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PubMed1986

Effects of verapamil and diltiazem on human platelet function.

In this study the antiplatelet properties of two calcium channel blockers, verapamil and diltiazem, were evaluated. In 20 random aspirin-abstaining donors, both diltiazem and verapamil (0.01-10 microM) reduced epinephrine-induced aggregation [46 +/- 6% (SE) inhibition] and demonstrated a dose-dependent inhibition of epinephrine-induced [14C]serotonin release (43 +/- 3% reduction). However, at equimolar concentrations, verapamil was twice as effective. Neither drug altered ADP, collagen, thrombin, or calcium ionophore-induced platelet aggregation or platelet granule secretion. Neither drug prevented formation of thromboxane B2 during secondary aggregation. Verapamil, but not diltiazem, increased the Kd of [3H]yohimbine binding from 2.03 to 46.99 nM without altering the calculated number of binding sites per platelet (124 sites/platelet). Supplemental calcium added to citrated platelet-rich plasma reversed both verapamil and diltiazem-induced inhibition of platelet aggregation. We conclude that, at the concentrations tested, both verapamil and diltiazem are specific inhibitors of epinephrine-induced platelet activation. Clearly, both agents may be acting by preventing epinephrine-induced increases in plasma membrane permeability to calcium. However, the greater potency of verapamil compared with diltiazem with only verapamil binding to alpha2-adrenergic receptors suggests that alpha-blockade represents a significant component of verapamil-induced platelet inhibition.

Benzazepines↗
PubMed1999

Use of the platelet histogram maximum in evaluating thrombocytopenia.

The purpose of this study was to compare the mean platelet volume (MPV) and the highest peak of the platelet volume distribution curve (maximum of the platelet histogram) with regard to their ability to discriminate between thrombocytopenia due to decreased platelet production or increased platelet destruction. A total of 156 children were studied. Twenty-eight had a diagnosis of idiopathic thrombocytopenic purpura (ITP) and 128 had a low platelet count due to decreased production. MPV and maximum of the platelet histogram were obtained by using the Coulter Counter Max M (Coulter Diagnostics, Hialeah, FL). A comparison of the sensitivity and specificity for the MPV and the maximum of the histogram has been made using the method of the receiver operating characteristic curves. The results show that the maximum of the histogram is superior to the MPV and is a highly effective test for the evaluation of thrombocytopenia. We recommend the use of the maximum rather than the MPV to help distinguish between ITP and thrombocytopenia secondary to decreased platelet production.

Adolescent↗
PubMed1997

Inhibition of platelet aggregation as a surrogate marker.

Using acetylsalicylic acid-dipyridamole, a combined thromboxane receptor antagonist-thromboxane synthase inhibitor, and a fibrinogen receptor antagonist as examples, this article discusses the predictive value of several methods that may be employed in the evaluation of antiaggregatory effects and their suitability as surrogate markers for the planning of patient studies. Platelet aggregation in various ex vivo tests and the effects of drugs on these tests were investigated using platelet aggregation in platelet-rich plasma and in whole blood, and in thrombus formation on a thrombogenic surface. Drug-induced inhibition of platelet aggregation is based on the modulation of metabolic processes or interactions at the membrane-receptor level. These effects must be assessed by methods adapted specifically to each mode of action, for example, mediator synthesis inhibition (cyclooxygenase), thromboxane receptor antagonism-thromboxane synthase inhibition, or fibrinogen receptor blockade. Thus a combination of both general and specific methods adapted to the respective mode of action of the test substance can serve as surrogate markers of drug efficacy for the efficient planning of clinical trials.

Animals↗
PubMed2001

A micromethod to measure platelet aggregation and atp release by impedance.

A standard electrode has been modified in order to detect platelet aggregation by impedance in small volumes of whole blood. The modified electrode was constructed to fit into a standard 0.5-ml cuvette normally employed for detecting platelet aggregation in platelet-rich plasma (PRP) on a Chrono-log Aggregometer (Haverford, PA). Whole blood samples were mixed 1:1 with saline and total volumes of 1 ml, 500 microl and 300 microl were tested. ATP release was recorded concurrently with aggregation by measuring the luminescence from the firefly luciferin-luciferase reaction. The modified electrode could detect aggregation in the 300- and 500-microl samples with the same efficiency as the 1-ml samples. ATP release in the 300- and 500-microl samples yielded equivalent levels of release as detected with the 1-ml samples. This electrode is well suited for evaluation of platelet function in research and clinical blood samples where only small volumes of blood are available.

