Acute Thrombus Formation Research Articles

TCT-442 Comparison of contemporary DES of different stent geometry and Absorb in a Swine Carotid – Jugular Thrombogenicity Shunt Model

Polymer coatings of drug eluting stents (DES) have been shown to offer a protective barrier against acute thrombus formation compared with bare metal stents (BMS). While this anti-thrombotic function has been assigned to contemporary DES utilizing permanent polymeric coatings, the impact of

Coronary Kinking in a Marathon Runner: A “Dangerous Liaison”?

We report the case of a 48-year-old male marathon runner, without any cardiovascular risk factor, referred to our hospital for an anterior ST-segment elevation myocardial infarction that occurred during endurance training. Coronary angiography showed thrombus in the mid segment of the left descending artery, localized just before a sharp angle of the vessel that produced a peculiar ‘‘kinking’’ of the coronary artery (Figure A), with preserved TIMI 3 flow. Successful manual thromboaspiration (Eliminate, TERUMO, Japan), together with abciximab bolus followed by 12-hour infusion, were performed with almost complete resolution of thrombus in the acute phase (Figure B). After 3 days, a new coronary angiography confirmed persistence of artery patency with complete resolution of thrombus (Figure C). This is an emblematic case allowing us to unravel a pathophysiological cause of acute coronary syndrome. Previous in vitro studies demonstrated that high-intensity exercise is able to induce platelet hyperreactivity and a hypercoagulable state mediated by the shear stress mechanism. In addition, systolic kinking of coronary artery, often associated with myocardial bridging, might cause ischemia through direct damage to the underlying endothelial cells. Furthermore, anatomic properties of myocardial bridging may predispose to myocardial infarction through the convergence of increased atherosclerosis at the entry site of the tunneled coronary segment. In our case, exercise-induced high heart rate, shortened diastolic perfusion time, increased contractility, compression of artery and increased flow velocity might have caused myocardial ischemia and locally impaired shear stress with subsequent acute thrombus formation. This case could represent a paradigm of ST-segment elevation myocardial infarction in which long-term antiplatelet therapy may be preferred over stent implantation. Figure.

TCT-382 Chronic Total Occlusions: Are They Truly Stable?

Background: Acute coronary syndromes (ACS) for ST elevation (STEACS) and non-ST elevation (NSTEACS) are known to be caused by acute coronary plaque disruption plus thrombus formation resulting in acute myocardial ischemia. Chronic, totally occluded (CTO) arteries are believed to represent a stable

Hazel Wilkinson

<h3>Introduction</h3> A new generation of carotid artery stents that use a dual micromesh layer to reduce embolic events during carotid artery stenting has recently been introduced. We aimed to analyze...

Neferine exerts its antithrombotic effect by inhibiting platelet aggregation and promoting dissociation of platelet aggregates

IntroductionNeferine, a kind of isoquinoline alkaloid, extracted from the seed embryo of Nelumbo nucifera Gaertn, has long been recognized in traditional medicine as a medicinal plant with various usages. Neferine has many biological activities, including anti-hypertensive, anti-arrhythmic, negative inotropic effect and relaxation on vascular smooth muscle. Although previous studies have reported its antithrombotic effect, the mechanisms by which it exerts antithrombotic effect have not been thoroughly studied. MethodWashed mice platelets and mice platelet-rich-plasma (PRP) were used to investigate the effects of neferine on platelet aggregation, secretion induced by various agonists and dissociation of agonist-formed platelet aggregates. Bioflux plates coated with collagen were used to investigate the effect of neferine on platelet adhesion and thrombosis in vitro. With collagen-epinephrine-induced acute pulmonary thrombus formation mouse model, the effect of neferine on thrombosis in vivo was also examined. ResultsNeferine, significantly and dose-dependently, inhibited collagen-, thrombin-, U46619-induced platelet aggregation in mice washed platelets, or ADP-induced platelet aggregation in PRP. Neferine treatment decreased platelet dense granule secretion initiated by collagen, thrombin and U46619. Also, Neferine dramatically and dose-dependently promoted the dissociation of platelet aggregates pre-formed by various agonists including collagen, thrombin, U46619 or ADP. Neferine can significantly reduce the area of mice platelets adhesion to the collagen and inhibit thrombosis in vitro. In collagen-epinephrine-induced acute pulmonary thrombus mouse model, neferine, at 6mg/kg, significantly attenuated thrombus formation. ConclusionsNeferine remarkably prevents thrombus formation by inhibiting platelet activation, adhesion and aggregation, as well as promoting disassembly of pre-formed platelet aggregates. The inhibitory effects of neferine on platelet activation might be relevant in cases involving aberrant platelet activation where neferine could be used as an anti-platelet and antithrombotic agent.

