1. THROMBOTIC COMPLICATIONS IN PATIENTS WITH POLYCYTHEMIA VERA Coordinator: Asist. Univ. Dr. Marcela Candea Authors: Ioana-Violeta Oltean Ioana Barsan Madalina Crisan

2. Introduction Polycythemia Vera (PV) is a myeloproliferative disorder with predominantly erythroid hyperplasia, but also leukocytosis and thrombocytosis. Nutrimedical.com

3. Introduction A mutation or change, in the body’s JAK2 (janus- associated kinase 2) is the main cause of Polycythemia Vera. Rachel Eastwood

4. Introduction

5. Objective To analyse the: clinical characteristics laboratory data association of thrombotic complications of Polycythemia Vera with various patient characteristics.

6. Material and Method  retrospective study  60 patients  Hematology Clinic in Tg- Mures  2000-2013  Polycythemia Vera WHO criteria: - Major criteria: - Hb >18,5 g/dl in men, 16,5 g/dl in women or elevated RCM > 25% above mean normal predicted value - presence of JAK2 V617F mutation or other similar mutation - Minor criteria: - bone marrow biopsy (hypercellularity with prominent erythroid, granulocytic and megakaryocitic proliferation) - serum erythropoietin level below range - endogenous erythroid colony formation in vitro WHO = World Health Organization Hb = Hemoglobin RCM = red cell mass

7. Material and Method Parameters: sex age laboratory data: - hemoglobin - hematocrit - white blood cell count - platelets count vascular risk factors: - hypertension - diabetes - dyslipidemia - smoking Statistical analysis: - Microsoft Excel - GraphPad p<0,05 thrombotic complications: - acute coronary syndrome ( acute myocardial infarction, unstable angina pectoris) - cerebrovascular disease (ischemic stroke, transient ischemic attacks) - venous thromboembolism (deep venous thrombosis, pulmonary embolism) - erythromelalgia - superficial thrombophlebitis

8. Results Average age: 57 years

9. Baseline characteristics: Hemoglobin (g/dl, mean±SD) 18,2±4,1 Hematocrit (%, mean±SD) 55,7±9,3 White cells (x10 9 /l, mean±SD) 13,7±7,8 Platelets (x10 9 /l, mean±SD) 468±255 Splenomegaly n (%) 40 (66,6%) JAK2 mutation, n13

10. Results

11. With thrombosis Without thrombosis p value Median hemoglobin, g/dl 16,8517,020,1759 Median hematocrit, % 51,1152,960,3524 Median white blood cell count, x10 9 /l 16,6815,360,5515 Median platelet count, x10 9 /l 493,12468,720,626

12. Results OR 95% CI: lower limit 95% CI upper limit p value Diabetes mellitus 0,4920,09042,6770,698 Smoking0,2960,0571,5180,177 Hypertension1,3720,4813,9090,743 Dyslipidemia4,6551,48314,610,0142

13. - A De Stefano V. study showed that from 235 PV patients, 21,4% had an acute coronary syndrome and 38,6% a cerebrovascular disease. - Stein BL et al. discovered that dyslipidemia was marginally independent associated with a history of vascular complication in PV patients (p=0,045). - A report by Varma et al. showed that was not statistically difference in the mean hemoglobin, white cell count and platelet count in patients with thrombosis as compared to patients without thrombosis.

14. 1. PV is more frequent on male patients over the age of 50 years. 2. More than half of patients develop arterial or venous thrombosis. 3. Thrombotic complications in PV are more frequent at patients with raised platelets count (>450x10 9 /l), raised white blood cell count (>15x10 9 /l) and dyslipidemia.

15. 1. Tefferi A., Thiele J., Orazi A. et al. – Proposals and rationale for revision of the WHO diagnostic criteria for Polycythemia Vera: recommendations from an ad hoc international expert panel. Blood 2007 Aug. 15; 110(4): 1092-7. 2. De Stefano V., Za T., Rossi E., Elli E. et al. – Recurrent thrombosis in patients with Polycythemia Vera and Essential Thrombocythemia. Haematol. March 1, 2008 vol.93 no.3 372-380. 3. Varma S., Sharma A., Malhotra P., Varma N. – Thrombotic complications of Polycythemia Vera. Hematology 2008 Dec; 13 (6): 319-23. 4. Landolfi R., Di Gennaro L., Barbui T., Marchioli R. Et al. – Leukocytosis as a major thrombotic risk factor in patients with Polycythemia Vera. Blood 2007; 109: 2446-2452. 5. Stein B. L., Rademarker A., Spivak J. L. and Moliterno A. R. – Gender and vascular complications in the JAK2V617F positive myeloproliferative neoplasms. Thrombosis 2011 1-8. 6. Landolfi R., Marchioli R., Patrono C. Et al. – Mechanisms of bleeding and thrombosis in myeloproliferative disorders. Thromb. Haemost. 1997; 78: 617-621.