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.

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.

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.

PROTHROMBIN AND ANTITHROMBIN III IN PATIENTS WITH HEPATOCELLULAR CARCINOMA

1987 ◽  
Author(s):  
G Leone ◽  
V De Stefano ◽  
R Ferrelli ◽  
C Barone ◽  
C Garufi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antithrombin Iii ◽  
Previous History ◽  
Extensive Study ◽  
Normal Range ◽  
Normal Pattern ◽  
At Iii ◽  
History Of ◽  
Large Peak ◽  
Plasma Absorption

Prothrombin (F.II) and antithrombin III (AT III) levels were measured in 11 patients (mean age 61 years) with hepatocellular carcinoma; F.II antigen (Ag) mean levels (Laurell) were 1.39±0.53 U/ml and F.II activity (Ac) (clotting method) 0.9±0.21 U/ml; AT III Ag mean levels (radial immunodiffusion) were 1.18±0.32 U/ml and AT III heparin cofactor (HC) (amidolytic method) 1.15±0.31 U /ml. In 5 patients F.II Ag was higher than 1.2 U/ml; no patient had F.II Ag lower than 0.8 U/ml (normal range 0.7-1.2 U/ml). F.II Ac was in the normal range in all patients. In 4 patients both AT III Ag and HC were higher than 1.2 U/ml; no patient had AT III Ag and HC lower than 0.8 U/ml (normal range 0.75-1.2 U/ml). Seven patients had a long history of liver cirrhosis and 2 of them sho wed AT III Ag and HC of 1.8 U/ml; one of these two patients had F.II Ag and Ac around 1.00 U/ml, whereas the other had F.II Ag 2.4 U/ml and F.II Ac 1.2 U/ml. In these two patients a prelimina ry more extensive study was performed. In both subjects AT III plasma crossed immunoelectrophoresis was normal in the presence and absence of heparin and AT III crossed immunoelectrofocusing (CIEF) showed a normal pattern of 6 peaks (pH 5.2-4.6) and two additional small peaks at pH 4.5 and 5.4. In the patient with in creased F.II Ag the CIEF of plasma prothrombin showed a large peak with asymmetric branches at pH 5.2-4.9, as in the control, and a large additional peak at pH 5.9; after plasma absorption with Al(OH), the F.II CIEF pattern showed only the abnormal peek. We conclude that in patients with hepatocellular carcinoma F.II and AT III are normal, independently of previous history of cirrhosis; moreover, in agreement with previous studies (N.Engl.J. Med. 310,1427,1984), an abnormal prothrombin, which we demonstra ted characterizable by the CIEF, can be synthesized.

Inherited Antithrombin III Deficiency and Cerebral Thrombosis in a Child

PEDIATRICS ◽  
1980 ◽  
Vol 65 (1) ◽  
pp. 125-131
Author(s):  
Daniel R. Ambruso ◽  
Linda J. Jacobson ◽  
William E. Hathaway
Keyword(s):  
Antithrombin Iii ◽  
Index Case ◽  
Cerebral Thrombosis ◽  
Recurrent Thrombosis ◽  
Normal Pattern ◽  
Crossed Immunoelectrophoresis ◽  
Warfarin Sodium ◽  
At Iii ◽  
History Of ◽  
Antithrombin Iii Deficiency

Identification of a family affected by antithrombin III-heparin cofactor (AT-III) deficiency was made after diagnosis of the index case, a 15-year-old boy who suffered cerebral thrombosis. The proband had a two-year history of recurrent thrombosis involving the lower extremities. His mother and sister were also affected. Studies showed a decreased biological activity (AT-IIIc) and antigen (AT-IIIag) by the Laurell technique in the proband (AT-IIIc = 0.32, AT-IIIag = 46%), his sister (AT-IIIc = 0.29, AT-IIIag = 47%), and his mother (AT- IIIc = 0.41, AT-IIIag 56%). Crossed immunoelectrophoresis (CIE) of the affected individuals' plasma in agarosecontaining heparin demonstrated a normal pattern of migration. Treatment with warfarin sodium (Coumadin) resulted in an increase in activity in two of three affected family members, and in antigen in all three. Anticoagulant therapy did not affect the pattern of AT-III on CIE. This family represents a quantitative deficiency in antithrombin III. A review of the reported cases of antithrombin III deficiency indicates that individuals with this disorder may have thromboembolic disease in childhood.

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.

Effects of an Enzymatically Depolymerized Heparin as Compared with Conventional Heparin in Healthy Volunteers

1987 ◽  
Vol 57 (01) ◽  
pp. 097-101 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Per Østergaard
Keyword(s):  
Molecular Weight ◽  
Body Weight ◽  
Healthy Volunteers ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Normal Range ◽  
Factor Xa Inhibition ◽  
At Iii ◽  
Mean Molecular Weight ◽  
Enzymatic Depolymerization

SummaryA low molecular weight heparin (LMW-heparin) with a mean molecular weight of 4900 dalton was prepared by controlled enzymatic depolymerization of conventional porcine mucosal heparin. The effects of 2,500, 5,000 and 10,000 U (Xal; 29,58 and 116 mg) on factor Xa inhibition (Xal), factor Ila inhibition (Hal), APTT, AT III and platelet count were compared to those of 5,000 U (Xal; 26 mg) of conventional heparin given s. c. to 6 healthy volunteers. 5,000 U (Xal; 58 mg) of LMW-heparin was given i. v. A dose related response with regard to the Xal and the Ila-inhibitory activities with peak values at 4 hours after the s. c. injections was obtained. An increase of the Xal/IIal ratio over the time after injection was seen only after i. v. administration of the LMW-heparin. The APTT was only slightly prolonged and remained within normal range after s. c. injection. AT III and platelet counts were unaffected. The biological half life of the LMW-heparin was 111 minutes if assayed by Xa inhibition, 76 minutes if assayed by Ila inhibition and 40 minutes if assayed by APTT. A strong correlation between the Xal activities obtained and body weight was seen, indicating that LMW-heparin should be administered individually according to body weight.

