bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse Effects of Treatment with Porcine Factor VIII
Authors: Gringeri A , Santagostino E , Tradati F , Giangrande P LF , Mannucci P M 
Published: July 2018

SummaryIn the last 10 years 63 courses (283 infusions) of porcine FVIII were given to 25 hemophiliacs with high titer alloantibodies and to 5 patients with autoantibodies to factor VIII. Although the product was in general clinically efficacious, adverse effects of treatment were more frequent and severe than previously reported. After 63 courses there was a median percentage fall in baseline platelet count of 54% (range 8-86%); for 10 courses (16%), thrombocytopenia was severe or moderately severe (<100 × 109/1), with nadirs of platelet count ranging from 10 to 99 × 109/1 (median 67). Allergic reactions were seen in 15 of 30 patients (50%), in 20 of 63 courses (32%), more frequently but not exclusively after the first infusion. Relatively mild symptoms (fever, Hushing, urticaria, shivering) occurred in 15 courses; 5 courses, however, were accompanied by more severe anaphylactoid reactions, 2 of which required resuscitation therapy. Allergic reactions were observed both in patients pretreated with steroids or anti-histamines (in 7 of 18 courses, 39%) and in nonpretreated patients (in 13 of 45 courses, 29%). In conclusion, adverse reactions are frequent after porcine FVIII (in 30 of 63 courses, 47%), and can occur also with infusions subsequent to the first. Hence, the recently proposed use of porcine FVIII as home treatment should be implemented with caution.
Platelet and Fibrinogen Survival with 75Se Selenomethionine in Acute Infectious Hepatitis
Authors: Musumeci S , D’Agata A , Panebianco M. G , LI Volti S 
Published: July 2018

SummarySimultaneous platelet and fibrinogen survival with 75Se selenomethionine was determined in eight patients with acute infectious hepatitis of intermediate severity. Fibrinogen survival alone was estimated in another nine patients, seven of whom were receiving heparin treatment. Platelet survival was found to be normal (7–9 days) in seven of the 8 patients ; it was reduced (4.6 days) only in one patient, who was also affected by measles. Fibrinogen survival was markedly reduced (1–3.7 days) and fibrinogen turnover sharply increased (0.59–2.80 mg/ml/day) in all but one patient, who had thalassaemia major, with normal fibrinogen survival and fibrinogen turnover. Heparin treatment did not affect either platelet survival or fibrinogen turnover. In all patients the coagulation defect was mild and no sign of disseminated intravascular coagulation or of increased fibrinolytic activity could be demonstrated by routine tests. These results are consistent with the hypothesis that in acute infectious hepatitis the decreased survival and increased turnover of fibrinogen might be due to a pathological pathway of defibrination independent of thrombin or plasmin.
Light Scattering Changes of Edetic Acid-Treated, Washed Rat Platelets
Authors: Shibata Sachiko , Kobayashi Bonro 
Published: July 2018

SummaryThe effects of adenosine diphosphate (ADP) and Ca2+ on platelet morphology were studied in edetic acid (EDTA)-treated, washed platelets of rat by means of light scattering measurement at right angles. ADP caused a transient change of light scattering, which was independent of concentration above 5 μM and of pH between 4 and 10. When the platelets were pretreated with ADP or chilled persistently, Ca2+ also caused another transient change of light scattering. The effect of Ca2+ was abolished at pH below 6.5. The velocity of both ADP- and Ca2+-induced response was dependent on temperature, and the magnitude was reduced by metabolic inhibitors and SH-blocking agents. Adenosine triphosphate (ATP) competitively inhibited the ADP-induced response, but not the Ca2+-induced one. The response to Ca2+ of the control and chilled platelets was compared by scanning electron microgram. Apparent similarity of the effect of chilling on membrane structure to that of ADP was suggested.
Performances of an Artificial Reagent for the One-stage Factor IX Assay
Authors: Meunier L , Allain J. P , Frommel D 
Published: July 2018

