bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factor VIII and Ristocetin-Induced Aggregation in Sickle Cell Disease
Authors: Mackie I. J. , Bull H. , Walford D. , Brozovic M. 
Published: May 2019

Haemostatic variables were studied in 23 patients with sickle cell disease.(SCD) who were followed over a year. Investigations included measurements of factor VIIIc, VIIIAg, antithroabin III biological and antigen levels, fibrinogen and platelet aggregation to ADP, collagen, porcine AHG and ristocetin. All eight SS patients in the steady state had normal levels of F VIIIc and high levels of F VIIIAg with narked discordance between the two values (mean VIIIc:VIIIAg ratio 0.3). By contrast, 15 patients with SC disease or S thalassaemia tended to show less narked discordance between levels of F VIIIc and F VIIIAg(mean VIIIc:VIIIAg0-7). Patients in the steady state showed normal platelet aggregation to ADP, collagen and porcine AHG, but ristocetin induced aggregation was absent or markedly reduced. Platelet aggregation to ristocetin is absent in most individuals of Afro-Carribean origin and the ristocetin co-factor activity nay be difficult to assess in this ethnic group.During crisis both factor VIIIc and factor VIIIAg invariably high. Factor VIIIAg was studied using crossed isnunoelectrophoresis in 5 patients. in one patient two peaks were found and in the others the F VIIIAg had more anodal nobility than normal. These findings are suggestive of the presence of lower molecular weight fragments of factor VIIIAg and may account for the apparent very high levels as measured by Laurell rocket technique.
Chromogenic Peptide Substrates for Kallikreins and Urokinase
Authors: Claeson G. , Gustavsson S. , Aurell L. , Karlsson G. , Friberger P. 
Published: May 2019

A chromogenic substrate for plasma kallikrein has been modelled after the amino acid sequence preceding one of the scissile bonds of kininogen, that is, the C-terminal part of bradykinin. Similar attempts to use the natural substrates as models for designing synthetic substrates for glandular kallikrein and urokinase have not been successful. However, by means of trial and error (variations of the amino acids in positions P1, P2 and P3) we have obtained correlations between substrate structure and activity. These correlations were then used to construct chromogenic peptide substrates for glandular kallikrein and urokinase.The new substrates have been utilized in methods for the determination of prekallikrein in plasma, kallikrein in urine and urokinase in urine respectively.
Further Evidence of the Involvement of Thrombin in Platelet Release by ADP and Other Agents
Authors: Ardlie N. G. , Akbar Huzoor- 
Published: May 2019

There is evidence of the involvement of coagulation factors in platelet aggregation and the release reaction caused by ADP and collagen but this has been challenged. This report concerns further experiments which can explain the apparently conflicting observations of various laboratories and which provide additional evidence of the involvement of coagulation factors and thrombin in the platelet release reaction caused by ADP and other agents.Washed platelets suspended in a buffer solution responded poorly to ADP with no second phase aggregation or release of [3H]5HT. In contrast, washed platelets suspended in dialysed plasma underwent second phase aggregation and released radioactivity. This response depended on calcium. Dialysed plasma deficient in factors XI or X did not restore second phase aggregation or the release reaction. Hirudin and heparin inhibited second phase aggregation and release by ADP and epinephrine. However, the inhibitory effects of heparin and hirudin on ADP,epinephrine and collagen were not observed when citrate was present. To explore the possibility that a reduction of the free calcium concentration accounts for the inhibition of action of these antithrombin agents by citrate experiments with EGTA were carried out. This alternative chelating agent also prevented the inhibitory actions of heparin and hirudin.These observations support the view that platelets and clotting function cooperatively in platelet reactions involved in haemostasis. We suggest that small amounts of thrombin formed prior to fibrin clotting mediate platelet reactions in haemostasis initiated by collagen and ADP and that secondary aggregation does not represent a citrate artifact.
Hereditary Antithrombin III Deficiency. Evidence of Increased Thrombin Formation in the Early Stage of Hemostasis
Authors: Josso F. , Aurousseau M. H. , Fischer A. M. , Dautzenberg M. D. , Beguin S. 
Published: May 2019

