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At least 433 records · Page 24Linked to original sources
PubMed1983

Controlled trial of ancrod in ischemic stroke.

In a randomized, single-blind study, 30 patients with acute ischemic stroke were treated with either low-molecular weight dextran and mannitol alone (group A, mean age, 63.3 +/- 11.8 years, n = 15) or in combination with the viper venom enzyme ancrod (group B, mean age, 67.9 +/- 7.6 years, n = 15). Lowering of plasma fibrinogen levels to 100-130 mg/dL with ancrod resulted in a significant reduction of the apparent blood viscosity, ie, of 37% at a shear rate of 0.03 s-1, compared with only 7% in group A. Fibrin degradation products increased considerably from 3.1 +/- 0.4 to 154.3 +/- 31.6 mg/L on day 3, while plasminogen decreased from 98.2% +/- 2.0% to 79.8% +/- 2.9% in group B. Global coagulation and platelet function tests were not influenced by either treatment. Neurological score improved by 1.1 arbitrary units (AU) in group A and by 2.6 AU in group B. Five patients in group A and two in group B died during the first two weeks. This preliminary study indicated a slightly better outcome in the ancrod treated patients. The beneficial effect may be due to the anticoagulative and fibrinolytic activity of ancrod rather than its effect on blood viscosity.

Ancrod↗
PubMed2007

Platelet GPIIb/IIIa antagonist, XV459, in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a serious, immune-related complication of heparin therapy. One of the most severe manifestations of HIT is the development of thromboembolic events, which is based on platelet activation and aggregation caused by HIT-associated antibodies. Therapeutic options for patients with HIT are limited despite advancement toward the development of alternative (nonheparin) anticoagulants, such as direct thrombin inhibitors and indirect anti-factor Xa agents. Platelet GPIIb/IIIa receptor antagonists have been shown to be the final common pathway for platelet aggregation regardless of the use of activator or anticoagulant. In this study, the ability of a novel platelet GPIIb/IIIa antagonist, a free acid form of roxifiban (XV459), to block platelet activation/aggregation in response to highly characterized heparin-PF4 antibody-positive plasma/heparin was examined using light transmittance aggregometry, serotonin release, and (125)I-fibrinogen binding assays to human platelets. XV459 at 20 nM maximally inhibited (P < 0.001) the platelet-activation/aggregation responses as mediated by the HIT antibody-positive plasma (in the presence of therapeutic heparin concentrations). Compared with controls, both HIT antibodies/heparin and TEAC (a mixture of thrombin [0.1 IU/ml], epinephrine [1 microg/ml], arachidonate [0.1 mM], and collagen [10 microml]) resulted in significantly higher levels of fibrinogen binding to human platelets (5-7-fold increase; P < 0.001). Concentration-dependent profiles of XV459 on the mean percent inhibition of (125)I-fibrinogen binding in the presence of HIT antibodies and TEAC were achieved ( approximately 50% inhibition at 10 nM XV459). The platelet GPIIb/IIIa receptor antagonist (XV459) might be of potential benefit in the management of thrombotic thrombocytopenia produced by heparin and/or related glycosaminoglycans.

Amino Acids↗
PubMed1989

Hermansky-Pudlak syndrome: correction of bleeding time by 1-desamino-8D-arginine vasopressin.

The effect of the synthetic vasopressin derivative 1-desamino-8D-arginine vasopressin (DDAVP = desmopressin) on bleeding time was studied in three patients with Hermansky Pudlak syndrome. A good response was observed in this type of storage pool disease. DDAVP might be useful in managing the bleeding disorder found in patients with the Hermansky-Pudlak syndrome.

Adolescent↗
PubMed1988

Hydroxyethyl starch: an alternative to plasma for postoperative volume expansion after cardiac surgery.

Hydroxyethyl starch (HES) is a recently developed synthetic volume expander. Forty patients undergoing coronary artery surgery were randomized to receive either HES or plasma protein fraction (PPF) as non-blood volume replacement according to standard haemodynamic criteria. The two groups were comparable in all respects. The median colloid use in the first 24 h was 950 ml (range 500-1500) in the HES group and 975 ml (350-2000) in the PPF group (not significant). There was no difference in blood use, urine output or blood loss between the two groups. Tests of coagulation showed the postoperative changes usual in cardiac surgical patients. There was no difference between the two groups in thrombin time, prothrombin time, activated partial thromboplastin time, or fibrinogen concentration. Similarly, tests of platelet function and Factor VIII and von Willebrand Factor activity showed no difference between the two groups. We conclude that HES is a safe and effective volume expander, and its relative lack of expense and ease of availability make its routine use after cardiac surgery an attractive proposition.

