Acquired Haemophilia: Functional Study of Antibodies to Factor VIII

1981 ◽  
Vol 45 (03) ◽  
pp. 285-289 ◽  
Author(s):  
J P Allain ◽  
A Gaillandre ◽  
D Frommel
Keyword(s):  
Factor Viii ◽  
Functional Study ◽  
Factor Viii Inhibitor ◽  
Acquired Haemophilia ◽  
Viii Inhibitor ◽  
Kinetics Of ◽  
Antibody Function ◽  
Native Plasma

SummaryFactor VIII complex and its interaction with antibodies to factor VIII have been studied in 17 non-haemophilic patients with factor VIII inhibitor. Low VIII:C and high VIIIR.Ag levels were found in all patients. VIII:WF levels were 50% of those of VTIIRrAg, possibly related to an increase of poorly aggregated and electrophoretically fast moving VIIIR:Ag oligomers.Antibody function has been characterized by kinetics of VIII :C inactivation, saturability by normal plasma and the slope of the affinity curve. Two major patterns were observed:1) Antibodies from 6 patients behaved similarly to those from haemophiliacs by showing second order inhibition kinetics, easy saturability and steep affinity slope (> 1).2) Antibodies from other patients, usually with lower titres, inactivated VIII :C according to complex order kinetics, were not saturable, and had a less steep affinity slope (< 0.7). In native plasma, or after mixing with factor VIII concentrate, antibodies of the second group did not form immune complexes with the whole factor VIII molecular complex. However, dissociation procedures did release some antibodies from apparently low molecular weight complexes formed in vivo or in vitro. For appropriate management of non-haemophilic patients with factor VIII inhibitor, it is important to determine the functional properties of their antibodies to factor VIII.

Factor-VIII Inhibitor in Less Severely Affected Haemophilic Patients

1975 ◽  
Author(s):  
E. G. D. Tuddenham ◽  
A. L. Bloom ◽  
J. C. Giddings ◽  
C. A. Barrett
Keyword(s):  
Factor Viii ◽  
Factor Viii Inhibitor ◽  
Factor Viii Level ◽  
Replacement Treatment ◽  
Viii Level ◽  
Viii Inhibitor ◽  
In Vivo Recovery ◽  
Better Than

The occurrence of factor VIII inhibitor in five mild or moderately affected liaemophilic patients is described. In four patients the inhibitor inactivated endogenous factor VIII an dtemporarily converted them to severely affected haemophiliacs with factor VIII level of 0%. In the fifth patient, a brother of one of the others, the inhibitor although more potent did not inactivate the patient’s own factor VIII and did not completely inactivate normal factor VIII in vitro. This patient responded to treatment with factor-VIII concentrate but the in-vivo recovery was reduced. The patient’s plasma was tested against a panel of normal donors but it inactivated factor VIII in each to a similar extent and no evidence for normal factor-VIII groups was obtained. In the other patients the response to replacement treatment was also better than that usually seen in severely affected haemophilic patients with inhibitor. In the two related patients the inhibitors have so far persisted but in the unrelated patients the inhibitors eventually disappeared and did not always recur with subsequent therapy. The incidence of factor- VIII inhibitor in less severe haemophiliacs (factor VIII > 3% ) in this centre is 6% suggesting that the complication is more frequent in this type of patient than hitherto recognised.

Quantitative Effects of the Reaction between Factor VIII and Factor VIII Inhibitors

1971 ◽  
Vol 26 (01) ◽  
pp. 124-134
Author(s):  
C. W McMillan ◽  
R. C Elston
Keyword(s):  
Factor Viii ◽  
Factor Viii Inhibitor ◽  
Inhibitor Activity ◽  
Viii Inhibitor ◽  
In Vitro Effects ◽  
Logarithmic Relation

SummaryTo study the effects of factor VIII and factor VIII inhibitor on each other an assay was developed in which inhibitor activity could be directly related to units of factor VIII. Inhibitor activity in units per ml is defined as the number of factor VIII units reduced to 0.01 factor VIII unit by 1 ml inhibitor plasma after incubation for 1 h at 37° C. Whereas factor VIII was destroyed by inhibitor in accord with a double-logarithmic relation between initial and 1-h residual factor VIII activities, final inhibitor activity was found to be inversely proportional to the ratio of initial concentrations of factor VIII to inhibitor. The latter process resembles “dilution”, rather than direct neutralization, of inhibitor by factor VIII. These effects were observed both in the system for inhibitor assay and in more concentrated mixtures of factor VIII and inhibitor sources in vitro. Results of infusion of factor VIII into a subject with classic hemophilia and an acquired inhibitor suggested that in vivo and in vitro effects of factor VIII and inhibitor activities on each other are comparable, if not identical.

