Antithrombin III Alger: A New Homozygous AT III Variant

1986 ◽  
Vol 55 (02) ◽  
pp. 218-221 ◽  
Author(s):  
A M Fischer ◽  
P Cornu ◽  
C Sternberg ◽  
F Mériane ◽  
M D Dautzenberg ◽  
...  
Keyword(s):  
Family History ◽  
Antithrombin Iii ◽  
Antigen Concentration ◽  
Crossed Immunoelectrophoresis ◽  
The Family ◽  
At Iii ◽  
Molecular Abnormality ◽  
Slow Moving ◽  
Cofactor Activity ◽  
Plasma Heparin

SummaryA qualitative abnormality of antithrombin III (AT III) was found in the plasma of a 41-year old patient. The plasmatic AT III antigen concentration was 130% and the progressive anti-F IIa and anti-F Xa activities were normal (105% and 137%). The plasma heparin cofactor activity was less than 10%, when measured by F Ila or F Xa inhibition. Crossed immunoelectrophoresis of AT III in the presence of heparin revealed in the plasma an abnormal slow-moving peak. When tested by affinity chromatography on heparin Sepharose, this abnormal AT III did not bind to heparin. Among the investigated relatives, 5 subjects had normal AT III levels, whatever the test used, the nine others having reduced levels of antithrombin heparin cofactor activity (45-61%) but normal levels of immunoreactive AT III (97-122%). Consanguinity was found in the family history. We therefore considered our patient as homozygous for an AT III molecular abnormality affecting the binding site for heparin.

AT III Barcelona: A Familial Quantitative-Qualitative AT III Deficiency

1988 ◽  
Vol 59 (01) ◽  
pp. 013-017 ◽  
Author(s):  
E Grau ◽  
J Fontcuberta ◽  
J Félez ◽  
I de Diego ◽  
R Soto ◽  
...  
Keyword(s):  
Antithrombin Iii ◽  
Normal Range ◽  
Affinity Adsorption ◽  
Crossed Immunoelectrophoresis ◽  
At Iii ◽  
Spanish Family ◽  
Slow Moving ◽  
Cofactor Activity ◽  
Ph Range ◽  
Thrombotic Tendency

SummaryA quantitative and qualitative deficiency of antithrombin III (AT III) was found in four members of a Spanish family with thrombotic tendency. In all affected members, levels of AT III antigen and activity (heparin cofactor activity) were reduced to 50% of the normal range. When crossed immunoelectrophoresis (CIE) was performed in the presence of heparin, an abnormal slow-moving peak was found. Crossed immunoelectrofocusing (CIEF) from normal and affected individuals showed that normal AT III migrated between pH 4.9–5.3 while the AT III under study was asymetrically distributed between two pH ranges: 4.9–5.3 and 4.6–4.8. Affinity adsorption of affected members’ plasma to heparin-sepharose beads revealed one population of AT III in the supernatant corresponding to the abnormal AT III, devoid of heparin cofactor activity and showing a peak between pH range: 4.6–4.8 in CIEF.Our data supports the view that a quantitative-qualitative deficiency was present in the heterozygous state in all the affected family members. Both normal and abnormal ATIII were present in plasma of the affected individuals. This abnormal ATIII was characterized by a lack of affinity for heparin. This familial ATIII deficiency was named ATIII Barcelona.

A NEW ASYMPTOMATIC TYPE III VARIANT OF ANTITHROMBIN III WITH DECREASE HEPARIN COFACTOR ACTIVITY : AT III AMIENS

1987 ◽  
Author(s):  
B ROUSSEL ◽  
J DIEVAL ◽  
S GROSS ◽  
J F CLAISSE ◽  
J DELOBEL
Keyword(s):  
Factor Xa ◽  
Normal Range ◽  
Normal Pattern ◽  
Type Iii ◽  
Crossed Immunoelectrophoresis ◽  
At Iii ◽  
History Of ◽  
Routine Laboratory Examination ◽  
Slow Moving ◽  
Cofactor Activity

