Thrombocytosis in patients with polycystic ovary syndrome: reactive or culpable?

Polycystic ovary syndrome (PCOS) affects about 6Y10% of women in the reproductive age-group, and is a common cause of female infertility. PCOS is a heterogeneous endocrine condition which in its classic phenotype is characterized by hyperandrogenism, chronic ovulation abnormalities, and the presence of polycystic ovaries on ultrasound. About 60% of PCOS patients have central or abdominal obesity, and 50Y70% of these patients have evidence of impaired glucose tolerance due to peripheral insulin resistance, regardless of coexistent obesity. In addition, young patients with PCOS are vulnerable to a host of other cardiovascular risk factors such as type 2 diabetes mellitus, hypertension and dyslipidemia, and many patients meet the criteria for the metabolic syndrome. Although the diagnostic criteria for PCOS have been updated several times over the past decade, the overall epidemiological evidence suggests that the cardiovascular risk in classic PCOS patients is much higher than women without this condition. There has been considerable research to identify the molecular mechanisms by which hyperandrogenism, obesity and insulin resistance the three major metabolic abnormalities in most PCOS patients interact to produce the various clinical and biochemical manifestations of this disease. In recent years, PCOS is being increasingly recognized as a state of chronic, low-grade inflammation, and inflammation has been proposed as the potential link between the metabolic perturbations in PCOS patients and its long-term consequences, including the increased cardiovascular risk. Several markers of chronic inflammation have been shown to be elevated in PCOS patients; these include C-reactive protein, ferritin, osteoprotegerin, and homocysteine. Serum levels of inflammatory cytokines such as TNF->, IL-6, and IL-18, chemokines such as MCP-1, and adipokines such as the adiponectin/leptin ratio are also elevated in PCOS patients. In addition, studies have shown that PCOS patients have evidence of endothelial dysfunction, and also have evidence of greater subclinical atherosclerosis as measured by an increase in carotid artery intima-media thickness or coronary artery calcification. Patients with PCOS have also been shown to have significantly higher total white blood cell counts as compared to normal controls. Leukocytosis is considered as another marker of chronic low-grade inflammation and has been strongly correlated with measures of peripheral insulin resistance in PCOS patients. In the March issue of the Journal, Dasanu and colleagues describe a small cohort of 5 young women with PCOS who were referred to their practice for persistent thrombocytosis, with blood platelet counts ranging from 463,000 to 613,000 per ml of blood. These patients also had moderate leukocytosis, with total white blood cell counts ranging from 11,300 to 13,800 cells per ml. Although small elevations in C-reactive protein (CRP) levels were seen in all 5 women, no significant correlation was found between the CRP level and the elevated white blood cell or platelet counts. Contrary to previous studies, platelet aggregation studies and mean platelet volume were normal in these women, as were measures of prothrombotic tendency such as homocysteine or lipoprotein(a) levels. A detailed hematological work-up, including a bone marrow examination, was performed in each patient to rule out a neoplastic or myelodysplastic etiology for the persistent thrombocytosis. A small case-control study previously reported that patients with PCOS have higher mean platelet volume (MPV) a marker of platelet activation, as well as increased ADPinduced platelet aggregation and reduced responsiveness to nitric oxidewhich collectively contribute to a prothrombotic state. In this study, MPV positively correlated with serum insulin levels, measures of peripheral insulin resistance, as well as hyperandrogenism. However, in this group of PCOS patients the mean platelet count was normal (250,000 per ml). In a follow-up study in the same group of PCOS patients, treatment with metformin with or without oral contraceptives (ethinyl estradiol/cyproterone acetate) for three months significantly decreased MPV as well as the total white blood cell and total platelet counts. The authors of the current report did not Sandeep Ajoy Saha, MD, FACP Editorial