In Vitro Thrombogenicity Tests of Factor IX Concentrates

1979 ◽  
Vol 42 (05) ◽  
pp. 1355-1367 ◽  
Author(s):  
C V Prowse ◽  
A Chirnside ◽  
R A Elton
Keyword(s):  
Factor Viii ◽  
Partial Thromboplastin Time ◽  
Generation Time ◽  
Activated Partial Thromboplastin Time ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Factor Viii Inhibitor ◽  
Factor Ixa ◽  
Viii Inhibitor

SummaryVarious factor IX concentrates have been examined in a number of in vitro tests of thrombogenicity. The results suggest that some tests are superfluous as in concentrates with activity in any of these tests activation is revealed by a combination of the non-activated partial thromboplastin time, the thrombin (or Xa) generation time and factor VIII inhibitor bypassing activity tests. Assay of individual coagulant enzymes revealed that most concentrates contained more factor IXa than Xa. However only a small number of concentrates, chiefly those that had been purposefully activated, contained appreciable amounts of either enzyme.

scholarly journals Feiba Immuno: A Preparation with Factor Eight Inhibitor Bypassing Activity

1977 ◽  
Author(s):  
F. Elsinger
Keyword(s):  
Factor Viii ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Active Principle ◽  
Factor Viii Inhibitor ◽  
Factor V ◽  
In Vitro Experiments ◽  
Factor X ◽  
Viii Inhibitor

FEIBA IMMUNO is a preparation in which a new activity is generated capable of bypassing factor VIII. The preparation which is used to treat patients with inhibitors (especially inhibitors to factor VIII) is standardized in FEIBA units, i.e. in terms of its in vitro capacity to shorten the activated PTT of a factor VIII inhibitor plasma.It could be concluded from different in vitro experiments that none of the classic’ activated coagulation factors is responsible for the factor VIII bypassing reaction; FEIB-activity seems to be correlated to a new complex of coagulation factors.To get an answer to the question which coagulation factors are essential for FEIB-activity, we tried to generate this activity from different deficient plasmas; from these experiments the following conclusions could be drawn:, the presence of at least factors VII, IX, and X is essential for the generation of the molecular species responsible for factor VIII as well as factor X bypassing activity, but factor V is not bypassed. This activity is not factor Xa itself. Factors VIII and V are not necessary for the generation of this active principle, but factor V is finally needed for its bypassing action.

scholarly journals Characterization and Properties of an Inhibitor of Factor VIII in the Plasma of Patients with Hemophilia A Following Repeated Transfusions

Blood ◽  
1967 ◽  
Vol 30 (2) ◽  
pp. 137-150 ◽  
Author(s):  
HERBERT S. STRAUSS ◽  
EZIO MERLER
Keyword(s):  
Factor Viii ◽  
Strong Evidence ◽  
Inhibitory Activity ◽  
Hemophilia A ◽  
Deae Cellulose ◽  
Factor Viii Inhibitor ◽  
Inhibitor Activity ◽  
Low Level ◽  
Viii Inhibitor

Abstract A circulating anticoagulant, which specifically inhibits Factor VIII (AHF), has been detected in some patients with hemophilia A who had received multiple transfusions. The inhibitor was quantitated by measurement of the degree of inactivation of Factor VIII. The data presented provide strong evidence for the antibody nature of the Factor VIII inhibitor in hemophilia: (1) All specific inhibitory activity of serum was detected in the γG globulin obtained by chromatography of the sera on DEAE cellulose. (2) Fab fragments obtained by digestion of the γG globulin with papain, contained 18-22 per cent of the specific inhibitory activity, while Fc fragments contained 0.4-3 per cent. F(ab')2 fragments obtained by digestion with pepsin contained 36-61 per cent of the specific inhibitory activity of γG globulin. (3) The level of the inhibitor of Factor VIII increased sharply following transfusions of blood and decreased slowly to its preinfusion level. (4) When small amounts of inhibitor were incubated in vitro with excess Factor VIII, the inhibitor activity was decreased. Infusion of Factor VIII into a patient with a low level of inhibitor decreased the inhibitor activity. (5) Clearance of the isologous inhibitor from the circulation of a normal subject was rapid.

