VEGF, D-dimer and Coagulation Activation Markers in Indonesian Patients with Polycythemia Vera and Essential Thrombocythemia and Their Relation with Recurrence of Thrombosis
Keywords:PV/ET, VEGF, D-dimer, recurrence of thrombosis
Background. PV and ET have high predisposition to thrombosis and recurrence of thrombosis. We determined VEGF, D-dimer and coagulation activation markers in clinically stable patients and recurrence of thrombosis.
Methods. Thirty-five Indonesian patients diagnosed with PV and ET and under treatment for the disease were recruited. The following assays were performed: VEGF, D-dimer, fibrinogen, TAT-complex, vWF, Î²-TG and JAK2 V617F mutation. Data between patients who were clinically stable(n=20) and those with recurrent thrombosis (n=15) at the time of study was analysed.
Results. The mean age for PV/ET was 51.7 Â± 14.9 years. Thrombosis episode was recorded for 94.3% (33/35) patients. Twenty (57.1%) clinically stable and 15 (42.9%) patients had recurrence of thrombosis. D-dimer (P=<0.001), fibrinogen (P=0.005) were statistically significant and VEGF (P=0.06) were seen in recurrence of thrombosis compared to clinically stable patients who had normal D-dimer. Elevated D-dimer seen in recurrence thrombosis was significantly correlated with VEGF (P=0.002) levels. Elevated VEGF were seen in 45% of clinically stable patients and 73.3% in recurrence of thrombosis.
Conclusions. Elevated D-dimer and fibrinogen with higher mean VEGF levels were seen in recurrence of thrombosis. VEGF and D-dimer measurements have clinical use in determining the risk of patients with vascular complications.
Vannucchi MA, Guglielmelli P, Tefferi A. Advances in understanding and management of myeloproliferative neoplasms. A Cancer J for Clinicians 2009; 59:171-91.
Campbell PJ, Green AR. Mechanisms of diseases: the myeloproliferative disorders. N Engl J Med 2006; 355:2452-66.
Elliot MA, Tefferi A. Thrombosis and haemorrhage in polycythemiavera and essential thrombocythemia. Br J Haematol 2005; 128:275-90.
Cortelazzo S, Viero P, Finazzi G, Dâ€™EmilioA, Rodeghiero F, Barbui T. Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J ClinOncol 1990; 8:556-62.
Tefferi A, Vainchecker W. Myeloproliferative neoplasms in molecular pathophysiology, essential clinical understanding and treatment strategies. J Clin Oncol 2011; 29:573-82.
Robertson B, Urquhart C, Ford I, Townend J, Watson GH, Vickers MA et al. Platelet and coagulation markers in myeloproliferative diseases:relationships with JAK2V617F status, clonality, and antiphospholipid antibodies. Journal of Thrombosis and Haemostasis 2007; 5:1679-85.
Vianello F, Battisti A, Cella G, Marchetti M, Falanga A. Defining the thrombotic risks in patients with myeloproliferative neoplasms. The Scientific World J 2011; 11:1131â€“37.
Landolfi R, Di Gennaro L. Pathophysiology of thrombosis in myeloproliferative neoplasms. Haematologica 2011; 96(2):183-6.
Wautier MP, El Nemer W, Gane P, Rain JD, Cartron JP, Colin Y, Le Van Kim C,Wautier JL. Increased adhesion to endothelial cells of erythrocytes from patients with polycythemiavera is mediated by laminin alpha5 chain and Lu/BCAM. Blood 2007; 110:894-901.
Casini A, Fontana P, Lecompte TP. Thrombotic complications of myeloproliferative neoplasms: risk assessment and risk-guided management. JThrombHaemost 2013; 11:1215-27.
Connolly DT. Vascular permeability factor: a unique regulator of blood vessel function. J Cell Biochem 1991; 47:219-23.
Mohle R, Green D, Moore MAS, Nachman RL, Rafii S. Constitutive production of thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. ProcNatlAcadSci 1997; 94:663-8.
Raimondo DF, Giuseppe PA, Stefano M, Rosario G. Angiogenesis in chronic myeloproliferative diseases. ActaHaematologica 2001; 106:177-83.