Rescue Treatment of Thromboembolic Complications During Endovascular Treatment of Cerebral Aneurysms

Acute intraprocedural thrombus formation complicating endovascular cerebral aneurysm treatment is often treated with intra-arterial or intravenous administration of thrombolytic agents or glycoprotein IIb/IIIa (GpIIb/IIIa) inhibitors. We sought to evaluate the morbidity and mortality associated with such treatments using a large multihospital database. Using the Premier Perspective Database, we examined outcomes for patients receiving endovascular coiling for ruptured and unruptured aneurysms requiring rescue therapy, defined as treatment with GpIIb/IIIa inhibitors and fibrinolytic therapy. We compared discharge status, length of stay, and complication rates across 3 groups: (1) patients receiving GpIIb/IIIa inhibitors only, (2) patients receiving fibrinolytic therapy only, and (3) patients receiving both GpIIb/IIIa inhibitors and fibrinolytics. Student t test was used to compare continuous variables, and Fisher exact test was used to compare categorical variables. Seven-percent (254/3627) of patients treated for unruptured aneurysms received rescue therapy. When compared with patients receiving GpIIb/IIIa inhibitors alone, patients receiving only fibrinolytics had significantly higher rates of discharge to institutions other than home (37.5% [9/24] versus 7.4% [15/201]; P<0.0001). Eight-percent of patients (338/4204) treated for ruptured aneurysms received rescue therapy. When compared with patients receiving GpIIb/IIIa inhibitors alone, patients receiving only fibrinolytics had significantly higher rates of mortality (26.0% [18/69] versus 14.5% [35/241]; P=0.02) and discharge to institutions other than home (59.4% [41/69] versus 36.5% [88/241]; P<0.0001). Pharmacological rescue therapy occurred in 7% to 8% of endovascular coiling patients with unruptured and ruptured intracranial aneurysms. Rescue therapy with thrombolytic agents resulted in significantly more morbidity and mortality than rescue therapy with GpIIb/IIIa inhibitors.

Prothrombotic markers in patients with acute myocardial infarction and left ventricular thrombus formation treated with pci and dual antiplatelet therapy

BackgroundThe aim of the present study was to compare circulating levels of selected prothrombotic markers in patients suffering acute myocardial infarction (AMI) with and without left ventricular (LV) thrombus.MethodsOne hundred patients with AMI treated with PCI on the LAD and dual antiplatelet therapy were included. LV thrombus formation was detected by echocardiography and/or MRI in 15 patients. Fasting blood samples were drawn 4–5 days (baseline), 6–7 days, 8–9 days, 2–3 weeks and 3 months after the AMI for determination of haemostatic markers.ResultsWe found higher levels of soluble tissue factor (TF) and D-dimer in the LV thrombus group 4–5 days, 8–9 days and 3 months (only TF) after the AMI compared to the patients without thrombus formation (p<0.05). Patients with TF in the upper quartile at baseline had significantly higher risk for LV thrombus (OR 4.2; 95% CI 1.2 -14.5; p=0.02, adjusted for infarct size).The levels of prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were significantly lower in the thrombus group after 8–9 days (only ETP), 2–3 weeks and 3 months. The levels of plasminogen activator inhibitor 1 activity and tissue plasminogen activator antigen did not differ between the groups.ConclusionIn the acute phase of AMI, we found higher levels of TF and D-dimer in the LV thrombus group, indicating hypercoagulability of possible importance for the generation of mural thrombus. Lower levels of F1+2, ETP and D-dimer in the thrombus group late during follow-up are probably induced by the initiated anticoagulation therapy.