Autoimmune Factor VIII Inhibitor Responsive to Gammaglobulin without In Vitro Neutralisation

1988 ◽  
Vol 60 (02) ◽  
pp. 343 ◽  
Author(s):  
Luis O Carreras ◽  
Graciela N Perez ◽  
David L Xavier ◽  
Alicia N Blanco ◽  
Leticia B Penalva
Keyword(s):  
Factor Viii ◽  
Factor Viii Inhibitor ◽  
Viii Inhibitor

scholarly journals Factors Affecting the Factor X Activator Activity of Human Platelets

1977 ◽  
Author(s):  
J. Vermylen ◽  
N. Semeraro
Keyword(s):  
Factor Viii ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Activate Factor ◽  
Factor Viii Inhibitor ◽  
Factor X ◽  
Factors Affecting ◽  
Coagulant Activity ◽  
Viii Inhibitor

Several recent studies have indicated that patients with a thrombotic tendency have enhanced platelet coagulant activity. It therefore is of importance to attempt to identify factors which modify platelet coagulant activities. Recent work in our laboratory has provided evidence that human platelets possess the capacity to directly activate factor X.Adenosine-5'-diphosphate, collagen, acetylsalicylic acid and prostaglandin E1 do not modify this activity. All endotoxins studied however clearly enhanced this activity.Furthermore, infusion of ‘activated’ prothrombin concentrates in haemophiliacs with or without factor VIII inhibitor enhanced the activity of this platelet activator of factor X. The hypothesis has been put forward that this may be the mechanism through which ‘activated’ prothrombin concentrates ‘bypass’ factor VIII of IX inhibitors. Platelet isolated from platelet-rich plasma to which the ‘activated’ prothrombin concentrate had been added at a concentration approaching the maximal concentration achieved following in vivo infusion, also showed an increase in platelet coagulant activity. Work is in progress to identify the component in ‘activated’ prothrombin concentrates which enhances platelet coagulant activity.

scholarly journals A Study of Lymphocyte Transformation as a Mechanism for Spontaneous Factor VIII Inhibitor Formation

1977 ◽  
Author(s):  
J. Katz ◽  
R. Lea ◽  
E.D. Gomperts
Keyword(s):  
Factor Viii ◽  
Mononuclear Cells ◽  
Lymphocyte Transformation ◽  
Factor Viii Inhibitor ◽  
Bleeding Tendency ◽  
Normal Plasma ◽  
Plasma Factor ◽  
Lymphocyte Cultures ◽  
Viii Inhibitor

Two elderly patients with a bleeding tendency due to spontaneous Factor VIII inhibition were investigated. An in vitro study was designed to investigate lymphocyte transformation and the production of Factor VIII inhibitor. Blood samples from patients were separated on a ficoll-hypaque gradient and the mononuclear cells were cultured with haemophiliac plasma. Factor VIII concentrate and normal plasma as sources of Factor VIII antigen. The results showed that the patients lymphocytes were stimulated by some samples of haemophiliac plasma, but not by the Factor VIII concentrates or normal plasma. However, normal control lymphocytes were similarly stimulated by these samples of haemophiliac plasma suggesting that immune complexes were present in the haemophiliac plasma and probably caused the stimulation. Furthermore, the patients lymphocytes were stimulated with phytohaemagglutinin candida and tuberculin and normal responses were obtained with AB serum. However, the sera of both patients inhibited candida and tuberculin stimulated lymphocyte cultures and the inhibition correlated with the presence of Factor VIII inhibitor. In this study a cellular immune mechanism for the production of spontaneous Factor VIII inhibitor could not be demonstrated, however a serum inhibitor of candida and tuberculin stimulated lymphocyte cultures was found.

scholarly journals Clinical Use of Factor IX Concentrates

1977 ◽  
Author(s):  
D. Ménaché
Keyword(s):  
Beneficial Effect ◽  
Factor Viii ◽  
Radical Change ◽  
Factor Ix ◽  
Severe Bleeding ◽  
Factor Viii Inhibitor ◽  
Anamnestic Response ◽  
Viii Inhibitor ◽  
Factor Ix Deficiency

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.

Sign in / Sign up

Export Citation Format

Share Document