Adult↗
PubMed2001

A comparative study of light transmission aggregometry and automated bedside platelet function assays in patients undergoing percutaneous coronary intervention and receiving abciximab, eptifibatide, or tirofiban.

Platelet inhibition is central to the efficacy of glycoprotein (GP) IIb-IIIa antagonist therapy, but is not routinely measured during percutaneous coronary intervention (PCI). Data directly comparing the antiplatelet effects of these agents are also limited. Therefore, we compared ex vivo platelet function by standard light transmission aggregometry (LTA) and two automated bedside platelet function assays in 36 patients undergoing PCI with GP IIb-IIIa inhibitors. At baseline and 10 min following clinically recommended bolus and infusion of abciximab (0.25 mg/kg, 0.125 microg/kg/min), eptifibatide (180 microg/kg, 2 microg/kg/min), or tirofiban (10 microg/kg, 0.1 microg/kg/min), we measured 20 microM ADP- and 1.9 mg/mL collagen-induced platelet aggregation using LTA. Platelet function was also assessed using the bedside Accumetrics Ultegra-Rapid Platelet Function Assay (RPFA) and the Xylum Clot Signature Analyzer (CSA). The degree of platelet inhibition, as assessed by LTA, varied significantly between the clinically recommended doses of these GP IIb-IIIa antagonists. RPFA measurements agreed closely with LTA for abciximab, but tended to overestimate the degree of platelet inhibition for small molecules. CSA demonstrated profoundly inhibited shear-induced platelet function, but lacked sensitivity to discriminate between agents. These findings may have implications for the results of trials comparing the efficacy of these agents in patients undergoing PCI.

Abciximab↗
PubMed2001

Use of ICHOR-platelet works to assess platelet function in patients treated with GP IIb/IIIa inhibitors.

Platelet glycoprotein GP IIb/IIIa inhibitors have been recently approved for use in treating patients with acute coronary syndromes and those undergoing PCI. The purpose of this study was to assess the feasibility of using a new device, the ICHOR platelet works, to detect platelet inhibition in patients undergoing PCI and treated with abciximab or tirofiban. The study was conducted at Baylor College of Medicine, Houston, Texas. Thirty patients undergoing PCI and treated with abciximab (n = 10) or tirofiban (n = 20) are included. Blood samples were obtained before, at 30 min, at 4 hr, and at 12 hr after starting the GP IIb/IIIa inhibitors and 2 hr after discontinuation. Baseline studies revealed > 95% platelet aggregability in all patients after exposure to ADP (20 microM). After starting tirofiban, 82%, 83%, and 82% of platelets were inhibited at 30 min, 4 hr, and 12 hr. Platelet inhibition decreased to 43% 2 hr after discontinuation of tirofiban. Similarly, ICHOR platelet works detected 91%, 92%, and 85% platelet inhibition at 30 min, 4 hr, and 12 hr after starting abciximab, respectively. Platelet inhibition decreased to 73% 2 hr after discontinuation. The ICHOR platelet works is a promising, simple, and rapid bedside method that may have clinical utility in assessing platelet inhibition in patients treated with GP IIb/IIIa inhibitors. Cathet Cardiovasc Intervent 2001;53:346-351.

Abciximab↗
PubMed1989

Correlated measurement of platelet release and aggregation in whole blood.

