Search

The stressed bleeding time is a simple 'global' test of haemostasis, dependent upon platelet function, rheology, thrombosis and intimal function. It could be of considerable value in clinical practice if it were shown to be predictive of vascular disease events. A stressed bleeding time test was done on 1319 men aged 55-69 years in the Caerphilly Cohort Study of Heart Disease, Stroke and Cognitive Decline. The men were followed-up and during the following 7-10 years 155 men had a myocardial infarction (MI) and 72 an ischaemic stroke. The mean bleeding time was 323 (SD 113) s. This was shorter in men who smoked by an average of 45 s, and lengthened in men who took aspirin daily by 40 s. After making statistical adjustments for numerous possible confounding factors, the relative odds (ROs) of an MI within the third of men with the longest bleeding times, compared to the third with the shortest times, was 0.90 (0.40-2.03). For ischaemic stroke, the ROs in the third of men with the longest times were 1.42 (0.39-5.21). The stressed bleeding time does not predict either MI or ischaemic stroke. It has no place in health screening. [ABSTRACT FROM AUTHOR]

Tissue factor (TF) is the most important initiator of intravascular coagulation. Activated platelets are able to adhere to leukocytes and this heterotypic cell-cell interaction results in a CD62P-dependent TF expression on monocytes. GPIIb/IIIa antagonists are inhibitors of the common pathway of platelet aggregation and they are widely used in patients with acute coronary syndromes undergoing coronary interventions. As GPIIb/IIIa antagonists do not prevent platelet activation we investigated the effect a GPIIb/IIIa antagonist, eptifibatide, on the formation of platelet-leukocyte conjugates and leukocyte TF expression. Flow cytometry was used to detect conjugates and TF. When platelets in citrated human blood were stimulated for 30 min with collagen there was a increase in the number of both neutrophils and monocytes with the platelet-specific antigen CD42a, indicating the formation of platelet-neutrophil (P/N) and platelet-monocyte (P/M) conjugates. P/M formation was associated with about a 2.5-fold increase in TF expression on monocytes, whereas P/N formation changed TF expression neutrophils only by about 10%. Eptifibatide enhanced dose-dependently (0.0625-1.5 microg/ml) both collagen-induced P/M formation and monocyte TF expression. Maximum enhancement by about 60 and 120%, respectively, was observed at 0.5 microg/ml eptifibatide. In contrast, eptifibatide had only a minor effect on P/N formation and no effect on neutrophil TF expression. The augmented P/M formation and monocyte TF expression in the presence of a GPIIb/IIIa antagonist may be relevant to the poor antithrombotic efficiency of oral GPIIb/IIIa antagonists as shown in recent large clinical trials.

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 < or = 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) 22.9 N (2.3) vs. 20.8 N (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, 364 s (136) vs. 483 s (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.

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.

Platelets play a crucial role in the pathophysiology of atherothrombotic disease and are involved in the early thromboembolic phase of ischaemic stroke. Large platelets are known to be more active. We hypothesized that thrombomegaly would be limited to patients with cortical infarction as compared with patients with lacunar infarcts, and that it would be associated with functional outcome. Mean platelet volume (MPV) and platelet count (PC) were studied in 167 hospitalized patients with stroke within 48 h of symptom onset, and 65 age, gender and race matched controls. Stroke was clinically and radiologically sub-typed. MPV was significantly higher in patients with ischaemic stroke than the control group: mean (SD) 7.35 (1.05) vs 7.09 (0.74) fl, 2 P = 0.04; this difference could be explained by MPV being higher in patients with cortical stroke: 7.46 (1.00) fl, 2 P = 0.039, but not lacunar infarction: 7.14 (1.16) fl, 2 P = 1.0. No difference was seen in PC between ischaemic patients and controls: 231 (82) 10(9)/l vs 236 (54) 10(9)/l, 2 P = 0.63. MPV did not change at 3 months post-stroke in surviving patients with ischaemic stroke: 7.39 (1.03) fl vs 7.34 (0.97) fl, 2 P = 0.53. Patients who were dead or dependent at 3 months had a significantly higher baseline MPV and a tendency to a lower PC than those who returned to independence. MPV and PC were not altered in patients with primary intracerebral haemorrhage. No differences in red cell volume was observed. Platelet volume is elevated in acute ischaemic stroke, a finding that persists at 3 months post-stroke and is limited to patients with cortical infarction. Thrombomegaly is a risk factor for a poor outcome after ischaemic stroke.