Download PDF
Thromb Haemost 1986; 55(03): 375-378
DOI: 10.1055/s-0038-1661567
Original Article
Schattauer GmbH Stuttgart

α2-Antiplasmin: Functional Characterization and Metabolism in a Heterozygote Deficient Patient

E A R Knot
The Departments of Haematology, Division of Haemostasis and Thrombosis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
J W ten Cate
The Departments of Haematology, Division of Haemostasis and Thrombosis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
R J Lamping
The Departments of Haematology, Division of Haemostasis and Thrombosis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Liem Kian Gie
The Departments of Haematology, Division of Haemostasis and Thrombosis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 30 July 1985

Accepted 14 April 1986

Publication Date:
18 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

An 81-year-old male with a mild life-long bleeding history and an α2-antiplasmin (α2-AP) plasma level of 55% biological activity and 41% antigen activity (normal range 80-140%) was studied. The ratio of plasminogen binding (PB): non-plasminogen binding (NPB) α2-AP assayed by modified crossed immunoelectrophoresis (CIE) was 7.3/2.7 (controls 6.3 ± 0.49 SD/3.7 ± 0.49 SD). The patient’s α2-AP showed decreased affinity for fibrin, i. e. 8.3% versus 32.4% of normal control α2-AP associated with fibrin during clotting of plasma. A metabolic study performed with human purified 125I-α2-AP(PB/NPB 7.7/2.3) showed a plasma radioactivity disappearance half-life of 72.9 h (n 60.1 ± 5.3 h) with a normal fractional catabolic rate and a reduced absolute catabolic (synthetic) rate of 0.70 mg/kg/day (n 2.10 ± 0.60 mg/kg/day). The exchange between the central and third compartment was increased. The increased α2-AP PB form and the increased plasma radioactivity disappearance half-life are suggestive of a slower conversion of the PB form into the NPB form and/or slower degradation of the PB form. The bleeding tendency in this patient could be explained by decreased synthesis of α2-AP and decreased binding to fibrin.

