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ESANSIYEL TROMBOSITEMIDE PLAZMINOJEN AKTIVATÖR İNHIBITÖR-1 PAI-1 , ÜROKINAZ PLAZMINOJEN AKTIVATÖR UPA

Year 2015, Volume: 19 Issue: 4, 186 - 193, 01.12.2015

Abstract

Giriş: Tromboembolik ataklar esansiyel trombositemi ET hastalarında sık görülmekte olup tromboembolizmin nedenleri JAK 2 gibi genetik faktörlere ek olarak birçok edinsel nedeni de kapsar. Bu çalışma tromboembolik ataklarda PAI-1, uPA, TM, TFPI, ve vWF von Willebrant Faktör gibi koagülasyon parametrelerinin düzeylerini değerlendirmeyi amaçlamaktadır. Materyal ve Metod: Çalışma grubunu ortalama yaşı 59.5±9.9 30 esansiyel trombositemi hastası ile ortalama yaşı 56.2±6.1 olan 30 sağlıklı kontrol oluşturmaktadır. Plazma PAI, uPA, TM, TFPI, and vWF düzeyleri üreticininin talimatları doğrultusundaki ELISA yöntemi ile belirlenmiştir. Bulgular: Hasta ve kontrol grubu arasında PAI-1, uPA, TM, ve TFPI düzeyleri bakımnıdan anlamlı bir farklılık mevcuttu p0.05 . Sonuç: Yüksek PAI-1, uPA, TM ve TFPI düzeyleri bazı koagülasyon parametrelerinin aktive olduğunu gösterir ve biz inanıyoruz ki bu durum genetik faktörlerden bağımsız olarak tromboembolik ataklara yol açabilir

