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

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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Prevalence of antithrombin III deficiency in blood donors selected for personal or familial history of venous thrombosis

La Ricerca in Clinica e in Laboratorio ◽

10.1007/bf03029836 ◽

1985 ◽

Vol 15 (2) ◽

pp. 173-176

Author(s):

Guido Finazzi ◽

Eneina Radice ◽

Antonino Armato ◽

Tiziano Barbui

Keyword(s):

Venous Thrombosis ◽

Blood Donors ◽

Antithrombin Iii ◽

Familial History ◽

History Of ◽

Antithrombin Iii Deficiency

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661305 ◽

1985 ◽

Vol 53 (03) ◽

pp. 314-319 ◽

Cited By ~ 10

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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Familial Thrombosis Due to Antithrombin III Deficiency

Blood ◽

10.1182/blood.v43.2.219.219 ◽

1974 ◽

Vol 43 (2) ◽

pp. 219-231 ◽

Cited By ~ 197

Author(s):

Ewa Marciniak ◽

Claude H. Farley ◽

Philip A. DeSimone

Keyword(s):

Antithrombin Iii ◽

Clinical Symptoms ◽

Oral Anticoagulants ◽

Laboratory Diagnosis ◽

Blood Component ◽

History Of ◽

Antithrombin Iii Deficiency ◽

Recurrent Venous Thrombosis

Abstract A large kindred from eastern Kentucky, with extensive history of recurrent venous thrombosis and pulmonary embolism, was studied. Low antithrombin III titers, ranging from 26% to 49% of normal values, were found in plasma of nine members in three consecutive generations; another five members, four of whom were not available for study, are suspected of having the biochemical defect. There was a good correlation between clinical symptoms and antithrombin III deficiency, although three of the younger members with the defect still remained free of thrombosis. In serum of the affected subjects antithrombin III was almost completely utilized, which indicates that stoichiometric binding to coagulation enzymes dominates under biological conditions. Antithrombin and antifactor Xa activities residing in the macroglobulin region of plasma and serum remained unchanged. The responsiveness to heparin in vitro and in vivo confirmed the evidence that antithrombin III is the sole blood component through which heparin exerts its anticoagulant effect. In five affected members therapy with oral anticoagulants increased very significantly the level of antithrombin III in plasma and contributed to a remarkable increase of residual antithrombin III in serum. This objective improvement after warfarin therapy may create significant difficulties in the laboratory diagnosis of antithrombin III deficiency.

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Hereditary Heparin Cofactor II Deficiency and the Risk of Development of Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651093 ◽

1987 ◽

Vol 57 (02) ◽

pp. 196-200 ◽

Cited By ~ 74

Author(s):

R M Bertina ◽

I K van der Linden ◽

L Engesser ◽

H P Muller ◽

E J P Brommer

Keyword(s):

Liver Disease ◽

Venous Thrombosis ◽

Healthy Volunteers ◽

Mean Value ◽

Age Group ◽

Normal Range ◽

Heparin Cofactor Ii ◽

History Of ◽

Group 2 ◽

Hereditary Nature

SummaryHeparin cofactor II (HC II) levels were measured by electroimmunoassay in healthy volunteers, and patients with liver disease, DIC, proteinuria or a history of venous thrombosis. Analysis of the data in 107 healthy volunteers revealed that plasma HC II increases with age (at least between 20 and 50 years). HC II was found to be decreased in most patients with liver disease (mean value: 43%) and only in some patients with DIC. Elevated levels were found in patients with proteinuria (mean value 145%). In 277 patients with a history of unexplained venous thrombosis three patients were identified with a HC II below the lower limit of the normal range (60%). Family studies demonstrated hereditary HC II deficiency in two cases. Among the 9 heterozygotes for HC II deficiency only one patient had a well documented history of unexplained thrombosis. Therefore the question was raised whether heterozygotes for HC II deficiency can also be found among healthy volunteers. When defining a group of individuals suspected of HC II deficiency as those who have a 90% probability that their plasma HC II is below the 95% tolerance limits of the normal distribution in the relevant age group, 2 suspected HC II deficiencies were identified among the healthy volunteers. In one case the hereditary nature of the defect could be established.It is concluded that hereditary HC II deficiency is as prevalent among healthy volunteers as in patients with thrombotic disease. Further it is unlikely that heterozygosity for HC II deficiency in itself is a risk factor for the development of venous thrombosis.

