Plasma beta-TG Research Articles

Systemic and transcardiac platelet activity in acute myocardial infarction in man: resistance to prostacyclin.

There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore an understanding of factors that influence platelet performance is important. This study was undertaken (1) to characterize during evolving myocardial infarction platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and (2) to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving myocardial infarction were studied. Twenty-two patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 min. In 15 patients with anterior myocardial infarction, transcardiac platelet function and response to PGI2 were studied. Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, were elevated three- and 10-fold. 6-Keto-prostaglandin F 1 alpha, the stable end product of PGI2, was less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets circulating during evolving myocardial infarction ("ischemic platelets") were hyperaggregable in response to ADP and relatively resistant to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic AMP and the cyclic AMP response to PGI2 were diminished. The platelet hyperreactivity, expressed by plasma beta-TG, platelet aggregation, and PGI2-induced inhibition of aggregation, was most intense early during infarct evolution and decreased with time. The increased platelet performance resulted in "platelet fatigue," indicated by decreased contents of beta-TG of the ischemic platelet and decreased TxA2 production in response to collagen. However, the ischemic platelet produced twice normal TxA2 in response to arachidonic acid (stimulus and substrate), demonstrating a heightened metabolic capacity. TxA2 was produced across the ischemic/infarcting compartment in 10 of 15 patients with anterior myocardial infarction. The antiplatelet effect of PGI2 was greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving myocardial infarction, characterized by a proaggregatory environment, heightened platelet reactivity in both the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequences of the data are that the patient in the acute phase of myocardial infarction may benefit from suppression of platelet function and requires significantly greater doses of PGI2 than normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Beta-Thromboglobulin in patients with breast cancer.

beta-Thromboglobulin (beta TG) plasma levels were determined in 52 female breast cancer patients at different stages and in 39 healthy controls (22 women and 17 men) of similar age distribution. Beta TG levels were high (mean +/- SD:61.6 +/- 59.1 ng/ml) in patients before any treatment compared to controls (mean +/- SD:21.2 +/- 7.4 ng/ml) and the difference was statistically significant (p less than 0.001). No correlation with disease stage was observed. No other coagulation parameters were abnormal except fibrinogen, which increased. Fibrinogen degradation products (FDP) also increased but only in metastatic patients. Chemotherapy appeared to induce a considerable decrease in initial values at the end of the first cycle without modifying the platelet count. In addition, an attempt was made to correlate the beta TG plasma level investigated serially for several months with disease evolution.

Measurement of platelet life-span in normal subjects and patients with myeloproliferative disease with indium oxine labelled platelets.

The use of 111Indium oxine as a platelet label for the performance of platelet life-span studies has been examined. Platelet life-span in normal subjects varied between 8 X 10 and 10 X 36 d. Patients with primary thrombocythaemia had clearly reduced platelet life-span whether or not they presented with vascular occlusion and this abnormality persisted after reduction of the platelet count to normal by busulphan therapy. Patients with similarly elevate platelet counts due to chronic granulocytic leukaemia or after splenectomy had platelet life-span values in the normal range. Plasma beta-TG levels could not be used to predict platelet life-span in these groups of patients. Measurement of platelet life-span using 111Indium labelled platelets is a useful technique in the examination of platelet function in occlusive vascular disease.

Study of platelet activation in migraine: control by low doses of aspirin.

Although platelet activation is known to occur during migraine attacks, the cause-effect relationship remains to be determined. This problem was approached by studying the possible occurrence of platelet activation in vivo in headache-free periods of subjects affected by common or classic migraine and, subsequently, by verifying the possibility of its pharmacological control through administration of a classic anti-aggregation drug such as aspirin (ASA). The plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4), indices of the occurrence of platelet activation in vivo, were therefore first assayed in both groups of migraine sufferers in the absence of therapy and then during the administration of aspirin (50 mg/daily). In the group of 15 patients affected by classic migraine, basal plasma levels of beta-TG and PF4 were significantly higher than control subjects. On the other hand, only beta-TG plasma levels were significantly higher in the group of 18 patients affected by common migraine. Patients suffering from classic migraine showed a high incidence of platelet activation (greater than 90%) in comparison with common migraine patients (approximately 33%). This suggests that platelet activation occurs in vivo in migrainous patients also during headache-free periods. Administration of aspirin to the patients affected by common and classic migraine caused a decrease in plasma beta-TG and PF4 concentration. Consequently, pharmacological treatment with aspirin in adequate dose may prove to be helpful in diminishing the vascular side-effects known to occur in migraine sufferers.

Clinical significance of beta-thromboglobulin in patients with high platelet count.