Stent graft composition plays a material role in the postimplantation syndrome

In patients undergoing endovascular aneurysm repair (EVAR), the postimplantation syndrome (PIS), comprising fever and inflammation, occurs frequently. The cause of PIS is unclear, but graft composition and acute thrombus formation may play a role. The objective of this study was to evaluate these possible causes of the inflammatory response after EVAR. One hundred forty-nine patients undergoing elective EVAR were included. Implanted stent grafts differed mainly in the type of fabric used: either woven polyester (n=82) or expanded polytetrafluorethylene (ePTFE; n=67). Tympanic temperature and C-reactive protein (CRP) were assessed daily during hospitalization. PIS was defined as the composite of a body temperature of ≥38°C coinciding with CRP>10 mg/L. Besides graft composition, the size of the grafts and the volume of new-onset thrombus were calculated using dedicated software, and results were correlated to PIS. Implantation of grafts made of polyester was associated with higher postoperative temperature (P<.001), CRP levels (P<.001), and incidence of PIS (56.1% vs 17.9%; P<.001) compared to ePFTE. After multivariate analysis, woven polyester stent grafts were independently associated with an increased risk of PIS (hazard ratio, 5.6; 95% confidence interval, 1.6-19.4; P=.007). Demographics, amount of graft material implanted, or new-onset thrombus had no association with PIS. The composition of stent grafts may play a material role in the incidence of postimplantation syndrome in patients undergoing EVAR. Implantation of stent grafts based on woven polyester was independently associated with a stronger inflammatory response.

SERUM LEVELS OF VON WILLEBRAND FACTOR ARE ASSOCIATED WITH ANGIOGRAPHIC ANGIOGRAPHIC NO-REFLOW AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ST SEGMENT ELEVATION MYOCARDIAL INFARCTION

ObjectivesPrimary percutaneous coronary intervention (PPCI) is an important therapy for patients with acute ST-segment elevation myocardial infarction (STEMI). However, the restoration of epicardial coronary patency after coronary occlusion does not...

Local Thrombus Formation at the Coil–Parent Artery Interface during Endovascular Coil Embolization of Cerebral Aneurysms

Fresh thrombus formation at the coil-parent artery interface around the neck of aneurysms is sometimes observed during coil embolization of cerebral aneurysms. We retrospectively analyzed the factors associated with local acute thrombus formation from the data of patients treated over a period of 5 years at our institute. Between November 2004 and March 2009, 242 patients harboring 250 aneurysms were treated with endovascular coil embolization at our institute. The patients were divided into two groups: Group A included 107 patients who were treated and followed up during the initial 29 months of the study, and group B included 135 patients who were treated and followed up during the later 24 months of the study. Clinical and angiographic variables of the procedures were statistically tested for correlation with thrombus formation in the parent arteries. Fresh thrombus formation occurred in six patients with unruptured aneurysms (15%) and 11 patients with ruptured aneurysms (14%) in group A. Among the patients with unruptured aneurysms, the dome-to-neck ratio and location of the aneurysms were independently associated with the risk of thrombus formation, whereas among patients with ruptured aneurysms, a higher World Federation of Neurological Surgeons (WFNS) grade and longer interventional duration were significantly associated with thrombus formation. However, fresh thrombus formation occurred in only two patients with unruptured aneurysms (2.9%) and three patients with ruptured aneurysms (4.4%) in group B. There were no factors that were significantly associated with thrombus formation in all Group B patients. With regard to coil embolization treatment, anatomical and morphological factors seem to be related to intraprocedural thrombus formation in patients with unruptured aneurysms, whereas duration of the intervention and preoperative status are associated factors in patients with ruptured aneurysms. Careful comparison of the thrombus with control angiograms is important to prevent thrombembolic complications. Moreover, the rate of fresh thrombus formation during coil embolization has decreased over the past 5 years at our institute, suggesting the possibility of lowering the incidence of these complications by early detection and treatment.

Platelets enter atherosclerotic plaque via intraplaque microvascular leakage and intraplaque hemorrhage: A histopathological study in carotid plaques

BackgroundPlatelets foster an inflammatory environment that influences atherosclerotic lesion progression and facilitates plaque rupture, in addition to their role in acute thrombus formation. The route of entry of platelets into the atherosclerotic plaque and their exact location inside the plaque are however not completely understood. Methods and results188 carotid plaques were examined for the presence of platelets using immunohistochemistry (CD42b), and 76/188 (40.4%) were platelet positive. Platelets were observed in intraplaque hemorrhages, around plaque microvessels, mostly without leakage of erythrocytes; and in mural thrombi. Platelet positive staining was associated with a higher plaque microvessel density, and elevated plaque-levels of interleukin-8. ConclusionDue to their short life span, platelets reflect recent bleeding. It can be hypothesized that platelets might serve as a marker for leaky microvessels inside atherosclerotic plaques that are at risk for development, or progression of plaque hemorrhage.