Adenosine Triphosphate↗
PubMed2002

Clinical application of the PFA-100.

The PFA-100 (platelet function analyzer) is a relatively new tool for the investigation of primary hemostasis. Recent studies have shown its utility as a screening tool for investigating possible von Willebrand disorder (VWD) and various platelet disorders. More recently, the PFA-100 has been shown to be valuable in monitoring desmopressin acetate (DDAVP) therapy in both VWD and platelet disorders. The PFA-100 has also been evaluated in many other studies for its utility in assessing drug effects, for potential monitoring of antiplatelet medication (including aspirin), or for evaluation of overall primary hemostasis in various clinical disorders or during surgical procedures. This article reviews current findings and highlights the benefits and limitations of the clinical utility of the PFA-100. Ultimately, the greatest strengths of the PFA-100 are its simplicity of use and excellent sensitivity to particular hemostatic disturbances such as VWD, platelet disorders, and platelet-affecting medication. However, because it is thus a global test system, this also creates a significant limitation because the PFA-100 is not specific for, nor predictive of, any particular disorder. However, used appropriately, the PFA-100 can be considered a worthwhile addition to any hemostasis laboratory involved in the diagnosis or therapeutic monitoring of bleeding disorders and potentially of antiplatelet medication. This review should be valuable to both hemostasis scientists and clinical specialists.

Blood Coagulation Disorders↗
PubMed1983

Preeclampsia associated with hemolysis, elevated liver enzymes, and low platelets--an obstetric emergency?

A study was undertaken of 27 patients with severe preeclampsia who had hemolysis, liver enzyme elevation, and thrombocytopenia as described by Weinstein. In addition to this triad, all patients exhibited the symptoms and signs of pregnancy-induced hypertension by which the diagnosis is usually established. These patients were admitted to the hospital for strict bed rest. Patients who showed evidence of rapid maternal or fetal deterioration were delivered promptly. The remainder were managed without immediate delivery and with the institution of magnesium sulfate to prevent eclamptic seizures. Patients were monitored closely, and amniocentesis was performed to ascertain fetal lung status. If the lungs were mature, the infant was delivered. Attempting to delay delivery until a lecithin: sphingomyelin (L:S) ratio was mature resulted in only two infants developing respiratory distress syndrome (RDS); both had L:S ratios of less than 1.5 and were delivered for maternal indications. Maternal condition rapidly improved within 72 hours of delivery, and there was no persistence of thrombocytopenia or elevation of liver enzymes. Immediate delivery of preeclamptic patients who have thrombocytopenia and elevated liver enzymes may not be warranted. These findings suggest that the syndrome of hemolysis, elevated liver enzymes, and low platelets is not a separate entity, but merely a cluster of signs seen in some patients with hypertensive disorders in pregnancy.

Adolescent↗
PubMed1993

Hemodynamic effects of amrinone and colloid administration in children following cardiac surgery.

Amrinone was used as the sole vasoactive medication in 9 of 14 children (aged 5 months to 8.25 years) given the drug following open repair of congenital cardiac lesions. Four children received a concomitant dopamine infusion and one infant had the infusion stopped after 5 hours for low mean arterial pressure (49 mmHg). In the 10 children receiving only amrinone, cardiac index increased 21% (range, 0 to 94%) after a total loading dose of 4.5 mg/kg given over 1 hour. Four of 14 patients (29%) required dopamine infusions to maintain mean arterial pressure over 55 mmHg and in these children cardiac index increased from baseline and was maintained during the amrinone infusion. Preload was held constant by administration of whole blood or plasmanate during amrinone loading; a decrease in systemic vascular resistance index was seen resulting in a stable arterial blood pressure. Minimal chronotropic effect was seen and no arrhythmias occurred. The sole child with postoperative pulmonary hypertension had a beneficial decrease in pulmonary artery pressure, increase in cardiac index, and stable systemic blood pressure during amrinone use. Cardiac index changes during amrinone loading in these children were variable and less clearly related to serum levels than reported in adults. Pharmacokinetic analysis in 12 children showed a clearance of 3.4 mL/min/kg, a volume of distribution of 1.65 L/kg, and an elimination half-life of 5.75 hours. Decreases in platelet counts were seen in 6 children and platelet transfusion was needed in 1; thus, serial platelet counts should be monitored.(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗
PubMed2005

A new point-of-care method for monitoring anti-platelet therapy: application of the cone and plate(let) analyzer.

