Download PDF
Thromb Haemost 1998; 79(05): 919-923
DOI: 10.1055/s-0037-1615094
Review Article
Schattauer GmbH

Increased Plasma Levels of Free Tissue Factor Pathway Inhibitor in Patients with Graves’ Disease

Eriko Morishita
1   From the Department of Laboratory Sciences, School of Health Science, Kanazawa University, Kanazawa
2   From the Third Department of Internal Medicine, Kanazawa University, Kanazawa
,
Takuma Hashimoto
3   From the Department of Laboratory Medicine, School of Medicine, Kanazawa University, Kanazawa
,
Hidesaku Asakura
2   From the Third Department of Internal Medicine, Kanazawa University, Kanazawa
,
Masanori Saito
2   From the Third Department of Internal Medicine, Kanazawa University, Kanazawa
,
Masahide Yamazaki
2   From the Third Department of Internal Medicine, Kanazawa University, Kanazawa
,
Keiji Aoshima
2   From the Third Department of Internal Medicine, Kanazawa University, Kanazawa
,
Tomotaka Yoshida
3   From the Department of Laboratory Medicine, School of Medicine, Kanazawa University, Kanazawa
,
Hisao Kato
4   From the National Cardiovascular Center Research Institute, Osaka, Japan
,
Tamotsu Matsuda
2   From the Third Department of Internal Medicine, Kanazawa University, Kanazawa
› Author Affiliations
Further Information

Publication History

Received 20 May 1997

Accepted after resubmission 27 January 1998

Publication Date:
07 December 2017 (online)

    Permissions and Reprints

Summary

Tissue factor pathway inhibitor (TFPI) is present in a free-form and in lipoprotein-associated forms in plasma. In this study, the plasma concentrations of total TFPI (tTFPI) and free-form TFPI (fTFPI) were measured in 25 patients with Graves’ disease and 25 age-matched healthy subjects, and the relationship between thyroid state and plasma TFPI was examined. Plasma concentrations (median) of tTFPI and fTFPI in Graves’ patients who were hyperthyroid were significantly increased compared with Graves’patients who were euthyroid (152 ng/ml versus 124 ng/ml, p <0.01 and 41.3 ng/ml versus 20.2 ng/ml, p <0.0001, respectively), and control subjects (152 ng/ml versus 96 ng/ml, p <0.0001 and 41.3 ng/ml versus 18.7 ng/ml, p <0.0001, respectively). There was no significant difference in plasma fTFPI concentrations between the euthyroid group and the control group. Plasma fTFPI concentrations correlated closely with thyroid hormone (T3) levels in the patients (r = 0.559, p <0.005). Serial measurement of individual patients revealed that plasma concentrations of fTFPI and tTFPI were significantly decreased, reaching normal control values upon attainment of euthyroidism. In conclusion, the close correlation between plasma fTFPI and serum thyroid hormone levels suggests that thyroid hormones might influence the synthesis or metabolism of TFPI on the surface of endothelial cells in patients with Graves’ disease. This is the first report concerning high concentrations of plasma fTFPI in patients with hyperthyroidism.

 

