title: Prothrombotic megakaryocyte and platelet changes in hypertension are reversed following treatment: a pilot study.
abstract: Platelets are formed from, and their function determined by, bone marrow megakaryocytes (MK). Previous studies have found that hypertension is associated with accentuated platelet function and that some antihypertensive drug classes have antiplatelet activity. We measured MK ploidy (DNA content), size, granularity, and expression of the adhesion molecule glycoprotein (GP) IIIa, using flow cytometry and measures of platelet function, in 12 untreated hypertensive patients and 14 normotensive subjects. Eight hypertensive patients were then treated with losartan (50 mg daily), an angiotensin receptor antagonist that lowers blood pressure, and MK and platelet parameters re-measured after 6 weeks. Hypertensive patients had, as compared with matched 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 +/- 1.03fl versus 9.26 +/- 0.72fl (2P < 0.001); increased platelet expression of GP IIIa, 108.6 +/- 22.5 versus 92.0 +/- 12.3 (2P = 0.036); and reduced platelet 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 +/- 86s versus 563 +/- 164s (2P = 0.011), in hypertensive patients. Losartan did not alter MK granularity or GP IIIa expression, or platelet count, size, mass, GP IIIa expression, or aggregation. The data suggest that platelet changes in hypertension may be secondary to changes in MKs, and that anti-hypertensive treatment can alter MKs and the function of platelets they produce. Since antihypertensive therapy reduces the risk of stroke and myocardial infarction, MKs are a novel therapeutic target for the prevention of vascular events.
authors: Department of Medicine, King's College London, Denmark Hill, London, UK.
authors: R
authors: R
authors: Pathansali
authors: N M
authors: NM
authors: Smith
authors: P M
authors: PM
authors: Bath
mesh_terms: D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D016022:Case-Control Studies; D048429:Cell Size / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects* / Q000473:pathology; D008875:Middle Aged; D010865:Pilot Projects; D011003:Ploidies; D019851:Thrombophilia / Q000097:blood / Q000188:drug therapy
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D019808:Losartan