SummaryA mixture of adsorbed normal human plasma and chicken plasma was prepared as reagent for factor IX measurement using a one-stage method. The substrate was found to be specific for factor IX. Its performances tested on samples displaying factor IX activity ranging from <l%–2,500% compared favorably with those obtained when using the plasma of severe haemophilia B patients as substrate.
Further Investigations on Antithrombin III in the Plasmas of Patients with the Abnormality of ‘Antithrombin III Budapest’
Authors: Sas Géza , Pepper Duncan S , Cash John D 
Published: July 2018

SummaryAntithrombin III (AT-III) was studied in a thrombophilic family with an abnormal AT-III molecule (antithrombin III Budapest) using a modified crossed Immunoelectrophoresis technique, gel filtration, ‘rocket’ Immunoelectrophoresis and a heparin cofactor assay.When plain agarose was applied in the first phase of the crossed Immunoelectrophoresis, the normal and the pathological AT-III revealed identical electrophoretic mobility. However, when heparin was mixed with agarose in the first phase of electrophoresis, the propositus’ plasma displayed a different AT-III pattern from normal plasma. His plasma contained the first component of the normal plasma (Immune Antithrombin III1, IAT-III1) in a concentration of only 5% of normal, and a protein in high concentration which although immunoreactive to AT-III antisera, had an electrophoretic mobility similar (but not identical) to that of IAT-III2. This ab-normal protein had no heparin cofactor activity and a molecular size greater than normal plasma AT-III. Unlike normal AT-III, the addition of heparin did not change the molecular size of the pathologic AT-III molecule significantly.The abnormal protein was present in lower concentrations in the patient’s children and at the time of study they had no clinical or laboratory evidence of intravascular coagulation.
A Simplified Thromboplastin Calibration Procedure for Standardization of Anticoagulant Control
Authors: Loeliger E. A , van Halem-Visser L. P 
Published: July 2018

SummaryIn thromboplastin calibration, the possibility of replacing fresh individual plasmas by pooled fresh plasmas (used immediately after preparation or after storage at —25° C) or by pooled lyophilized plasmas has been investigated. It was found that the thromboplastin sensitivity ratios (TSR’s) assessed with pooled fresh plasmas show no divergence from those obtained with the original Biggs/Denson calibration procedure. With pooled lyophilized plasmas a small divergence can be found in particular with so-called PIVKA-insensitive rabbit-tissue thromboplastins. Since, in contrast to the original procedure, only a limited number of determinations with pooled fresh or lyophilized plasmas are needed to obtain an accurate TSR value, the modification substantially simplifies thromboplastin calibration. Moreover, the technique using lyophilized plasmas can be applied in laboratories where an insufficient number of patients are available or none at all. However, as long as pooled lyophilized plasmas display a more or less pronounced activation, it might be preferable to restrict calibration to qualified expert laboratories, i.e. national reference laboratories.The merits of pooled lyophilized plasma are those of good stability even under the condition of accelerated degradation. They might be just as useful as thromboplastins for use as (long-term) reference material in the standardization and quality control program of manufacturers of thromboplastins, and for laboratorians preparing their own thromboplastin for the anticoagulant control.Conditions for the preparation and use of lyophilized reference plasmas have been worked out and are presented.
Haemophilia A in a Patient with Testicular Feminization
Authors: Andrejev Yu. N , Korenevskaya M. I , Rutberg R. A , Dukarevitch M. Z , Pokrovskiy P. I , Tokarev Yu. N 
Published: July 2018