Recent studies suggest that anti-platelet agents are not equally effective in all individuals. We have developed a new method to evaluate the effect of anti-platelet drugs using the cone and plate(let) analyzer (CPA) test. The method is based on the ability of activators to reduce platelet adhesion under flow conditions. Treatment of a blood sample with arachidonic acid (AA) or ADP in vitro significantly decreased platelet deposition to a surface coverage (SC) of 2.1+/-0.4 and 1.3+/-0.6%, respectively, compared with the basic SC of 12.3+/-6.8%. The effect of AA was prevented by aspirin (SC 8.1+/-3.8%) and that of ADP was reduced by 2-methylthio-AMP, a P2Y12 ADP receptor inhibitor (SC 4.8+/-2.0%). Pre-incubation with AA of whole blood samples from untreated healthy volunteers resulted in a marked decline of SC (from SC 9.8+/-2.2 to 0.6+/-0.3%). In contrast, in volunteers treated with 100, 300, and 500 mg aspirin per day, AA (but not ADP) decreased SC only to 3.5+/-1.3, 4.4+/-1.7, and 4.1+/-2.0%, respectively (P<0.001 versus SC with AA before treatment). A good correlation was observed between the modified CPA and aggregometry (R2=0.55). In conclusion, the modified CPA test is a useful tool to evaluate the efficacy of anti-platelet therapy.

Adenosine Diphosphate↗
PubMed1999

Haemostatic disorders in nonsplenectomized and splenectomized thalassaemic children.

A group of 40 thalassaemic patients (20 splenectomized and 20 nonsplenectomized) from the Haematology Unit of Tanta University Hospital (age range: 3-14 years) were studied to identify the mechanisms by which haemorrhagic and thrombotic complications occur in thalassaemic patients. The patients' levels of protein C, antithrombin III and in vitro platelet aggregation in response to collagen were compared with those of 20 controls. The study suggests that thrombocytosis, increased platelet aggregation and decreased natural coagulation inhibitors (protein C and antithrombin III) in splenectomized thalassaemic children may be significant in thrombotic complications in such patients. Defective platelet aggregation and prothrombin activity in nonsplenectomized children may also give rise to haemorrhagic tendencies.

Adolescent↗
PubMed1988

Platelet regeneration time: a statistical approach.

The determination of platelet regeneration half-time (PRT t1/2) by measuring malondialdehyde after intake of acetylsalicylic acid is a simple nonisotopic method for the estimation of platelet survival. There is no available information concerning the populational distribution of PRT t1/2. Consequently, there is controversy about the utilization of parametric or nonparametric statistical tests in studies of PRT. In the present study, we demonstrate the closeness of the fit of log PRT t1/2 to the normal (Gaussian) distribution.

Aspirin↗
PubMed2003

[Platelet aggregation test: application in the control of antiplatelet aggregation in the secondary prevention of stroke].

INTRODUCTION: Stroke is the leading cause of death in Brazil. The risk of suffering a recurrent stroke is around 30% in 5 years. Antiplatelet therapy has been frequently used to prevent recurrent strokes without laboratory control. OBJECTIVE: To determine the value of the platelet aggregation test in the control of antiplatelet aggregation in the secondary stroke prevention. METHOD: Retrospective study from January 1990 to January 2001 with 189 patients with stroke that were followed up during this period with platelet aggregation curve. Patients with cardioembolic disease were excluded. Low aggregation rates of platelet aggregation activated by ADP and/or epinephrine lower or equal to 50% were considered. Patients were followed up for a period from one to six years to verify differences in stroke recurrence. RESULTS: Nine patients had had a recurrent stroke; 2,6% of the strokes occurred among the group with low aggregaton and 15,1% among the group with normal aggregation (0,03<OR<0,69, p<0,05). Most of the cases occurred in the second year after the first stroke. CONCLUSION: Platelet aggregation curve is a valid and a helpful laboratory test to therapeutic control of antiplatelet aggregation in secondary stroke prevention.

Female↗
PubMed1994

Inhibition of platelet aggregation by transdermal glyceryl trinitrate.

