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 precurs or cell, were altered in subjects with primary hypercholesterolaemia and wh ether these changes were linked with platelet function. MK and platelet fun ction were assessed in eight untreated patients with primary hypercholester olaemia (total cholesterol, TC > 7 mmol/l), and 14 control subjects (TC les s than or equal to 7 mmol/l): MK ploidy (DNA content), size, granularity, a nd 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 fl ow cytometry; mean platelet volume, platelet count, plasma thrombopoietin, and cutaneous bleeding time were also assessed. Hypercholesterolaemic patie nts had increased MK ploidy, mean (SD) 22.9N (2.3) vs. 20.8N (1.6) (2P=0.02 1); 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 reduce d in the hypercholesterolaemic patients, 364s (136) vs. 483s (165) (2P=0.11 ). No differences in MK size, granularity or GP IIIa expression, or platele t count, mass, RNA content, P selectin or CD 63 expression, or plasma throm bopoietin were seen. The data suggest that aspects of megakaryocytes and pl atelets are altered in hypercholesterolaemia, as has also been seen in othe r vascular risk factors states, including hypertension and diabetes mellitu s. Furthermore, changes in megakaryocytes may have contributed to the alter ed platelet function seen here. Further study is now required to assess whe ther lipid lowering therapy 'normalises' these changes in the megakaryocyte -platelet haemostatic axis.