We have used a technique for the simultaneous measurement of platelet activation and aggregation in whole blood using two-color immunofluorescence and flow cytometry to study the relationship between the release reaction and aggregation. A monoclonal antibody specific for the alpha granule membrane protein GMP-140 was used to measure the release reaction, and a monoclonal antibody specific for platelet membrane glycoprotein Ib (GPIb) was used to identify platelets and platelet aggregates. Aggregates were identified as particles expressing both levels of GPIb and size larger than that of resting single platelets. Anticoagulated whole blood was incubated with platelet agonists. At various times samples of the blood were removed and immediately fixed with paraformaldehyde. Blood that had been anticoagulated with ethylenediamine tetraacetic acid showed progressive release of platelets but little or no aggregation. However, blood anticoagulated with citrate or heparin showed correlated release and aggregation. The degree of aggregation was greater in heparin than in citrate. The expression of GPIb and GMP-140 increased in direct proportion to the size of the aggregates. Aggregates were observed varying in apparent diameter up to approximately 20 microns. During prolonged incubation there was progressive disaggregation of adenosine diphosphate (ADP)-induced aggregates. After disaggregation the proportion of GMP-140 negative single platelets increased, indicating that both released and nonreleased platelets participated in the aggregation. There was little or no disaggregation of phorbol myristate acetate (PMA)-induced aggregates. The relatively small size and reversibility of platelet aggregates that we have observed in whole blood may be relevant to phenomena occurring in vivo and in extracorporeal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1989

[Megakaryocytic myelosis--clinical aspects, morphology and platelet function].

The study reviews 22 patients, aged between 19 to 73 years, with megakaryocytic myelosis. In the course of the disease 11 patients presented haemorrhagic manifestations, 12 patients thrombotic complications, and 6 patients the association of haemorrhage and thrombosis. The maximum platelet counts ranged from 524 to 2700 x 10(9)/l. The bone marrow showed a conspicuous megakaryocytic proliferation with polyploidy of the nuclei, giant forms and clusters. Marked alterations of erythro- and granulopoiesis were excluded. There was no evidence for a reactive thrombocytosis in any case. Patients with thrombocythaemia due to megakaryocytic myelosis (n = 14), with secondary thrombocytosis of various origin (n = 16), and a control group of healthy donors (n = 20) were investigated with respect to the aggregation behaviour and the total calcium content of blood platelets. In 9 of 14 patients with megakaryocytic myelosis platelet rich plasma did not respond to epinephrine (15 mumol/l), a concentration which induced at least weak aggregation in 14 of 16 patients with secondary thrombocytosis and also in healthy subjects. In patients with megakaryocytic myelosis the mean extent of aggregation induced by epinephrine, collagen or adenosine diphosphate was significant lower as compared to controls whereas in patients with secondary thrombocytosis in most cases this parameter did not differ significantly from that of controls. The total calcium content of platelets was significantly lower in both groups of patients as compared to controls. In 14 patients with megakaryocytic myelosis the concentration of the glycoprotein (GP) IIb-IIIa complex was estimated by crossed- and rocket-immunoelectrophoresis and found to be decreased in 8 of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Lack of platelet response to collagen associated with autoantibodies against glycoprotein (GP) Ia/IIa and Ib/IX leading to the discovery of SLE.

An increased bleeding time and a prolonged APTT (activated partial thromboplastin time) observed in a 48-year-old woman led to the discovery of SLE confirmed by immunological tests. Platelet function and analysis of membrane glycoproteins revealed an isolated impaired collagen induced platelet aggregation and allowed the detection of autoantibodies directed against GpIa/IIa and GpIb/IX.

Antigens, CD↗
PubMed2005

The effect of glycoprotein IIIa PIA 1/A2 polymorphism on the PFA-100 response to GP IIb IIa receptor inhibitors-the importance of anticoagulants used.

Antithrombotic drugs including glycoprotein (GP) IIb IIIa receptor inhibitors have significantly reduced ischaemic events in coronary disease. Variability in the response to GP receptor inhibitors has been observed both with healthy individuals and in clinical studies. One single nucleotide polymorphism on GP IIIa (PI(A1/A2)) correlates with increased risk for cardiovascular events in many studies. In this study we investigated whether this polymorphism associates with individual differences in the response to GP IIb IIIa receptor inhibitors in healthy individuals. Fresh blood samples were collected randomly from individuals without a history of coronary disease. Blood samples were anticoagulated with either sodium citrate or with PPACK. The ability of different GP IIb IIIa receptor inhibitors (tirofiban, eptifibatide and abciximab) to inhibit platelet aggregation was investigated using a commercial PFA-100 analyser. At baseline, the function of platelets with different PI(A) genotypes did not differ from each other. With sodium citrate anticoagulated samples, tirofiban prolonged the closure time slightly more rapidly when platelets with PI(A 2 A 2) genotype were used than with other genotypes (p<0.05) both on epinephrine-collagen and ADP-collagen coated membranes. With eptifibatide or abciximab no differences were observed. If an anticoagulant not affecting Ca(2+) concentration (PPACK) was used, no differences were observed between different GP IIIa genotypes and the ability of any of the GP IIb IIIa receptor inhibitors to prolong the closure time. The effect of tirofiban and eptifibatide was significantly affected by the anticoagulant used (p<0.001), whereas abciximab functioned equally regardless of the anticoagulant. Glycoprotein IIIa PI(A2) allele has been found in many studies to associate with risk of thrombosis. In healthy controls the function of GP IIb IIIa receptor inhibitors on platelets with different PI(A) genotypes was modified by anticoagulants used. PI(A) polymorphism does not explain the interindividual variance in the response to GP IIb IIIa receptor inhibitors in healthy individuals. The study, however, demonstrates the importance of the anticoagulant used in in vitro studies and the important role of Ca(2+) concentration with tirofiban and eptifibatide, but not with abciximab.

