test is based on the phenomenon that blood platelets present in blood in the form of aggregates, are more rapidly deposited during centrifugation than platelets present in dispersed form.

A comparative study was made of platelet concentration in the supernatant plasma of slowly centrifuged EDTA-blood, heparinized blood and heparinized blood mixed with ADP (end concentration 4.5 μg/ml).

As expected, the platelet concentration was always highest in the EDTA-plasma because EDTA prevents platelet aggregation and disperses platelet aggregates if already present. The difference in platelet count between EDTA-plasma and heparin-ADP, expressed as per cents of the count in EDTA-plasma, was called ADP-aggregation. The ADP-aggregation exceeded 79% in 35 normal subjects. It was lower than 79% in 6 of 9 von Willebrand patients, 11 of 13 relatives of these patients and 7 of 8 uraemic patients.

The percentual difference in platelet concentration between EDTA-plasma and heparinized plasma was called spontaneous aggregation. This was significantly lower in von Willebrand patients and their relatives than in the control group. By comparing all groups of patients collectively with the normal control group, an even more marked difference in spontaneous aggregation was found.
Interaction of Bacterial Endotoxin and Liquoid with Blood Platelets: Aggregation and Decrease in the Electrokinetic Charge
Authors: Gröttum K. A , Hjort P. F , Jeremic M
Published: June 2018

The effects of Endotoxin and Liquoid on the electrophoretic mobility of human platelets and erythrocytes in vitro and on rabbit platelets and erythrocytes in vivo and in vitro have been investigated.

Liquoid reduced the electrophoretic mobility of human platelets to 74% of normal and rabbit platelets to 59% in vitro and to 68% of normal in vivo, while the erythrocytes were unchanged. Liquoid induced massive aggregation of both human and rabbit platelets. In very high concentrations, Liquoid increased the electrophoretic mobility of human platelets and did not induce aggregation.

Endotoxin reduced the electrophoretic mobility of rabbit platelets to 83% of normal and aggregated the platelets, but had none of these effects on human platelets.

The effects of Endotoxin and Liquoid were inhibited by EDTA, but not by ADPase, suggesting that aggregation was not mediated through ADP.

We conclude that Liquoid has the same pattern of effects on the electrokinetic charge of platelets and platelet aggregation as the acid polymeric agents dextran sulphate and heparin. There was good correlation between reduction in the electrokinetic charge of the platelets and platelet aggregation. There were striking similarities between the effects of these agents and Endotoxin.
Über eine Neuraminidase in den Thrombozyten und Erythrozyten des Rindes
Authors: Gielen W , Etzrodt Jacqueline , Uhlenbruck G
Published: June 2018

Das Homogenat lysierter Rinderthrombozyten weist eine Neuraminidase-Aktivität auf. Das Enzym ist strukturgebunden. In den Überständen nach Zentrifugation lysierter Thrombozyten fanden wir nur eine sehr geringe Neuraminidasewirkung. Ebenso wie die Influenzavirus-neuraminidase (13) und die Gehirnneuraminidase der Ratte (22) kann die Neuraminidase der Thrombozyten und der Erythrozyten durch Pronase solubilisiert werden. Die Neuraminidase der Thrombozyten und der Erythrozyten dürfte für die Funktion dieser Zellen und für den Stoffwechsel neuraminsäure-haltiger Thrombozyten- bzw. Erythrozytenbestandteile von Bedeutung sein.
The Kidneys and the Fibrinolytic Activity in the Blood
Authors: Isacson S , Marie Nilsson Inga
Published: June 2018

Extensive analysis of the fibrinolytic activity of the blood after venous occlusion and histochemical determination of the activity in biopsy specimens of superficial veins from patients who had been bilaterally nephrectomized and treated with haemodialysis for 3-15 months pending the availability of suitable transplants appeared to warrant the conclusion that plasminogen activators form in the vessel walls and do not substantiate the earlier reports of an essential role of the kidney in maintaining fibrinolysis of the blood.
Abnormal Fibrin Stabilization in Renal Failure
Authors: Losowsky M. S , Walls W. D
Published: June 2018

Plasma F.S.F. activity was measured by a quantitative technique in 41 patients with renal failure. It was subnormal in 35, being undemonstrable in 32.

There was no significant difference in activity between patients with acute and patients with chronic renal failure, and co-existing jaundice had no significant effect on plasma F. S. F. activity.

Plasma fibrinogen concentrations were frequently increased. Patients with the highest levels of plasma fibrinogen tended to retain demonstrable F.S.F. activity.

Plasma F.S.F. activity was not related to the height of the blood urea.

Haemodialysis and peritoneal dialysis had no significant effect on plasma F.S.F. activity.

Plasma F.S.F. activity returned to normal following recovery of acute renal failure.

Diminished plasma F.S.F. activity did not appear to be responsible for abnormal haemorrhage although it may act as a contributory factor.

