Fibroblast Growth Factor-2 and Lactate Dehydrogenase Levels in Patients with Essential Thrombocythemia Treated with Anagrelide.
Authors: Cacciola Rossella R , Di Francesco Ernesto , Pezzella Francesca , Cacciola Emma 
Published: October 2019

Abstract
Abstract 4981
Essential thrombocythemia (ET) is characterized by platelet-coagulant-endothelial activation. Fibroblast growth factor-2 (FGF-2) is released and upregulated by platelet-fibrinogen(Fg)-endothelial activation and induces vascular and myeloid proliferation. Anagrelide (ANA) is a platelet-lowering drug that inhibits platelet activation. Therefore, we evaluated platelets, platelet factor 4 (PF4) and fibrinogen (Fg), as markers of platelet and coagulant activation, tissue factor pathway inhibitor (TFPI), tissue factor (TF) and von Willebrand factor (vWF), as markers of endothelial activation, FGF-2, vascular endothelial growth factor (VEGF), as indicator of angiogenesis, and white blood cell (WBC) count and haemoglobin (HB), as myeloproliferative indexes. As lactate dehydrogenase (LDH) is a cell cytolysis-associated marker, we determined LDH. To ensure that FGF-2 elevation did not associate with prefibrotic myelofibrosis, we evaluated the CD34 levels. We recruited 21 patients with ET (13 males and 8 females, mean age 52 years) who fulfilled PVSG and WHO. Their mean duration of disease was 9 years (range, 5-21 years). ANA was administered in dose of 0.5 mg/day, with increases of 0.5 mg/day every 7 days until the platelets decreased below 400×109/L and with a average maintenance dosage of 2.1 mg/day. PF4, Fg, FGF-2, VEGF, platelets, WBC, HB, TFPI, TF, vWF and LDH were measured before cytoreduction and to complete response defined as platelets <400×109/L. PF4, FGF-2, VEGF, TFPI, TF and vWF and Fg were assayed by ELISA and immunoturbidimetric and Clauss assay, respectively. LDH was determined by enzymatic method. CD34 levels were measured by flow cytometric assay. Considering that FGF and VEGF may be produced by platelets, we adjiusted FGF and VEGF per platelet (FGFPLT /106 and VEGFPLT/106). Platelets, WBC and HB were measured by automated analyser. Before ANA all patients had marked platelets (1005±314×109/L), high PF4 (127±45 IU/ml vs 4.1±2.4 IU7ml) (p<.0001) and Fg (369±106 mg% vs 237±42 mg%) (p<.0001), elevated TFPI (156±64 ng/ml vs 94±10 ng/ml) (p<.0001), TF (235±287 pg/ml vs 4.4±2.7 pg/ml) (p=<.0001) and low vWF ( 23±7.8 % vs 77±18%) (p<.0001), elevated FGF-2PLT (0.08±0.08 pg/106 vs 0.01±0.001 pg/106) (p<.0001) and VEGFPLT ( 1.8±1.1 pg/106 vs 0.5±0,5 pg/106) (p<.0001), leukocytosis (10.5±2.4×109/L vs 5.2±1.1×109/L) (p<.0001) and high HB (14±1.4 g/dL vs 12±0.4 g/dL) (p<.0001), elevated LDH (529±326 UI/L vs 173±37 UI/L) (p<.0001) and normal CD34 (0.2±0.1%. After ANA, all patients had platelets <400×109/L (386±55×109/L) and normal PF4 (8.5±3 IU/ml), Fg (295±46 mg%), TFPI (100±49 ng/ml), TF (8.7±0.8 pg/ml), vWF (91±35 %), FGF-2PLT (0.01±0.0 pg/106), VEGFPLT ( 1.1±0.6 pg/106), WBC (7.4±1.4×109/L), HB (12.6±1.1 g/dL), and LDH (225±23 UI/L). A positive correlation there was between PF4 and platelets and Fg and TFPI and TF and vWF (p<.0001 and p= 0.002 and p=0.005 and p=0.014 and p<.0001, respectively) and FGF-2PLT and LDH (p<.0001 and p<.0001, respectively). A correlation was found between Fg and FGF-2PLT (p=0.010) and FGF-2PLT and LDH and TFPI and TF and vWF (p=0.003 and p<.0001 and p<.0001, respectively, and p=0.002 and p<.0001 and p=0.001, respectively). A correlation there was between FGF-2PLT and VEGFPLT (p=0.011) and WBC and HB (p=0.011 and p=0.016, respectively). A significant correlation there was between FGF-2PLT and LDH (p<.0001). No correlation was found between FGF-2PLT and CD34. These data suggest that FGF-2PLT and LDH are platelet-endothelial activation-associated prognostic factors reversed by ANA.

Disclosures
No relevant conflicts of interest to declare.