Adult↗
PubMed2006

The role of aspirin resistance on outcome in patients with acute coronary syndrome and the effect of clopidogrel therapy in the prevention of major cardiovascular events.

BACKGROUND: Aspirin resistance may increase up to more then threefold the risk of major cardiovascular events (MACE) in patients with stable coronary artery disease. AIM: The aim of our study was to determine; the prevalence of aspirin resistance in patients with acute coronary syndromes, the role of aspirin resistance on outcome in the follow-up and the effect of clopidogrel therapy in the prevention of MACE in aspirin resistant subjects. MATERIAL AND METHODS: We detected the prevelance of aspirin resistance in 105 patients with acute coronary syndrome. Platelet functions were analyzed in Platelet Function Analyzer (PFA)-100 (Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and collagen and/or ADP (Col/ADP) cartridges. Primary end points of the study were myocardial infarction, unstable angina, cardiac death. RESULTS: 19% (n = 20) of patients were aspirin resistant by PFA-100. In the follow-up, MACE occured in 9 patients (45%) with aspirin resistance and in 10 patients (11.7%) with aspirin sensitive platelet aggregation (p = 0.001). Multivariate analysis showed that aspirin resistance was an independant predictor of MACE. The prevalence of MACE in patients who were on clopidogrel treatment for 12 months were lower compared to those who were on a clopidogrel treatment for the first six months (p = 0.040). CONCLUSIONS: We determined that the MACE risk in patients with acute coronary syndromes having detected aspirin resistance, was higher at statistically significant levels compared to patients having aspirin sensitive platelet aggregation. Our results showed that aspirin resistance, was an independant predictor of MACE in patients with acute coronary syndrome.

Angina, Unstable↗
PubMed1984

Prolonged bleeding time.

The bleeding time is the most frequently used test of platelet function. This review of the literature relating to the bleeding time outlines the causes and management of prolonged bleeding time. The bleeding time appears to have its greatest utility in evaluation of a patient with active bleeding or one with a well-documented bleeding history. It should not be used as a substitute for a clinical history, since there is insufficient information available to calculate its sensitivity, specificity, or predictive value with regard to peri- or postoperative hemorrhage.

Aspirin↗
PubMed1991

Circulating activated platelets in myeloproliferative disorders.

Platelet activation in patients with myeloproliferative disorders is often suggested by increased platelet alpha-granule secretion and an acquired storage pool defect of dense granules. To determine whether activated platelets circulate in patients with chronic myeloproliferative disorders, we evaluated the binding of monoclonal antibodies against activation-dependent epitopes on resting platelets (P 12, CD 63, and CD 62) in 12 patients with prominent megakaryocytic proliferation (8 patients with essential thrombocythemia, 2 with chronic myeloid leukemia, and 2 patients with polycythemia rubra vera). In addition, platelet aggregation in response to collagen, adenosine diphosphate, platelet activating factor, and agglutination with ristocetin was investigated. In 3 patients there was an increased percentage of platelets binding at least 1 activation marker. In 2 other patients, a trend towards increased antibody binding was observed. Binding of the antibody to thrombospondin (P 12) was related to expression of the GMP 140 protein (CD 62, r = 0.76, p = 0.004). There was no correlation of platelet aggregation defects in vitro to increased expression of platelet activation markers or to thrombohaemorrhagic complications. However, circulating activated platelets were detected in three out of five patients with a history of bleeding or thrombotic complications. The results of this preliminary study suggest that some but not all patients with myeloproliferative disorders showed increased amounts of circulating activated platelets. The relation of bleeding and thrombotic complications to the expression of activation-dependent epitopes on platelets in myeloproliferative disorders requires further investigation.