SummaryA case of typical haemophilia A in phenotypically “hairless” woman aged 18 with complete testicular feminization (primary amenorrhea, absence of palpated gonads, negative sex chromatin, fluorescence of Y chromosome in interphase nuclei, caryotype 46, XY by common and fluorescent methods) is reported in this paper. Both diseases are of familial character with transmission through female line. The propositus’ father did not suffer from haemophilia. Signs of Morris syndrome (delay of menses, absence of secondary hair) are present in the propositus’ mother and sister. The propositus’ niece, the daughter of her sister, also suffered from testicular feminization, but without any haemophilia, probably due to the crossing-over. The analysis of the pedigree gives no information in favour of sex-linked or autosome-dominant sex limited inheritance of testicular feminization. Haemophilia A in the propositus is characterized by the very low factor-VIII level – 1.66%, and typical joints bleedings since 3 years. At the age of 18 the patient had major surgery for a haemophilic thigh pseudotumor. There was rapid consolidation of the fracture and contracture was erradicated. In spite of severe factor VIII deficiency the course of haemophilia in the propositus is clinically milder than in male haemophiliacs in her family and in the general population.The similar findings were reviewed in literature including the case of hemyzygous haemophilia with testicular feminization and described women-homozygotes. The suggestion is made that the course of haemophilia in the propositus is affected by the female phenotype. The psychological status of the patient and the possibility of professional rehabilitation by surgical treatment is discussed. The need for detailed cytogenetical examination of the persons with “female” haemophilia or the other sex-linked diseases to establish the correct diagnosis and for exclusion of the possible mosaicism is discussed.
The Effect of Oral Contraceptive Estrogen on Blood Coagulation and Fibrinolysis
Authors: Hedlin Anne M 
Published: July 2018

SummaryThe changes in fibrinogen, antithrombin activity, spontaneous fibrinolytic activity, plasminogen and fibrinogen degradation products were studied in women, aged 18 to 30 years, who were using oral contraceptive preparations. Blood samples were obtained before use, as well as during the first month and again after several months of use. The results were divided into three groups based on the antiovulatory activity of the estrogen component of the oral contraceptive, ie. Mestranol, 50 μg, Mestranol 80 μg or Ethinyl estradiol 50 μg and Mestranol 100 μg. In each of the three groups there was a similar pattern of increase in spontaneous fibrinolytic activity and plasminogen but decrease in antithrombin levels during the monthly cycles. The fibrinogen level was increased in the first month of oral contraceptive use in the three groups but after several months of use the pattern of change seen in the first month was repeated with the lower estrogen compounds, but in the group using the preparation with 100 μg Mestranol, the fibrinogen level returned to that of the control month. The level of fibrinogen degradation products remained unchanged.
Lipids as Triggering Factors in Thrombosis
Authors: Nordøy Arne 
Published: July 2018

SummaryAn association has been established between acute and more persistent changes in lipid metabolism as reflected in plasma lipids, and platelet lipid metabolism. Platelet function is affected, particularly the activity and availability of platelet factor 3, however, also other changes making the platelets more sensitive to aggregating substances without interfering with the lipid part of platelet factor 3, have been documented. Experimental studies have demonstrated an increased tendency to thrombosis in animals given a diet with a high fat content with a high ratio of saturated to polyunsaturated fatty acids. Studies in man have mainly established a connection between dietary fats, plasma lipid abnormalities and frequency of coronary heart disease and clinical studies more directly relating thrombosis to lipid metabolism is highly warranted. Many open questions remain to be answered. Probably most relevant would be to understand how the antithrombotic mechanisms in the body are affected by changes in lipid metabolism. Even if thrombotic lesions are very common events in the western world our knowledge based on laboratory and experimental studies should indicate a much higher incidence, solely based on interactions between lipids and platelets in subjects exposed to our dietary habits and our way of life.
Clinical Trials in Thrombosis: Secondary Prevention of Myocardial Infarction
Authors: Klimt Christian R , Doub P. H , Doub Nancy H 
Published: July 2018

SummaryNumerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.
Evidence for an Ester Bond between Thrombin and Heparin Cofactor
Authors: Owen Whyte G , Penick George D , Yoder Elizabeth , Poole Barbara L 
Published: July 2018