A qualitative abnormality of AT III suggested by the discrepancy between a normal level of AT III antigen (0,33 g/1) and a decreased heparin cofactor activity (60 % of normal) was discovered in a 37 years old woman during a routine laboratory examination for oral contraceptive. The propositus was asymptomatic as she did not developpe any thrombo-embolic disease during three previous pregnancies. There was no familial history of thrombo-embolism. The AT III level measured by radial immuno-diffusion was within the normal range. The progressive anti factor lia and anti factor Xa activities (chromogenic substrates CBS 3 447 and CBS 3 139) were normal (92 % and 100 %). Plasma and serum crossed immunoelectrophoresis (CIE) showed a normal pattern. In the presence of heparin, anti factor Xa and anti factor Xa activities were decreased (60 % and 45 %); Plasma and serum crossed immunoelectrophoresis showed an abnormal slow moving peak exhibiting the inhability of the molecule to bind completely to heparin. CIE with various other glycosaminoglycans are on experiments.Familial study revealed that the daughter of the propositus was carrying the same molecular abnormality.We conclude that AT III Amiens is an hereditary type III variant.

ANTITHROMBIN III GENEVA : AN HEREDITARY ABNORMAL ANTITHROMBIN III (AT III) WITH DEFECTIVE HEPARIN COFACTOR ACTIVITY

1987 ◽  
Author(s):  
Ph de Moerloose ◽  
G Reber ◽  
Ph Minazio ◽  
C A Bouvier
Keyword(s):  
Antithrombin Iii ◽  
Protein S ◽  
The Family ◽  
Coagulation Tests ◽  
At Iii ◽  
Cofactor Activity ◽  
Low Incidence ◽  
Immunological Assays ◽  
Normal Inhibition ◽  
Two Populations

A 43-year old man presented a pulmonary embolism. Despite a negative family history for thromboembolic disorders, the unusual circumstances of apparition and the relatively young age of the patient prompted us to study carefully the coagulation parameters. Routine coagulation tests, as well as plasminogen, alpha-2-anti-plasmin, protein C and protein S were all within normal range. Biological and immunological assays of AT III were performed on 12 members of the family and showed a low AT III activity in the propositus and other members of this family (mean 50%), but normal immunologic levels. Crossed immunoelectrophoresis in absence of heparin showed a normal pattern, but in presence of heparin showed an abnormal peak as compared with controls. Kinetics experiments showed a normal inhibition of Xa and 11a in absence of heparin, but abnormal in presence of heparin. An affinity chromatography on heparin Sepharose revealed two populations of AT III, one of which was devoid of heparin cofactor activity.The toponym AT III Geneva is proposed for this new familial abnormal AT III with defective heparin cofactor activity. This family confirms the low incidence of thromboembolic events reported in this type of AT III variant.

Antithrombin III “Northwick Park”: A Variant Antithrombin with Normal Affinity for Heparin but Reduced Heparin Cofactor Activity

1985 ◽  
Vol 53 (03) ◽  
pp. 314-319 ◽  
Author(s):  
D J Howarth ◽  
Diana Samson ◽  
Yvonne Stirling ◽  
M J Seghatchian
Keyword(s):  
Venous Thrombosis ◽  
Fast Moving ◽  
Autosomal Dominant ◽  
Antithrombin Iii ◽  
Two Dimensional ◽  
Antithrombin Activity ◽  
The Family ◽  
At Iii ◽  
History Of ◽  
Cofactor Activity

SummaryFurther studies have been carried out in a previously reported family with congenital antithrombin III (AT III) deficiency due to an abnormal variant of AT III (AT III Northwick Park). The variant has been identified in five members of the family, three of whom had a history of venous thrombosis. Inheritance followed an autosomal dominant pattern. The affected family members have reduced levels of antithrombin heparin cofactor (41–67%) and progressive antithrombin activity (44–62%) but normal levels of immunoreactive AT III (91–162%). Two dimensional immunoelectrophoresis (2 DIE) of AT III in the absence of heparin revealed an abnormal fast-moving peak in addition to the normal peak but 2 DIE in the presence of heparin appeared normal. Further studies confirmed that the abnormal AT III binds completely to heparin but has no heparin cofactor or progressive antithrombin activity. These results would be consistent with a mutation affecting the binding site for thrombin.