Adult↗
PubMed1994

The in vitro pharmacological profile of SK&F 106760, a novel GPIIB/IIIA antagonist.

The properties of SK&F 106760 [N alpha-acetyl-cyclo(S,S)-cysteinyl-N alpha-methyl-arginyl-glycyl-aspartyl-penicillamine-amide] as a GPIIb/IIIa antagonist have been studied in vitro and compared with those of the parent molecule, Ac-RGDS-NH2. Ac-RGDS-NH2 inhibited biotinylated fibrinogen binding to purified human GPIIb/IIIa immobilized on plastic microtitre plates with a Ki of 530 +/- 73 nM. In canine platelet rich plasma Ac-RGDS-NH2 produced a concentration related inhibition of adenosine diphosphate-induced platelet aggregation following preincubation for 3 min with an IC50 of 91 +/- 1 microM. However, incubation in platelet rich plasma for 3 hr abolished the activity of Ac-RGDS-NH2. SK&F 106760 inhibited biotinylated fibrinogen binding to purified human GPIIb/IIIa immobilized on plastic microtitre plates with a Ki of 477 +/- 57 pM. SK&F 106760 inhibited adenosine diphosphate-induced platelet aggregation in human platelet rich plasma with an IC50 of 230 +/- 60 nM but did not inhibit the von Willebrand Factor receptor (GPIb/IX)-mediated platelet agglutination produced by ristocetin. In canine platelet rich plasma SK&F 106760 inhibited aggregation produced by adenosine diphosphate, collagen and epinephrine/U-46619 with IC50 values of 355 +/- 35, 260 +/- 20, and 490 +/- 90 nM, respectively and in gel filtered platelets inhibited thrombin-mediated aggregation with an IC50 of 188 +/- 10 nM. Preincubation of SK&F 106760 in platelet rich plasma for three hours had no significant effect on its ability to inhibit adenosine diphosphate-induced platelet aggregation. SK&F 106760 produced insurmountable inhibition of adenosine diphosphate-induced platelet aggregation in the presence of constant fibrinogen concentrations, but produced competitive inhibition of the concentration-response curve to fibrinogen in adenosine diphosphate-activated platelets with a Kb of 8.0 +/- 1.0 nM. Thus, SK&F 106760 is a potent, stable competitive GPIIb/IIIa antagonist with no detectable activity at the von Willebrand Factor receptor (GPIb/IX).

Amino Acid Sequence↗
PubMed1996

Factors that affect the size of platelet aggregates in epinephrine-induced activation: a study using the particle counting method based upon light scattering.

Platelet aggregate size was determined with a newly-developed platelet aggregometer, PA-100 (KOWA), which can quantitatively evaluate the size and number of platelet aggregates by means of the particle counting method based upon light scattering. Epinephrine-induced platelet aggregation consists of two phases, the former characterized by the formation of small-sized aggregates (less than 100 cells), which is followed by the phase of large aggregate formation with concomitant decrease in the number of small aggregates. These findings suggest that small aggregates fuse to form large aggregates. Effects of various inhibitors and antibodies directed against platelet membrane glycoproteins were evaluated on the size of platelet aggregates induced by epinephrine. Cyclooxygenase inhibitors, thromboxane A2 receptor antagonists, and a Na+/H+ exchanger inhibitor (ethylisopropylamiloride) inhibited the formation of large aggregates (more than 100 cells) but not that of small aggregates. Cytochalasin B, which interferes with microfilaments, suppressed large aggregate formation, whereas taxol, which reacts with microtubules, had no effects. Anti-GPIIb/IIIa monoclonal antibody (MoAb) inhibited both the formation of small and large platelet aggregates, while antibodies directed against GPIb, thrombospondin, P-selectin, or PECAM-1 had no effects on platelet aggregate formation. These findings, taken together, suggest that intracellular alkalinization, thromboxane A2 formation and microfilament rearrangement are prerequisites for large platelet aggregate formation. GPIIb/IIIa is involved in the formation of small as well as large aggregates, but a membrane glycoprotein(s) responsible for the transition of small aggregates into large aggregates awaits to be determined.

Arachidonic Acid↗
PubMed1994

Aprotinin effect on platelet function and clotting during cardiopulmonary bypass.

