Sex-Related Differences in Platelet Aggregation: Influence of the Hematocrit

A number of investigators have recently reported that human female platelets have increased reactivity in vitro compared to platelets from age-matched males. A possible explanation for these observations is that the lower hematocrit in females results in a larger volume of distribution of the anticoagulant, with resultant higher ionized calcium concentrations. To examine this possibility, we performed adenosine diphosphate (ADP) and collagen aggregations on platelets obtained from 11 male and 11 female healthy subjects. When aggregations were performed on blood samples using the standard amount of 3.8% sodium citrate as an anticoagulant (9:1, v:v, blood:anticoagulant), the female platelets were significantly more reactive than the male platelets over a wide range of ADP and collagen concentrations (p < 0.01). The same subjects were then retested, but on this occasion the citrate concentration was adjusted for the hematocrit according to a mathematically derived standard curve. The previously noted increased reactivity of female platelets disappeared, and there was no significant difference in reactivity to either ADP or collagen between the male and female platelets. The reported in vitro sex differences in platelet reactivity is contributed to by an artifact caused by differences in the size of the citrate distribution compartment. It is possible that a similar phenomenon is responsible for the increased platelet reactivity reported in certain disease states, which frequently have a concomitantly associated anemia.