Thromboglobulin Levels Research Articles

Effect of preoperative platelet alpha-granules secretion on hemostasis and blood loss in large joint arthroplasty

Background. Currently, it was proven that the role of platelets is not limited to the formation of a clot that stops blood loss and provides vascular wall repair. The importance of determining the functional characteristics of platelets in patients who underwent traumatic surgery is beyond doubt. However, there are few studies on this subject.
 Aim. To determine the effect of the preoperative platelet -granules secretory activity on the coagulation parameters and blood loss in total hip arthroplasty (THA).Material and methods. The study included 58 patients admitted to the hospital for primary total hip arthroplasty. All patients were divided into 2 groups according to the preoperative plasma level of the specific platelet -granules protein -thromboglobulin (-TG). The group with a low plasma level of -thromboglobulin (30 IU/ml) consisted of 30 patients, the group with a high level (30 IU/ml) 28 patients. Blood sampling was carried out 1 day before the operation, 30 minutes after surgery, on the 1st, 3rd, 7th 14th days after the total hip arthroplasty. The platelet count, -thromboglobulin, and D-dimer levels were determined. The plasma coagulation was examined by using thromboelastography. The volume of intraoperative blood loss was estimated by the gravimetric method, postoperative blood loss by drainage volume. Statistical analysis was carried out by using the Friedman, Wilcoxon, MannWhitney tests, calculating Spearman's rank correlation coefficient. All calculations were performed using the Statistica 8.0 software.
 Results. Before surgery, the group with a high level of -thromboglobulin showed significantly higher levels of D-dimer than the group with low levels: 132 [73; 191] ng/ml and 79 [37; 123] ng/ml (p=0.024); and shorter R times (time to onset of clotting): 13.7 [11.5; 15.3] min and 15.5 [13.0; 18.1] min (p=0.048), respectively. The maximum -thromboglobulin was observed at the end of the operation. The release of -thromboglobulin was significantly more intense in the group with low levels of -thromboglobulin than in the group with high levels: 35.6 [10.5; 78.0] IU/ml and 19.0 [0; 41.3] IU/ml, respectively (p=0.027). A relationship was found between -thromboglobulin levels and D-dimer concentration early after surgery (30 minutes), Spearman's correlation coefficients for groups with low and high levels of -thromboglobulin: r=0.57 and r=0.48, respectively (p 0.05 for both). Blood loss in the group with low -thromboglobulin levels was significantly higher than in the group with high levels: 850 [550; 1050] ml and 600 [500; 850] ml, respectively (p 0.05).
 Conclusion. In patients requiring total hip arthroplasty, an increase in the activity of platelet -granules secretion is associated with an increase in the activity of fibrin formation and a shortening of reaction time to onset of clotting; during surgery, the secretory activity of platelets is directly related to the activity of coagulation and affects blood loss volume.

Investigation of Platelet Functions in Chronic Myeloproliferative Disorders by Optical and Luminesance Method.

Background: Bleeding and thrombosis are common causes of morbidity and mortality in patients with myeloproliferative disorders (MPD). Qualitative platelet abnormalities are frequently found in these patients and range from platelet hypofunction as demonstrated by defective invitro platelet aggregation, acquired storage pool disease and/or platelet membrane defects, in addition to enhanced platelet aggregation, increased plasma beta thromboglobulin levels or shortened platelet survival. In this study we aimed to perform platelet aggregation studies by optical method (on platelet rich plasma=PRP) and luminesance method (on whole blood) in chronic myeloproliferative disorders.Methods:A total of twenty-five patients with MPD (17 chronic myeloid leukemia, 6 polycythemia vera, 2 essential thrombocytosis) were enrolled. Median age was 54,4 (29–76). Platelet aggregation was measured using the optic and luminesance method. The agonists used were adenosine diphosphate (ADP), arachidonic acid (AA) ristocetin and collagen. Platelets were considered to be hyperactive if at least one result (i.e. aggregation or ATP release with one agonist) was above the reference range, and hypoactive if at least one result (i.e. aggregation or ATP release) was below the reference range. Mixed hypo- and hyperactive platelets were considered present when at least one result (i.e. aggregation or ATP release) was below and above the reference range respectively.Results:Platelet aggregation test results by two methods in myeloproliferative disorders were shown in Table 1. The percent for detection of platelet function abnormality by luminesance method was found to be higher than the optic method and a significant difference was shown between two methods (p<0,05).Conclusion Our findings suggest that;1. Luminesance platelet aggregation study is more valuable than optic platelet aggregation study for invitro assessment of platelet function in patients with MPD. 2. The use of luminesance platelet aggregation study appears useful to select patients for antiplatelet therapy.Platelet aggregation test results in myeloproliferative disorders (n=25)NormalHypofunctionHyperfunctionMixTotal abnormalityLuminesance method1(%4)4(%16)8(%32)11(%44)24(%96)Optic method9(%36)11(%44)2(%8)3(%12)16(%64)

