Soluble P-selectin is influenced by cancer chemotherapy

The adhesion molecule P-selectin (CD62P) is a component of the platelet a -granule membrane, becoming exposed on the surface of the platelet upon activation, due to the fusing of the vesicle with the platelet outer membrane. A soluble form of P-selectin (i.e. soluble P-selectin) can be detected by enzyme-linked immunosorbent assay (ELISA) in plasma, and increased levels are found in thrombotic conditions, atherosclerosis, diabetes and connective tissue diseases. – 5 We have previously hypothesised that increased levels of soluble P-selectin indicate platelet activation, a viewpoint that is gaining acceptance. 9 It has also been suggested that soluble P-selectin is a more reliable marker of platelet activation than membrane expression of P-selectin determined by flow cytometry. Our recent pilot data demonstrate that soluble P-selectin is increased in subjects with breast or haematological cancer (e.g. leukaemia, lymphoma). In this study, we were careful to avoid the confounding effects of cytotoxic drugs by excluding patients on a current regime of chemotherapy. It is therefore unclear whether or not soluble P-selectin is influenced by chemotherapy, a hypothesis we set out to test in a casecontrol study of women aged less than 74 with ovarian cancer compared to healthy women. The sample population consisted of patients attending a chemotherapy out-patients clinic. All had ovarian cancer and were participating in standard three-week cycles of chemotherapy (e.g. carboplatin 500–700 mg daily (depending on renal function) or taxol (175 mg/m every 21 days). Fifty patients were compared to 37 agematched healthy females as control subjects (patients 55 ± 9 (mean/SD) years, controls 55±6 years, t-test p=0.63). Both groups had an EDTA and a citrated blood sample taken. In the patient population, the blood sample was collected immediately before administration of a further bolus of chemotherapy. The platelet count was measured as part of a full blood count on a Technicon H2 haematology analyser. Soluble P-selectin was measured using an ELISA (R&D Systems, Abingdon, UK). Soluble P-selectin was considerably lower in the cases than in the controls (Mann–Whitney U-test p<0.001) but there was no difference in platelet counts (Mann– Whitney p=0.309) (Table 1). The correlations between the platelet count and the soluble P-selectin level were not significant in either group. Although we have not controlled for all other possible influences on soluble P-selectin (e.g. smoking, diabetes etc.) 5 the difference in levels of this marker between the groups is striking. Furthermore, other clinical factors (such as risk factors and vascular disease) and the effect of the ovarian cancer itself seem likely to increase levels of soluble P-selectin, not reduce it. Notably, there was no difference in the platelet count between the groups. We suggest that effects of the previous course of chemotherapy (at least three weeks prior to venepuncture for the present study) do not have a long-standing quantitative effect on the platelet count, although the (qualitative? ) effect on one of its products (i.e. soluble P-selectin) is present. We conclude that chemotherapy is a powerful modulator of soluble P-selectin, and must be considered in studies where patients are taking cytotoxic agents. This may also have clinical consequences as patients on chemotherapy are at an added risk of thrombosis.