References

  • Colombi M, Radaelli F, Zocchi L, et al.Thrombotic and hemorrhagic complications in essential thrombocythemia.A retrospective study of 103 patients. Cancer ;67:2926–30.
  • Fenaux P SM, Caulier MT, Lai JL, et al. Clinical course of essential thrombocythemia in 147 cases. Cancer ;66:549–56. Cripe L, Hromas R. Malignant disorders of megakaryocytes. Semin Hematol 1998;35:200–9.
  • Posan E, Ujj G, Kiss A, et al. Reduced in vitro clot lysis and release of more active platelet PAI-1 in polycythemia vera and essential thrombocythemia. Thromb Res ;90:51–6. Watson KV. Vascular complications of essential thrombocythemia: A link to cardiovascular risk factors. Br J Haematol 1993;83:198–203.
  • Bellucci S, Tobelem G, Flandrin G,et al. Essential thombocythemia. Cancer 1986;58:2440–7.
  • Juhan-Vague I, Pyke SDM, Alessi MC, et al. Fibrinolytic factor and the risk of myocardial infarction or sudden death in patients with angina pectoris. Circulation ;94:2057–63.
  • Pappot H, Gardsvoll H, Romer J, et al. Plasminogen activator inhibitor type 1 in cancer: Therapeutic and prognostic implications. Biol Chem 1995;378:259–67.
  • Cancelas JA, Garcia-Avello A, Garcia-Frade LJ. High plasma level of plasminogen activator inhibitor 1 (PAI-1) in polycythemia vera and essential thrombocythemia are associated with thrombosis. Thromb Res 1994;75:513–20.
  • Bazzan M,Tamponi G,Gallo E, et al. Fibrinolytic imbalance in essential thrombocythemia: A role of platelets. Haemostasis1993;23:38–44.
  • Urden G, Chmielewska J, Carlsson T, et al. Immunological relationship between PAI-1 from different sources. Thromb Haemost 1987;57:29.
  • Dawson S,Henney A. The status of PAI-1 as a risk factor for arterial and thrombotic disease: A review. Atherosclerosis 1992;95:105–17.
  • Loskutoff D, Smad F.The adipocyte and hemostatic balance in obesity. Arterioscler Thromb Vasc Biol ;18:1–6. Simpson AJ, Booth NA, Moore NR. The platelet and plasma pools of plasminogen activator inhibitor (PAI-1) vary independently in disease. Br J Haematol ;75:543–8. Takada A, Takada Y, Urano T.The physiological aspects of fibrinolysis. Thromb Res 1994;76:1–31.
  • Winman B. Plasminogen activator inhibitor 1 (PAI-1) in plasma: Its role in thrombotic disease. Thromb Haemost ;74:71–6. Lindahl TL, Sigurdarttir O,Winman B. Stability of plasminogen activator-1 (PAI-1). ThrombHaemost ;62:748–51. Nordenham A, Wiman B. Plasminogen activator inhibitor (PAI-1) content in platelets from healthy individuals genotyped for the 4G/5G polymorphism in the PAI-1 gene. Scand J Clin Lab Invest 1997;57:453–61.
  • Konkle BA, Schick PA, Xiabli H, et al. Plasminogen activator inhibitor-1 mRNA is expressed in platelets and megakaryocytes and megakaryoblastic cell line CHRF-288. Arterioscler Thromb 1993;13:669–74.
  • Fay WP, Eitzman DT, Shapiro AD, et al. Platelets inhibit fibrinolysis in vitro by both plasminogen activator inhibitor-1-dependent and independent mechanisms. Blood 1994;83: –6.
  • Eriksson P, Nilsson L, Karpe F, et al. Very-low density lipoprotein response element in the promoter region of the human plasminogen activator inhibitor-1 gene. Arterioscler Thromb Vasc Biol. 1998;18:20–6.
  • Starnberg L, Lawrence D, Ny T.The organization of the human plasminogen activator inhibitor-1 gene.Implications on the evolution of the serine-protease inhibitor family. Eur J Biochem 1988;176:609–16.
  • Sartori MT, Winman B, Veltore S, et al. 4G/5G polymorphism of PAI-1 gene promoter and fibrinolytic capacity in patients with deep venous thrombosis. Thromb Haemost ;80:956–60. Glueck CJ, Fontaine RN, Gupta A, et al. Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity and resistance to activated protein C. Metabolism 1997;46:1470–2.
  • Margaglione M, Cappusi G, d’Addedda, et al. PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: Relation to environment and genetic determinants. Arterscler Thromb Vasc Biol ;18:562–7. Kato H. Regulation of functions of vascular wall cells by tissue factor pathway inhibitor: basic and clinical aspects. Arterioscler Thromb Vasc Biol 2002;22:539–8.
  • Crawley J, Lupu F, Westmuckett AD, Severs NJ, Kakkar VV, Lupu C. Expression, localization, and activity of tissue factor pathway inhibitor in normal and atherosclerotic human vessels. Arterioscler Thromb Vasc Biol 2000;20:1362–73.
  • Yin X, Yutani C, Ikeda Y, Enjyoji K, Ishibashi-Ueda H, Yasuda S, Tsukamoto Y, Nonogi H, KanedaY, Kato H. Tissue factor pathway inhibitor gene delivery using HVJ- AVE liposomes markedly reduces restenosis in atherosclerotic arteries. Cardiovasc Res 2002;56:454–63.
  • Westrick RJ, Bodary PF, Xu Z, Shen YC, Broze GJ, Eitzman DT. Deficiency of tissue factor pathway inhibitor promotes atherosclerosis and thrombosis in mice. Circulation 2001;103:3044–6.
  • Morange PE, Renucci JF, Charles MA, Aillaud MF, Giraud F, Grimaux M, Juhan-Vague I. Plasma levels of free and total TFPI, relationship with cardiovascular risk factors and endothelial cell markers. Thromb Haemost ;85:999–1003.
  • Soejima H, Ogawa H, Yasue H, Kaikita K, Nishiyama K, Misumi K, Takazoe K, Miyao Y, Yoshimura M, Kugiyama K, Nakamura S, Tsuji I, Kumeda K. Heightened tissue factor associated with tissue factor pathway inhibitor and prognosis in patients with unstable angina. Circulation ;99:2908–13.
  • Morange PE, Blankenberg S, Alessi MC, Bickel C, Rupprecht HJ, Schnabel R, Lubos E, Munzel T, Peetz D, Nicaud V, Juhan-Vague I, Tiret L. Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the AtheroGene study. J Thromb Haemost ;5:475–2. Sakkinen PA, Cushman M, Psaty BM, Kuller LH, Bajaj SP, Sabharwal AK, Boineau R, Macy E,Tracy RP. Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort.Thromb Haemost 1998;80:134–9.
  • Jensen MK, Holten-Andersen MN, Riisbro R, de Nully Brown P, Larsen MB, Kjeldsen L, Heickendorff L, Brünner N, Hasselbach HC. Elevated plasma levels TIMP-1 correlate with plasma suPAR/uPA in patients with chronic myeloproliferative disorders. Eur J Haematol 2003;71:377
  • Jensen MK, Riisbro R, Holten-Andersen MN, de Nully Brown P, Junker P, Brünner N, Hasselbach HC. Collagen metabolism and enzymesof the urokinase plasminogen activator system in chronic myeloproliferative disorders: correlation between plasma-soluble urokinase plasminogen activator receptor and serum markers for collagen metabolism. Eur J Hematol 2003;71:276-82.
  • Spivak JL, Silver RT. The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal. Blood.2008 15;112(2):231-9.

