XVIII Congress of the Italian Society for Hemostasis and Thrombosis Research, Rome, Sept. 30-Oct. 3, <strong>2004</strong>121generated by hyperhomocysteinemia. The pathwaysby which ADMA and SSAO are involved in the oxidativedamage caused by hyperHcy seem to be independent.This work was supported by a grant from Ministerodella SalutePO-054CHRONIC ENDOTHELIAL CELL DAMAGE/PROLIFERATION ANDINCREASED NEOANGIOGENESIS BY ENDOTHELIAL GROWTHFACTOR (VEGF), PLATELET-DERIVED GROWTH FACTOR (PDGF)AND INTERLEUKIN-6 (IL-6) SERUM ABNORMAL RELEASE INSICKLE CELL DISEASEMusso R, Cultrera D,* Chiarenza A,* Meo A,**Burgio N, Cipolla N, D'arpa S, Giustolisi R*Haemophilia and Thrombosis Reference RegionalCenter; *Institute of Hematology, University ofCatania; **Department of Pediatrics, Universityof Messina, ItalyAb<strong>no</strong>rmal circulating endothelial cells (EC)(SamuelO Sowemi<strong>no</strong>-Coker et al. American J Hematology 31;19<strong>89</strong>), as well as vascular endothelium chronic damagewith ab<strong>no</strong>rmal cytokines release (Musso R. et al.6 th Intern. Conference on Thalassemia and Haemoglobi<strong>no</strong>pathies,Malta, 1997) have previously beenreported in sickle cell disease (SCD). We here reportthat vascular endothelial growth factor (VEGF), themost important growth and survival factor forendothelium and platelet EC mitogen, is increased inSCD, thus suggesting an important role in the regulatio<strong>no</strong>f the vasculogenesis. We further carry evidencethat human platelet derived growth factor AB(PDGF), the major mitogenic factor, is also raised inthe serum of SCD patients. 18 SCD patients (10females and 8 males, age ranging 22-59 yrs,β+ thalassemia/S trait, 7 previously splenectomized,without renal <strong>no</strong>r liver dysfunctions), bothin steady state and during painful episodes (n=19)were studied. 15 healthy subjects, sex and age comparable,served as controls. Human VEGF by ELISAmethod (R&D Systems, Italy) in conjunction withvWF (ELISA procedure, Dade Behring Institute, Italy)as index of EC function and human PDGF-FAB (ELISA,R&D Systems, Italy), as indicator of platelet releaseand of chemotaxis for neutrophils and fibroblast inconjunction with Interleukin-6 (IL-6) (ELISA, R&DSystems, Italy) were assayed. Our results are belowreported (see Table below). Our data showed thatincreased VEGF circulating levels are present in SCDalso in the steady state. Human PDGF-FAB, vWF andD-dimer were parallely elevated. Among the severaleffects induced by VEGF, it is reported that thiscytokine increases micro-vascular permeability,vasodilatation, EC proliferation and cell migration,ab<strong>no</strong>rmal platelet release with elevated plateletcount and influences the neo-angiogenesis and vasculogenesis.VEGF also promotes extravasation ofplasma fibri<strong>no</strong>gen, leading to fibrin deposition andpromotes the migration of macrophages and fibroblastsand EC proliferation. By considering that ab<strong>no</strong>rmalplasma levels of vWF and PDGF with elevatedcirculating D-dimer as index of thrombin activationand fibrin deposition in vivo, in conjunction withraised amounts of IL-6, well k<strong>no</strong>wn cytokine-mediatorof coagulation process, were present in SCDpatients, we suggest that this observation stronglyconfirms their proneness to constantly increasedthrombogenic risk.VEGF vWF PDGF-FAB D-dimer IL-6pg/mL % pg/mL pg/mL pg/mLPatients ss pc ss pc ss pc ss pc ss pcn=18 70± 97± 115± 285± 23± 58± 485± 641± 33± 49.6±13.9* 4.3** 38* 69** 7.1* 2** 69* 93** 21.7* 30.3**Controlsn=15 57±7.1 95±18 13.6±6.4 210±80 22±9.4PO-055CHANGES IN COAGULATION VARIABLES FOLLOWING A6-MO R-HGH REPLACEMENT IN GROWTH HORMONE DEFICIENTADULTSValle D, 1 Cirillo F, 2 Merola B, 3 Beck-Peccoz P, 4Attanasio AF, 1 Lombardi G, 3 Di Min<strong>no</strong> G, 2,5 onbehalf of Eli-Lilly B9 REWGDED Italian Study Group1Eli Lilly, Florence, Italy, 2 Department of Clinical andExperimental Medicine, “Federico II” University,Naples, Italy; 3 Department of Endocri<strong>no</strong>logy,University of Naples; University of Milan; 4 Instituteof Endocrine Sciences, Ospedale Maggiore IRCCS,and 5 laboratory of Thrombosis and haemostasis,Ospedale “Casa sollievo della Sofferenza” IRCCS,S. Giovanni Rotondo, ItalyIn the frame of a large multicenter, internationalstudy, in a subset of 71 patients (28F, 43M) withgrowth hormone deficiency randomized to receivetwo different recombinant human GH (r-HGH) regimens(low dose, n=37, age:42.4±16.2 yr; BMI:26.7±5.3 Kg/m 2 ), 3 µg/Kg/d for three mo followed by6 µg/Kg/d; (high dose, n=34, age:38.3±15.7 yr; BMI:26.7±4.9 Kg/m 2 ) 6 µg/Kg/day for three mo followedby 12 µg/Kg/d, we have measured changes in fibri<strong>no</strong>gen,PAI-1 activity, t-PA antigen, protein C, and proteinS levels. Patients were on thyroid, adrenal andhaematologica vol. <strong>89</strong>(suppl. n. 8):september <strong>2004</strong>
122Postersgonadal hormone replacement therapy. Coagulationparameters were measured at baseline and after 6mo-treatment. In all patients, baseline fibri<strong>no</strong>genconcentrations were in the upper <strong>no</strong>rmal levels (200-400 mg/dL) and significantly correlated (r=0.32,p65 were considered(n=11; 347.00±83.<strong>89</strong>6 vs. 315.00±74.59,p=0.024). No change was seen in PAI-1 and TPAthroughout the 6-mo treatment and the baseline concentrationscorrelated with age (r=0.30,p
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