The aim of the study was to investigate the relevance of beta-thromboglobulin (beta tg) measurement in patients with thrombocytosis. We have, therefore, studied the level of plasma and platelet beta tg in 74 patients with high platelet count in addition to the evaluation of platelet aggregation and platelet serotonin (5-HT) content. The determinations of platelet serotonin content and aggregation are confirmed to be useful in the differentiation between primary and secondary forms of thrombocytosis. The mean plasma level of beta tg in patients with myeloproliferative disease was significantly raised, but the amount observed in subjects with secondary thrombocytosis is increased too. Considering the amount of beta tg in relation to whole blood platelet count (beta tg ratio), no difference was observed between all patients and controls. The beta tg ratio allowed the identification of a group of patients with an increased ratio and a decreased beta tg platelet content who showed the highest occurrence of thrombosis (66%).

Beta-thromboglobulin in inflammatory synovial fluid.

Activated platelets release substances which potentially can contribute to joint lesions in inflammatory arthritides. To elucidate a possible participation of platelets in inflammatory joint reactions, the concentrations of the platelet protein beta-thromboglobulin (beta-TG) were measured in 90 inflammatory synovial fluids. Seven percent of the patients with rheumatoid arthritis and none of the patients with other inflammatory joint diseases (e.g., Reiter's disease, reactive or crystal arthritides) had beta-TG concentrations in synovial fluid exceeding the upper normal range of plasma beta-TG. The absent or very modest signs of local platelet activation were contrasted by the pronounced neutrophilic and monocytic activation, as assessed by the measurements of some granule proteins: lactoferrin, myeloperoxidase, lysozyme, and ferritin. No correlation was found between these inflammatory cell markers and beta-TG. A positive correlation (p less than 0.001) was noted between beta-TG and beta 2-microglobulin, which appeared in particularly high amounts in rheumatoid arthritis. This correlation may reflect a disturbed permeability of synovial membrane for LMW proteins or a related activation of platelets and lymphocytes. The present results do not give any evidence of platelet activation playing a major role in proliferative or destructive processes in arthritis.

Platelets, Coagulation and Fibrinolysis in Patients with Diabetic Retinopathy

Twenty control subjects, 12 insulin treated and 10 non-insulin treated diabetics were studied. All diabetics had retinopathy documented by fluorescein angiography and fluorophotometry. Factor VIIIR:Ag and plasma fibrinogen concentrations were elevated in both diabetic groups, but more so in the insulin treated patients. Within this latter group the plasma fibrinogen was also correlated with the degree of retinopathy. Platelets separated on linear isosmolar Percoll gradients showed an increase in intraplatelet beta TG content and concentration and a slight increase in volume of the lightest platelets in the insulin treated diabetics. Plasma platelet factor 4 and antithrombin III concentrations were normal and plasma beta TG levels were elevated only in those patients with renal insufficiency. Platelet aggregometry was performed in 18 diabetic subjects and found to be normal. It is concluded that abnormalities of coagulation and platelets in diabetes are determined by metabolic factors rather than the severity of microvascular disease per se.

Platelet release and thromboxane synthesis in symptomatic coronary artery disease.

The incidence and significance of platelet activation in myocardial ischemia was evaluated by serial measurement of plasma thromboxane B2 (TXB2) and beta thromboglobulin (beta TG) in plasma and urine in 98 patients admitted to a coronary care unit with chest pain. All measurements were normal in the 26 patients with noncardiac chest pain. Mean plasma TXB2 and beta TG concentration, but not urine beta TG, were elevated in the 25 patients with myocardial infarction and the 47 patients with angina. The beta TG levels remained normal in 61% of the patients with angina or infarction. The TXB2 levels were significantly higher in patients with recurrent episodes of angina at rest than in those without ischemic episodes after admission. There was a weak correlation between plasma TXB2 and plasma beta TG (r = 0.20, p less than 0.01) and between plasma and urine beta TG (r = 0.31, p less than 0.01). Results indicate that platelets are frequently activated with myocardial ischemia or infarction. However, the measurement of beta TG and TXB2 is of limited value in detecting or differentiating myocardial ischemia from infarction and therefore lacks clinical value in the management of patients with ischemic heart disease.

Cerebral ischemia in young patients: it is associated with mitral valve prolapse and abnormal platelet activity in vivo?