BLOOD LEVELS OF TGF??1 IN LIVER TRANSPLANT RECIPIENTS RECEIVING EITHER TACROLIMUS OR MICRO-EMULSIFIED CYCLOSPORINE

Transforming growth factor beta-1 (TGFbeta1) is pro-fibrotic in addition to being a potent immunosuppressive cytokine. Cyclosporine (cyclosporin A[CsA]) has been found to increase circulating TGFbeta1 levels in patients (1, 2). To determine whether tacrolimus (FK506) similarly increases TGFbeta1 we have measured TGFbeta levels in blood samples from liver graft recipients who were of known TGFbeta1-responder status. Sequential serum and plasma samples were obtained from liver transplant recipients in the UK trial of tacrolimus versus microemulsified CsA, with a follow up period of between 50 and 265 days. Twelve patients received CsA and 13 received tacrolimus. Active and total TGFbeta1 protein were measured and plasma beta thromboglobulin (betaTG) levels were used as an indirect indication of platelet-derived TGFbeta contamination of samples. We found no correlation between trough drug levels and active TGFbeta1 levels in serum of either set of patients. Plasma beta thromboglobulin was detected in platelet-depleted plasma samples, indicative of platelet damage before plasma separation. Neither CsA nor tacrolimus induced active TGFbeta1 blood levels in liver transplant recipients during a follow up period of < or = 265 days.

Increased in vivo platelet activation and reduced intravascular endothelium-derived relaxing factor and nitrate/nitrite production in patients with insulin-dependent diabetes mellitus

Limited information seems to be available about the role of reduced endothelial production of endotheliumderived relaxing factor (EDRF)-nitrate/nitrite (NO) in the pathogenesis of diabetic angiopathy in insulindependent diabetes. A report of urinary and serum nitrate/nitrite, glucometabolic parameters, endothelial and in vivo platelet activation markers of 22 insulin dependent diabetics (IDDM) patients are given. Urinary and serum nitrate/nitrite concentrations were reduced in IDDM. This was independent of disease duration, presence of angiopathy and the glucometabolic parameters. A significant and inverse correlation of nitrate/nitrite excretion with endothelial markers (von Willebrand factor, soluble thrombomodulin) was documented. Moreover, reduced nitrate/nitrite excretion was strongly associated with elevated plasmatic beta -thromboglobulin levels. EDRF-NO production is reduced in IDDM and this reduction correlates with endothelial damage. Decreased nitrate/nitrite excretion may also influence in vivo platelet function, which results in increased in vivo platelet activation and suggests that the reduced intravascular production of EDRF-NO might play a role in the pathogenesis of angiopathy in IDDM.

Filling a Dialysis Circuit with Albumin Does Not Prevent Platelet Activation During Hemodialysis: In Vivo Study

The aim of our prospective clinical study was to evaluate whether filling a dialysis circuit with albumin before hemodialysis (HD) can prevent platelet activation during the procedure. Eight patients with chronic HD participated in the study, each dialyzed first with albumin and a week later without it. All other parameters of the HD procedure were unchanged (cellulose acetate hollow fiber dialyzer, blood flow of 300 ml/min, and low dose heparin). Before HD with albumin, 6.7% human albumin in saline was recirculated in the dialysis circuit for 10 min at a flow rate of 100 ml/min, and infused into the patient. We found a significant increase in the beta-thromboglobulin levels during both procedures. We found no difference in plasma coagulation system activation measured by fibrinopeptide A concentration. Neither was there any difference in the macroscopic antithrombotic activity assessed at the end of HD by measuring the volume of clots in the arterial and venous bubble trap and by counting the number of clotted fibers in the dialyzer. It seemed that filling the dialysis circuit, which had a cellulose acetate dialyzer, with human albumin did not improve its thrombogenicity.

Thromboembolism in inflammatory bowel disease: role of platelets.

Patients with inflammatory bowel disease are susceptible to thromboembolism and recently small vessel thrombosis has been implicated as an aetiological factor in Crohn's disease. This study therefore investigated platelet function in 104 patients with inflammatory bowel disease of whom eight had previous thromboembolism. Thirty five patients had reproducible spontaneous platelet aggregation of more than 30% (0 in controls) (p < 0.0001). A further 20 patients showed hypersensitivity of platelets to low concentrations of aggregating agents (p < 0.001). Plasma thromboxane B2 and beta thromboglobulin levels were significantly higher than controls (p < 0.001 and p < 0.001), but platelet lifespan studies were normal. There was no correlation with disease activity. Patients with inflammatory bowel disease have abnormal platelet activity, which may contribute to the inflammatory process.

