Inherited Antithrombin III Deficiency and Cerebral Thrombosis in a Child

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.

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

10.1055/s-0038-1644370 ◽

1987 ◽

Cited By ~ 1

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.

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

10.1055/s-0038-1653103 ◽

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.

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PROTHROMBIN AND ANTITHROMBIN III IN PATIENTS WITH HEPATOCELLULAR CARCINOMA

10.1055/s-0038-1643209 ◽

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.

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Management of antithrombin III deficiency in pregnancy: a representative case and a literature review

Obstetrics Gynecology and Reproduction ◽

10.17749/2313-7347/ob.gyn.rep.2021.230 ◽

2021 ◽

Vol 15 (4) ◽

pp. 441-450

Author(s):

S. V. Akinshina ◽

P. K. Genina ◽

V. O. Bitsadze ◽

J. Kh. Khizroeva ◽

V. I. Tsibizova ◽

...

Keyword(s):

Antithrombin Iii ◽

Blood Clot ◽

Low Molecular Weight ◽

Monitoring Therapy ◽

At Iii ◽

History Of ◽

Antithrombin Iii Deficiency ◽

Therapeutic Doses ◽

Generation Test ◽

Indications For Use

The work is aimed at discussing pregnancy management for the most thrombogenic genetic thrombophilia - antithrombin III (AT-III) deficiency. A detailed analysis of the literature and clinical case of pregnancy management in a patient with AT-III deficiency, pulmonary embolism and habitual history of miscarriage has been performed and presented. Patients with AT-III deficiency are at high risk for developing thrombotic and obstetric complications even despite using therapeutic doses of anticoagulants. Indications for use and modes of administration of AT-III concentrate have not been currently defined clearly. Monitoring therapy with low molecular weight heparin is largely complicated because a test for determining anti-Xa activity is AT-III-dependent. In addition to standard methods for controlling antithrombotic therapy, we used tests characterizing the dynamic blood clot parameters: thromboelastography and thrombin generation test. The peak risk resulting in both thrombotic and hemorrhagic complications in such patients occurs during period of labor and the postpartum period, when a change in the regimen of anticoagulant therapy is required with its temporary withdrawal and additional administration of AT-III concentrate.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651085 ◽

1987 ◽

Vol 57 (02) ◽

pp. 154-157 ◽

Cited By ~ 4

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.

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The Prevalence of Hereditary Antithrombin-III Deficiency in Patients with a History of Venous Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660123 ◽

1985 ◽

Vol 54 (04) ◽

pp. 744-745 ◽

Cited By ~ 29

Author(s):

R Vikydal ◽

C Korninger ◽

P A Kyrle ◽

H Niessner ◽

I Pabinger ◽

...

Keyword(s):

Venous Thrombosis ◽

Antithrombin Iii ◽

Positive Family History ◽

Normal Range ◽

The Family ◽

History Of ◽

Antithrombin Iii Deficiency ◽

Recurrent Venous Thrombosis ◽

Antithrombin Iii Activity ◽

Slight Deficiency

SummaryAntithrombin-III activity was determined in 752 patients with a history of venous thrombosis and/or pulmonary embolism. 54 patients (7.18%) had an antithrombin-III activity below the normal range. Among these were 13 patients (1.73%) with proven hereditary deficiency. 14 patients were judged to have probable hereditary antithrombin-III deficiency, because they had a positive family history, but antithrombin-III deficiency could not be verified in other members of the family. In the 27 remaining patients (most of them with only slight deficiency) hereditary antithrombin-III deficiency was unlikely. The prevalence of hereditary antithrombin-III deficiency was higher in patients with recurrent venous thrombosis.

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Antithrombin III Alger: A New Homozygous AT III Variant

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661525 ◽

1986 ◽

Vol 55 (02) ◽

pp. 218-221 ◽

Cited By ~ 30

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.

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Congenital Antithrombin III Deficiency in 3 Families (7 Affected Members)

10.1055/s-0038-1665841 ◽

1979 ◽

Author(s):

J. Conard ◽

M. Samama ◽

M. H. Horellou ◽

B. Cazenave ◽

P. Griguer ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Antithrombin Iii ◽

Oral Anticoagulants ◽

Vena Cava ◽

Oral Contraception ◽

Vein Thrombosis ◽

Heparin Treatment ◽

At Iii ◽

Antithrombin Iii Deficiency ◽

Deep Vein

A congenital Antithrombin III (AT III) deficiency affecting 7 members of 3 families is reported.The first throrabo-embolic accidents were observed between the age of 22 and 35 : they were spontaneous or occured after delivery or oral contraception. in one patient, a deep vein thrombosis was observed during heparin treatment. in 2 cases, recurrent pulmonary embolic episodes required vena cava ligation. No thromboembolic accident was observed during oral anticoagulation.AT III was measured by an amidolytic method and by the Mancini method on plasma and serum ; the antithrombin activity was determined on serum by the von Kaulla method. in 7 patients, a decreased AT III was found by all the methods performed. The AT III level was around 50 % in patients treated or not by oral anticoagulants One patient was studied during heparin treatment and then under oral anticoagulants : AT III levels were lower under heparin.

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Antithrombin III, Heparin Cofactor and Antifactor Xa in Relation to Age, sex And Pathological Conditions

10.1055/s-0039-1684568 ◽

1979 ◽

Author(s):

F. Panicucci ◽

A. Sacripanti ◽

E. Pinori ◽

M. Vispi ◽

B. Conte ◽

...

Keyword(s):

Oral Contraceptive ◽

Antithrombin Iii ◽

Normal Subjects ◽

Cerebral Thrombosis ◽

Positive Correlation ◽

Pathological Conditions ◽

At Iii ◽

The Mean ◽

Antifactor Xa ◽

Cofactor Activity

Determinations of AT-III activity, heparin cofactor activity, antifactor Xa activity and AT-III protein were carried out in 200 healthy adults, evenly distributed within age and sex groups, in 60 patients with cerebral thrombosis and in 20 oral contraceptive users. There was a positive correlation between AT-III protein and its activitiesin normal subjects and in patients with cerebral thrombosis. In oral contraceptive users the positive correlation was between AT-III protein and its activities, antifactor Xa activity excepted. The mean AT-III protein and heparin cofactor activity values decreased in males with age and were significantly lower in the groups between 50 and 70 years. The mean AT-III protein and heparin cofactor activity values decreased slightly in women in fertile age and were lower in the 40 to 50 age-group. The mean AT-III protein and its activities values did not show any variation in the patients with cerebral thrombosis. The mean antifactor Xa activity value in the women, taking the pill for 3 months, decreased, whereas the other AT-III activities and AT-III protein were unchanged.

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