The etiology of cerebrovascular disease (CDV) in young patients is difficult to establish if the common causes of a focal neurological deficit are excluded by appropriate investigations. Since in some observations prolapse of the mitral-valve (MVP), alterations of platelet function, or both have been linked with cerebral ischemic events, we studied the in vivo platelet release reaction and the incidence of MVP in 47 patients (12 males, 35 females) under 45 years of age with TIA or stroke of unknown cause and in an age- and sex-matched control group. The mean plasma beta-thromboglobulin (beta-TG) level of the patients (mean = 54.9 +/- 31.4 ng/ml) was significantly higher than that of the controls (mean = 20.6 /- 6.9 ng/ml, p less than 0.001). MVP was demonstrated in 13 of 47 patients in contrast to 4 of the controls (p less than 0.01). However, the beta-T levels of patients with MVP (n = 13, 52.9 +/- 25.5 ng/ml) did not differ from those of patients without MVP (n = 34, 55.7 +/- 33.7 ng/ml) significantly (p less than 0.4). Our results confirm that the incidence of MVP is higher in young patients with cerebral ischemia of unknown cause than in asymptomatic controls. The significantly elevated plasma beta-TG concentrations in the patient's group indicate an increased platelet activity in vivo. Since there was no significant difference between beta-TG levels of patients with and without MVP, the mitral-valve abnormality can not be the cause for the altered platelet activity.

Platelet aggregation and thromboxane A2 production after adrenergic stimulation in young healthy humans.

The effects of adrenergic stimulation on platelet aggregation (platelet aggregation ratio; PAR), beta-thromboglobulin (beta-TG) release and plasma thromboxane B2 (TxB2) levels were investigated in 25 healthy young volunteers. Adrenergic stimulation induced by cold application was checked by evaluating the changes in the calculated vascular resistance in the forearm. A prompt increase in platelet aggregates and plasma beta-TG and TxB2 concentrations was observed after adrenergic stimulation. PAR changed from resting values of 0.97 +/- 0.05 to 0.75 +/- 0.08 (p less than 0.001) at the end of cold application. At the same time, beta-TG plasma concentration increased from 32.09 +/- 19.64 to 135.48 +/- 37.97 ng/ml (p less than 0.001) and TxB2 plasma levels changed from 0.49 +/- 0.24 to 0.99 +/- 0.39 pmol/ml (p less than 0.001). TxB2 levels, but not PAR and beta-TG concentration came back to the resting values at the end of the observation period (10 min). Aspirin, as the lysine acetylsalicylate equivalent to 5 mg/kg i.v. of acetylsalicylic acid, although able to completely inhibit platelet cyclooxygenase failed to inhibit the plasma TxB2 increase induced by adrenergic stimulation. This strongly suggests that the increase in plasma TxB2 following adrenergic stimulation is of extraplatelet origin. Also beta-TG and PAR changes were not affected by aspirin administration.

Effect of Aspirin on Platelet 5-Hydroxytryptamine and Beta-Thromboglobulin Plasma Levels in Patients with Myeloproliferative Diseases

14 patients with myeloproliferative diseases (MD) showed low 5-hydroxytryptamine (5-HT) platelet content and high beta-thromboglobulin (beta-TG) plasma levels. This pattern could support the view that MD platelets undergo "in vivo" degranulation. A single dose of aspirin was unable to induce modifications of platelet 5-HT and plasma beta-TG, whereas 6 out of 14 patients treated over 7 days period with the drug showed a decrease but not normalization in their beta-TG levels. No modification of platelet 5-HT was obtained suggesting that the cause of dense bodies deficiency may lie in the production of abnormal platelets and not be related to "in vivo" degranulation.

Platelet aggregation and plasma levels of beta-thromboglobulin in diabetes mellitus.

In view of the tendency toward vascular complications in diabetes mellitus, we studied platelet aggregation and plasma beta-thromboglobulin (beta-TG) levels in 35 healthy controls, 25 non-diabetic patients with ischemic heart disease (IHD) and 85 diabetic patients. Blood platelets from diabetic patients showed no significant hyperaggregation induced by ADP, collagen or epinephrine, as compared with controls and non-diabetic patients with IHD, nor could be demonstrated significant differences in platelet aggregation between diabetics with diabetic microangiopathies and those without diabetic vascular complications. Significantly high levels of plasma beta-TG were observed in diabetics in comparison with those in controls and non-diabetic patients with IHD. Patients with diabetic microangiopathy had more significantly elevated beta-TG levels than diabetics without diabetic microangiopathies. Diabetics without diabetic microangiopathy had similar levels of beta-TG to those of controls and non-diabetic patients with IHD. High levels of plasma beta-TG in diabetics with diabetic microangiopathy seem to indicate a platelet hyperfunction in vivo due to diabetic vascular complications.

Plasma beta-thromboglobulin values in thrombocytopenic patients with acute leukemia.