Plasminogen Activators, Plasminogen Activator Inhibitors and Markers of Intravascular Coagulation in Pre-Eclampsia

In pre-eclampsia (PE), reduced levels of plasma urokinase-like plasminogen activator (u-PA) and plasminogen activator inhibitor-2 (PAI-2), and increased levels of plasma tissue-type plasminogen activator (t-PA) antigen were seen. The majority of moderate and severe pre-eclamptic women (7 out of 10) ended up with pre-term delivery as compared with 2 out of 11 who went on to term. Patients with moderate and severe PE had significantly lower levels (mean +/- SD, ng/ml) of PAI-2 (58.4 +/- 34.9) and u-PA antigen (1.61 +/- 0.62) as compared to those with mild PE (95.6 +/- 39.3 and 1.61 +/- 0.62 and 2.12 +/- 0.61, respectively). Significantly raised t-PA antigen (14.6 +/- 5.7 ng/ml) was seen in moderate and severe PE as compared with mild PE (9.9 +/- 3.4 ng/ml). PAI-1 activity was significantly raised only in moderate and severe PE as compared with normal pregnancy. There were no significant differences in thrombin-antithrombin-III complexes, D-dimer and beta-thromboglobulin levels between the PE group and normal pregnancy, although these parameters were above the non-pregnant levels. Platelets in PE were within the range found in normal pregnancy. It appears that measurements of plasma u-PA and PAI-2 levels in patients with PE may have prognostic value in determining the outcome of pregnancy in this pregnancy disorder.

Platelet function and conjugated diene concentrations in diabetic and non-diabetic survivors of acute myocardial infarction

The aim was to compare platelet function in diabetic and non-diabetic survivors of acute myocardial infarction and to relate it to an index of free radical activity in these patients. In vivo and in vitro indices of platelet function and diene conjugate molar ratios were measured in diabetic and non-diabetic infarct survivors on admission to hospital and sequentially for 72 h. The patients were 17 diabetics (age 61.9 years, range 32-74) and 12 non-diabetics (60.8 years, range 39-75) admitted to hospital with acute myocardial infarction confirmed according to WHO criteria. Agonist induced platelet aggregation, beta thromboglobulin levels, and linoleic acid 18:2(9,11)/18:2(9,12) molar ratios did not differ between diabetic and non-diabetic patients on admission. Concentrations of adrenaline producing 50% maximum platelet aggregation (EC50) in whole blood on admission were lower than non-infarct controls in both patient groups. The EC50 values in platelet rich plasma in both groups fell during the 72 h following admission (increases in platelet sensitivity). beta Thromboglobulin concentrations fell following admission in the diabetic group. Diene conjugate molar ratios were higher at 12 h and 24 h compared to admission in diabetic patients. Increases in diene conjugate ratios between admission and 24 h correlated with peak aspartate transaminase levels in both patient groups. No correlations were observed between platelet aggregation, beta thromboglobulin levels, or diene conjugate molar ratios. During 72 h following myocardial infarction there is a reduction in platelet activation in vivo and an increase in platelet sensitivity to exogenous agonists in vitro. Free radical generated isomers of linoleic acid increase in relation to infarct size, but are unrelated to platelet function. There were no differences in platelet function between diabetic and non-diabetic subjects.

Blood Coagulation and the Nephrotic Syndrome: Deficiency or Excess?

Normal hemostasis can be disrupted in patients with nephrotic syndrome. More commonly a thrombotic diathesis is seen but there are also sporadic reports of abnormal bleeding. These abnormalities ap...

9] Platelet interaction with artificial surfaces: in vitro evaluation

This chapter describes the in vitro evaluation of platelet interaction with artificial surfaces. The glass-bead-column method allows surface-induced platelet adhesion, aggregation, and secretion to be examined for any material that can be prepared in a bead form or coated onto glass beads by deposition from solution. Bead columns are exposed to flowing whole blood, anticoagulated with sodium citrate, and maintained at 37° temperature. Platelet retention is determined by comparing the number of platelets entering and leaving the columns. Platelet secretion is assayed by measuring extracellular serotonin and β -thromboglobulin levels in the effluent blood. Platelet lysis is monitored by measuring extracellular lactate dehydrogenase levels, and the relative effects of adhesion and aggregation are assessed by scanning electron microscopy. The passage of blood through columns packed with small polymer-coated glass beads is a severe test of platelet–surface compatibility because of the large surface area to blood volume ratio. A 2-mL column packed with 0.3-mm-diameter beads provides ∼300 cm 2 of surface area, which, at a point in time, is exposed to ∼0.5 mL of blood. This is equivalent to spreading a film of blood 17 pm thick on a flat surface and represents approximately one-tenth of the surface-to-volume ratio of a capillary bed.

