Prothrombotic megakaryocyte and platelet changes in hypertension are reversed following treatment: a pilot study

Platelets are formed from, and their function determined by, bone marrow me gakaryocytes (MK). Previous studies have found that hypertension is associa ted with accentuated platelet function and that some anti-hypertensive drug classes have antiplatelet activity. We measured MK ploidy (DNA content), s ize, granularity, and expression of the adhesion molecule glycoprotein (GP) IIIa, using flow cytometry and measures of platelet function, in 12 untrea ted hypertensive patients and 14 normotensive subjects. Eight hypertensive patients were then treated with losartan (50 mg daily), an angiotensin rece ptor antagonist that lowers blood pressure, and MK and platelet parameters re-measured after 6 weeks. Hypertensive patients had, as compared with matc hed normotensive subjects: increased MK ploidy (mean +/- SD) 22.9 +/- 2.2 N versus 20.8 +/- 1.6 N (2P = 0.009); increased platelet size, 10.67 +/- 1.0 3 fl versus 9.26 +/- 0.72 fl (2P < 0.001); increased platelet expression of GP IIIa, 108.6 +/- 22.5 versus 92.0 +/- 12. 3 (2P = 0.036); and reduced pl atelet count, (207 +/- 52) x 10(9)/l versus (257 +/- 55) x 10(9)/l (2P = 0. 026). Losartan significantly reduced MK ploidy, 22.6 +/- 2.2 N versus 21.4 +/- 1.9 N (2P = 0.006); MK size, 607 +/- 22 versus 579 +/- 16 (2P = 0.003); and lengthened cutaneous bleeding time, 424 +/- 86 s versus 563 +/- 164 s (2P = 0.011), in hypertensive patients. Losartan did not alter MK granulari ty or GP IIIa expression, or platelet count, size, mass, GP IIIa expression , or aggregation. The data suggest that platelet changes in hypertension ma y be secondary to changes in MKs, and that anti-hypertensive treatment can alter MKs and the function of platelets they produce. Since antihypertensiv e therapy reduces the risk of stroke and myocardial infarction, MKs are a n ovel therapeutic target for the prevention of vascular events.