It is suggested that impaired fibrin stabilization might be responsible for abnormal wound healing in uraemia.
The Influence of Various Plasma Components on the Lysis of Dilute Human Blood Clots
Authors: Gallimore M. J , Shaw J. T. B
Published: June 2018

The influence of various plasma components on the lysis of dilute blood clots has been investigated. Blood from normal subjects was diluted with 0.12 M sodium acetate and the component being investigated was added; the clots which formed on the addition of thrombin were incubated and their lysis was observed. Fibrinogen and factor XIII were found to retard clot lysis. Plasminogen activator accelerated lysis, and the serum antiplasmins and plasminogen had only marginal effects at the concentrations studied. The significance of the dilute blood clot lysis assay is discussed in the light of these observations.
The Purification of Fibrinogen Degradation Products by Pevikon Block Electrophoresis
Authors: Marder V. J , James H. L , Sherry S
Published: June 2018

The use of Pevikon block electrophoresis for the purification of bulk quantities of the major end-products of plasmin digestion of fibrinogen has been described. Greater than 50% yields of Fragments D and E were obtained, each free of contamination with the other.
Diffusion Characteristics of Human Plasminogen(as Shown by Two Agar Diffusion Techniques)
Authors: Stuckey R. J , Wolf P
Published: June 2018

The relative diffusion rates of human plasminogen in agar has been compared with immune rabbit γ globulin and with streptokinase. A ratio of 1.1106 was found for plasminogen/immune rabbit γ globulin diffusion and a ratio of 0.80 for plasminogen/ streptokinase. These values were unaltered when plasminogen in normal fresh plasma and serum was replaced by three differently prepared plasminogen concentrates. Taking the D20 value for rabbit γ globulin as 4.23 × 10–7 cm2 sec−1 and for streptokinase the value of 6.1 × 10–7 cm2 sec–1, the corresponding values for human plasminogen were 4.7 and 4.9 × 10–7 cm2 sec–1. The widely divergent D20 values for human plasminogen and plasmin in the literature are reviewed and discussed.
Fibrinolytic Activity of the Arterial Wall
Authors: Onoyama K , Tanaka K
Published: June 2018

The tissue fibrinolysis was studied in 550 specimens of 7 kinds of arteries from 80 fresh cadavers, using Astrup’s biochemical method and Todd’s histochemical method with human fibrinogen.

In the microscopically normal aortic wall, almost all specimens had the fibrinolytic activity which was the strongest in the adventitia and the weakest in the media.

The fibrinolytic activity seemed to be localized in the endothelium.

The stronger activity lay in the adventitia of the aorta and the pulmonary artery and all layers of the cerebral artery.

The activity of the intima and media of the macroscopically normal areas seemed to be stronger in the internal carotid artery than in the common carotid artery.

Mean fibrinolytic activity of the macroscopically normal areas seemed to decrease with age in the intima and the media of the thoracic aorta and seemed to be low in the cases with a high atherosclerotic index.

The fibrinolytic activities of all three layers of the fibrous thickened aorta seemed to decrease, and those of the media and the adventitia of the atheromatous plaque to increase.

The fibrinolytic activity of the arterial wall might play some role in the progress of atherosclerosis.
Fibrinolytic and Renin Activity in Renal Vein Blood of Patients with Renovascular Hypertension
Authors: Nowak A , Kokot F , Czekała Z , Dosiak J , Kuska J
Published: June 2018

The fibrinolytic system has been studied in 20 patients with renovascular hypertension.

Renal and hepatic venous blood was drawn by selective cathetherisations, while peripheral blood was obtained from the inferior vena cava above the bifurcation. In all blood samples the euglobulin fibrinolysis, antiplasmin, plasminogen, fibrinogen, and plasma renin activity were determined.

Samples were taken at recumbency and after tilting to 80° for 30 min. In contradistinction to plasma renin activity no differences of the fibrinolytic activity between renal and peripheral venous blood even in that obtained from ischemic kidneys were proved.

No diminished secretion of plasminogen activator by ischemic kidneys in man was stated.

In the light of the data obtained the participation of fibrinolytic system in the pathogenesis of renovascular hypertension is doubtfal.
The Effect of Intravenously Injected Adenosine Diphosphate in Rat and Rabbit
Authors: Bosshardt D. K , Howe E. E
Published: June 2018

Very large quantities of ADP injected intravenously into rats and rabbits were found to disappear within a matter of minutes. Dietary changes which favor thrombus pro duction did not alter this capacity for ADP elimination. It seems unlikely that varia tions in circulating ‘ADPase’ are involved in thrombus formation.
On the Effect on Human Thrombocytes of Synthetic Organic Fibrinolytic Compounds
Authors: Molinas F , von Kaulla K. N
Published: June 2018

The effect of various synthetic organic fibrinolysis-inducing compounds was investigated on platelets in plasma and on washed platelets. To a varying degree the com pounds induced a concentration-dependent platelet aggregation. Some at higher molarities cause lysis of platelets. The same molecular modifications which reduce the fibrinolytic activity also seem to reduce the effects of the compounds on platelets. Platelet aggregation by the compounds was reduced by adenosine, adenosine monophosphate, and some other ADP-inhibitors, but there was no proof that the compounds act by releasing ADP from the platelets. With fluorescent compounds their attachment to platelets was demonstrated.
Clumping of Blood Platelets by Heat Aggregated Gamma-Globulin
Authors: Davis R. B , Holtz G. C
Published: June 2018