High incidence of thromboembolism in observed in families with antithrombin III deficiency, despite the rather moderate defect (25 to 50 per cent) observed in the affected subjects, considered as heterozygous for the disease. The mechanism by which such a mild deficiency may promote thrombosis still remains unknown.A new family with antirhrombin III deficiency is reported, including three affected generations. Three young male adults of a same sibship died from massive pulmonary embolism aged from 22 to 28 years. In four living members of the family, three of which had antecedents of thrombophlebitis, antithrombin III level was close to 50 per cent by all assay methods used. Electro-phoretic and immunochemical studies failed to demonstrate any qualitative defect of the antithrombin III molecule.In these patients the only abnormalities of hemostasis lied in the early stage of the hemostatic pathway. In vitro, thrombin formation occured very rapidly after initiation of coagulation, as demonstrated by the kinetics of thrombin generation and factors V and VIII activation. In vivo, factors V and VIII were activated during bleeding much more rapidly than in controls and this activation was not suppressed by low doses of heparin (10 u./kg) as in the controls.These findings indicate that antithrombin III acts chiefly in the regulation balance of the early stages of hemostasis and thrombosis.
The Preparation of Platelet-Rich Plasma
Authors: Clarke Noel , McCabe Vincent 
Published: May 2019

Different gravity forces and times have a marked effect on the yield of platelets and plasma obtained from the centrifugation of whole blood (Woods et al. Thrombosis & Haemostasis, 36, 302-310, 1976).The sedimentation of red cells and harvesting of platelets and plasma by centrifugation with step change in the gravity field was modelled in a computer programme, and the effect of the reflux of plasma and platelets was taken into account (methods in reference). The optimum method (at present) was based on a high centrifugal field (Gay = 1740g; Gmax = 1992g; 3000 rpm; rav = 173 mm; rmax = 198 mm) for a short period (75 seconds) followed by a low centrifugation field (Gav = 48g; Gmax = 55g; 500 rpm) for about 3 minutes. During the first stage platelets refluxed to the plasma zone, and during the second stage the red cell zone moves outwards faster than the platelets. The recovery of platelets was 12.6 ± 3.6% higher than that obtained with the optimum single stage centrifugation method using ethylenediamine tetra-acetic acid (EDTA). It is not yet known how representative the recovered platelet populations are in regard to size. The platelet recovery is lower with citrate than EDTA using both methods. These findings were confirmed by optically monitoring the plasma zone in a circular transparent rotor.The centrifugal platelet and plasma yield is also influenced for each individual blood by unknown intrinsic sedimentation properties, e.g. erythrocyte sedimentation rate. The fitting of more precise information to the computer programme is required before the ideal method can be achieved.
Thrombolytic Therapy with Porcine Plasmin: Biochemical and Clinical Results
Authors: Asbeck F. , van de Loo J. 
Published: May 2019

Preliminary results are presented on the systemic action of porcine plasmin which was used as a thrombolytic agent. Patients suffering from acute arterial thromboembolism (2) or deep venous thrombosis (4) received porcine plasmin (pp) in the following dose schedule: 2000 U given as an initial dose within the first 60 minutes, and 2000 U given as a maintenance dose by continuous infusion within the following 8 hours. The maintenance dose was repeated at each of the 2, 3, or 4 consecutive days.Investigations of the plasmas showed a rapid drop of fibrinogen to 50% of the initial value. FDP raised up to 300 μg/ml. There was no change of the mean plasminogen concentration. Systemic fibrinolytic activity was very low and could only be demonstrated in traces during all stages of the therapy. Analysis of the inhibitors showed a continuous drop of the alpha2-macroglobulin to levels of 50-100 mg/dl. Plasmin-antiplasmin complexes were detected in considerable amounts.The treatment was well tolerated by all patients. In one patient, a complete recanalization of a teflon bypass of an iliac artery could be achieved. In the other patients, only partial recanalizations could be demonstrated. A combination of porcine plasmin with streptokinase therapy is possible.
Heparin Cofactor During Early Stage of Coagulation in Vitro and During Bleeding in Vivo
Authors: Birk-Jensen A. Hurlet , Moriau M. , Beys C. Col-De , Gillet C. , Masure R. 
Published: May 2019

