title: Thrombosis in thrombocythemic Ph- myeloproliferations is associated with higher platelet count prior to the event: results of analyses of prothrombotic risk factors from a registry of patients treated with anagrelide.
abstract: Controversies still exist regarding definition of the thrombotic risks in Ph- (BCR/ABL1-) myeloproliferative disorders with thrombocythemia (MPD-T). Platelet counts at diagnosis are currently not taken as a risk factor of thrombosis. In our cohort of 1179 patients with MPD-T, prospectively registered for anagrelide treatment, we found that the median platelet count prior to the thrombotic event was significantly higher than at time points without any ensuing thrombosis (453 vs. 400 × 10(9)/L, P < 0.001), albeit higher platelet counts at diagnosis tended to be connected with fewer thrombotic events (in contrast to WBC counts at diagnosis). The JAK2(V617F) mutation predicted both arterial and venous events, while age >65 yr, hypertension, diabetes mellitus, smoking, elevated triglyceride and homocysteine levels predicted arterial events only. For venous events, the specific thrombophilic risk factors (factor V 'Leiden' and others), antiphospholipid antibodies, and elevated factor VIII levels played a major role. During anagrelide treatment (± aspirin), we documented a decrease in both venous (6.7-fold) and arterial events (1.8-fold), while bleeding (mostly minor events) increased twofold compared to history. Our results suggest that keeping platelet counts at low levels may be a meaningful therapeutic measure to prevent thrombosis, although their counts at diagnosis lack any prognostic value.
authors: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.|Institute of Clinical and Experimental Hematology, 1st Medical Faculty, Charles University, Prague, Czech Republic.
authors: Jiří
authors: J
authors: Schwarz
authors: Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic.
authors: Petra
authors: P
authors: Ovesná
authors: Internal Hematology Clinic, Faculty Hospital Královské Vinohrady, Prague, Czech Republic.
authors: Olga
authors: O
authors: Černá
authors: Department of Clinical Hematology, Faculty Hospital Brno, Masaryk University, Brno, Czech Republic.
authors: Jarmila
authors: J
authors: Kissová
authors: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors: Jacqueline
authors: J
authors: Maaloufová Soukupová
authors: Department of Internal Medicine - Hematology and Oncology, Faculty Hospital Brno, Masaryk University, Brno, Czech Republic.
authors: Yvona
authors: Y
authors: Brychtová
authors: Department of Internal Medicine - Hematology and Oncology, Faculty Hospital Brno, Masaryk University, Brno, Czech Republic.
authors: Michael
authors: M
authors: Doubek
authors: Department of Internal Medicine - Hematology and Oncology, Faculty Hospital Brno, Masaryk University, Brno, Czech Republic.
authors: Libor
authors: L
authors: Červinek
authors: Department of Clinical Hematology of the 1st Department of Internal Medicine, 1st Medical Faculty, Charles University, Prague, Czech Republic.
authors: Eduard
authors: E
authors: Cmunt
authors: 4th Department of Internal Medicine - Hematology, Faculty Hospital, Charles University, Hradec Králové, Czech Republic.
authors: Petr
authors: P
authors: Dulíček
authors: Institute of Hematology and Blood Transfusion, Prague, Czech Republic.|Institute of Pathological Anatomy, 2nd Medical Faculty, Faculty Hospital Motol, Charles University, Prague, Czech Republic.
authors: Vít
authors: V
authors: Campr
authors: Department of Pathology, Faculty Hospital Brno, Masaryk University, Brno, Czech Republic.
authors: Leoš
authors: L
authors: Křen
authors: Department of Clinical Hematology, Faculty Hospital Brno, Masaryk University, Brno, Czech Republic.
authors: Miroslav
authors: M
authors: Penka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001241:Aspirin / Q000008:administration & dosage*; D005260:Female; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D010677:Philadelphia Chromosome; D010976:Platelet Count; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage*; D012042:Registries; D012307:Risk Factors; D013922:Thrombocytosis / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000235:genetics
chemical_list: C581634:BCR-ABL1 fusion protein, human; D011799:Quinazolines; D016044:Fusion Proteins, bcr-abl; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C021139:anagrelide; D001241:Aspirin
keywords: JAK2; anagrelide; myeloproliferative disorders; platelets; thrombophilia; thrombosis