THE LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 PAI-1 , UROKINASE PLASMINOGEN ACTIVATOR UPA , THROMBOMODULIN TM AND TISSUE FACTOR PATHWAY INHIBITOR TFPI IN ESSENTIAL THROMBOCYTHEMIA

Year 2015, Volume: 19 Issue: 4, 186 - 193, 01.12.2015

Abstract

Introduction: Thromboembolic attacks are frequent in essential thrombocythemia ET patients, and the causes of thromboembolism include many acquired causes in addition to some genetic factors like JAK 2. This study is intended to evaluate the levels of some coagulation parameters such as PAI-1, uPA, TM, TFPI, and vWF von Willebrant Factor in thromboembolic attacks. Materials and Methods: The study group consisted of 30 essential thrombocythemia patients with a mean age of 59.5±9.9 and 30 healthy controls with a mean age of 56.2±6.1. Plasma PAI, uPA, TM, TFPI, and vWF levels were determined by ELISA method according to manufacturer’s instructions. Results: There was a significant difference in PAI-1, uPA, TM, and TFPI levels between the patient and control groups p0.05 . Conclusions: High levels of PAI-1, uPA, TM and TFPI indicate that some coagulation parameters are activated, and we believe that this may cause thromboembolic attacks regardless of genetic factors

References

  • Colombi M, Radaelli F, Zocchi L, et al.Thrombotic and hemorrhagic complications in essential thrombocythemia.A retrospective study of 103 patients. Cancer ;67:2926–30.
  • Fenaux P SM, Caulier MT, Lai JL, et al. Clinical course of essential thrombocythemia in 147 cases. Cancer ;66:549–56. Cripe L, Hromas R. Malignant disorders of megakaryocytes. Semin Hematol 1998;35:200–9.
  • Posan E, Ujj G, Kiss A, et al. Reduced in vitro clot lysis and release of more active platelet PAI-1 in polycythemia vera and essential thrombocythemia. Thromb Res ;90:51–6. Watson KV. Vascular complications of essential thrombocythemia: A link to cardiovascular risk factors. Br J Haematol 1993;83:198–203.
  • Bellucci S, Tobelem G, Flandrin G,et al. Essential thombocythemia. Cancer 1986;58:2440–7.
  • Juhan-Vague I, Pyke SDM, Alessi MC, et al. Fibrinolytic factor and the risk of myocardial infarction or sudden death in patients with angina pectoris. Circulation ;94:2057–63.
  • Pappot H, Gardsvoll H, Romer J, et al. Plasminogen activator inhibitor type 1 in cancer: Therapeutic and prognostic implications. Biol Chem 1995;378:259–67.
  • Cancelas JA, Garcia-Avello A, Garcia-Frade LJ. High plasma level of plasminogen activator inhibitor 1 (PAI-1) in polycythemia vera and essential thrombocythemia are associated with thrombosis. Thromb Res 1994;75:513–20.
  • Bazzan M,Tamponi G,Gallo E, et al. Fibrinolytic imbalance in essential thrombocythemia: A role of platelets. Haemostasis1993;23:38–44.
  • Urden G, Chmielewska J, Carlsson T, et al. Immunological relationship between PAI-1 from different sources. Thromb Haemost 1987;57:29.
  • Dawson S,Henney A. The status of PAI-1 as a risk factor for arterial and thrombotic disease: A review. Atherosclerosis 1992;95:105–17.
  • Loskutoff D, Smad F.The adipocyte and hemostatic balance in obesity. Arterioscler Thromb Vasc Biol ;18:1–6. Simpson AJ, Booth NA, Moore NR. The platelet and plasma pools of plasminogen activator inhibitor (PAI-1) vary independently in disease. Br J Haematol ;75:543–8. Takada A, Takada Y, Urano T.The physiological aspects of fibrinolysis. Thromb Res 1994;76:1–31.
  • Winman B. Plasminogen activator inhibitor 1 (PAI-1) in plasma: Its role in thrombotic disease. Thromb Haemost ;74:71–6. Lindahl TL, Sigurdarttir O,Winman B. Stability of plasminogen activator-1 (PAI-1). ThrombHaemost ;62:748–51. Nordenham A, Wiman B. Plasminogen activator inhibitor (PAI-1) content in platelets from healthy individuals genotyped for the 4G/5G polymorphism in the PAI-1 gene. Scand J Clin Lab Invest 1997;57:453–61.