The influence of heat-aggregated γ-globulin on the in vitro clumping of rabbit blood platelets was investigated in detail. Clumping was found to be dependent on the amount of γ-globulin added to the system. Clumping began within 60 sec, and was influenced by the amount of heparin in the system. Incubation of platelet-rich plasma with adenosine prior to the addition of heat-aggregated γ-globulin reduced the extent of platelet aggregation but did so only after aggregation was well under way, 150 sec after addition of γ-globulin. The extent of platelet clumping by aggregated γ-globulin was significantly increased by non-aggregating quantities of epinephrine, nor-epinephrine, and 5-hydroxytryptamine in the system; however, bradykinin and histamine were without effect. Electron microscopic observations of platelet aggregates showed that variable destructive changes were present in platelet aggregates, with loss of organelles and platelet hyaloplasm. Marked pseudopod formation was observed in platelet aggregates formed by epinephrine and aggregated γ -globulin. The significance of the findings in relation to the problem of arterial thrombosis is discussed.
An Abnormal Pattern of Adenosine Diphosphate-Induced Platelet Aggregation in Acute Myocardial Infarction
Authors: Zahavi J , Dreyfuss F
Published: June 2018

Platelet aggregation as induced by A.D.P. has been studied using the fragiligraph. With this instrument continuous registration for 60 min of the aggregation - disag gregation - behaviour of platelet rich plasma (P.R.P.) has become practicable and a number of parameters of the curves could then be defined and analysed. Specimens from 24 male patients with acute myocardial infarction and 14 normal controls were compared. P.R.P. of the controls exhibited a short phase of an initial rise in optical density (O.D.) lasting 10-20 sec, a phase of decreasing O.D. (5 min), pointing to platelet aggregation and a phase of disaggregation afterwards. The samples of the myocardial patients differed clearly in several aspects : in most of them (18) the initial rise in O.D. was absent and aggregation started immediately; it was though slower but reached a greater extent. The time of maximum aggregation was significantly greater in the patients and there was no overlap with the controls. Coarse aggregates were clearly visible. Final disaggregation was either minimal or absent. At a concen tration of A.D.P. 0.59 γ/ml, the aggregation curve was biphasic in most patients, whereas it was monophasic in the controls. The curves obtained were mathematically analysed including the definition of a parameter called “aggregation time”, τ, and an attempt was made to clarify several of the properties of the curves in terms of platelet behaviour.
Tierexperimentelle Untersuchungen über die Verlegung der Lungenstrombahn durch Thrombozytenaggregate
Authors: Neuhof H , Heckers H , Mittermayer Ch
Published: June 2018

Die Transfusion von thrombozytenaggregatreichem Konservenblut führt im Tierexperiment, abhängig von der Blutmenge und den darin enthaltenen aggregierten Thrombozyten, zu einer Verlegung der Lungenstrombahn mit einer Drucksteigerung im kleinen Kreislauf und der Gefahr der akuten Rechtsherzinsuffizienz. Die in der Lunge abgefilterten Mikroemboli können mehrere Tage in der Endstrombahn verweilen, so daß auch wiederholte kleinere Transfusionen mit aggregatreichem Blut trotz mehrtägiger Intervalle eine wirksame Verlegung der Lungengefäße verursachen können. Im Hinblick auf die humane Transfusionspraxis erscheinen Patienten mit bereits reduziertem Gesamtquerschnitt der Lungenstrombahn am meisten gefährdet. Bei erforderlichen Bluttransfusionen sollte bei diesen Patienten nur frisches Konservenblut Verwendung finden und der zeitliche Abstand zwischen den einzelnen Transfusionen möglichst groß gehalten werden.
Thrombin’s Esterase Activity in the Presence of Anticoagulant and Other Salts
Authors: Roberts Phyllis S. , Burkat Rosalind K. , Braxton W. E
Published: June 2018

The rates of hydrolysis of TAME by bovine thrombin were studied in the presence and absence of various salts at 37° in 0.25 M Tris . HCl buffer, pH 8.1, with the following results :

1. The rates were inhibited to the same extent in the presence of 0.1 M sodium chloride, citrate, oxalate and sulfate and they averaged 49% of rates in the absence of added salts (controls). In contrast to this, rates in the presence of 0.1 M of the corresponding potassium salts averaged 91 % of the controls.

2. 0.01 and 0.1 M LiCl, KC1, NH4C1 or CaCl2 inhibited the rates 5 and 17% respectively but the same concentrations of NaCl inhibited them 14 and 49% respectively. The inhibition by 0.1 M NaCl was not prevented or reversed by the presence of the same concentrations of any of these chlorides, except to a small extent by KCl.

3. As the concentration of KC1 or NaCl was increased, the rates fell to minimum values and then increased linearly. The minimum rates occurred in the presence of from 0.15 to 0.4 M salts, and with KC1 they were 85% but with NaCl they were 52% of the controls. With 2.5 M KC1 the rates were 141 % but with 2.5 M NaCl they were 68% of the controls.

