Some Aspects of Kinetics of the First Stages of Blood Thromboplastin Formation

1959 ◽  
Vol 03 (01) ◽  
pp. 098-109 ◽  
Author(s):  
U Fisch ◽  
F Duckert
Keyword(s):  
Intermediate Product ◽  
Factor Ix ◽  
Haemophilia B ◽  
Hageman Factor ◽  
Viii And Ix ◽  
Lag Period ◽  
Kinetics Of

SummaryThe first stages of blood thromboplastin generation were investigated. Plasma Thromboplastin Antecedent, Prephase Accelerator, and Hageman factor are involved in the reactions taking place during the lag period. This phase is followed by the formation of intermediate product I. Studying the kinetics of this particular reaction it was possible to attribute to factors VIII and IX the rôle of substrates and to Stuart-Prower factor the rôle of an enzyme. It appears that in haemophilia B serum two distinct factors are lacking, the genuine factor IX, and the prephase accelerator (PPA). An hypothesis explaining tentatively the activation of a precursor to PPA and genuine factor IX is offered.

The Formation of Intermediate Product I in a Purified System The Role of Factor IX or of its Precursor and of a Hageman Factor-PTA Fraction

1961 ◽  
Vol 6 (02) ◽  
pp. 224-234 ◽  
Author(s):  
E. T Yin ◽  
F Duckert
Keyword(s):  
Intermediate Product ◽  
Factor Ix ◽  
Assay Method ◽  
Lag Phase ◽  
Factor X ◽  
Haemophilia B ◽  
Hageman Factor ◽  
One Stage ◽  
The One

Summary1. The role of two clot promoting fractions isolated from either plasma or serum is studied in a purified system for the generation of intermediate product I in which the serum is replaced by factor X and the investigated fractions.2. Optimal generation of intermediate product I is possible in the purified system utilizing fractions devoid of factor IX one-stage activity. Prothrombin and thrombin are not necessary in this system.3. The fraction containing factor IX or its precursor, no measurable activity by the one-stage assay method, controls the yield of intermediate product I. No similar fraction can be isolated from haemophilia B plasma or serum.4. The Hageman factor — PTA fraction shortens the lag phase of intermediate product I formation and has no influence on the yield. This fraction can also be prepared from haemophilia B plasma or serum.

Assessment Levels of Factor VIII and IX Inhibitors in Patients with Hemophilia in North West of Iran: What Is the Main Reason of Low Inhibitor Titer and Rate in Our Patients?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4662-4662
Author(s):  
Roya Dolatkhah ◽  
Ali Akbar Movasaghpour Akbari ◽  
Iraj Asvadi Kermani ◽  
Zohreh Sanaat ◽  
Azim Rezamand ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Factor Ix ◽  
Haemophilia A ◽  
Inhibitor Development ◽  
Haemophilia B ◽  
On Demand ◽  
Viii And Ix

Abstract Abstract 4662 Introduction Today, the development of inhibitors against Factor VIII (FVIII) and Factor IX (FIX) is seen as the most serious complication of haemophilia A and B therapy. Recent studies on the role of the causative haemophilic mutation, race and ethnicity, family history of inhibitors and the possible influence of HLA genotype in inhibitor formation have revealed new and exciting insights. That is challenging conventional thinking about inhibitor development risk and type of factor products, recombinant or plasma-derived. The use of recombinant factor concentrates has revolutionized the treatment of severe factor VIII and IX deficiency. One of the most important complications is the development of antibodies (Inhibitors). Material and Methods Ninety two patients with haemophilia A and 12 patients with Haemophilia B have been studied. Confirmatory tests including one stage FVIII and FIX assay has been performed using STA Deficient FVIII and FIX, an immune-depleted plasma intended in plasma by analyzers of the STA line suitable with these reagents (Diagnostica Stago,France).Presence of Factor VIII and IX inhibitors have been tested by Bethesda Assay. All of the patients use mostly plasma-derived factor products, and on-demand treatment. Results Among 92 haemophilia A patients, FVIII levels were between 0.14–14.40 IU/dl (mean 2.91 ± 2.62), FIX levels were between 0.17 to 4.37 IU/dl (mean 1.53 ± 1.38) in12 haemophilia B patients. PT activity was 68.7–134 (mean 101.05 ± 15.13), APTT was 28.90 – 102 (mean 60.66 ± 13.50). FVIII inhibitor levels were between 0–1.14 BU (mean 0.04 ± 0.20) in 5 severe Hemophilia A patients (5.45%) and FIX Inhibitor levels were between 0–0.65 BU (mean 0.10 ± 0.23) in 2 Hemophilia B patients. Discussion Alloantibodies (inhibitors) against FVIII or FIX represent a major complication in patient care because they render classical substitution therapy ineffective. Inhibitors occur at a frequency of 20–30% in severe and 3–13% with mild or moderate haemophilia A, and 3% in haemophilia B, respectively. An alternative pathomechanism may underlie inhibitor development in patients with mild hemophilia A. Although it has been reported that inhibitors in patients with mild haemophilia are related to periods of intensive treatment or surgery, this has never been properly studied in children with severe haemophilia. The low inhibitor rate with Low Titers in our patients may be demonstrate the role of type of factor products, recombinant or plasma-derived, which in this study was mostly use of plasma-derived factor products, and on-demand treatment. Also detailed evaluation of major risk factors of development of Factor VIII and IX inhibitors in our patients is required. Disclosures: No relevant conflicts of interest to declare.