Heparin cofactor activity is measured with the amidolytic method according to 0degard (1975) during in vitro coagulation and during bleeding.Heparin cofactor activity decreases differently during coagulation process of PRP or PFP. It is suggested this is due to heparin neutralization by PF4 and/or to thrombin formation. Antithrombin III level is not modified.During bleeding, the same phenomenon is observed when the amount of heparin in the buffer is low enough. Decrease in heparin cofactor activity is already observed on a sample collected less than 90 seconds after the puncture, before any detectable thrombin formation.Decrease in heparin cofactor activity during bleeding is studied in pathological conditions. It is more marked in some hypercoagulable states.
Method for the Control of Fibrinolytic Inhibitors
Authors: Badimón L. , Villaverde C.A. , Borruel M.T. , Valdecasas F.G. 
Published: May 2019

To determine easily and with precision the inhibitors of fibrinolysis, we have developed a method studying the critical Urokinase amount that can produce the fibrin plate lysis in 20 hours of incubation (37° C), by its addition to the fibrinogen solution when the fibrin plate is prepared. Placed on the coagulated fibrin layer samples (20 μl) of blood, plasma, serum or isolated inhibitors from euglobulins supernatant, we obtained circular areas of unlysed fibrin; plotting sample dilution, in logarithmic scale, against unlysed fibrin diameter, in decimal scale, a linear response is obtained. To give a standarization pattern we assayed a Trasylol curve that showed a linear response between 1 and 40 I.U./ml., so the results can be expressed in diameters of unlysed fibrin or in Trasylol units. As standard can also be used Iniprol in a range of 0.5 to 8 I.U./ml. or a pool of normal plasma, or whatever we have to evaluate in progressive dilutions. We have been contrasted this method with thromboelastographic and Blix ones, obtaining correlative results.This is an easy performance method that can be of clinical interest to study a great number of samples and to control the fibrinolytic agent treatment.
Increased Procoagulant Activity of Phospholipid in Thrombo-Embolic Diseases
Authors: Boffa M.C. , Gozin D. 
Published: May 2019

Procoagulant activity of phospholipid has been measured in recalcified plasma as previously described (l), by means of a viperidae anticoagulant phospholi pase A2, specific inhibitor of phospholipid in clotting (2).With reference to a control normal group and to a group of atherosclerotic patients, phospholipid activity was found significantly increased in thrombo-embolic diseases, with maximum frequency after recent embolism,, In the oral contraceptives group, this assay appeared as useful for selecting women predisposed to thrombosis : in fact, about 5% of the treated women showed a high phospholipid activity contrarly to the control group. One month after interruption of the oestrogen treatment, the phospholipid activity became normal. The few cases examined during thrombosis presented a very high activity.In patients with high plasma phospholipid content (hyperlipoproteinemia) phospholipid activity was practically normaL This shows that procoagulant activity of phospholipid is related only to a very small fraction of phospholipid, indépendant of the lipoprotein phospholipid and very likely from platelet origin.
Haemostasis and High Altitude
Authors: Singh I. , Chohan I.S. 
Published: May 2019

On arrival at high altitude there is a tendency towards hypercoaguiation associated with an increase in platelet count, factors X and XII, and thrombo-test activity (TA) which is reflected by decrease in prothrombin time (PT), bleeding time (BT), clotting time in glass (CT-gl) and in silicone (CT-sl), and stypven time (ST). Clot retraction is impaired. This hypercoaguiation state is countered by a compensatory rise in fibrinolytic activity reflected by reduction of clot lysis time (CLT), plasma fibrinogen, and factor VIII.This hypercoaguiation state persists throughout the early fortnight after arrival at high altitude and then starts regressing. On day 3, factor V decreases, BT, and ST are further reduced, and factor VIII shows a rise. On day 7, a progressive rise occurs in factors V, VIII, X and XII, TA, platelet counts and platelet factor 3 (PF-3).CT-gl, CT-sl, PT and ST are further shortened. On day 14, haematocrit rises and of all the parameters, factors V and X and clot retraction return to normal. Throughout the fortnight, factor XII remains high, CLT is short, and platelet adhesiveness remains within normal range.After 2 years’ stay at high altitude, a regression in hypercoagulability occurs and is indicated by persistent short CLT, prolonged BT, CT-sl, PT, ST and reduced TA. Platelet adhesiveness, PF-3, factors V, VIII and XII and clot retraction are restored to normal.
Antibody-Induced von Willebrand’s Disease. Dissociation of Factor VIII Molecular Complex Activities by the Autoantibody
Authors: Gazengel C. , Prieur A.M. , Jacques C. , Girot R. , Josso F. 
Published: May 2019

