Download PDF
Thromb Haemost 1986; 55(02): 218-221
DOI: 10.1055/s-0038-1661525
Original Article
Schattauer GmbH Stuttgart

Antithrombin III Alger: A New Homozygous AT III Variant

A M Fischer
*   The Département d’Hématologie, C. H. U. Necker-Enfants Malades, Paris, France
,
P Cornu
*   The Département d’Hématologie, C. H. U. Necker-Enfants Malades, Paris, France
,
C Sternberg
*   The Département d’Hématologie, C. H. U. Necker-Enfants Malades, Paris, France
,
F Mériane
**   The Laboratoire d’Hématologie, C. H. U. Mustapha, Alger, Algérie
,
M D Dautzenberg
*   The Département d’Hématologie, C. H. U. Necker-Enfants Malades, Paris, France
,
O Chafa
**   The Laboratoire d’Hématologie, C. H. U. Mustapha, Alger, Algérie
,
S Beguin
*   The Département d’Hématologie, C. H. U. Necker-Enfants Malades, Paris, France
,
M Desnos
***   The Service de Cardiologie, Hôpital Boucicaut, Paris, France
› Author Affiliations
Further Information

Publication History

Received 20 November 1985

Accepted 30 January 1986

Publication Date:
18 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

A 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.

Key words

Antithrombin III - Homozygosity - Heparin cofactor Summary
 

  • References

  • 1 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thrombos Diathes Haemorrh 1965; 13: 516-530
    PubMedGoogle Scholar
  • 2 Sas G, Blaskó GY, Bánhegyi D, Jákó J, Palos LA. Abnormal antithrombin III (antithrombin III “Budapest”) as a cause of a familial thrombophilia. Thrombos Diathes Haemorrh 1974; 32: 105-115
    PubMedGoogle Scholar
  • 3 Koide T, Takahashi K, Odami S, Ono T, Sakuragawa N. Isolation and characterization of a hereditary abnormal antithrombin III “antithrombin III Toyama”. Thrombosis Res 1983; 31: 319-328
    CrossrefPubMedGoogle Scholar
  • 4 Josso F, Prou-Wartelle O. Tests de l’hémostase. In: Techniques en hématologie Alagille D, Colombani J, Dausset J, Fine JM, Josso F. (Eds.) Paris: Flammarion; 1972: 141-191
  • 5 Abildgaard U, Larsen ML. Assay of dermatan sulfate cofactor (heparin cofactor II) activity in human plasma. Thromb Res 1984; 35: 257-266
    CrossrefPubMedGoogle Scholar
  • 6 Laurell CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45-52
    CrossrefPubMedGoogle Scholar
  • 7 Ødegard OR, Lié M, Abildgaard U. Antifactor Xa activity measured with amidolytie methods. Haemostasis 1976; 5: 265-275
    PubMedGoogle Scholar
  • 8 Aiach M, Leon M, Michaud A, Capron L. Adaptation of synthetic peptide substrate-based assays on a discrete analyzer. Semin Thromb Hemostasis 1983; 9: 206-216
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Fischer AM, Tapon-Bretaudiére J, Bros A, Josso F. Respective roles of antithrombin III and α-2 macroglobulin in thrombin inactivation. Thromb Haemostas 1981; 45: 51-54
    PubMedGoogle Scholar
  • 10 Fischer AM, Dautzenberg MD, Aurousseau MH, Béguin S, Goudemand J, Hemker HC. Comparison between the effect of pentosan polysulphate, heparin and antithrombine III injections in antithrombin III deficient patients. Thromb Res 1985; 37: 295-307
    CrossrefPubMedGoogle Scholar
  • 11 Nagy I, Losonczy H. Three types of hereditary AT III deficiency. Thromb Haemostas 1979; 42: 187 (Abstr)
    PubMedGoogle Scholar
  • 12 Penner JA, Hassouna H, Hunter MJ, Chockley MA. A clinically silent antithrombin III defect in an Ann Arbor family. Thromb Haemostas 1979; 42: 186 (Abstr)
    PubMedGoogle Scholar
  • 13 Tran TH, Bounameaux H, Bondeli C, Honkanen H, Marbet GA, Duckert F. Purification and partial characterization of a hereditary abnormal antithrombin III fraction of a patient with recurrent thrombophlebitis. Thromb Haemostas 1980; 44: 87-91
    PubMedGoogle Scholar
  • 14 Girolami A, Fabris F, Cappellato G, Sainati L, Boeri G. Antithrombin III (AT III) Padua 2: A new congenital abnormality with defective heparin cofactor activities but no thrombotic disease. Blut 1983; 47: 93-103
    CrossrefPubMedGoogle Scholar
  • 15 Wolf M, Boyer C, Lavergne JM, Larrieu MJ. A new familial variant of antithrombin III: „Antithrombin III Paris”. Brit J Haematol 1982; 51: 285-295
    CrossrefPubMedGoogle Scholar
  • 16 Fischer AM, Gazengel C, Dautzenberg MD, Benhammo J, Béguin S, Vergoz D. A pew case of abnormal antithrombin III (AT III): biological characteristics and thromboembolic accidents management. Thromb Haemostas 1983; 50: 358
    PubMedGoogle Scholar
  • 17 Chasse JF, Esnard F, Guitton JD, Mouray H, Perigois F, Fauconneau G, Gauthier F. An abnormal plasma antithrombin with no apparent affinity for heparin. Thromb Res 1984; 34: 297-302
    CrossrefPubMedGoogle Scholar
  • 18 Thaler E, Lechner K. Antithrombin III deficiency and thromboembolism. In: Clinics in Haematology Prentice CRM. (Eds) London Saunders; 1981. 10 369-390
  • 19 Abildgaard U. Inhibition of the thrombin fibrinogen reaction by heparin m the absence of cofactor. Scand J Haemat 1968; 5: 432-439
    PubMedGoogle Scholar
  • 20 Tran TH, Zbinden B, Lämmle B, Duckert F. Influence of heparin cofactor II (HC II) on the determination of Antithrombin III (AT). Thromb Haemostas 1985; 54: 204 (Abstr)
    PubMedGoogle Scholar
  • 21 Boyer C, Wolf M, Vedrenne J, Larrieu MJ. Antithrombin III Fontainebleau: un variant homozygote de I’antithrombine III. Nouv Rev hematol 1985; 27: 106 (Abstr)
    PubMedGoogle Scholar
  • 22 Koide T, Odani S, Takahashi K, Ono T, Sakuragawa N. Antithrombin III Toyama: replacement of arginine-47 by cysteine in hereditary abnormal antithrombin III that lacks heparin binding ability. Proc Nat Acad Sci USA 1984; 81: 289-293
    CrossrefPubMedGoogle Scholar