Kinetics of factor IX activity differ from that of factor IX antigen in patients with haemophilia B receiving high-purity factor IX replacement

Haemophilia ◽  
1999 ◽  
Vol 5 (3) ◽  
pp. 174-180 ◽  
Author(s):  
Liebman ◽  
Rosenwald-Zuckerman ◽  
Retzios ◽  
Yasmin ◽  
Kasper
Keyword(s):  
High Purity ◽  
Factor Ix ◽  
Haemophilia B ◽  
Kinetics Of

One-stage Assay for Hageman Factor (Factor XII). Further Studies on the Role of Hageman Factor in Blood Coagulation

1963 ◽  
Vol 09 (03) ◽  
pp. 557-569 ◽  
Author(s):  
C Haanen ◽  
John G. G Schoenmakers
Keyword(s):  
Factor Ix ◽  
Factor Xii ◽  
Charged Surface ◽  
Dilution Curve ◽  
Adsorbed State ◽  
Hageman Factor ◽  
High Affinity ◽  
One Stage ◽  
Glass Surfaces

SummaryA one stage assay for Hageman Factor (HF) activity is described. Maximal standardization was achieved by lyophilizing substrate plasma, cephalin suspension and standard reference plasma in small aliquots. A dilution curve was constructed, using a highly purified HF preparation. The assay is not completely specific and is invalidated by the presence of activated Factor IX and XI. So all materials to be tested were first adsorbed on Al(OH)3-gel to exclude Factor IX and possibly most of Factor XI.Purified activated HF still possesses a high affinity for glass surfaces, thus activation may not alter the molecule at the side of affinity for the glass surface. Moreover purified activated HF is still more active in the presence of glass thus in the adsorbed state. These observations support the idea that the so called activation of Hageman Factor is a reversible phenomenon, whereby the molecule unfolds and uncovers active groups as soon as it is adsorbed on a negatively charged surface.

On The Nature Of The Activated Prothrombin Complex

1981 ◽  
Author(s):  
J A Penner ◽  
R Cobel-Geard ◽  
H I Hassouna
Keyword(s):  
Active Sites ◽  
Cyanogen Bromide ◽  
Active Form ◽  
Factor Ix ◽  
Batch Adsorption ◽  
Viii And Ix ◽  
Successful Removal ◽  
Specific Factors ◽  
Sepharose 4B

Prothrombin complex concentrates containing FVIII bypassing activity have been employed effectively in the management of patients with factor VIII and IX inhibitors. The active component has not been identified although the protease forms of factor IX and X, as well as VII exist in variable concentrations in these products.As a means of establishing the role of each factor in the concentrates, monospecific antibodies to prothrombin, FX and FVII were coupled to Sepharose 4B by means of cross linking reagent cyanogen bromide. These insol- ubilized antibodies were used to selectively remove all prothrombin FX or FVII from the therapeutic concentrate, Autoplex (570 u/vial) supplied by Hyland Labs, Costa Mesa, by batch adsorption. A control was prepared by reacting the concentrate with cyanogen bromide treated beads whose active sites had been blocked with ethanolamine. Successful removal of specific factors from concentrates was evaluated by immunodiffusion assays and by standard clotting assays using substrate deficient plasma. Thrombin was not found to be present in any of the products following extraction. Thrombogenicity was tested in an animal model. Concentrates reacted with cyanogen bromide beads as a control and those lacking prothrombin were found to shorten clotting time of FVIII deficient plasma and to trigger intravascular coagulation in the animals (D.I.C.). Removal of FVII produced a concentrate that was more active than the control with respect to FVIII correction and induction of D.I.C. Concentrates depleted of FX, on the other hand, lost their capacity to correct FVIII deficient plasma and to initiate D.I.C. Our findings would suggest that the content of FX and its active form FXa plays a major role in the concentrates FVIII correcting activity and most likely is responsible for its thrombogenic characteristics.

scholarly journals The cellular origin of glyoxysomal proteins in germinating castor-bean endosperm