4. Protamine sulfate (2 or 3 mg/ml) had no significant effects on the reaction when tested at either pH 7.4 or 8.1 (Tris buffers). Inhibition was found only when NaCl was present, whether or not protamine sulfate was also present.

Since potassium citrate, oxalate, sulfate and chloride as well as lithium, ammonium and calcium chlorides inhibited the rates only slightly and all to about the same degree, it was concluded that the inhibition was probably due to non-specific ionic strength effects and not to inhibition by any of the anions or cations tested. On the other hand, the inhibitions found in the presence of the sodium salts were concluded to be due only partly to a non-specific ionic strength effect, but primarily to a specific inhibitory effect of Na+.
Zur Frage der Hageman-Faktor-Aktivität von Prothrombinpräparaten
Authors: Krause W , Egli H
Published: June 2018

Aus gereinigtem Rinderprothrombin, das wir nach der Methode von Seegers isolierten, wurden durch BaSO4-Adsorption sowie nachfolgendes, halbstündiges Erhitzen auf 56° C die Faktoren des Prothrombinkomplexes sowie evtl. Beimengungen von Faktor V und Faktor VIII entfernt. In dem dabei erhaltenen Substrat konnte jedoch mit Hilfe des Kontaktaktivierungstests von Egli und Buscha hohe Hageman - Faktor-Aktivität nachgewiesen werden. Diese war weitgehend unabhängig von der spezifischen Prothrombinaktivität des Ausgangspräparates.
Plasma Fibrin Stabilising Factor (F. S. F.) Activity in Normal Subjects and Patients with Chronic Liver Disease
Authors: Walls W. D , Losowsky M. S
Published: June 2018

A kinetic method for the quantitative estimation of plasma F.S.F. activity is described and discussed.

This method was applied to normal subjects and to patients with chronic liver disease. The plasma F.S.F. activity was uninfluenced by either sex or age, and the normal range has been defined.

A significant decrease in plasma F.S.F. activity was observed in patients with chronic liver disease. Subnormal levels of activity were found in 25% of such patients but were unrelated to episodes of abnormal haemorrhage. Plasma F.S.F. activity tended to be lower in patients with disease of greater clinical severity. In 2 patients showing clinical improvement there was an increase in plasma F. S. F. activity.

It was confirmed that plasma fibrinogen levels increase with age.
In Vivo and In Vitro Binding of Factor VIII to Human Platelets
Authors: Karpatkin Margaret Howell , Karpatkin S
Published: June 2018

Human platelets were tested for the presence of factor VIII employing a modified partial thromboplastin system. Factor VIII was present on the surface of normal platelets after they had been washed five times in human Ringer solution containing 0.1 mM EDTA. Washed platelets from VIII deficient patients adsorbed factor VIII from normal plasma both in vitro and in vivo.
Serum Effects Following Tissue Thromboplastin Infusion
Authors: Astrup T , Albrechtsen O. K
Published: June 2018

Tissue thromboplastin injected into the femoral vein of anesthetized rabbits produced intravascular clotting in the vessels through which the thromboplastin flowed. In the systemic arteries macroscopically visible clots were never observed. No trace of tissue thromboplastin could be demonstrated in blood drawn from the carotid artery following infusion of tissue thromboplastin into the femoral vein. The slight, transient enhancement of coagulation of the arterial blood following tissue thromboplastin infusion was caused by a serum effect. After intravenous injection of serum, enhanced activation of coagulation could be observed for a period of up to 2 hrs. It is concluded that tissue thromboplastin, intravenously injected, is removed from the blood during its passage from the femoral vein to the systemic arteries, probably in the capillaries of the lung. True hypercoagulability appears to be due to a serum effect or caused by partial activation of the intrinsic coagulation system. The levels of coagulation precursors in blood are of minor significance.
Fibrin Deposition and Growth of Connective Tissue
Authors: Triantaphyllopoulos D. C , Triantaphyllopoulos E
Published: June 2018

Inhibition of coagulation by the 25-50% ammonium sulfate fraction of lysed fibrinogen or by heparin delays the formation of adhesions between polyvinyl sponges and peritoneum and retards the invasion of the sponges by connective tissue.
Effect of Phlogodym on Tourniquet Shock
Authors: Lázár G , Karády S , Husztik E
Published: June 2018

Our experiments revealed that Phlogodym had a marked adverse effect on the sublethal tourniquet shock of rats. This effect was associated with a simultaneous drop in fibrinogen levels and platelet counts. In the hind limbs of the animals treated with Phlogodym and submitted to tourniquet, a thrombo-hemorrhagic phenomenon which macroscopically and microscopically resembled the Shwartzman Reaction, developed 5 to 20 hrs after the removal of the tourniquet.
Cardioversion et Fibrinolyse
Authors: Częstochowska W Tymiński et Eugenia
Published: June 2018

On a démontré que la cardioversion, au contraire de l’électrochoc employé en psychiatrie, n’augmente pas l’activité fibrinolytique.
Inhibition of the Thrombin-Fibrinogen Reaction by α2-Macroglobulin, Studied by N-Terminal Analysis
Authors: Abildgaard U
Published: June 2018

The influence of α2-macroglobulin on the thrombin-fibrinogen reaction was studied with purified human reagents. The N-terminal changes reflecting fibrinopeptide release was measured.