Acquired Von Willebrand’s disease is reported in a 16 year old girl with systemic lupus erythematosus. Routine coagulation studies showed a normal platelet count, prolonged bleeding time and abnormal glass bead retention. Factor VIII molecular complex respective activities were 8% for VIIIAHF and undetectable for VIIIVWF (Ristocetin aggregation of washed platelets) and VIIIAGN (electro-immunodiffusion).In vitro, the patient’s plasma exhibited an inhibitory activity against exogenous VIIIAGN and VIIIywF but did not neutralize VIIIAHF activity of control plasma, even after a 2 hour incubation at 37°C. This inhibitory activity was supported by the purified plasma IgG fraction. In vivo, following cryoprecipitate administration (20U. VIIIAHF/kg), only 50% of the infused VIIIAHF activity was recovered after 15 mn and the original level was reached 4 hours later. It was only observed a transient peak of VIIIVWF activity and VIIIAGN level did not increase at all after the infusion.After the start of immuno depressive therapy the three factor VIII related activities returned to normal level in the following order : VIIIAHF and VIIIVWF (9-12 days); VIIIAGN (3 weeks).These findings could be explained by the formation of a short-living cirulating immune complex between the antibody and the factor VIII molecular complex. In such an hypothesis the auto-antibody would respect the site of VIIIAHF activity and would mask the site reacting with anti VIIIAGN hetero antibodies.
The Clinical Application of Feiba Immuno in Factor VIII Inhibitor Patients
Authors: Anderle K. 
Published: May 2019

The aim of this report is to summarize the clinical and laboratory effect and possible side-effects arising in the use of FEIBA IMMUNO for treating Factor VIII and IX inhibitor patients.In the time between 22nd November 1974 and today FEIBA IMMUNO was supplied for 104 treatment periods. More than 70 patients in 22 hemophilia centers all over Europe were treated, 59 case reports from 19 of the centers were sent to IMMUNO AG for further evaluation.In 8 cases minor surgery was carried out, of which only one case was complicated by post-operative bleeding. In all other cases different bleeding complications were treated. The clinical effect was difficult to evaluate, but the impression was favourable.FEIBA’s effect on WBCT, the r-value of TEG, and on aPTT are statistically evaluated for two different mean dosages.Acute side-effects were allergic reactions in 5 cases and laboratory signs of DIC in 4 cases, two of which had received extremely high dosages. Calculation of the mean pre- and post-treatment values for platelets and fibrinogen did not show any differences.
Oral Surgery and Dental Treatment for Hemophiliacs
Authors: Evans Bruce E. 
Published: May 2019

The dental needs of hemophilic patients should be managed routinely by conventional dental treatment. Unfortunately many patients do not receive optimal dental care. Consequently such patients develop complications requiring oral surgical procedures. Management of oral surgery for the hemophiliac is based on:1. Thorough preoperative evaluation in conjunction with the hematology service.2. Surgical treatment including antifibrinolytic therapy and local hemostatic measures.3. Postoperative management of complications and followup.
Clinical Use of Factor IX Concentrates
Authors: Ménaché D. 
Published: May 2019

The clinical efficacy of Factor IX concentrates in the treatment of patients with Factor IX deficiency is well recognized. The availability of such concentrates has brought a radical change in the management of these patients. The basis for treatment is to obtain an effective Factor IX hemostatic level in vivo. In these conditions, concentrates have been used to reduce the incidence of hemorrhagic episodes in patients particularly exposed and more often to control hemorrhagic episodes or to prevent hemorrhage in the post operative period. Although thromboembolic complications have occured in some instances the major indication of Factor IX concentrates still remains replacement therapy in patients with Factor IX deficiency.More recently Factor IX concentrates have been used for the treatment of patients with antibody to Factor VIII. Although the therapeutic principle(s) responsible for the Factor VIII inhibitor bypassing activity has not yet been characterized several beneficial effect of both “activated” and non activated Factor IX concentrates have been observed in such patients experiencing minor or severe bleeding episodes. On the other hand we are aware of some cases without beneficial effect of Factor IX concentrates in patients with Factor VIII inhibitor. The major complication would seem to be an anamnestic response in some patients resulting in either a moderate or a considerable increase of the Factor VIII inhibitor titer when compared to the initial level before Factor IX concentrates therapy. If Factor IX concentrates prove to be efficacious in the treatment of patients with Factor VIII antibody special attention would be required in the manufacturing processing in order to avoid an anamnestic response.
Activation of Bovine Blood Coagulation Factor V, A Prerequisite for it of Bind Both Prothrombin and Factor Xa.
Authors: Guillin M.C. , Bezeaud A. , Freeman J.P. , Jackson C.M. 
Published: May 2019