A Prospective Study of Haemostatic Tests at 28 Weeks Gestation as Predictors of Pre-Eclampsia and Growth Retardation

A panel of haemostatic tests was performed on 400 primiparous women at 28 weeks to test whether one or more could predict the development of pregnancy complications. Fifteen women subsequently developed pre-eclampsia with significant proteinuria and 13 delivered growth retarded infants. There were no significant differences between mothers in the pre-eclampsia group and 22 randomly selected controls. A stepwise logistic discriminant analysis of the data did not produce a significant model. In the growth retarded group only beta thromboglobulin levels were significantly lower than in the controls (p less than 0.05), although in the logistic discriminant analysis the inclusion of both beta thromboglobulin and fibrin degradation products led to a borderline significant improvement in fit of the model. We conclude that the haemostatic variables studied are not significantly changed at 28 weeks nor clinically useful predictors of either pre-eclampsia or fetal growth retardation.

Anti-Hypertensive Drugs Non-Specifically Reduce “Spontaneous” Activation of Blood Platelets

Abnormal activation of blood platelets may be a contributory factor in the accelerated vascular disease which occurs in hypertension. We investigated the effects of lowering blood pressure in 12 patients with mild hypertension on several aspects of platelet function, initially in a placebo-controlled, double-blind, cross-over study with nisoldipine, and subsequently in the same patients comparing nisoldipine with the patients' usual anti-hypertensive therapy. Values were compared with those from an age, sex-matched control population. Seven hypertensive patients with renal failure were also studied. Administration of nisoldipine reduced ex vivo "spontaneous" aggregation of blood platelets significantly, and a similar significant effect was seen when blood pressure was lowered by the patients usual anti-hypertensive therapy. "Spontaneous" aggregation occurring in the control population was similar to that in the treated hypertensives. Blood platelet count, and aggregation in response to ADP and adrenalin were unaffected by treatment. Median plasma beta thromboglobulin levels were significantly higher in the untreated hypertensive patients (43 ng ml-1) than in the controls (30 ng ml-1), and there was a trend to reduced values for beta thromboglobulin on treatment of the hypertension. These results indicate that blood platelet activity is enhanced in hypertension and that function returns towards normal when blood pressure is lowered by treatment.

Efficacy of iloprost (ZK36374) versus aspirin in preventing heparin-induced platelet activation during cardiac operations

For patients with heparin-induced platelet activation, reexposure to heparin can result in profound thrombocytopenia, intravascular thrombosis, and hemorrhage. We compared the ability of aspirin to that of iloprost (ZK36374), an analogue of prostacyclin, in preventing heparin-induced platelet activation and thus permitting a cardiac operation in a patient with heparin-induced platelet activation. Despite abolishing thromboxane A2 synthesis, aspirin (4 mmol/L) failed to prevent either in vitro heparin-induced platelet aggregation (65.0% without versus 59% with aspirin) or carbon 14-serotonin release (81.8% without versus 59.7% with aspirin). In contrast, iloprost (0.01 mumol/L) prevented both in vitro heparin-induced platelet aggregation (65% without versus 5.0% with iloprost) and release (81.8% without versus 0% with iloprost). Consequently, a continuous infusion of iloprost was begun before administration of heparin, continued throughout cardiopulmonary bypass, and discontinued 15 minutes after administration of protamine. The whole blood platelet count (209,000/microliter) remained stable after intraoperative administration of heparin (238,000/microliter) and was 115,000/microliter after the operation. No spontaneous platelet aggregates were observed in samples of platelet-rich plasma after heparin administration, and no platelet transfusions were required. Plasma levels of platelet factor 4 rose from 27 to 725 ng/ml after heparin administration but then declined during bypass to 50 ng/ml. Beta thromboglobulin levels only rose from 92 to 496 ng/ml with administration of heparin. Fibrinopeptide A levels fell from 72 to 22 ng/ml after heparin and remained stable throughout bypass. The template bleeding time was 7.5 minutes preoperatively and 8.0 minutes postoperatively. The postoperative chest tube drainage (12 hours) was 475 ml, and platelets responded normally to adenosine diphosphate. In conclusion, iloprost but not aspirin completely prevented heparin-induced platelet activation in vitro. Furthermore, iloprost effectively prevented this syndrome clinically, which permitted a safe cardiac operation in this patient with heparin-induced platelet activation.

