Abstract

Primary or essential thrombocythaemia (PT), a rare myeloproliferative disorder, is characterised by high platelet numbers, an increased risk of thrombosis and haemorrhage, and a reduced life expectancy. In addition to thrombocytosis, additional platelet abnormalities include alterations in soluble P-selectin (sP-selectin), platelet P-selectin (pP-selectin) and platelet factor 4 (Musolino et al, 2000; Villmow et al, 2002). Vascular endothelial growth factor (VEGF) is an angiogenic product of several cells, including endothelial cells and platelets (Blann et al, 2004), and increased levels (thereby possibly implying alterations in angiogenesis), are present in PT and other myeloproliferative disorders (Di Raimondo et al, 2001; Musolino et al, 2002). The implications of this finding are unknown. Furthermore, the source of this VEGF is unclear and could have pathophysiological and/or therapeutic connotations. We therefore set out to test the hypothesis that platelets are a major source of plasma VEGF in patients with PT. To do this we measured levels of VEGF in and plasma and platelet lysates in a simple cross-sectional study comparing patients to healthy age- and sex-matched controls, and compared levels to those of sP-selectin. This study was a sub-analysis of a group of patients previously studied (Blann et al, 2004). Patients were recruited if they fulfilled diagnostic criteria of PT. Almost all were being treated with combinations of aspirin (75 mg/d) and anagrelide (mean ± SD 1·6 ± 0·6 mg/d) or hydroxycarbimide (0·95 ± 0·3 g/d). Patients were compared with 15 age- and sex-matched healthy controls recruited from hospital staff. All subjects gave written informed consent and the study had the approval of the Ethics Committee of City Hospital, Birmingham, UK. In the routine Haematology laboratory, EDTA-plasma was tested for platelet count (Advia, Bayer, Newbury, UK). In the research laboratory, VEGF and sP-selectin were measured in citrated plasma by enzyme-linked immunosorbent assay (ELISA; R&D Systems, Abingdon, UK). The total mass of VEGF per platelet was estimated by lysing a set number of thrice-washed platelets with 0·5% Triton X-100 (Sigma, Poole, UK), and then measuring VEGF in the lysate by ELISA to give the mean mass of P-selectin per platelet (Kamath et al, 2002). The results are shown in Table I. As expected (Musolino et al, 2000; Villmow et al, 2002; Blann et al, 2004), patients had a higher platelet count, sP-selectin and VEGF than controls. However, there was no difference in the mass of VEGF per platelet. Within the patient group, there were no significant Spearman's correlations between the platelet count and VEGF (r = −0·059, P = 0·752), nor between sP-selectin and VEGF (r = 0·081, P = 0·659). However, the platelet count correlated with sP-selectin (r = 0·373, P = 0·036). Increased levels of plasma VEGF in PT are an established finding and the presence of this angiogenic growth factor in platelets naturally leads to the question of whether or not this is important. Interest lies in the possibility that platelet VEGF may contribute to angiogenesis within the bone marrow and thus the disease process. The observations of the present study suggest this may not be the case. First, despite differences in plasma levels, there was no difference in platelet VEGF between the patients and matched controls. Secondly, neither platelet nor plasma VEGF correlated significantly with either the platelet count, or with sP-selectin. We therefore suggest that raised plasma VEGF in PT is not the direct consequence of altered platelet activity.

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