Inherited Deficiency Of Antithrombin III In Two Italian Families. Different Behaviour After Long-Term Anticoagulant Treatment

1981 ◽  
Author(s):  
C Manotti ◽  
M Pini ◽  
R Poti ◽  
R Quintavalia
Keyword(s):  
Antithrombin Iii ◽  
Oral Anticoagulants ◽  
Immunological Methods ◽  
Anticoagulant Treatment ◽  
Normal Pattern ◽  
Vein Thrombosis ◽  
Congenital Deficiency ◽  
At Iii ◽  
History Of

An inherited deficiency of antithrombin III (AT III), measured with four different, functional and immunological, methods, was found in 8 out of 11 examined members and in 3 out of 11 examined members of two Italian families (D.M. and A. families). Biological activity, measured with Abildgard’s clotting assay and with an amidolytic method, ranged between 17 and 75%. Cross immunoelectrophoresis, with or without heparin, performed in the two propositi and in 1; other relatives, showed a normal pattern of migration.A different behaviour of AT III after anticoagulation with acenocoumarin was seen in two long-term treated subjects. The proposita of the D.M. family, who had a history of recurrent thrombotic accidents, did not show any increase of AT III levels, measured in the first two weeks and after 6 and 12 months of therapy. A significant (about 50%) increase both with the functional and immunological methods was on the contrary observed in the propositus of A. family, who had undergone surgery because of mesenteric vein thrombosis. Until now both patients have been free of thrombotic recurrences.Our findings confirm previous reports of variable effects of oral anticoagulants on AT III levels in subjects with congenital deficiency.

A Comparison of Pentosan Polysulphate (SP54) and Heparin I: Mechanism of Action on Blood Coagulation

1982 ◽  
Vol 47 (02) ◽  
pp. 104-108 ◽  
Author(s):  
A-M Fischer ◽  
T W Barrowcliffe ◽  
D P Thomas
Keyword(s):  
Factor Xa ◽  
Factor X ◽  
Factor Ixa ◽  
Crossed Immunoelectrophoresis ◽  
Low Concentrations ◽  
At Iii ◽  
Pentosan Polysulphate ◽  
High Concentrations ◽  
Marked Suppression ◽  
Inhibition Of Thrombin

SummaryThe effects of SP54 on inhibition of thrombin, factor Xa and factor IXa, in the presence and absence of antithrombin III (At III), have been examined and compared to those of heparin. SP54 potentiated inhibition of thrombin and Xa by purified At III, but crossed immunoelectrophoresis data indicated that these effects were mediated by binding to the enzyme, rather than to At III. Relatively high concentrations of SP54 were required for inhibition of thrombin and Xa in plasma, but at concentrations less than 2 μg/ml there was a marked suppression of the intrinsic activation of factor X. This effect was shown to be independent of At III, and to be due largely to inhibition of factor IXa. Prothrombin activation by factor Xa and phospholipid was also suppressed by SP54 in the absence of At III, and its effect on the APTT was also shown to be independent of At III. It is concluded that at relatively low concentrations the anticoagulant actions of SP54 are mainly due to these At III-independent pathways.

Homozygous Variant of Antithrombin III : AT III Fontainebleau

1986 ◽  
Vol 56 (01) ◽  
pp. 018-022 ◽  
Author(s):  
C Boyer ◽  
M Wolf ◽  
J Vedrenne ◽  
D Meyer ◽  
M J Larrieu
Keyword(s):  
Antithrombin Iii ◽  
Oral Anticoagulant Therapy ◽  
Low Molecular Weight ◽  
Normal Amount ◽  
Homozygous State ◽  
Normal Range ◽  
At Iii ◽  
Cofactor Activity ◽  
Intracardiac Thrombosis ◽  
Tunisian Family

SummaryA qualitative defect of antithrombin III (AT III) was demonstrated in four members of a large Tunisian family by the discrepancy between a normal amount of antigen and decreased or absent heparin cofactor activity. The propositus, a 3-year-old girl, died from massive intracardiac thrombosis despite oral anticoagulant therapy. Heparin cofactor activity measured in the presence of thrombin or F. Xa was undetectable in her plasma. Anti-F. Xa activity was also absent when using low molecular weight heparin or a synthetic pentasaccharide, representing the binding site to AT III. The lack of affinity of the propositus AT III for heparin was demonstrated by two-dimensional immunoelectrophoresis and chromatography on heparin-Sepha-rose. The parents, first cousins, and the sister of the propositus also demonstrated a qualitative abnormality of AT III, with levels of heparin cofactor activity close to 50% of the normal range. Our data support the view that the abnormal protein was present at the heterozygous state in the parents and sister and at the homozygous state in the propositus. None of the affected family members had thrombotic episodes, except for the propositus. The name of AT III Fontainebleau is proposed for this 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.

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