Beta-Thromboglobulin and Platelet Factor 4 in Juvenile Myocardial Infarction

In acute coronary syndromes, and especially in acute myocardial infarction (AMI), inflammation mechanisms involving platelets and leukocytes play a key role. These cells show a state of activation: Evaluation of proteins released by platelets and leukocytes may provide an index for the estimation of their activation. Two platelet-specific proteins, secreted by αgranules during the release reaction, are used as activation markers: β-thromboglobulin (β-TG) and platelet factor 4 (PF4). Generally these proteins are dosed together in the same sample for a better evidence of in vivo release. In patients with AMI, plasma levels of β-TG are increased (1,2) and inversely correlated with the time elapsed from symptom onset to admission to the hospital (3). In patients with postinfarction angina there is a further increase in β-TG plasma levels (2). Elevated plasma levels of β-TG were found to persist for several weeks after AMI, in spite of the treatment with aspirin (4). Patients with ischemic heart disease show higher basal plasma concentration of PF4 compared with normal controls; in these patients PF4 levels further increase after exercise (5). Thrombolytic treatment induces an increase in β-TG levels, except in patients admitted within 2 hours from the onset of symptoms, in whom platelet activation is near maximal (3). Also coronary artery bypass induces a persistent increase in plasma levels of β-TG, even if revascularization was successful and symptoms were relieved (1). In a Japanese study (6) β-TG and PF4 plasma levels were similar in subjects with AMI or chronic coronary heart disease (CHD) or without coronary lesions. Few are the data concerning these platelet activation markers in young AMI patients. Our group previously examined the behavior of the hemorheological profile (7) and leukocyte rheological pattern (8) in young patients with AMI, and more recently (9) we determined the behavior of β-TG and PF4 (employing enzyme-linked immunosorbent assay methods) in 49 subjects (46 men and 3 women, mean age 38.8 ± 6.8 years; range 19–44 years) with the same clinical condition. The time interval between AMI onset and first examination (T1) was 13.0 ± 7.0 days and the patients were reexamined 3 months after the first evaluation (T2). All the patients were treated with angiotensin-converting enzyme inhibitors, statins, and platelet antiaggregation agents (aspirin or ticlopidine or clopidogrel). Our results showed that β-TG and PF4 were increased in AMI patients, compared with the control group, at T1 as well as at T2. In control subjects and in AMI patients, at either T1 or T2, there was a significant and positive correlation between βTG and PF4 (p < 0.001, for all the three groups) whereas no relationship was found between these platelet activation markers and platelet count. In conclusion, our data showed an increase of β-TG and PF4 at the initial stage of AMI, which was still present after 3 months and emphasized that the antiplatelet aggregation drugs did not modify platelet activation during the observation period. All these findings need further investigation considering that we enrolled young patients