Women, Platelets & Cardiovascular Risk

Author: Maria Shapoval (ND)

November, 2015    |



Cardiovascular disease has an earlier onset of 7-10 years in women compared to men (Maas 2010) and remains the leading cause of death in women (CDC 2013). One of the many links between the female sex hormone, estrogen, and cardiovascular risk may be through platelets, which express the estrogen receptor β and increase its expression upon activation (Wang 2012). Conflicting studies report increased coagulation during the luteal menstrual phase, as evident by increased binding of platelets to fibrinogen resulting in platelet aggregation (Kurrelmeyer 2003) while other studies report no significant menstrual related changes (Jones 1983). The continuous presence of estrogen has been correlated to a reduction of pro-coagulant substances such as fibrinogen, antithrombin and plasminogen activator inhibitor and thus supports the possibility of fluctuation in coagulation with the menstruation. Studies exploring platelet reactivity and platelet count observe sex-related difference and thus set the stage for this review, which hopes to explore the differences in platelet physiology between males and females and their impact on cardiovascular health.


Platelets: Quick to React

Platelet reactivity implies greater rate of activation and platelet aggregation. When compared, platelets from female participants were more reactive than those from males when activated by agonists such as adenosine diphosphate (ADP) and thrombin receptor agonist protein (Wang 2012). While the overall level of fibrinogen is higher in women, platelets from women additionally bind more fibrinogen and demonstrate more spontaneous aggregations than in men. The increased platelet reactivity is associated with an increased risk of myocardial infarctions (MI)(Wang 2012).


MPV: Why Size Matters

Large platelets, as measured by the mean platelet volume (MPV), are more enzymatically and metabolically active, contain more α-granules with prothrombic substances and have been associated with increased platelet aggregation, increased thromboxane synthesis and β-thromboglobulin release (Chu 2010). Epidemiologically, elevated MPV have been cited as an independent risk factor for recurrent ischemia and death post MI and associated with other cardiovascular morbidities such as obesity, hypertension, diabetes and smoking. The size of the platelets correlates with thrombopoetin, which stimulates platelet production, and interleukin 6; a pro-inflammatory cytokine. While an analysis of the Framingham Heart Study revealed no statistically significant difference in MPV between males and females (Sloan 2015) a small observation study comparing the impact of smoking cessation demonstrated a significant reduction in MPV with smoking cessation in female participants but not in males (Cho 2014).


Aspirin: Different Impact?

Aspirin may benefit women to a different extent than it does men as studies report statistically significant differences in platelet aggregation post treatment. According to the Gene STAR study, platelet aggregation in response to collagen, after aspirin therapy, was 31.8 per cent for women and 27.2 per cent for men (p<0.001) (Wang 2012). However this difference may be due to the higher baseline reactivity of platelets in females (Bailey 2009).


Another Player: Microvesicle

Microvesicles (MV) are submicron-sized vesicles that are released from the plasma of various activated cells including erythrocytes, platelets, leukocytes, endothelial cells and others. MV differ in their functions depending on their cell of origin and state of function and can thus be pro- or anticoagulant and/or pro-inflammatory (Gustafson 2015). MV carrying phosphatidylserine are used to catalyze thrombin production and as such have a pro-coagulant impact. Phosphatidylserine positive MV have been found to be significantly higher (p<0.05) in healthy women as compared to age-matched, healthy men, along with MV containing P-selectin, another pro-coagulant. There were no significant differences in the anticoagulant MV. This may be an additional mechanism contributing to elevated risk of cardiovascular events through induction of a more pro-coagulative state.


Genetic Polymorphism

The impact of sex hormones on cardiovascular risk may differ depending on genetic predisposition. A genetic study by Bray et al (2007) demonstrated two opposing effects from hormone therapy on risk of coronary disease. Postmenopausal women with -5HT>C and 13254T>C polymorphisms in the platelet glycoprotein genes experienced a 6 per cent increase in absolute risk, while women with complementary genotypes experienced a 5 per cent absolute risk reduction. Future studies are needed to explore the mechanism by which these changes are produced.



This review introduces several different risk factors associated with the female sex that remain to be further explored in research in the hopes of refining tools of screening for cardiovascular risk and open new avenues for therapeutic interventions. One wonders if the plants termed as “alteratives” and “blood purifiers” by traditional herbalism have any impact on platelet reactivity and volume and thus, subsequently, cardiovascular health.

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