Homozygous Variant of Antithrombin III that Lacks Affinity for Heparin, AT III Kumamoto

1989 ◽  
Vol 61 (01) ◽  
pp. 020-024 ◽  
Author(s):  
Kenji Okajima ◽  
Hidetsugu Ueyama ◽  
Youichiro Hashimoto ◽  
Yasuto Sasaki ◽  
Keiko Matsumoto ◽  
...  
Keyword(s):  
Affinity Chromatography ◽  
Autosomal Dominant ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Heparin Cofactor Ii ◽  
At Iii ◽  
Antifactor Xa ◽  
Cofactor Activity ◽  
Inhibition Of Thrombin ◽  
Plasma Heparin

SummaryAbnormal antithrombin III (AT III) was found in the plasma of a 31-year-old female who suffered from recurrent thrombotic episodes. Heparin cofactor activity was 28% of normal and undetectable when measured by inhibition of thrombin and factor Xa (F. Xa), while both progressive antithrombin and antifactor Xa activities were normal. The concentration of plasma AT III antigen was 37 mg/dl. Analysis by crossed-immunoelec- trophoresis (CIE) in the presence of heparin and affinity chromatography on heparin-Sepharose revealed that the propositus’ AT III did not bind to heparin. When heparin cofactor II (HC II) was removed from propositus’ plasma, heparin cofactor activity of AT III was not detected. Thus, HC II seemed to account for the plasma heparin cofactor activity found in the presence of thrombin. The patient’s parents and three of her brothers demonstrated qualitative abnormality of AT III; heparin cofactor activity was 30-50% of normal levels in the presence of both thrombin and F. Xa. These findings indicate that the propositus’ AT III lacks affinity for heparin and the mode of its inheritance seems to be autosomal dominant and, hence, the propositus would be a homozygote. For this variant, the name of AT III Kumamoto is proposed.

A New Variant of Antithrombin III. Study of three Related Cases.

1979 ◽  
Author(s):  
M. Wolf ◽  
C. Boyer ◽  
J.M. Lavergne ◽  
M.J. Larrieu
Keyword(s):  
Electrophoretic Mobility ◽  
Antithrombin Iii ◽  
Chromogenic Substrates ◽  
Double Peak ◽  
Enzymatic Assays ◽  
Crossed Immunoelectrophoresis ◽  
New Variant ◽  
At Iii ◽  
Cofactor Activity ◽  
Two Peaks

A qualitative abnormality of antithrombin III (AT III) was demonstrated in three member from the same family. The mother (58 y.) had recurrent episodes of venous thrombosis an pulmonary embolism whereas the affected daughters (20 and 29 y.) are asymptomatic. AT III was investigated in presence and absence Of heparin hy enzymatic assays using chromogenic substrates (S-2238 and S-2160) and by rocket - and crossed - immunoelectro phoresis using two different monospecific anti-AT III antisera. In the three patients the qualitative abnormality of AT III was suggested by the discrepancy between a norml level of AT III antigen and decreased heparin-cofactor activity (49, 51, 54%). By crossed immunoe1ectrophoresis, patients’ AT III migrated as a single peak in absence of heparin, with the same electrophoretic mobility as that of the control. In presence of heparin (25 u/ml), crossed immunoelectrophoresis demonstrated the presence of two peaks, one with a normal, and the other with a decreased electrophoretic mobility. A double peak was also observed by rocket immunoelectrophoresis in presence of heparin. In this family with a variant of AT III, the three heterozygous affected cases demonstrate two popu1ations of AT III, with a different affinity for heparin.

Further Investigations on Antithrombin III in the Plasmas of Patients with the Abnormality of ‘Antithrombin III Budapest’

1975 ◽  
Vol 33 (03) ◽  
pp. 564-572 ◽  
Author(s):  
Géza Sas ◽  
Duncan S Pepper ◽  
John D Cash
Keyword(s):  
Electrophoretic Mobility ◽  
Antithrombin Iii ◽  
Gel Filtration ◽  
Molecular Size ◽  
High Concentration ◽  
Abnormal Protein ◽  
Crossed Immunoelectrophoresis ◽  
Normal Plasma ◽  
At Iii ◽  
Cofactor Activity

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.