Emergent stent placement following intra-arterial thrombolysis for the treatment of acute basilar artery occlusion

Acute basilar artery occlusion (BAO) is a condition producing high rates of morbidity and mortality. Intravenous thrombolysis or intra-arterial thrombolysis are therapeutic options; however, the clinical outcomes remain poor. The purpose of the present study was to evaluate feasibility, safety, and efficacy of emergency stent placement following intra-arterial thrombolysis for patients with acute BAO. Thirty-six consecutive patients were treated for acute BAO using intra-arterial therapy from September 2004 to October 2009. Nine patients, with a Glasgow Coma Scale (GCS) score ranging from 8 to 12, underwent emergency stent placement following inadequate revascularization after thrombolysis. Neurological status prior to treatment was evaluated using the GCS score. Modified Rankin Scale (mRS) scores at 90 days post-treatment were used to assess functional outcome and we reviewed clinical records for frequency of procedure-related complications. Stents were deployed at the target lesion in all patients. Successful revascularization was achieved in eight of nine (88.9%) patients (residual stenosis <50%). The median GCS score prior to thrombolysis was 9 (range: 6–12) and prior to stent placement was 10 (range: 8–12). Four patients (44.4%) achieved good outcomes as determined by the mRS scale (0–2 at 90 days). Mortality was 33.3% in all procedures with one patient (11.1%) experiencing acute intrastent thrombus formation. No patient developed symptomatic intracerebral hemorrhage. Data from our small case series demonstrates that emergency stent placement following intra-arterial thrombolysis is a feasible treatment for patients with acute BAO and may reduce mortality and prevent re-occlusion of the basilar artery.

Acute thrombus formation on an Amplatzer device during transcatheter closure of an atrial septal defect in a patient with homozygous factor V Leiden mutation

A 32-year-old woman underwent transcatheter closure of a secundum type atrial septal defect with the Amplatzer device. The procedure was started under premedication with aspirin, clopidogrel, and heparin. During the procedure, a highly mobile thrombus attached to the left atrial disc of the device was detected by transesophageal echocardiography (TEE). The device and the associated thrombus were successfully withdrawn and the patient was started on a combination of heparin and tirofiban infusion. The procedure was successfully completed without any recurrent thrombus formation or residual shunt. Further investigation for thrombophilia revealed homozygous factor V Leiden mutation and the patient was started on a life-long warfarin therapy. Follow-up TEE showed proper device position with no recurrent thrombus and the follow-up was uneventful.

Novel insights into the development of atherosclerosis in hemophilia A mouse models

Cardiovascular diseases in aging people with hemophilia (PWH) represent a growing concern. The underlying hypocoagulability probably provides a protective effect against acute thrombus formation, but the limited data available show no preventive effect against the development of atherogenesis in PWH. Atherosclerosis-prone mice are attractive tools for the study of atherosclerosis development, and may provide insights into disease progression in PWH. Severe hemophilia A (factor VIII-deficient [FVIII(o)]) mice were crossed with mice lacking apolipoprotein E (ApoE(-/-)) or mice lacking the LDL receptor (LDLR(-/-)), and then compared to hemostatically normal littermate controls. After mice had received atherogenic diets for 8, 22 or 37 weeks, atherosclerotic lesion size and phenotypic characterization were analyzed in the aortic sinus and whole aortas. ApoE(-/-)/FVIII(o) mice showed a time-dependent protective effect against the development of atherosclerosis, beginning after 22 diet-weeks and persisting to 37 diet-weeks in both the aorta sinus and whole aorta as compared with ApoE(-/-) mice. Notably, the FVIII deficiency did not influence the progression of atherosclerosis in the FVIII(o)/LDLR(-/-) model as compared with controls at early or late time points. Hypocoagulability ameliorates vascular disease in the ApoE-deficient model in a lipid-independent manner. Interestingly, FVIII deficiency did not affect the development of atherosclerosis in LDLR(-/-) mice. In contrast to the ApoE model, the LDLR model resembles the lipid profile that is commonly observed in humans with atherosclerosis. These findings, to a certain extent, support the notion of atherosclerosis development in the complete absence of FVIII.

The missing link between atherosclerosis, inflammation and thrombosis: is it tissue factor?