OBJECTIVE: To determine the optimum conditions for the demonstration of an antiplatelet effect of nitric oxide and to use these conditions to elucidate the effects of a transdermal glyceryl trinitrate patch on platelet aggregation in normal volunteers. METHODS: An open prospective crossover study. The effects of nitric oxide on platelet aggregation in whole blood and platelet rich plasma as stimulated by adenosine diphosphate and U46619 was assessed in the presence and absence of iloprost and MB22948. Optimum conditions for the demonstration of an antiplatelet effect of nitric oxide were then applied to whole blood from normal volunteers in the presence and absence of a transdermal glyceryl trinitrate patch. SETTING: University hospital. SUBJECTS: Eight normal volunteers. MAIN OUTCOME MEASURES: Platelet aggregation in the presence and absence of transdermal glyceryl trinitrate. RESULTS: The optimum conditions for the demonstration of an antiplatelet effect of nitric oxide in whole blood were collecting blood into a tube containing MB22948 and citrate and stimulating platelet aggregation with adenosine diphosphate in the presence or absence of iloprost. Using this method a significant effect of transdermal glyceryl trinitrate on platelet aggregation was shown (P < 0.03) in the presence and absence of iloprost. CONCLUSIONS: These results are consistent with an inhibitory effect on platelet aggregation of nitric oxide liberated by transdermal glyceryl trinitrate. Optimum test conditions are needed to show this effect. The clinical significance of the antiplatelet effect of transdermal glyceryl trinitrate is unknown.

Adenosine Diphosphate↗
PubMed2005

Resistance to antiplatelet therapy.

Cardiovascular mortality continues to be high and events continue to occur in patients taking antiplatelet medications. Aspirin and clopidogrel have become integral parts of management in patients with coronary artery disease and after percutaneous angioplasty. However, the platelet responses to aspirin and clopidogrel are not uniform. Diminished or lack of response to these agents has been termed aspirin resistance and clopidogrel resistance. These phenomena have tremendous clinical significance as together they may occur in more than 50% of all patients on chronic therapy with aspirin or clopidogrel. Postulated mechanisms of aspirin and clopidogrel resistance include alterations in genetic, pharmacokinetic, and platelet properties. There is a dearth of information in regard to their clinical significance, methods to test them, and strategies to treat them. Further research is necessary in these areas to identify these patients and treat them appropriately.

Angioplasty, Balloon, Coronary↗
PubMed1986

The preoperative bleeding time as a predictor of postoperative hemorrhage after cardiopulmonary bypass.

To determine whether the preoperative bleeding time, the most reliable indicator of in vivo platelet dysfunction, can prognosticate excessive postoperative hemorrhage and, hence, the need for infusion of platelet concentrations, we studied blood loss versus bleeding time in 43 patients undergoing coronary bypass grafting. There was no correlation between bleeding time and either fall in hemoglobin level (r = 0.04) or chest tube drainage (r = 0.004). In addition, bleeding time did not correlate with the number of units of platelet concentrate (r = 0.12) or packed red cells (r = 0.2) infused. The bleeding time, which has been recommended as an essential screening test before all cardiopulmonary bypass procedures, need not be performed as a preoperative screen in otherwise healthy patients with no history of bleeding abnormalities and a normal coagulation profile.

Bleeding Time↗
PubMed1993

Platelet serotonin is a mediator potentially involved in anaphylactic reaction to neuromuscular blocking drugs.

A platelet serotonin release test was performed on blood from 10 patients who had suffered from an IgE-dependent allergic reaction to a neuromuscular blocking drug. The results were compared with those of a leukocyte histamine release test. The upper limit of serotonin release induced by neuromuscular blockers was estimated to be 2.3% in non-allergic patients. The test was positive in six patients and was consistent with histamine release in five. Serotonin release induced by neuromuscular blockers comprised 2.9-25% of total platelet serotonin content. We conclude that serotonin is one of the mediators associated with histamine release during anaphylaxis to neuromuscular blockers. Platelet serotonin release tests may be useful for the investigation of anaphylactic responses to neuromuscular blocking drugs.

Adolescent↗
PubMed1982

Platelet adhesiveness to glass beads in liver disease.

Patients with liver disease have abnormal platelet function. We have investigated the retention of platelets to glass beads in fulminant hepatic failure, cirrhosis and normal controls. Glass bead retention was significantly increased in fulminant hepatic failure (91.5 +/- 4.8%, n = 10) compared with controls (80.2 +/- 8.5%, n = 10) whereas it was significantly reduced in cirrhosis (46.2 +/- 26.8%, n = 10). The increased platelet adhesiveness might predispose to the formation of platelet aggregates in the blood observed during charcoal haemoperfusion in patients with fulminant hepatic failure.

Acetaminophen↗