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HEREDITARY AND ENVIRONMENTAL FACTORS IN THE PATHOGENESIS OF RHEUMATIC FEVER

PEDIATRICS ◽

10.1542/peds.19.5.908 ◽

1957 ◽

Vol 19 (5) ◽

pp. 908-915

Author(s):

Eugene F. Diamond

Keyword(s):

Family History ◽

Rheumatic Fever ◽

Autosomal Recessive ◽

Positive Family History ◽

Recessive Gene ◽

Environmental Groups ◽

Environmental Group ◽

The Family ◽

History Of ◽

Unfavorable Environmental Factor

A study of cases of rheumatic fever admitted to La Rabida Sanitarium over a 5-year period was carried out to evaluate heredity and environment as etiologic factors in rheumatic disease. The incidence of rheumatic fever was shown to be higher in families where one or both parents were known to have a positive family history of rheumatic fever. The incidence of rheumatic fever was compared in environmental groups. A totally unfavorable environment was shown to increase the incidence of rheumatic fever. No single unfavorable environmental factor changed the incidence of rheumatic fever. The incidence of rheumatic fever in each environmental group was higher when there was a positive family history for rheumatic fever, indicating an hereditary factor in the family incidence of rheumatic fever. Analysis of the various mating types in the families with a positive rheumatic trait was carried out. Agreement with a simple autosomal recessive gene inheritance was obtained in families where both parents had a definite family history, but no agreement was obtained in cases where only one parent gave a positive family history.

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Antithrombin III Deficiency in a Japanese Family

10.1055/s-0039-1684570 ◽

1979 ◽

Author(s):

M. Nakagawa ◽

T. Kawamura ◽

H. Tsuji ◽

Y. Okajima ◽

S. Urano ◽

...

Keyword(s):

Antithrombin Iii ◽

Sinus Thrombosis ◽

Elevated Serum ◽

Peptic Ulcers ◽

Autosomal Dominant Disorder ◽

Japanese Family ◽

Vein Thrombosis ◽

Chromogenic Assay ◽

History Of ◽

Antithrombin Iii Deficiency

Antithrombin III has been reported to be decreased in the cases of several thrombotic disorders and the decreased Antithrombin III is known to induce the hypercoagulable state. This study was started from the 28 year-old male patient who developed the superior sagital sinus thrombosis after appendectomy and it was followed by deep vein thrombosis of extremities. Antithrombin III level was 19 mg/dl and activity was 68% by the progressive antithrombin assay and other laboratory examinations were within normal range excepts for the elevated serum lipids. Antithrombin III was assayed for his family members in three consecutive generations by single radial immunodifusion method, coagulation assay, and chromogenic assay. Four out of eight members were confirmed to have low Antithrombin III level and activity ranging from 59%-68% of normal values, although the two of this four members had no history of thrombosis. Mother of this propositus is deceased, but it was suspected of having the defect of Antithrombin III. History of peptic ulcers were found in all members of this family. The inheritance pattern of Antithrombin III deficiency was characteristic of an autosomal dominant disorder.

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Familial Thrombosis Due to Antithrombin III Deficiency: An Extensive Family Study

10.1055/s-0039-1680524 ◽

1977 ◽

Author(s):

Bruce Bennett ◽

Michael Mackie ◽

Alexander S. Douglas

Keyword(s):

Small Bowel ◽

Antithrombin Iii ◽

Massive Pulmonary Embolism ◽

Autosomal Dominant Disorder ◽

Bowel Infarction ◽

North West ◽

Mesenteric Vein ◽

The North ◽

The Family ◽

Antithrombin Iii Deficiency

A family living in Lewis (a Hebridean Island off the north west coast of Scotland) affected by antithrombin III deficiency has been studied. Two members have died, one of massive pulmonary embolism and one of major mesenteric infarction secondary to mesenteric vein occlusion. A further individual has sustained major small bowel infarction secondary to mesenteric vein thrombosis but survived after two small bowel resections followed by anticoagulant therapy. Other members of the family have suffered from nonfatal thrombotic events particularly during pregnancy. 57 individuals representing several generations have been studied and will be presented. Levels of antithrombin III measured by functional assays correlated well with those of antithrombin III measured immunologically. 12 members of the family showed moderate to severe deficiency of antithrombin III, the occurrence of thrombotic symptoms correlating well with deficiency of this protein. Transmission of the disorder as an autosomal dominant disorder is confirmed in the patients studied and by historical evidence over many generations.

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