Acute thrombus formation on disrupted atherosclerotic plaques plays a key role during the onset of acute coronary syndromes. Lesion disruption facilitates the interaction between circulating blood and prothrombotic substances, such as tissue factor (TF) present within the atherosclerotic lesion. For a long period of time, vessel-wall TF has been considered the major determinant of thrombosis. However, this old dogma has been recently changed owing to the discovery of a different pool of TF that circulates in flowing blood (blood-borne TF). Several studies have shown that blood-borne TF circulates in different pools that are associated with selected blood cells, such as monocytes, granulocytes and platelets in cell-derived microparticles, and as a soluble protein generated by alternative splicing of its full-length mRNA. Recent studies have identified a hypercoagulable state associated with an increased circulating TF activity, leading to the concept of ‘vulnerable blood’. Part of the blood-borne TF circulates in an ‘inactive’ form and it is required to be ‘activated’ to exert its thrombogenic potential. Certain pathological conditions, such as smoking, hyperlipidemia and diabetes, show a higher incidence of thrombotic complications. These conditions are also characterized by the presence of high levels of circulating TF activity. Recent evidence may also suggest that an increased circulating TF activity may potentiate the initial thrombogenic stimulus represented by vessel wall-associated TF, leading to the formation of larger and/or more stable thrombus, and thus more severe acute coronary syndromes. It has been reported that inflammation increases TF expression and activity by different cell types. On the other hand, TF upregulation may facilitate inflammation by enhancing intravascular fibrin deposition, formation of proinflammatory fragments of fibrin, and by generating coagulation proteases, including FVIIa, FXa and thrombin, that activate protease-activated receptors. Furthermore, the biology of TF is know known to be more complex than previously thought by the demonstration that this protein, apart from its known effects on blood coagulation, can also function as a signaling receptor.

Acute Thrombus Formation as a Complication of Right Ventricular Biopsy

While using echocardiography to guide endomyocardial biopsy (EMB), the authors have identified acute intracardiac thrombus formation related to the procedure, a hitherto unreported complication. The aims of this study were to identify the procedural details and characteristics of patients who developed this complication between June 2008 and April 2009 and to describe their outcomes and management. In total, 415 right ventricular biopsies were performed during this period. Of these, 189 were echocardiographically guided, and the medical records of these patients were reviewed retrospectively. There were eight cases of acute right-sided intracardiac thrombus formation in seven patients (about 4% of the echocardiographically guided group) at the time of biopsy. The indications for EMB were heart transplant surveillance in six patients and suspected cardiac amyloidosis in one patient. Three cases were performed via a transjugular approach and four via a femoral approach. Four patients had histories of prior thromboses, and one patient had a defined clotting diathesis. Management included either immediate thrombus aspiration or postprocedural anticoagulation. There were no overt occurrences of pulmonary thromboembolism. Acute thrombus formation is a complication of EMB. If this complication is unrecognized, and therefore untreated, pulmonary thromboembolism may result. This may have important clinical implications in patients undergoing routine repeated surveillance EMB after cardiac transplantation. The authors recommend performing transthoracic echocardiography during EMB, particularly in patients with histories of thrombosis, because this group of patients may be at increased risk for procedural thrombosis, and procedural echocardiography permits early recognition and treatment of this complication.

Acute Intraprocedural Thrombus Formation During Wingspan Intracranial Stent Placement for Intracranial Atherosclerotic Disease

Treatment of intracranial atherosclerotic disease with the Wingspan-Gateway intracranial stent and balloon angioplasty system has been reported in several multicenter registries. To date, the incidence of acute intraprocedural thrombus formation during Wingspan stent placement has not been reported. We reviewed the incidence of acute thrombus formation, treatment, and outcome for patients who underwent Wingspan stent placement by the senior author (B.L.H.) between June 2006 and April 2009. We routinely perform angiograms every 10 minutes for at least 30 minutes after placement of a Wingspan stent to check for acute thrombus formation. Acute thrombus was graded: (1) visible thrombus but not flow limiting, (2) visible and flow-limiting thrombosis, and (3) complete stent occlusion. Recanalization was graded according to Thrombosis In Myocardial Infarction score. Forty-one patients underwent Wingspan stent placement for intracranial stenosis. Acute intraprocedural thrombus formation developed in 6 (14.6%) within 20 minutes after stent placement: 3 grade 1, 1 grade 2, and 2 grade 3. All 6 were successfully recanalized with Thrombosis In Myocardial Infarction score 3 after intravenous abciximab with or without intra-arterial tissue plasminogen activator and/or balloon angioplasty. There was no morbidity, and all 6 patients were discharged home at their neurological baseline. We recommend serial angiography every 10 minutes for at least 30 minutes after placement of Wingspan stents. Once detected, acute thrombosis can be successfully treated with intravenous abciximab with or without intra-arterial tissue plasminogen activator and/or balloon angioplasty.