SummaryHeparin cofactor, a thrombin inhibitor, is purified from human plasma by affinity chromatography on heparin-agarose. The nature of the binding between thrombin and the inhibitor is studied by treatment of the complex with 6 M guanidinium chloride, hydroxylamine, and dilute alkali. The complex is not dissociated during gel chromatography in 6 M guanidinium chloride. This result supports an earlier proposal that formation of the complex includes the formation of a covalent bond. Treatment of dodecyl sulfate-denatured complex with hydroxylamine results in dissociation of the complex to yield free thrombin and heparin cofactor. Hydroxylamine does not dissociate the complex unless it is denatured. The complex is also dissociated in dilute sodium hydroxide (pH 12) solutions. These results indicate that the covalent bond between thrombin and the inhibitor is a carboxylic ester.
Biological Control of Factor VII
Authors: Nemerson Yale 
Published: July 2018

SummaryThe tissue factor pathway is initiated by factor VII in the presence of tissue factor. The first proteolytic reaction involves cleavage of factor X by factor VII. Activated factor X, the product of this reaction, can activate factor VII by cleavage of a specific bond. The apparent coagulant activity of factor VII then rises about 60-fold. Activated factor X can also inactivate factor VII by catalyzing the cleavage of a second bond which results in a three chain molecule. Fragments of Hageman factor and perhaps kallikrein can also activate factor VII. Hageman factor, however, does not catalyze the inactivating cleavage of factor VII at a significant rate.Recent data showing that the tissue factor pathway can activate the intrinsic system are discussed. We have shown that activated factor X, which can be generated by the tissue factor pathway, can feed back and activate factor IX in a calcium and phospholipid requiring reaction.
Specificity of Antisera to Human Fibrinopeptide A Used in Clinical Fibrinopeptide A Assays
Authors: Nossel Hymie L , Butler Vincent P , Wilner George D , Canfield Robert E , Harfenist Elizabeth J 
Published: July 2018

SummaryDistinction between fibrinopeptide A (FPA) and larger polypeptides containing the FPA sequence is critical for the interpretation of clinical results with FPA immunoassay methods. Therefore, the immunochemical reactivity of 14 rabbit anti-FPA sera with six different FPA containing antigens was studied in detail. Antigens tested included: fibrinogen; fragment E of fibrinogen; the amino-terminal disulfide knot of fibrinogen; Aα 1 (Ala)-51 (Met); Aα l(Ala)-23(Arg); and, FPA. Synthetic partial sequences of FPA were also tested. The 14 FPA-specific antisera were divided into 3 distinct categories with: I, FPA immuno-reactivity of larger polypeptides containing FPA approximately 1/100 of FPA on a molar basis; II, FPA immunoreactivity of the larger polypeptides intermediate between I and III; and III, FPA immunoreactivity of the larger polypeptides approximately equal to that of FPA on a molar basis. The antigenic determinants of a category I antiserum (R 2) are included in Aα 7(Asp)-16(Arg) with Asp(7), Phe(8) and Arg(16) being essential. When attached to FPA, the sequence Gly(17)-Arg(23) decreases the immunoreactivity of FPA with category I antisera 100-fold.The practical consequence of these findings is that, when category III antisera are employed, both FPA and larger FPA-containing polypeptides are equally immunoreactive. Since thrombin treatment of the larger polypeptides does not alter their immunoreactivity, category III antisera cannot discriminate between FPA and the larger polypeptides. On the other hand, with category I antisera, although the immunoreactivity of FPA itself is unaltered by thrombin treatment, larger polypeptides [e.g., Aα l(Ala)-23(Arg)] show a 100-fold increase in immunoreactivity following thrombin treatment and thus can readily be identified and separately quantitated. It is concluded that antisera with the specificity of category I are essential for the specific and accurate measurement of FPA, and for its distinction from larger FPA-containing polypeptides, in clinical plasma samples.
Immunologie Studies in von Willebrand’s Disease
Authors: Sultan Y , Simeon J , Maisonneuve P , Caen J. P 
Published: July 2018