  • Konkle BA, Schick PA, Xiabli H, et al. Plasminogen activator inhibitor-1 mRNA is expressed in platelets and megakaryocytes and megakaryoblastic cell line CHRF-288. Arterioscler Thromb 1993;13:669–74.
  • Fay WP, Eitzman DT, Shapiro AD, et al. Platelets inhibit fibrinolysis in vitro by both plasminogen activator inhibitor-1-dependent and independent mechanisms. Blood 1994;83: –6.
  • Eriksson P, Nilsson L, Karpe F, et al. Very-low density lipoprotein response element in the promoter region of the human plasminogen activator inhibitor-1 gene. Arterioscler Thromb Vasc Biol. 1998;18:20–6.
  • Starnberg L, Lawrence D, Ny T.The organization of the human plasminogen activator inhibitor-1 gene.Implications on the evolution of the serine-protease inhibitor family. Eur J Biochem 1988;176:609–16.
  • Sartori MT, Winman B, Veltore S, et al. 4G/5G polymorphism of PAI-1 gene promoter and fibrinolytic capacity in patients with deep venous thrombosis. Thromb Haemost ;80:956–60. Glueck CJ, Fontaine RN, Gupta A, et al. Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity and resistance to activated protein C. Metabolism 1997;46:1470–2.
  • Margaglione M, Cappusi G, d’Addedda, et al. PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: Relation to environment and genetic determinants. Arterscler Thromb Vasc Biol ;18:562–7. Kato H. Regulation of functions of vascular wall cells by tissue factor pathway inhibitor: basic and clinical aspects. Arterioscler Thromb Vasc Biol 2002;22:539–8.
  • Crawley J, Lupu F, Westmuckett AD, Severs NJ, Kakkar VV, Lupu C. Expression, localization, and activity of tissue factor pathway inhibitor in normal and atherosclerotic human vessels. Arterioscler Thromb Vasc Biol 2000;20:1362–73.
  • Yin X, Yutani C, Ikeda Y, Enjyoji K, Ishibashi-Ueda H, Yasuda S, Tsukamoto Y, Nonogi H, KanedaY, Kato H. Tissue factor pathway inhibitor gene delivery using HVJ- AVE liposomes markedly reduces restenosis in atherosclerotic arteries. Cardiovasc Res 2002;56:454–63.
  • Westrick RJ, Bodary PF, Xu Z, Shen YC, Broze GJ, Eitzman DT. Deficiency of tissue factor pathway inhibitor promotes atherosclerosis and thrombosis in mice. Circulation 2001;103:3044–6.
  • Morange PE, Renucci JF, Charles MA, Aillaud MF, Giraud F, Grimaux M, Juhan-Vague I. Plasma levels of free and total TFPI, relationship with cardiovascular risk factors and endothelial cell markers. Thromb Haemost ;85:999–1003.
  • Soejima H, Ogawa H, Yasue H, Kaikita K, Nishiyama K, Misumi K, Takazoe K, Miyao Y, Yoshimura M, Kugiyama K, Nakamura S, Tsuji I, Kumeda K. Heightened tissue factor associated with tissue factor pathway inhibitor and prognosis in patients with unstable angina. Circulation ;99:2908–13.
  • Morange PE, Blankenberg S, Alessi MC, Bickel C, Rupprecht HJ, Schnabel R, Lubos E, Munzel T, Peetz D, Nicaud V, Juhan-Vague I, Tiret L. Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the AtheroGene study. J Thromb Haemost ;5:475–2. Sakkinen PA, Cushman M, Psaty BM, Kuller LH, Bajaj SP, Sabharwal AK, Boineau R, Macy E,Tracy RP. Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort.Thromb Haemost 1998;80:134–9.
  • Jensen MK, Holten-Andersen MN, Riisbro R, de Nully Brown P, Larsen MB, Kjeldsen L, Heickendorff L, Brünner N, Hasselbach HC. Elevated plasma levels TIMP-1 correlate with plasma suPAR/uPA in patients with chronic myeloproliferative disorders. Eur J Haematol 2003;71:377
  • Jensen MK, Riisbro R, Holten-Andersen MN, de Nully Brown P, Junker P, Brünner N, Hasselbach HC. Collagen metabolism and enzymesof the urokinase plasminogen activator system in chronic myeloproliferative disorders: correlation between plasma-soluble urokinase plasminogen activator receptor and serum markers for collagen metabolism. Eur J Hematol 2003;71:276-82.
  • Spivak JL, Silver RT. The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal. Blood.2008 15;112(2):231-9.
There are 27 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Ferda Bilgir This is me