Antikoagulation in der Dermatologie

The coagulation system protects the body from uncontrolled blood loss by means of highly regulated processes. In case of an injury the coagulation system instantly switches from controlled blood flow to acute coagulation and thrombus formation with the goal of stopping the blood loss. Minor changes in this well-maintained equilibrium of coagulation and blood flow tip the balance towards uncontrolled blood loss or even fatal thromboembolic events. Iatrogenic manipulation of this highly regulated system is possible with a variety of therapeutic agents. We review the basics of coagulation physiology and then discuss dermatologically relevant aspects of thrombosis prevention, as well as the use of anticoagulants to treat dermatologic diseases.

High‐density lipoproteins, platelets and the pathogenesis of atherosclerosis

1. Prospective and interventional studies demonstrate an inverse relationship between plasma high-density lipoprotein (HDL)-cholesterol and the incidence of coronary artery disease. Although the atheroprotective effects of HDL are usually attributed to the reverse cholesterol transport, in which HDL shuttles cholesterol from cells in the arterial wall to the liver, other mechanisms are also under investigation. 2. Platelets are involved in both the initiation and progression of atherosclerotic lesions. In addition, the formation of thrombi over ruptured atherosclerotic plaques results in the narrowing or complete occlusion of coronary arteries. Current experimental evidence suggests that HDL may exert antiplatelet effects and thereby counteract the development of atherothrombotic vascular disease. 3. In vitro studies show that HDL inhibits agonist-stimulated platelet aggregation, fibrinogen binding, granule secretion and liberation of thromboxane A(2). Inhibitory effects of HDL are mediated, in part, by scavenger receptor type B1 and/or the apolipoprotein E receptor apoER2/LRP8 and are linked to the induction of intracellular signalling cascades encompassing stimulation of protein kinase C, cytoplasmatic alkalization and generation of nitric oxide. 4. Populational studies demonstrate that there is an inverse association between plasma HDL levels and recurrent venous thromboembolism. In addition, HDL-cholesterol has been identified as an independent predictor of acute platelet thrombus formation. The administration of reconstituted HDL particles in humans attenuates ex vivo platelet activation. 5. The present review summarizes recent advances in understanding HDL-platelet interactions and discusses the potential use of HDL-like particles in the therapy of thrombosis.

Magnetic Resonance Molecular Imaging of Thrombosis in an Arachidonic Acid Mouse Model Using an Activated Platelet Targeted Probe

Atherosclerotic plaque rupture leads to acute thrombus formation and may trigger serious clinical events such as myocardial infarction or stroke. Therefore, it would be valuable to identify atherothrombosis and vulnerable plaques before the onset of such clinical events. We sought to determine whether the noninvasive in vivo visualization of activated platelets was effective when using a target-specific MRI contrast agent to identify thrombi, hallmarks of vulnerable or high-risk atherosclerotic plaques. Inflammatory thrombi were induced in mice via topical application of arachidonic acid on the carotid. Thrombus formation was imaged with intravital fluorescence microscopy and molecular MRI. To accomplish the latter, a paramagnetic contrast agent (P975) that targets the glycoprotein alpha(IIb)beta(3), expressed on activated platelets, was investigated. The specificity of P975 for activated platelets was studied in vitro. In vivo, high spatial-resolution MRI was performed at baseline and longitudinally over 2 hours after injecting P975 or a nonspecific agent. The contralateral carotid, a sham surgery group, and a competitive inhibition experiment served as controls. P975 showed a good affinity for activated platelets, with an IC(50) (concentration of dose that produces 50% inhibition) value of 2.6 micromol/L. In thrombosed animals, P975 produced an immediate and sustained increase in MRI signal, whereas none of the control groups revealed any significant increase in MRI signal 2 hours after injection. More important, the competitive inhibition experiment with an alpha(IIb)beta(3) antagonist suppressed the MRI signal enhancement, which is indicative for the specificity of P975 for the activated platelets. P975 allowed in vivo target-specific noninvasive MRI of activated platelets.