  • References

  • 1 Rogers JS II, Shane SR, Jencks FS. Factor VIII activity and thyroid function. Ann Intern Med 1982; 97: 713-6.
    CrossrefPubMedGoogle Scholar
  • 2 Marongiu F, Conti M, Mameli G, Murtas ML, Balzano S, Sorano GG, Mamusa AM, Martino E. Fibrinogen and fibrinotic activity in hyperthyroidism before and after antithyroid treatment. J Endocrinol Invest 1988; 11: 723-5.
    CrossrefPubMedGoogle Scholar
  • 3 Morikawa YY, Morikawa A, Makino I. Relation of thyroid states and serum thrombomodulin (TM) levels in patients with Graves’ disease: TM, a possible new marker of the peripheral activity of thyroid hormones. J Clin Endocrinol Metab 1993; 76: 609-14.
    PubMedGoogle Scholar
  • 4 Sandset PM, Abildgaard U. Extrinsic pathway inhibitor: the key to feedback control of blood coagulation initiated by tissue thromboplastin. Haemostasis 1991; 21: 219-39.
    PubMedGoogle Scholar
  • 5 Bajaj MS, Kuppuswamy MN, Saito H, Spitzer SG, Bajaj SP. Cultured normal human hepatocytes do not synthesize lipoprotein-associated coagulation inhibitor: evidence that endothelium is the principal site of its synthesis. Proc Natl Acad Sci USA 1990; 87: 8869-73.
    CrossrefPubMedGoogle Scholar
  • 6 Novotny WF, Palmier M, Wun TC, Broze GJ, Miletich JP. Purification and properties of heparin releasable lipoprotein associated inhibitor. Blood 1991; 78: 394-400.
    PubMedGoogle Scholar
  • 7 Girard TJ, Broze GJ. Tissue factor pathway inhibitor. Methods in Enzymol. Lorand L, Mann KG. eds. Academic Press; San Diego: 1993. 222, pp 195-209.
    Google Scholar
  • 8 Abumiya T, Enjyoji K, Kokawa T, Kamikubo Y, Kato H. An anti tissue factor pathway inhibitor (TFPI) monoclonal antibody recognized the third Kunitz (K3) of free form of TFPI but not lipoprotein-associated forms in plasma. J Biochem 1995; 118: 178-82.
    CrossrefPubMedGoogle Scholar
  • 9 Hansen JB, Huseby NE, Sandset PM, Svensson B, Lyngmo V, Nordøy A. Tissue factor pathway inhibitor and lipoproteins: evidence for association with and regulation by LDL in human plasma. Arterioscler Thromb 1994; 14: 223-9.
    CrossrefPubMedGoogle Scholar
  • 10 Moor E, Hamsten A, Karpe F, Bävenholm P, Blombäck M, Silveira A. Relationship of tissue factor pathway inhibitor activity to plasma lipoproteins and myocardial infarction at a young age. Thromb Haemost 1994; 71: 707-12.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Novotny WF, Brown SG, Miletich JP, Rader DJ, Broze Jr GJ. Plasma antigen levels of lipoprotein-associated coagulation inhibitor in patient samples. Blood 1991; 78: 387-93.
    PubMedGoogle Scholar
  • 12 Bajaj MS, Rana SV, Wysolmerski RB, Bajaj SP. Inhibition of the factor VIIa-tissue factor complex is reduced in patients with disseminated intravascular coagulation but not in patients with severe hepatocellular disease. J Clin Invest 1987; 79: 1874-8.
    CrossrefPubMedGoogle Scholar
  • 13 Sandset PM, Larsen ML, Abildgaard U, Lindahl AK, Ødegaard OR. Chromogenic substrate assay of extrinsic pathway inhibitor (EPI): levels in the normal population and relation to cholesterol. Blood Coagul Fibrinolysis 1991; 2: 425-33.
    CrossrefPubMedGoogle Scholar
  • 14 Abumiya T, Nakamura S, Takenaka A, Takenaka O, Yoshikuni Y, Miyamoto S, Kimura T, Enjyoji KI, Kato H. Response of plasma tissue factor pathway inihibitor to diet-induced hypercholesterolemia in crab-eating monkeys. Arterioscler Thromb 1994; 14: 483-8.
    CrossrefPubMedGoogle Scholar
  • 15 War TA, Warn-Cramer BJ, Rao LVM, Rapaport SI. Human plasma extrinsic pathway inhibitor activity: I. Standardization of assay and evaluation of physiological variables. Blood 1989; 74: 201-6.
    PubMedGoogle Scholar
  • 16 Sandset PM, Lund H, Norseth J, Abildgaard U, Ose L. Treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors in hyper-cholesterolemia induces changes in the components of the extrinsic coagulation system. Arterioscler Thromb 1991; 11: 138-45.
    CrossrefPubMedGoogle Scholar
  • 17 Kokawa T, Enjyoji K, Kumeda K, Kamikubo Y, Harada-Shiba M, Koh H, Tsushima M, Yamamoto A, Kato H. Measurement of the free form of TFPI antigen in hyperlipidemia; Relationship between free and endothelial cell-associated forms of TFPI. Arterioscler Thromb Vasc Biol 1996; 16: 802-8.
    CrossrefPubMedGoogle Scholar
  • 18 Staels B, van Tol A, Chan L, Will H, Verhoeven G, Auwerx J. Alterations in thyroid status modulate apolipoprotein, hepatic triglyceride lipase and low density lipoprotein receptor in rats. Endocrinology 1990; 127: 1144-52.
    CrossrefPubMedGoogle Scholar
  • 19 Davidson NO, Carlos RC, Lukaszwicz AM. Apolipoprotein B mRNA editing is modulated by thyroid hormone analogs but not growth hormone administration in the rat. Mol Endcrinol 1990; 4: 779-85.
    CrossrefPubMedGoogle Scholar
  • 20 Davidson NO, Powell LM, Wallis SC, Scott J. Thyroid hormone modulates the introduction of a stop codon in rat liver apoprotein B messenger RNA. J Biol Chem 1988; 263: 13482-5.
    PubMedGoogle Scholar
  • 21 Rogers JS II, Shane SR. Factor VIII activity in normal volunteers receiving oral thyroid hormone. J Lab Clin Med 1983; 102: 444-9.
    PubMedGoogle Scholar