Mehmet Calan This is me

Giray Bozkaya This is me

Oktay Bilgir This is me

Publication Date December 1, 2015
Published in Issue Year 2015 Volume: 19 Issue: 4

Cite

APA Bilgir, F., Calan, M., Bozkaya, G., Bilgir, O. (2015). THE LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 PAI-1 , UROKINASE PLASMINOGEN ACTIVATOR UPA , THROMBOMODULIN TM AND TISSUE FACTOR PATHWAY INHIBITOR TFPI IN ESSENTIAL THROMBOCYTHEMIA. İzmir Eğitim Ve Araştırma Hastanesi Tıp Dergisi, 19(4), 186-193.
AMA Bilgir F, Calan M, Bozkaya G, Bilgir O. THE LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 PAI-1 , UROKINASE PLASMINOGEN ACTIVATOR UPA , THROMBOMODULIN TM AND TISSUE FACTOR PATHWAY INHIBITOR TFPI IN ESSENTIAL THROMBOCYTHEMIA. İzmir EAH Tıp Der. December 2015;19(4):186-193.
Chicago Bilgir, Ferda, Mehmet Calan, Giray Bozkaya, and Oktay Bilgir. “THE LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 PAI-1 , UROKINASE PLASMINOGEN ACTIVATOR UPA , THROMBOMODULIN TM AND TISSUE FACTOR PATHWAY INHIBITOR TFPI IN ESSENTIAL THROMBOCYTHEMIA”. İzmir Eğitim Ve Araştırma Hastanesi Tıp Dergisi 19, no. 4 (December 2015): 186-93.
EndNote Bilgir F, Calan M, Bozkaya G, Bilgir O (December 1, 2015) THE LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 PAI-1 , UROKINASE PLASMINOGEN ACTIVATOR UPA , THROMBOMODULIN TM AND TISSUE FACTOR PATHWAY INHIBITOR TFPI IN ESSENTIAL THROMBOCYTHEMIA. İzmir Eğitim ve Araştırma Hastanesi Tıp Dergisi 19 4 186–193.
IEEE F. Bilgir, M. Calan, G. Bozkaya, and O. Bilgir, “THE LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 PAI-1 , UROKINASE PLASMINOGEN ACTIVATOR UPA , THROMBOMODULIN TM AND TISSUE FACTOR PATHWAY INHIBITOR TFPI IN ESSENTIAL THROMBOCYTHEMIA”, İzmir EAH Tıp Der, vol. 19, no. 4, pp. 186–193, 2015.
ISNAD Bilgir, Ferda et al. “THE LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 PAI-1 , UROKINASE PLASMINOGEN ACTIVATOR UPA , THROMBOMODULIN TM AND TISSUE FACTOR PATHWAY INHIBITOR TFPI IN ESSENTIAL THROMBOCYTHEMIA”. İzmir Eğitim ve Araştırma Hastanesi Tıp Dergisi 19/4 (December 2015), 186-193.
JAMA Bilgir F, Calan M, Bozkaya G, Bilgir O. THE LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 PAI-1 , UROKINASE PLASMINOGEN ACTIVATOR UPA , THROMBOMODULIN TM AND TISSUE FACTOR PATHWAY INHIBITOR TFPI IN ESSENTIAL THROMBOCYTHEMIA. İzmir EAH Tıp Der. 2015;19:186–193.
MLA Bilgir, Ferda et al. “THE LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 PAI-1 , UROKINASE PLASMINOGEN ACTIVATOR UPA , THROMBOMODULIN TM AND TISSUE FACTOR PATHWAY INHIBITOR TFPI IN ESSENTIAL THROMBOCYTHEMIA”. İzmir Eğitim Ve Araştırma Hastanesi Tıp Dergisi, vol. 19, no. 4, 2015, pp. 186-93.
Vancouver Bilgir F, Calan M, Bozkaya G, Bilgir O. THE LEVELS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 PAI-1 , UROKINASE PLASMINOGEN ACTIVATOR UPA , THROMBOMODULIN TM AND TISSUE FACTOR PATHWAY INHIBITOR TFPI IN ESSENTIAL THROMBOCYTHEMIA. İzmir EAH Tıp Der. 2015;19(4):186-93.