SummaryTwo patients with a severe von Willebrand’s disease characterized by no detectable factor VIII related antigen in their plasma received transfusions of cryoprecipitate. The bleeding time was corrected for a short period of time and returned to its pretransfusional value although the other parameters of the disease were still corrected. Electrophoretic and immunologic properties of factor VIII related antigen infused were determined serially after transfusion. Modifications of these properties occurred progressively after transfusion. The half disappearance time of F. VIIIR. A. was determined and found to be considerably shorter than in hemophilic recipients. This study suggests an alteration in vivo of F. VIIIR. A. infused into von Willebrand recipients.
Metabolie Properties of Human Platelet Membranes
Authors: Kaulen Hermann Dietrich , Gross Rudolf 
Published: July 2018

SummaryWashed human platelets have been labeled with either 32Pi or glycerol- 1-14C and the distribution of the label in the phospholipids determined. 32Pi was introduced primarily into polyphosphoinositides, i. e. di- and triphosphoinositide, whereas the label from glycerol which indicates de novo synthesis of lipid molecules did not appear in these phospholipids. In the course of thrombin-induced aggregation and release the phosphate incorporation into phos-phatic acid, di- and triphosphoinositide was rapidly stimulated in parallel to the platelet reaction. The incorporation of glycerol did not change under the same conditions.It is concluded that phosphoinositides with rapid incorporation of phosphate groups are not as rapidly synthesized de novo and presumably form a separate phospholipid pool in the platelets. Only the phosphorylating reactions are stimulated by the thrombin aggregation. The necessary enzymes for these reactions, namely diglyceride kinase, phosphatidylinositol kinase, and phosphatidylinositol-phosphate kinase all can be shown to be associated with a well characterized platelet membrane fraction.
Studies on the Thromboplastic Effect of Human Plasma Lipoproteins
Authors: Sandberg Helena , Andersson Lars-Olov 
Published: July 2018

SummaryHuman plasma lipoprotein fractions were prepared by flotation in the ultracentrifuge. Addition of these fractions to platelet-rich, platelet-poor and platelet-free plasma affected the partial thromboplastin and Stypven clotting times to various degrees. Addition of high density lipoprotein (HDL) to platelet-poor and platelet-free plasma shortened both the partial thromboplastin and the Stypven time, whereas addition of low density lipoprotein and very low density lipoprotein (LDL + VLDL) fractions only shortened the Stypven time. The additions had little or no effect in platelet-rich plasma.Experiments involving the addition of anti-HDL antibodies to plasmas with different platelet contents and measuring of clotting times produced results that were in good agreement with those noted when lipoprotein was added. The relation between structure and the clot-promoting activity of various phospholipid components is discussed.
Effect of Thrombin on Phosphorylation of Platelet Membrane Proteins
Authors: Steiner M 
Published: July 2018

SummaryThe effect of thrombin on the phosphorylating activity of platelet membranes was compared to that of trypsin. Preincubation of non-32P phosphorylated platelet membranes with or without either of these two enzymes resulted in a considerable loss of membrane protein kinase activity which was most severe when trypsin was used. Protein kinase activity and endogenous protein acceptors decreased in parallel. 32P-phosphorylated membranes showed a slow but progressive loss of label which was accelerated by trypsin. Thrombin under these conditions prevented the loss of 32P-phosphate. These results are interpreted to indicate a thrombin-induced destruction of a phosphoprotein phosphatase. The protein kinase activity of phosphorylated platelet membranes using endogenous or exogenous protein substrates showed a significant reduction compared to non-phosphorylated membranes suggesting a deactivation of protein kinase by phosphorylation of platelet membranes. Neither thrombin nor trypsin caused a qualitative change in the membrane polypeptides accepting 32P-phosphate but resulted in quantitative alterations of their ability to become phosphorylated.