Seminars in thrombosis and hemostasis
-
Semin. Thromb. Hemost. · Jun 2006
Review Comparative Study Historical ArticleAnagrelide: what was new in 2004 and 2005?
Anagrelide is an established platelet-reducing drug. Although there are gaps in the understanding of its mechanism of action, two randomized comparisons with other drugs used for therapy of patients with essential thrombocythemia (ET) have been performed. Recent progress has been made in this field with the development of better determination techniques, with the characterization of metabolites, and with studies of their mechanism of action on megakaryocytes and platelets. ⋯ Results of the first phase III trial (PT1) that compared anagrelide/aspirin with hydroxyurea/aspirin have sparked an intense discussion, given that the combination of anagrelide and aspirin causes more bleeding complications in the gastrointestinal tract. It has been speculated that the higher number of transient ischemic attacks in this study arm is not caused by thrombotic events but by small bleedings that would be responsible for transient hemorrhagic attacks. More insights are expected from the recently completed ANAHYDRET trial that compared monotherapy with hydroxyurea and anagrelide.
-
Semin. Thromb. Hemost. · Jun 2006
ReviewThe role of JAK2 V617F mutation, spontaneous erythropoiesis and megakaryocytopoiesis, hypersensitive platelets, activated leukocytes, and endothelial cells in the etiology of thrombotic manifestations in polycythemia vera and essential thrombocythemia.
Exaggerated erythropoiesis and megakaryocytopoiesis are present at a variable extent in polycythemia vera (PV) and essential thrombocythemia (ET). With the recent discovery of the V617F mutation in the Janus kinase 2 (JAK2) tyrosine kinase in almost all cases of PV and in a subset of patients with ET, studies are now pending to assess the role of this mutation in the hematopoietic cell activation process and/or in the occurrence of thromboses in ET and PV. The JAK2 V617F point mutation makes the normal hematopoietic progenitor cells hypersensitive to thrombopoietin, erythropoietin, and myeloid progenitor cells, leading to trilinear hematopoietic myeloproliferation. ⋯ Depending on the biological background of individual patients, heterozygous and homozygous JAK2 V617F ET/PV may preferentially induce myeloid metaplasia with myelofibrosis with a relative suppression of megakaryocytic and erythropoietic myeloproliferation leading to clinical pictures of fibrotic chronic idiopathic myelofibrosis (CIMF) or agnogenic myeloid metaplasia. The main conclusion is that JAK2 V617F is a 100% specific clue to a new distinct clonal myeloproliferative disorder. JAK2 V617F-positive ET/PV and CIMF should be distinguished from wild-type JAK2 ET, rare cases of PV, and CIMF, and should be evaluated during life-long follow-up.