α2-macroglobulin inhibited progressively the release of fibrinopeptides A and B. Fibrin polymerization was not influenced. The amount of fibrin formed depended on thrombin and α2-macroglobulin concentrations. When initial thrombin concentration was below 0.2 NIH units/ml, physiological α2-macroglobulin concentrations reduced fibrin formation. The contribution of α2-macroglobulin to the inhibition of the thrombin-fibrinogen reaction in plasma was evaluated.
Factor V and Thrombin in the Intrinsic Clotting System
Authors: Ferguson J. H , Ennis Ella Gray W. , Hitsumoto S , White Norma B.
Published: June 2018

Allegedly factor V 1-stage bioassays and an established mode of 2-stage thrombingeneration tests are performed with three alternative prime activators : (A) thrombokinase; (B) Russell’s viper venom (Stypven); (C) tissue thromboplastin (Simplastin), each with adequate cofactors. Study of effects of thrombin and factor V mixtures or preincubates shows a marked apparent potentiation in the 1-stage tests, but no real evidence of such in the 2-stage methods, although these are equally sensitive to changes in factor V activity. Cited (13) new observations in the 1-stage experiments record: (a) that no preincubation of thrombin and factor V is necessary; (b) that thrombin-treated factor V (= Vt) potentiates anew with a second thrombin addition ; and (c) that Vt + thrombin again shows a shift in the Sephadex G-200 elution pattern similar to the difference between the original V and Vt. These facts all constitute a convincing refutation of the theory that factor V is activated by thrombin to a postulated ‘Va’. What is obviously needed is a complete reinterpretation of the uniquely 1-stage results. A novel approach is based on testings of selective combinations of the 5 basic components (prothrombin, thrombokinase, Ca++, phospholipid, and factor V) required for thrombin generation by <1 ìg/ml thrombokinase. The results permit the conclusion that the true explanation is to be found in activities of the prime activator, especially thrombokinase, as controlled by availabilities of the 3 cofactors, namely, factor V, Ca++ions, and phospholipid. Factor V was previously shown to be a determinant of thrombokinase activity during thrombin generation. In no way should the evidence be misinterpreted as any V → Va activation. A new enzymic and colloidal clotting mechanism (12) is reaffirmed, in which factor V has a dual role.
Removal from Bovine Prothrombin of the Substrate for Russell’s Viper Venom
Authors: Milstone J. H , Oulianoff N
Published: June 2018

Bovine prothrombin was prepared by adsorption on barium sulfate. After elution, it was passed through thick filter-cakes of Standard Super-Cel, which removed some venom substrate (factor X). Almost all the remaining venom substrate was removed by repeated passage through columns of DEAE-cellulose. Finally, the ratio of venom substrate to prothrombin was considerably less than 1/1,000 that of plasma. The prothrombin was also poor in factor V. It yielded very little thrombin upon incubation with Russell’s viper venom, factor V, phospholipid and calcium chloride. However, inclusion of bovine plasma at a final dilution of 1/10,000 caused the mixture to produce thrombin rapidly. This system offers promise for the assay of venom substrate in plasma.

Thrombokinase derived from bovine plasma was able, at 0.000071 mg/ml, to substitute for both the venom and its substrate in thrombin-producing systems. However, with this small amount of thrombokinase, phospholipid was indispensable. The system was sensitive to 0.00001 mg phospholipid/ml.

With 1,000 times as much thrombokinase, prothrombin was activated without addition of accessory factors, in the presence of oxalate. Removal of venom substrate did not affect this response of prothrombin. Nor did removal of venom substrate from the prothrombin prevent its activation by crystallized trypsin in the presence of oxalate.
Studies on Tissue Thromboplastin - Its Splitting into Two Separable Parts
Authors: Hvatum M , Prydz H
Published: June 2018

1. Sodium deoxycholate (DOC) splits tissue thromboplastin into two inactive parts, fraction A and fraction B, separable by gel filtration in the presence of DOC.

2. By recombination and subsequent removal of the DOC, the fractions reaggregate and regain full thromboplastic activity.

3. Fraction A consists mainly of protein, while phospholipid is the main constituent of fraction B.
Studies on Tissue Thromboplastin - Electron Micrography
Authors: Hvatum M , Hovig T , Prydz H
Published: June 2018

The ultrastructure of tissue thromboplastin from human brain, purified by sodium deoxycholate extraction and gel filtration, has been studied. A correlation is found between the reaggregation of solubilized thromboplastin, the reappearance of procoagulant activity, and the formation of concentric membraneous structures.

