Altered megakaryocyte-platelet haemostatic axis in hypercholesterolaemia

Hypercholesterolaemia is associated with accentuated platelet function. We assessed in a pilot study whether megakaryocytes (MK), the platelet precursor cell, were altered in subjects with primary hypercholesterolaemia and whether these changes were linked with platelet function. MK and platelet function were assessed in eight untreated patients with primary hypercholesterolaemia (total cholesterol, TC > 7 mmol/l), and 14 control subjects (TC less than or equal to 7 mmol/l): MK ploidy (DNA content), size, granularity, and expression of the adhesion molecule GP IIIa, and platelet expression of GP IIIa, P selectin and CD 63, and RNA content, were each measured using flow cytometry; mean platelet volume, platelet count, plasma thrombopoietin, and cutaneous bleeding time were also assessed. Hypercholesterolaemic patients had increased MK ploidy, mean (SD) 22.9N (2.3) vs. 20.8N (1.6) (2P=0.021); platelet size, 10.6 fl (1.2) vs. 9.3 fl (0.7) (2P=0.006); and platelet expression of GP IIIa, 111.3 (18.9) vs. 92.0 (12.3) (2P=0.010), as compared with matched control subjects. Cutaneous bleeding time tended to be reduced in the hypercholesterolaemic patients, 364s (136) vs. 483s (165) (2P=0.11). No differences in MK size, granularity or GP IIIa expression, or platelet count, mass, RNA content, P selectin or CD 63 expression, or plasma thrombopoietin were seen. The data suggest that aspects of megakaryocytes and platelets are altered in hypercholesterolaemia, as has also been seen in other vascular risk factors states, including hypertension and diabetes mellitus. Furthermore, changes in megakaryocytes may have contributed to the altered platelet function seen here. Further study is now required to assess whether lipid lowering therapy 'normalises' these changes in the megakaryocyte-platelet haemostatic axis.