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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4061-4068. Prepublished online as a Blood First Edition Paper on September 3, 2008; DOI 10.1182/blood-2008-06-164087. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-06-164087v1 112/10/4061    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Marchetti, M. Articles by Falanga, A. Search for Related Content PubMed PubMed Citation Articles by Marchetti, M. Articles by Falanga, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Thrombin generation and activated protein C resistance in patients with essential thrombocythemia and polycythemia vera Marina Marchetti1,2, Elisabetta Castoldi3, Henri M. H. Spronk1, René van Oerle1, Donatella Balducci2, Tiziano Barbui4, Jan Rosing3, Hugo ten Cate1,5, and Anna Falanga2 1 Department of Internal Medicine, Laboratory for Clinical Thrombosis and Haemostasis, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; 2 Thrombosis and Hemostasis Center, Department of Hematology-Oncology, Ospedali Riuniti di Bergamo, Bergamo, Italy; 3 Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; 4 Research Foundation, Ospedali Riuniti di Bergamo, Bergamo, Italy; and 5 Department of Internal Medicine, Division of Haematology, University Hospital Maastricht, Maastricht, The Netherlands We used the thrombin generation assay to evaluate the hypercoagulable state according to JAK2V617F mutational status in essential thrombocythemia (ET) and polycythemia vera (PV) patients. Thrombin generation was determined in the presence and absence of activated protein C (APC), and APC resistance was expressed as normalized APC sensitivity ratio (nAPCsr). Tissue factor pathway inhibitor (TFPI), total and free protein S (PS), prothrombin (FII), factor V (FV), and neutrophil elastase were measured in plasma; CD11b was measured on neutrophils. Compared with normal controls, patients had a lower endogenous thrombin potential in the absence of APC but had a higher endogenous thrombin potential in the presence of APC, showing the occurrence of APC resistance. The nAPCsr increased in JAK2V617F carriers compared with noncarriers and was highest in JAK2V617F homozygous patients. FII, FV, free PS, and TFPI levels were reduced in patients, mainly in JAK2V617F carriers. Multiple regression analysis indicated the low free PS level as major determinant of the increased nAPCsr. Elastase was increased in patients and inversely correlated with free PS. In conclusion, these data indicate the occurrence of acquired APC resistance in ET and PV patients, probably because of a reduction in free PS levels. The APC-resistant phenotype is influenced by the JAK2V617F mutational load. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. C. Trappenburg, M. van Schilfgaarde, M. Marchetti, H. M. Spronk, H. t. Cate, A. Leyte, W. E. Terpstra, and A. Falanga Elevated procoagulant microparticles expressing endothelial and platelet markers in essential thrombocythemia Haematologica, July 1, 2009; 94(7): 911 - 918. [Abstract] [Full Text] [PDF] S. Shaikh and E. M. Van Cott The Effect of Argatroban on Activated Protein C Resistance Am J Clin Pathol, June 1, 2009; 131(6): 828 - 833. [Abstract] [Full Text] [PDF] V. De Stefano, T. Za, E. Rossi, A. Fiorini, A. Ciminello, C. Luzzi, P. Chiusolo, S. Sica, and G. Leone Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essential thrombocythemia Haematologica, May 1, 2009; 94(5): 733 - 737. [Abstract] [Full Text] [PDF]

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