1976 ◽  
Vol 154 (2) ◽  
pp. 501-506 ◽  
Author(s):  
L Bowden ◽  
J. M Lord
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Synthesis ◽  
Castor Bean ◽  
Developmental Stages ◽  
Endoplasmic Reticulum Membrane ◽  
Endosperm Tissue ◽  
Cellular Origin ◽  
Lag Period ◽  
Kinetics Of

The capacity of castor-bean endosperm tissue to incorporate [35S]methionine into proteins of the total particulate fraction increased during the first 3 days of germination and subsequently declined. At the onset of germination 66% of the incorporated 35S was found in the separated endoplasmic-reticulum fraction, with the remainder in mitochondria, whereas at later developmental stages an increasing proportion of 35S was recovered in glyoxysomes. The kinetics of [35S]methionine incorporation into the major organelle fractions of 3-day-old endosperm tissue showed that the endoplasmic reticulum was immediately labelled, whereas a lag period preceded the labelling of mitochondria and glyoxysomes. When kinetic experiments were interrupted by the addition of an excess of unlabelled methionine, incorporation of [35S]methionine into the endoplasmic reticulum rapidly ceased, but incorporation into mitochondia and glyoxysomes continued for a further 1h. Examination of isolated organelle membranes during this period showed that the addition of unlabelled methionine resulted in a stimulated incorporation of [35S]no methionine into the endoplasmic-reticulum membrane for 30 min, after which time the 35S content of this fraction declined, whereas that of the glyoxysomal membranes continued to increase slowly. The 35S-labelling kinetics of organelles and fractions derived therefrom are discussed in relation to the role of the endoplasmic reticulum in protein synthesis during glyoxysome biogenesis.

The Prephase Accelerator. Present Status

1961 ◽  
Vol 6 (02) ◽  
pp. 254-260 ◽  
Author(s):  
F Duckert
Keyword(s):  
Present Status ◽  
Factor Ix ◽  
Quantitative Assay ◽  
Assay Method ◽  
Clotting Factors ◽  
Haemophilia B ◽  
Hageman Factor ◽  
One Stage ◽  
The One ◽  
Generation Test

SummaryThe properties of the prephase accelerator (PPA) are indicated as well as its differentiation from other known clotting factors. PPA is either a reaction product or a degratation product. For its normal formation genuine factor IX, PTA and ? Hageman factor are necessary.The one-stage quantitative assay method for factor “IX” does not determine the factor lacking in haemophilia B. This method gives a measure of PPA.Some practical observations are made concerning the value of the one-stage assay method for factor “IX” and of the thromboplastin generation test for the diagnosis of haemophilia B.

Performances of an Artificial Reagent for the One-stage Factor IX Assay

1975 ◽  
Vol 33 (03) ◽  
pp. 547-552 ◽  
Author(s):  
L Meunier ◽  
J. P Allain ◽  
D Frommel
Keyword(s):  
Human Plasma ◽  
Factor Ix ◽  
Severe Haemophilia ◽  
Normal Human Plasma ◽  
Haemophilia B ◽  
One Stage ◽  
Normal Human ◽  
The One

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.

Management of Haemophilia in Sweden

1976 ◽  
Vol 35 (03) ◽  
pp. 510-521 ◽  
Author(s):  
Inga Marie Nilsson
Keyword(s):  
Factor Viii ◽  
Total Population ◽  
Age Groups ◽  
Factor Ix ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Haemophilia B ◽  
Human Fraction ◽  
Mild Haemophilia

SummaryThe incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophilia B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40 % have severe, 18 % moderate, and 42 % mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B.There are 2 main Haemophilia Centres (Stockholm, Malmo) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction 1-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Sufficient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 million units of factor IX are given per year. Treatment is free of charge.Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4–18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40–50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.

The Activation of Human Factor X in Sodium Citrate: the Role of Factor VII

1976 ◽  
Vol 36 (01) ◽  
pp. 104-114 ◽  
Author(s):  
D. L Aronson ◽  
A. J Mustafa
Keyword(s):  
Sodium Citrate ◽  
Human Factor ◽  
Deae Cellulose ◽  
Factor Ix ◽  
Factor Vii ◽  
Factor X

SummaryHuman factor X was purified by several different procedures yielding products which had varying amounts of factor VII and factor IX. Treatment with CHC13 during the fractionation of the factor X removed 95% of the factor VII and factor IX activity and the resulting factor X activated more slowly when incubated in 25% sodium citrate. Removal of residual factor VII by DEAE cellulose chromatography yielded a factor X which activated still more slowly and less completely. When the factor VII, removed by chromatography, was added to the chromatographed factor X, the ability to be activated in 25% sodium citrate was restored. Confirmatory evidence for the role of factor VII in this reaction was the inhibition of the conversion of the factor X by both DFP and SBTI.

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