Stamatia T, Timoleon V, Sofia V, Vassilios P, Konstantinos T, Athanassions V et al. Elevated levels of serum vascular endothelial growth factor in patients with polycythemiavera. ActaHaematologica 2003; 110:16-9.
Verheul HM, Hoekman K, Luykx-de Bakker S et al. Platelet transporter of vascular endothelial growth factor. Clinical Cancer Research 1997; 3:2187-90.
Dvorak HF, Senger RD, Dvorak AM, Harvey VS, McDonagh J. Regulation of extravascular coagulation by microvascular permeability. Science (Washington DC) 1985; 227:1059-61.
Zucker S, Mirza H, Conner CE. Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: conversion of prothrombin to thrombin results in progelatinase-A activation and cell proliferation. Int J Cancer 1998; 75:780-6.
Cacciola RR, Di Francesco E, Glustolisi R, Cacciola E. Elevated serum vascular endothelial growth factor levels in patients with polycythemiavera and thrombotic complications. Haematologica 2002; 87:774-5.
Goodacre S, Sampson FC, Sutton AJ, Mason S, Morris F. Variation in the diagnostic performance of D-dimer for suspected deep vein thrombosis. Q J Med 2005; 98:513-27.
Kovacs MJ, MacKinnon C, Ginsberg J, Wells PS. A comparison of three rapid D-dimer methods for the diagnosis of venous thromboembolism. Br J Haematol 2001; 115:140-4.
Prisco D, Grifori E. The role of D-dimer testing in patients with suspected venous thromboembolism. SeminThrombHemost 2009; 35:50-9.
Kleinegris MC, Ten Cate H, Ten Cate HAJ., 2013. D-dimer as a marker for cardiovascular and arterial thrombotic events in patients with peripheral arterial disease. A systematic review.ThrombHaemost 2013; 110(2):233-43.
Gomez K, Tuddenham EGD, McVey JH., 2011. Normal Haemostasis. Post Graduate Haematology 2011; 6thed:747-71. Wiley Blackwell.
Landolfi R and Marchioli R et al. Efficacy and safety of low dose aspirin in polycythemia vera .The New England Journal of Medicine 2004;350:114-24.
Tefferi A, VardimanJw. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point of care diagnostic alogrithms. Leukemia 2008; 22:14-22.
Marchioli R, Finazzi G, Landolfi R, Kutti J, Gisslinger H, Patrono C et al. Vascular and neoplastic risk in a large cohort of patients with polycythemiavera. J ClinOncol 2005; 23:2224-32.
Ruggeri M, Gisslinger H, Tosetto A, Rintelen C, Mannhalter C, Pabinger I, et al. Factor Leiden mutation carriership and venous thromboembolism in polycythemiavera and essential thrombocythemia. Am J Hematol 2002; 71:1-6.
De Stefano V, Tommaso Z, Rossi E, Vannucchi AM, Ruggeri M, Elli E, et al. Recurrent thrombosis in patients with polycythemiavera and essential thrombocythemia: incidence, risk factors, and effects of treatments. Haematologica 2008; 93:372-80.
, Trelinski J, Wierzbowska A, KrawczynskaA,Sakowicz A, Pietrucha T, Smolewski P, Robak T, Chojnowski K. Circulating endothelial cells in essential thrombocythemia and polycythemiavera: correlation with JAK2-V617F mutational status, angiogenic factors and coagulation activation markers. Int J Hematol 2010; 91:792-8.
Nelson ME, Steensma DP. JAk2 V617 in myeloid disorders: what do we know now, and where ae we headed? Leuk Lymphoma 2006; 47:177-94.
Cross NC. Genetic and epigenetic complexity in myeloproliferative neoplasms. Hematology Am SocHematolEduc Program 2011; 2011:208-14.
Jones AV, Silver RT, Waghorn K, Cutis C KreilS, Zoi K et al. Minimal molecular response in polycythemiavera patients treated with imatinib or interferon alpha. Blood 2006; 107:3339-41.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under aÂ Creative Commons Attribution LicenseÂ that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeÂ The Effect of Open AccessÂ and Benefits of Publishing Open Access).