Sodium deoxycholate splits tissue thromboplastin into two fractions, A and B. The ultrastructure of fraction B, which contains 80-90% phospholipid, has been studied.
The Venom of the Boomslang (Dispholidus Typus): In Vivo and in Vitro Studies
Authors: Mackay N , Ferguson J.C , Bagshawe Antonia , Forrester A.T.T , Mcnicol G.P
Published: June 2018

An account is given of the effects of boomslang venom in man. Evidence was found of a fibrinolytic state apparently secondary to the coagulant action of the venom. These features rapidly responded to the administration of specific antivenom. In vitro studies, using a homogenate of boomslang parotids, confirmed the coagulant properties of the venom and showed them to be of much greater potency than the proteolytic actions.
Congenital Factor VII Deficiency Two Cases in Children of Cousins
Authors: Heikinheimo R , Reinikainen M
Published: June 2018

Two siblings with factor VII deficiency are described, whose parents are cousins. The factor VII levels of the parents and 32 other family members were determined. The parents and 17 other relatives were found to be heterozygotes.

One patient (Case No. 1) had a post-operative pulmonary embolism. During her pregnancies, the prothrombin time values did not change.
Circulating Anticoagulant (Antifactor VIII) Treated with Immunosuppressive Drugs
Authors: Sherman L. A , Goldstein M. A , Sise H. S
Published: June 2018

Three cases have been presented who had a circulating antifactor VIII anticoagulant developing spontaneously in non-hemophilic subjects. Following two short courses of azathioprine in one case there were transient incomplete remissions of a degree not seen in the previous 4 months of observation. In the other two cases complete remissions were observed within three weeks of beginning administration of 6-mercaptopurine. In one of these, a brief relapse was retreated successfully. In 4 other cases not given these drugs and in cases reported in the literature, such a rapid remission was not seen to occur spontaneously and happened only infrequently in cases given corticosteroids. On the basis of this experience, we suggest that in the treatment of antifactor VIII, if the disorder shows no improvement with conventional therapy (blood, factor VIII concentrates, and corticosteroids), a trial with immunosuppressive drugs is warranted.
Assay Methods and Standard Preparations for Plasmin, Plasminogen and Urokinase in Purified Systems, 1967-1968
Authors: Johnson A. J , Kline D. L , Alkjaersig Norma
Published: June 2018

To facilitate communication between investigators, the Committee on Thrombolytic Agents of the National Heart Institute suggests standardized reagents and assay methods for the measurement of standard preparations of plasmin, plasminogen, and urokinase with use of casein, fibrin and synthetic esters as substrates.
The Immunoassay of Human Urokinase
Authors: Day Eugene D. , Ball Anne P. , Jeffords D , Woodard W.T , Silver D
Published: June 2018

Urokinase with an activity of 45,200 CTA nnits/mg was used in 0.4 mg amounts with Freund’s adjuvant to immunize four individual rabbits by two injections spaced 4 weeks apart. All antisera were titrated for inhibition of urokinase activation of plasminogen, for double diffusion in Agarose, and for immunoelectrophoresis. Against constant portions of 125I-labelled IgG from each antiserum, 131I-labelled urokinase was titrated by the quantitative precipitin technique. The results from these 4 methods of titration were compared and out of them the following conclusions were drawn :

1. There were 3 main immunogens in the urokinase preparations, one inactive as an activator, one with questionable activity, and one definitely and strongly active as a urokinase. The first two comprised less than 5% of the total antigen mixture; the active third component was more than 20% of the total. About 75% of the total protein was non-precipitable with antibody and was inactive as an activator. One inactive immunogen, I, was a fast β-protein in immunoelectrophoresis at pH 8.2, ionic strength 0.05: the questionably active immunogen, II, was a γ-protein; the active third component, III, was a slow β-protein whose specific activity was estimated to be 230,000 CTA units/mg protein.

2. Antibodies against I and II were in considerably higher titer than the ones to III and their equivalence points were reached at much higher concentrations of added urokinase preparation. A single precipitin line instead of 3 could be obtained by the use of very dilute antisera, but the line was due to the inactive I, not the slow active β-protein, III, nor the questionably active γ-protein, II.

3. All 4 antisera were 100% inhibitory of plasminogen activation activity at the equivalence point of III, but were not inhibitory at the equivalence points of I and II.

4. Urokinase when added to normal human serum could be visualized as easily in double diffusion as when tested in buffer alone.
A Study of Possible Causes of Increased Fibrinolytic Activity during Exercise
Authors: Menon I. S , Burke F. D , Smith P. A , Newell D. J , Dewar H. A
Published: June 2018

The prolonged effect in human volunteers of brief but moderately intense exercise in enhancing fibrinolytic activity has been used to test various parameters which might have been causatively associated with the change.

HMMA, venous blood glucose, body temperature and diastolic blood pressure did not alter significantly at any time. The increase in pulse rate immediately after exercise did not correlate closely with the rise in fibrinolytic activity and disappeared much sooner.

Plasma cortisol and systolic blood pressure had both fallen significantly 1 hr after exercise as compared to their preexercise levels, but there was no significant inverse relationship between these parameters and the changes in fibrinolytic activity.