It is known that prior to bind bovine prothrombin and to become fully functional, bovine Factor V must itself be “activated” by either thrombin or an enzyme isolable from Russell’s viper venom. The purpose of this work was to determine if Factor V activation is also required in order for it to bind bovine Factor Xa.This has been investigated by measuring the binding of both “native” (unactivated) Factor V and Factor V activated by the Russell’s viper venom activating enzyme, to a column of agarose-bound Factor Xa. The experiments were also performed using diisopropylfluorophosphate (DFP) inhibited Factor Xa covalently bound to agarose. Both purified bovine Factor V (Va) and bovine plasma were used and gave the same results. In order to prevent initiation of clotting in bovine plasma, heparin wad added to the plasma to promote inactivation of Factor Xa by antithrombin III.The results indicate that Factor V activation is a prerequisite for it to bind Factor Xa ; Factor Va binds both Factor Xa and DFP inhibited Factor Xa, unmodified Factor V does not.These experiments suggest that Factor V may not participate in prothrombin activation at all, until after some thrombin has been formed. If this is so, an alternate pathway by which the first thrombin is generated must be considered and may be proposed to be simply that involving Factor Xa, phospholipid and Ca2+ alone.
The Activation of Plasminogen by Hageman Factor and Hageman Factor Fragments
Authors: Goldsmith G. , Saito H. , Ratnoff O.P. 
Published: May 2019

The mechanism of action of Hageman factor (HF, Factor Xll) in surface-mediated conversion of plasminogen to plasmin was investigated, assaying plasmin with H-D-valy 1-L-leucy1-L-1ysi ne p-nitroanalide·2HCL. Unexpectedly, amidolytic activity for this substrate evolved in the presence of kaolin in mixtures of purified preparations of plasminogen and HF, both devoid of detectable prekallikrein and high MW kininogen. The same result was obtained when plasminogen preparations were incubated in the absence of kaolin with HF-fragments prepared by digestion of HF with insoluble trypsin or with gel-filtered HF fragments (approximate MW 30,000). High MW kininogen did not enhance amidolysis in mixtures of plasminogen and HF with kaolin or HF fragments, but both amidolysis and fibrinolysis were enhanced by the fraction of normal plasma not absorbed at low ionic strength to QAE-Sephadex gels at ph 7-5-The analogous fraction of Fletcher trait (prekallikrein deficient) plasma, did not enhance amidolysis or fribrinolysi s. Kinetic study of the HF-kaolin-plasm inogen interaction indicated a direct enzymatic role for the HF moiety acting on plasminogen as a substrate.These data suggest that, contrary to earlier observations, HF or HF-fragments may play a direct role in the activation of plasminogen.
An Aorta Intima Inhibitor of Platelet Aggregation
Authors: Heyns A.duP. , Badenhorst C.J. , Retief F.P. 
Published: May 2019

The interaction of platelets and the vessel wall is of importance in the pathogenesis of intravascular thrombosis and atherosclerosis. We have previously described the presence of an inhibitor of platelet aggregation and a low Km ADPase in aorta intima extracts. The inhibitor was further characterized.Human aorta intimas were homogenized, centrifuged and supernatants used. Platelet aggregation was measured in a aggregometer.ADPase activity was measured by incubating 14C-ADP with intima, separating metabolites by high voltage electrophoresis and quantitated.Aggregation induced by ADP, collagen, Ristocetin and polylysine was inhibited by the intima extract. The inhibition was still evident in aspirin treated platelets. The inhibitor is present in the supernatant of 100 000g centrifuged extracts. This inhibitor appears not to be ADPase or the recently described prostacyclin (PGX) :- it is stable and not destroyed by incubation at 37°C, blocking of prostaglandin synthesis by pre-incubation of the intima with indomethacin has no effect on inhibitor activity.ADPase is inactivated by KCN whereas the inhibitor is not.The inhibitor of platelet aggregation and to a lesser extent ADPase, in the intima may be important regulators of platelet-vessel wall interaction.