Antithrombin III Geneva: A Hereditary Abnormal AT III with Defective Heparin Cofactor Activity

1987 ◽  
Vol 57 (02) ◽  
pp. 154-157 ◽  
Author(s):  
P A de Moerloose ◽  
G Reber ◽  
Ph Vernet ◽  
Ph Minazio ◽  
C A Bouvier
Keyword(s):  
Antithrombin Iii ◽  
Normal Pattern ◽  
Crossed Immunoelectrophoresis ◽  
At Iii ◽  
Normal Mean ◽  
Cofactor Activity ◽  
Normal Inhibition ◽  
Heparin Affinity ◽  
Two Populations ◽  
Inhibition Of Thrombin

SummaryA 43-year-old man presented a pulmonary embolism. The unusual circumstances of apparition, the age and the increased heparin requirements suggested an antithrombin III (AT III) deficiency. AT III activity was low in the propositus and seven other members of his family (mean 55%), but immunologic levels were normal (mean 110%). Crossed immunoelectrophoresis in absence of heparin showed a normal pattern, but in presence of heparin showed an abnormal peak as compared with controls. Kinetics experiments showed a normal inhibition of thrombin and Xa in absence of heparin, but abnormal in presence of heparin. Affinity chromatography on heparin-Sepharose revealed two populations of AT III, one of which was devoid of heparin cofactor activity. The toponym AT III Geneva is proposed for this new familial abnormal AT III with defective heparin cofactor activity.

Purification and Partial Characterization of a Hereditary Abnormal Antithrombin III Fraction of a Patient with Recurrent Thrombophlebitis

1980 ◽  
Vol 44 (02) ◽  
pp. 087-091 ◽  
Author(s):  
T H Tran ◽  
H Bounameaux ◽  
C Bondeli ◽  
H Honkanen ◽  
G A Marbet ◽  
...  
Keyword(s):  
Antithrombin Iii ◽  
Agarose Gel ◽  
Normal Range ◽  
Antigen Concentration ◽  
Superficial Thrombophlebitis ◽  
Antithrombin Activity ◽  
Crossed Immunoelectrophoresis ◽  
At Iii ◽  
Heparin Affinity

SummaryA relatively low heparin cofactor activity (0.60 U/ml) was observed in a patient with recurrent superficial thrombophlebitis of the left leg. However, the antigen concentration was in the normal range (1.04 U/ml) and the progressive antithrombin activity was normal. The crossed immunoelectrophoresis in presence of heparin in agarose gel separated the patient's AT-III antigen in 2 fractions with different mobilities. The patient's AT-III was purified for further characterization. The last step of the purification procedure, a heparin-agarose chromatography, led to a separation and a purification of 2 AT-III fractions with different heparin affinities: an abnormal AT-III with reduced heparin affinity and a normal AT-III with a heparin affinity similar to that of AT-III isolated from normal plasmas. Abnormal and normal AT-III share several identical properties as molecular weight, ability to form complexes with thrombin and progressive antithrombin activity.

Respective Roles of Antithrombin III and Alpha 2 Macroglobulin in Thrombin Inactivation

1981 ◽  
Vol 45 (01) ◽  
pp. 051-054 ◽  
Author(s):  
A M Fischer ◽  
J Tapon-Bretaudiere ◽  
A Bros ◽  
F Josso
Keyword(s):  
Antithrombin Iii ◽  
Practical Interest ◽  
High Plasma ◽  
At Iii ◽  
Human Material ◽  
Cofactor Activity

SummaryIn order to investigate the mechanism of thrombin inactivation in the presence of both antithrombin III (AT III) and α 2-macroglobulin (α 2 M), thrombin and the inhibitors have been purified from human material and thrombin inactivation studied using purified reagents either alone or added to defibrinated plasma. Comparison of clotting and amidolytic activities of residual thrombin allowed to measure the amount of thrombin bound to α 2 M. In a purified reagent system as well as in plasma, part of exogenous thrombin is bound to α 2 M. The amount of bound thrombin is related to α 2 M concentration. Conversely, previous plasma α 2 M depletion by immunoabsorption increases the consumption of heparin-cofactor activity by exogenous thrombin. Thus AT III and α 2 M compete for thrombin inactivation. This finding could be of practical interest in clinical situations associating high plasma α 2 M levels and a decrease of AT III concentration.

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