It is concluded that the parameters measured were unlikely to be responsible for the observed changes in fibrinolytic activity.
Fibrinolytic Activity of Cerebro-Spinal Fluid and the Development of Artificial Cerebral Haematomas in Dogs
Authors: Mihara H , Fujii T , Okamoto S
Published: June 2018

Blood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.
Enhancement of Fibrinolysis by Venous Occlusion Results of Long-Term Thrombelastography and Activator Determination
Authors: Holzknecht F , Spöttl F , Braunsteiner H
Published: June 2018

Global fibrinolysis and activator activity were investigated in venous blood before and after occlusion. Global fibrinolysis was determinated by thrombelastography with a low speed of the paper drive (longterm thrombelastography). The fibrinolysis on the thrombelastographic curves were evaluated by the slant (a°) of the inflectional tangent at the thrombelastographic branch.

A considerable increase of global fibrinolytic activity and also of the activator activity after venous congestion was found. There was a slight correlation between the global fibrinolysis and the activator before occlusion and a strong correlation after congestion. There was, however, no accordance between the regression lines of the two correlations. Other factors of activation of fibrinolysis may be involved.
Fibrinolytische Aktivität in der Pfotenhaut der Ratte im Rahmen der direkten passiven Arthus-Reaktion und pharmakologisch induzierter Pfotenödeme
Authors: Denk H , Förster O
Published: June 2018

Es wurde die fibrinolytische Aktivität bei der direkten passiven Arthus-Reaktion und bei einem Dextran- und Formalinödem in der Rattenpfote untersucht. Bei der direkten passiven Arthus-Reaktion zeigte sich eine Abnahme der Aktivatorwirkung der Endothe]zellen schon in sehr frühen Zeitpunkten; dies dürfte durch eine Endothelschädigung im Verlauf der Antigen-Antikörper-Reaktion bedingt sein. Dadurch wird möglicherweise die Entwicklung der für die DPA typischen Leukothromben ermöglicht. Beim Dextran- und Formalinödem fehlt die Abnahme der fibrinoly tischen Aktivität.
Intoxication with Phenprocoumon (Marcoumar) Pharmacokinetics and Side Effects
Authors: Seiler K , Duckert F
Published: June 2018

A case of severe Marcoumar intoxication is described. Eleven hours after the intake a plasma concentration of 15.75 µg/ml was found which corresponds approximately to the 5-fold therapeutic concentration. Repeated administration of vitamin K1 made it possible to avoid extreme lowering of the activity of the clotting factors II, VII and X and to prevent bleeding. Side effects were not observed. The biologic half-life of Phenprocoumon has been found to be shortened at high plasma concentration (3.7 instead of 5.9 days). It is probable that in extreme concentration the drug is less strongly bound to the plasma proteins.
Relationship between Electrical and Spontaneous Thrombosis
Authors: Brown J.C , Lavelle S.M , Sawyer P.N
Published: June 2018

The triggering of electrical thrombosis on electrodes depends on the coagulation steps prior to factor IX activation. Factor XII may be responsible for this phenomenon. The platelet may also play a role. It has been shown that platelet deposition is visible at potentials more positive than +0.3 V versus the normal hydrogen electrode. The same compounds which inhibit intravascular thrombosis will also impair electrical thrombosis.
Gerinnungsveränderungen bei orthotoper Lebertransplantation am Hund
Authors: Böhmig H. J , Fritsch A , Kux M , Lechner G , Lechner K , Reich N , Stockinger L , Zeitelberger P
Published: June 2018

Bei 16 Hunden wurden bei orthotopen Auto- und Homotransplantationen der Leber Gerinnungsuntersuchungen durchgeführt. Während die Anästhesie, die Präparation der Lebergefäße und Manipulationen an Leber und Lunge keine Gerinnungsveränderungen hervorriefen, kam es nach Anlegen des äußeren venösen Bypass und Entnahme der Leber zu einem Abfall von Fibrinogen, Thrombozyten, Faktor II, Faktor VIII und Antithrombin III. Diese Veränderungen werden als Ausdruck einer Verbrauchskoagulopathie angesehen. Eine leichte Fibrinolyse war gewöhnlich erst am Ende der anhepatischen Phase nachweisbar und dürfte sekundär sein. Nach Implantation der Leber war nach kurzer Latenzzeit ein Wiederanstieg der oben genannten Faktoren und der Thrombozyten zu beobachten. Die möglichen Ursachen für das Auftreten der Verbrauchsreaktion werden diskutiert.
Platelet Changes Induced by Elatericin A
Authors: Joshua H , Shohat B , Cohen I , Gitter S
Published: June 2018

Elatericin A at a concentration of 3 μg/ml causes spicule formation on platelets and inhibits spreading on glass surfaces, viscous metamorphosis and clot retraction. Elatericin A has no effect whatsoever on the activity of isolated platelet factors. However platelet factor 3-availability is decreased by elatericin A. Platelets treated with elatericin A up to a limiting concentration of 30 μg/ml regain their clot retracting activity if washed and reincubated in normal plasma.