Beta thromboglobulin and alcohol consumption.

Beta Thromboglobulin plasma levels were measured in three groups of hospital patients; a control group (n = 13) of non-drinkers, and test groups of patients who from their medical history regularly consumed either moderate amounts (80-200G/24 hours n = 31) or large amounts (200G/24 hours n = 10) of alcohol. Significant differences were detected between the control group, and both groups of drinkers. A correlation was demonstrated between the amount of alcohol consumed and the plasma Beta Thromboglobulin. It is necessary to consider a patient's drinking habits when interpreting Beta Thromboglobulin levels.

Elevated beta thromboglobulin in peripheral venous blood of patients with acute myocardial ischemia: Direct evidence for enhanced platelet reactivity in vivo

Levels of beta thromboglobulin, a platelet-specific protein, in platelet-poor plasma from peripheral venous samples of patients with acute myocardial ischemia were measured in order to obtain direct evidence for enhanced platelet reactivity in vivo in these patients and to determine the value of beta thromboglobulin assay in studying platelet reactivity in patients with ischemic heart disease. The normal beta thromboglobulin concentration in peripheral venous plasma, determined from normal volunteers and patients without known ischemic heart disease or disorders associated with enhanced platelet destruction (control group without platelet destruction), was 30.0 ± 12.6 ng/ml ( mean ± standard deviation) (range 10 to 59). The mean beta thromboglobulin level in hospitalized patients with chest pain judged not to be due to acute myocardial ischemia was 33.7 ± 12.0 (range 11 to 65). Patients with deep venous thrombosis, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic purpura provided a control group of patients with enhanced platelet destruction; the beta thromboglobulin level in this group was 131.0 ± 12.6 ng/ml (range 38 to 250). Elevated beta thromboglobulin levels were observed in 4 (16 percent) of 25 patients with stable angina pectoris (mean 45.0 ± 22.6 ng/ml, range 22 to 125), in 23 (59 percent) of 39 patients with unstable angina pectoris (mean 83.2 ± 73.7 ng/ml, range 14 to 910) and in 12 (80 percent) of 15 patients with acute myocardial Infarction (mean 118.5 ± 66.2 ng/ml, range 30 to 420) on one or more occasions during hospitalization. The mean values of patients with platelet destruction in the control group (p <0.001), patients with acute myocardial infarction (p <0.005) and patients with unstable angina pectoris (p <0.025) were significantly elevated with respect to values in patients without platelet destruction in the control group. The beta thromboglobulin levels of patients with acute myocardial infarction generally remained elevated during the first 3 to 4 hospital days. Elevation of beta thromboglobulin levels in patients with acute myocardial ischemia provides direct evidence for enhanced platelet reactivity in these patients. However, the temporal relation of the elevated beta thromboglobulin values with clinical deterioration was imprecise, so that it can not be determined from this study whether the enhanced platelet reactivity was a cause or an effect of the acute myocardial ischemia in these patients. Assay of beta thromboglobulin appears to be suitable as an indicator of enhanced platelet reactivity in patients with ischemic heart disease. Its use obviates many of the difficulties in interpretation of the various in vitro analyses of platelet function and platelet survival studies.

Platelet function in hypertension and effect of therapy

Platelet function was evaluated in 10 hypertensive and 11 normal subjects. In the placebo phase, the plasma beta thromboglobulin level (an index of platelet activation in vivo) was significantly (p <0.01) higher in the hypertensive than in the normal subjects; other tests of platelet function gave similar results in the two groups. After control of blood pressure with lofexidine (a centrally acting imidazoline derivative), plasma beta thromboglobulin levels decreased in 9 of the 10 hypertensive patients, but increased in one who showed no change in blood pressure. These studies suggest that enhanced platelet activation in primary hypertension may be associated with increased vascular resistance.

Evaluation of β thromboglobulin levels in cancer patients : Effects of antitumor chemotherapy

Evaluation of β thromboglobulin levels in cancer patients : Effects of antitumor chemotherapy

PLASMA-THROMBOGLOBULIN CONCENTRATIONS IN DIABETES MELLITUS

Abnormally high plasma-concentrations of the platelet protein thromboglobulin were demonstrated in a group of 72 diabetic patients. The highest concentrations were found in patients with clinical evidence of tissue damage. Many diabetic patients without such complications have elevated thromboglobulin levels, and this blood abnormality may pre-date recognisable clinical lesions.