A variety of studies have been performed on the preservation of hemostasis by aprotinin during cardiopulmonary bypass (CPB). It appears that the mechanism of aprotinin to preserve hemostasis can be interpreted in different ways. Our previous studies suggested that preservation of platelet glycoprotein Ib (GpIb) antigen, and counteraction of heparin anticoagulation in the extrinsic clotting pathway might partly explain the preservative effect of aprotinin. A clinical study was therefore conducted to evaluate these effects during the use of low dose aprotinin. Improved agglutination by ristocetin (P < 0.05), and improved GpIb antigen expression (P < 0.05) during CPB showed better preserved platelet adhesive capacity in the aprotinin group than in the control group. Glycoprotein Ib antigen expression and the agglutination capacity with ristocetin during CPB were closely related (P < 0.05). Platelet GpIIb/IIIa antigen and adenosine diphosphate (ADP) aggregation were not significantly different between the aprotinin and control groups. Aprotinin had no effect on the extrinsic clotting pathway in the blood, since the thromboplastin clotting time was similar in both groups. These results indicate that the protection of platelet adhesive capacity during CPB is a main function of aprotinin, whereas no evidence was collected for enhanced extrinsic clotting by aprotinin during CPB.

Adult↗
PubMed1992

Estrogen-associated thromboembolism.

Most of the linkage of atherosclerosis and thrombosis with estrogens is epidemiologic in origin. Although the effects of estrogens on the mechanisms of hemostasis are wide ranging, many are benign; only a few may account for thrombus formation. Platelet function tests have provided extensive but contradictory data, and interpretation is limited because it is uncertain whether a rise in one or more of these parameters is a primary or secondary effect. The most consistent effects of estrogens on coagulation proteins are elevations of fibrinogen; factors II, VII, IX, X, and XII; protein C; and plasminogen. Although these elevations have been attributed to the estrogenic component in oral contraceptives, the progestogen concentration may also influence these increases. Among other coagulation proteins studied, the following are unaffected by oral contraceptive use: factors V, VIII, and XI; prekallikrein; and high-molecular-weight kininogen. In contrast, protein S values are decreased. The plasma concentration of plasmin inhibitor is unchanged, whereas both proteinase inhibitor and macroglobulin are significantly increased by oral contraceptive use. Cl esterase inhibitor is decreased in women taking oral contraceptives and correlates with the increase in Hageman factor. Antithrombin III is one plasma inhibitor for which a decrease in quantity and activity have been associated with a thrombotic tendency in humans. Although data on estrogen-associated changes in the quantity of antithrombin III have been conflicting, the ability of plasma to inhibit factor Xa is significantly reduced in a dose-dependent manner among pre- and postmenopausal estrogen users.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Variable inhibition of high-shear-induced platelet plug formation by eptifibatide and tirofiban under conditions of platelet activation and high von Willebrand release: a randomized, placebo-controlled, clinical trial.

BACKGROUND: Glycoprotein (GP) IIb/IIIa antagonists have become a mainstay for the treatment of acute coronary syndromes. Yet, they have rarely been evaluated under relevant pathophysiologic conditions, for example, high shear rates in the presence of physiologic calcium concentrations. We compared the efficacy of eptifibatide and tirofiban versus placebo on high shear-induced platelet plug formation in a model in which healthy subjects exhibit von Willebrand factor concentrations and platelet activation comparable to patients with acute coronary syndromes. METHODS: Thirty male volunteers received 2 ng/kg endotoxin and standard doses of eptifibatide, tirofiban, or placebo over a period of 5 hours in a randomized, double-blinded, placebo-controlled, double-dummy parallel-group trial. Platelet inhibition was measured with the Platelet Function Analyzer-100 (PFA-100) and the Ultegra method. RESULTS: Although bolus infusion of both GPIIb/IIIa antagonists inhibited high shear-induced platelet plug formation, continuous infusion of eptifibatide prolonged closure times more effectively than did tirofiban (P <.008). Interestingly, tirofiban had only placebo-like effects on platelet plug formation after 2 hours. However, when additional drug was exogenously added, closure time values were maximally prolonged in all cases. CONCLUSIONS: Standard doses, particularly of tirofiban, have limited impact on high shear-induced platelet plug formation at physiologic Ca(2+) concentrations.

Adolescent↗