Elatericin A does not affect the ATP content nor the ATPase activity of platelets. A normal ADP-release is obtained upon addition of thrombin to elatericin A treated platelets. Addition of ATP and Mg ions does not restore the clot retracting activity of elatericin A treated platelets.
Effect of Inhibitors of Aggregation on Platelet Ultrastructure in Vitro
Authors: Mannucci P. M , Sirigu F
Published: June 2018

Electron microscopy observations are presented on the effect of inhibitors of aggregation on platelet morphology. Moreover the relationship existing between shape changes produced by inhibitors of platelet aggregation and the mechanism of inhibition has also been studied.

Among the inhibitors, nucleotides were without effect on platelet shape, so that their inhibitory action is likely to be related to competition with ADP.

Marked sphering of platelets with scanty modifications of the inner structure was produced by all other agents. They are thought to be active through a damage to the membrane, which is thus made insensitive to the aggregating agents.
Inhibition of Platelet Adhesiveness and Aggregation by Benzyl Alcohol and Phenol
Authors: Zweifler A.J , Sanbar S.S
Published: June 2018

Two amphipathic alcohols, benzyl alcohol and phenol, have been found to diminish adhesiveness of platelets to glass beads and to impair adenosine diphosphate (ADP)-induced platelet aggregation, while ethanol and isopropanol, both completely water soluble, had no inhibitory effects. Comparatively, phenol is a more potent inhibitor than benzyl alcohol. It is suggested that the basis for their antiadhesive effect may be similar to that which underlies their local anesthetic properties.
A Simple Technique for the Experimental Production of Acute Platelet Deficiency
Authors: Dutton R.C , Dedrick R.L , Bulli B.S
Published: June 2018

This report describes a new simple technique for producing acute controlled thrombocytopenia by allowing platelets to adhere to activated carbon granules or glass beads during hemoperfusion of an experimental animal. The level of platelet deficiency produced may be regulated by terminating perfusion when the desired level is reached. Perfusion on consecutive days removes the newly released platelets and restores the thrombocytopenic state.
The Effect of Adenosine Phosphates on the Spreading of Normal Human Platelets
Authors: Linker H , Reuter H
Published: June 2018

The spreading of human platelets requires the presence of ADP as do other platelet functions. In the plasma of patients with a failure of release of ADP from the platelets the also decreased ability to spread can be normalized by exogenous ADP. AMP and ATP inhibit the spreading of platelets.
Die Überführung von Blutplättchen in einen thrombasthenieähnlichen Zustand mit einem 1-Styryl-3.4-Dihydroisochinolinderivat (SDHI)
Authors: Markwardt F , Barthel W , Glusa E , Hoffmann A
Published: June 2018

Das Isochinolinderivat CSDHI bewirkt eine reversible Blockade der für den Ablauf der Hämostase und Thrombose wichtigsten Plättchenfunktionen. Die mit dem Hemmstoff behandelten menschlichen Plättchen verlieren ihre Fähigkeit zur Ausbreitung, Adhäsion, Aggregation und Retraktion sowie zu morphologischen und biochemischen Veränderungen, die durch Thrombin ausgelöst und unter dem Begriff der viskosen Metamorphose zusammengefaßt werden. Eine Hemmung der Gerinnung tritt nicht ein. Die Glykolyse und Atmung der Zellen werden ebenso wie die Fähigkeit zur Serotoninaufnähme nur wenig beeinflußt, dagegen wird die Plättchen-ATPase in gleicher Weise wie die durch Thrombin ausgelösten Reaktionen der Plättchen gehemmt.
Immunfluoreszenzmikrophotometrie zur quantitativen Erfassung antithrombozytärer Autoantikörper
Authors: Denk H , Fischer M , Pilgerstorfer H. W , Schnack H
Published: June 2018

In der vorliegenden Arbeit wurde eine Methode zur Bestimmung antithrombozytärer Antikörper mittels Immunfluoreszenz und Fhioreszenzmikrophotometrie beschrieben und an Beispielen erläutert. Es konnte eine lineare Beziehung zwischen Antikörpermenge (SerumVerdünnung) und Fluoreszenzintensität bei Anwendung der indirekten Immunfluoreszenzmethode nachgewiesen werden. Durch Bestimmung der mittleren Fluoreszenzintensität der Thrombozyten nach Inkubation mit in Stufen verdünntem Immunthrombozytopenikerserum und Vergleich der Werte mit der Basisfluoreszenz der Thrombozyten wurde ein Titer bestimmt, der jener Serumverdünnung entsprach, deren zugehöriger Thrombozytenfluoreszenzintensitätswert sich von der Basisfluoreszenz nicht mehr signifikant unterschied.
The Effect of Urea on Aggregation and Incubation Resistance of Human Platelets
Authors: Reuter H , Linker H
Published: June 2018

Investigations have been carried out to study the effect of urea on aggregation and incubation resistance of human platelets. Urea in high concentrations inhibits the Ca++-induced aggregation in platelet-rich EDTA-plasma while at low concentrations an increased aggregation takes place. Incubation of platelet-rich plasma at 37° C in the absence of divalent cations was performed in the presence and absence of 0.1 M urea. The temperature-induced percentage inhibition of aggregation was found to be significantly lower in the presence of urea.