Keywords

α2-Antiplasmin metabolism - Characterization - Heterozygote deficiency
 

  • References

  • 1 Collen D. Identification and some properties of a new fast reacting plasma inhibitor in human plasma. Eur J Biochem 1976; 69: 209-216
    CrossrefPubMedGoogle Scholar
  • 2 Moroi M, Aoki N. Isolation and characterization of α2-plasmin inhibitor from human plasma. J Biol 1976; 251: 5956-5965
    PubMedGoogle Scholar
  • 3 Miillertz S, Clemmensen I. The primary inhibitor of plasmin in human plasma. Biochem J 1976; 159: 545-553
    CrossrefPubMedGoogle Scholar
  • 4 Wiman B, Collen D. Purification and characterization of human antiplasmin, the fast-acting plasmin inhibitor in plasma. Eur J Biochem 1977; 78: 19-26
    CrossrefPubMedGoogle Scholar
  • 5 Collen D, Wiman B. Fast-acting plasma inhibitor in human plasma. Blood 1978; 51: 563-569
    PubMedGoogle Scholar
  • 6 Clemmensen I. Different molecular forms of α2-antiplasmin. In: The physiological inhibitors of coagulation and fibrinolysis Collen D, Wiman B, Verstraete M. (eds.) pp 131-136 Elsevier North Holland. Paramedical Press; Amsterdam: 1979
  • 7 Wiman B. Affinity-chromatographic purification of human α2-anti-plasmin. Biochem J 1980; 191: 229-232
    CrossrefPubMedGoogle Scholar
  • 8 Sakata Y, Aoki N. Cross-linking of α2-antiplasmin inhibitor to fibrin stabilizing factor. J Clin Invest 1980; 65: 290-297
    CrossrefPubMedGoogle Scholar
  • 9 Tamaki T, Aoki N. Cross-linking of α2-antiplasmin inhibitor and fibronectin to fibrin by fibrin stabilizing factor. Biochem Biophys Acta 1981; 661: 280-286
    CrossrefPubMedGoogle Scholar
  • 10 Christensen U, Clemmensen I. Purification and reaction mechanisms of the primary inhibitor of plasma from human plasma. Biochem J 1978; 175: 635-641
    CrossrefPubMedGoogle Scholar
  • 11 Bagge L, Saldeen T. The primary fibrinolysis inhibitor and trauma. Thromb Res 1978; 13: 1131-1136
    CrossrefPubMedGoogle Scholar
  • 12 Clemmensen I, Thorsen S, Miillertz S, Petersen LC. Properties of three different molecular forms of the α2-antiplasmin inhibitor. Eur J Biochem 1981; 120: 105-112
    CrossrefPubMedGoogle Scholar
  • 13 Kluft C, Los P. Demonstration of two forms of α2-antiplasmin in plasma by modified crossed immunoelectrophoresis. Thromb Res 1981; 21: 65-71
    CrossrefPubMedGoogle Scholar
  • 14 Kluft C, Los P, Jie AF H, Van Hinsbergh VW M, Vellenga E, Jespersen J, Henny ChP. The mutual relation of the two molecular forms of the major fibrinolysis inhibitor, α2-antiplasmin in blood. Blood 1986; 67: 616-622
    CrossrefPubMedGoogle Scholar
  • 15 Kluft C, Los P, Jie AF H. The molecular form of α2-antiplasmin with affinity for plasminogen selectively bound to fibrin by factor XIII. Thromb Res 1984; 33: 419-425
    CrossrefPubMedGoogle Scholar
  • 16 Saito H, Goodnough LT, Knowles BB, Aden DP. Synthesis and secretion of α2-plasmin inhibitor by established human liver cell lines. Proc Natl Acad Sci 1982; 79: 5684-5687
    CrossrefPubMedGoogle Scholar
  • 17 Hogstrop H, Saldeen T. Synthesis of α2-antiplasmin by rat liver cells. Thromb Res 1982; 28: 19-25
    CrossrefPubMedGoogle Scholar
  • 18 Koie K, Kamiya T, Ogata K, Takamatsu J, Kobakura M. α2-plasmin inhibitor deficiency (Miyasato disease). Lancet 1978; 2: 1334-1336
    PubMedGoogle Scholar
  • 19 Aoki N, Saito H, Kamiya T, Koie K, Sakata Y, Kobakura M. Congenital deficiency of α2-antiplasmin inhibitor associated with severe hemorrhagic tendency. J Clin Invest 1979; 63: 877-884
    CrossrefPubMedGoogle Scholar
  • 20 Aoki N, Sakata Y, Matsuda M, Tateno K. Fibrinolytic states in a patient with congenital deficiency of α2-plasmin inhibitor. Blood 1980; 55: 483-488
    PubMedGoogle Scholar
  • 21 Yoshioka A, Kamitsuji H, Takase T, Iida Y, Tsukada S, Mikami S, Fukui H. Congenital deficiency of α2-plasmin inhibitor in three sisters. Haemostasis 1982; 11: 176-184
    PubMedGoogle Scholar
  • 22 Kluft C, Vellenga E, Brommer EJ P. Homozygous α2-antiplasmin deficiency. Lancet 1979; 2: 206
    PubMedGoogle Scholar
  • 23 Kluft C, Vellenga E, Brommer EJ P, Wijngaards G. A familial hemorrhagic diathesis in a Dutch family: An inherited deficiency of α2-antiplasmin. Blood 1982; 59: 1169-1180
    PubMedGoogle Scholar
  • 24 Miles LA, Plow EF, Donnelly KJ, Hougie C, Griffin JH. A bleeding disorder due to deficiency of α2-antiplasmin. Blood 1982; 59: 1246-1257
    PubMedGoogle Scholar
  • 25 Stormorken H, Gogstad GO, Brosstad F. Hereditary α2-antiplasmin deficiency. Thromb Res 1983; 31: 647-651
    CrossrefPubMedGoogle Scholar
  • 26 Peters M, Breederveld C, Kahle LH, Ten Cate JW. Rapid microanalysis of coagulation parameters by automated chromogenic substrated methods. Application in neonatal patients. Thromb Res 1983; 28: 773-781
    PubMedGoogle Scholar
  • 27 Muszbek L, Polgar J, Fesus L. Kinetic determination of blood coagulation factor XIII in plasma. Clin Chem 1985; 31: 35-41
    PubMedGoogle Scholar
  • 28 Laurell CB. Quantitative estimations of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45-52
    CrossrefPubMedGoogle Scholar
  • 29 Mancini G, Carbonara AO, Heremans JF. Immunochemical quantitation of antigens by single radial immuno diffusion. Immunochemistry 1965; 2: 235-254
    CrossrefPubMedGoogle Scholar
  • 30 Weeke B. Crossed immunoelectrophoresis. In: A manual of quantitative immunoelectrophoresis Axelsen NH, Krøll J, Weeke B. (eds.) pp 47-56 Universiteits forlaget; Oslo: 1973
  • 31 Collen D, Wiman B. Turnover of antiplasmin in the fast-acting plasmin inhibitor of plasma. Blood 1979; 53: 313-324
    PubMedGoogle Scholar
  • 32 Knot EA R, Drijfhout HR, Ten Cate JW, de Jong E, Iburg AH C, Kahle LH, Grijm R. α2-Plasmin inhibitor metabolism in patients with liver cirrhosis. J Lab Clin Med 1985; 105: 353-361
    PubMedGoogle Scholar
  • 33 Salacinski PR P, Lean McC, Sykes JE C, Clement-Jones VV, Lowry PJ. Iodination of proteins, glycoproteins and peptides using a solidphase oxidizing agent 1, 3, 4, 6, tetrachloro-3α, 6α diphenyl glycoluril (Iodogen). Anal Biochem 1981; 117: 136-146
    CrossrefPubMedGoogle Scholar
  • 34 Matthews CM E. The theory of tracer experiments with 131I-labelled plasma proteins. Phys Med Biol 1957; 2: 36-53
    CrossrefPubMedGoogle Scholar
  • 35 Tamaki T, Sakata Y, Aoki N. Survival of transfused α2-plasmin inhibitor in a patient with its congenital deficiency. Thromb Res 1981; 22: 281-286
    CrossrefPubMedGoogle Scholar