Plasma beta-thromboglobulin (beta-TG) levels were measured in 14 healthy subjects and in 20 acute leukemia (AL) patients, newly diagnosed, with highly variable values for venous platelet counts. For healthy subjects the plasma beta-TG levels ranged 12-38 (mean 17) ng/ml. In this group of patients with AL, a highly significant positive correlation (P < 0.001) between the values for plasma beta-TG and venous platelet count was present. During a thrombocytopenic period, the plasma beta-TG concentraton was measured in nine of the AL patients immediately before and 10 to 12 hours after platelet transfusion therapy. Fourteen platelet transfusions were administered when the patient's highest temperature of the day was < 38.5 degrees C, and 18 when the highest temperature of the day was greater than or equal to 38.5 degrees C. The mean pre-transfusion and post-transfusion beta-TG values for the 14 platelet transfusions were 7 +/- 2 and 20 +/- 5 ng/ml, respectively. The corresponding means for the 18 transfusions given to febrile patients were 5 +/- 2 ng/ml and 11 +/- 2 ng/ml, respectively. Of the pretransfusion values, 11/14 and 14/18 were below the control range. We conclude that the plasma beta-TG values are considerably lower in thrombocytopenic patients than in subjects with normal platelet counts. Further work should provide reference values for plasma beta-TG over a wide range of venous platelet counts.

Plasma beta-thromboglobulin: differentiation between intravascular and extravascular platelet destruction

To elucidate the usefulness of beta-thromboglobulin (beta TG) in the differentiation of the mechanism of thrombocytopenia, plasma beta TG concentration was measured in one patient with amegakaryocytic thrombocytopenia, four patients with autoimmune thrombocytopenia (ATP), two patients with thrombotic thrombocytopenia (TTP), and one patient with thrombocytopenia secondary to disseminated intravascular coagulation (DIC). Plasma beta TG was not measurable in amegakaryocytic thrombocytopenia, was normal in ATP, and was increased in TTP and DIC. These data indicate that in thrombocytopenic patients, increased plasma beta TG concentration may result from intravascular platelet consumption with release of platelet constituents in contrast to extravascular platelet destruction by the macrophage-monocyte system.

Plasma ß-Thromboglobulin: Differentiation Between Intravascular and Extravascular Platelet Destruction

AbstractTo elucidate the usefulness of beta-thromboglobulin (beta TG) in the differentiation of the mechanism of thrombocytopenia, plasma beta TG concentration was measured in one patient with amegakaryocytic thrombocytopenia, four patients with autoimmune thrombocytopenia (ATP), two patients with thrombotic thrombocytopenia (TTP), and one patient with thrombocytopenia secondary to disseminated intravascular coagulation (DIC). Plasma beta TG was not measurable in amegakaryocytic thrombocytopenia, was normal in ATP, and was increased in TTP and DIC. These data indicate that in thrombocytopenic patients, increased plasma beta TG concentration may result from intravascular platelet consumption with release of platelet constituents in contrast to extravascular platelet destruction by the macrophage-monocyte system.

Beta-Thromboglobulin, platelet production time and pletelet function in vascular disease.

Plasma beta-thromboglobulin (beta TG) levels were measured in 103 healthy controls and 112 patients suffering from either peripheral vascular disease (PVD), or cerebrovascular disease (CVD) or deep vein thrombosis (DVT). Plasma beta TG was significantly elevated in 46 PVD patients and 24 recent DVT patients compared to controls, but did not differ significantly in 18 chronic DVT and 24 old CVD patients. In addition, heparin neutralizing activity (HNA) and platelet aggregation induced by adenosine diphosphate, 1-epinephrine and thrombin were compared in 33 out of the 46 PVD patients to 33 controls. The mean HNA was significantly shorter in the PVD patients than in controls. The rate and extent of platelet aggregation were increased in PVD patients compared to controls, but the difference was not statistically significant. Platelet production time (PPT) was measured in 20 controls, 35 PVD patients, nine chronic DVT and 12 chronic CVD patients; significantly shorter PPT was only observed in 14 patients with advanced PVD compared to controls, suggesting increased platelet consumption in these patients. All four assays (plasma beta TG, HNA, platelet aggregation and PPT) were performed in 25 patients; no correlation between the four tests was found in these patients suggesting that the tests were measuring various aspects of platelet function. These results suggest that in vivo platelet consumption as well as platelet aggregation and 'release reaction' are presumably enhanced in PVD and recent DVT patients and that plasma beta TG and PPT assays may be better and more specific indicators of in vivo platelet activation than in vitro platelet aggregation test.

Evidence for the platelet specificity of beta-thromboglobulin and studies on its plasma concentration in healthy individuals.

The concentration of normal human platelet beta-thromboglobulin (beta-TG) was measured in various washed organ samples by a radioimmunoassay. As only trace amounts were detected, beta-TG appears to be a platelet specific protein. Assay of beta-thromboglobulin in plasma samples from 180 normal individuals gave a range of 10--65 mg/ml. In the 10 subjects studied, plasma beta-TG concentration was related to platelet lifespan but not to turnover. The plasma beta-TG concentration rose with increasing age but did not correlate with the whole blood platelet count or the percentage of megathrombocytes. These results provide further substantial evidence that measurement of plasma beta-TG concentration is useful for assessing the participation of platelets in various disease processes.