Intracardiac thrombosis in a case of Behcet's disease associated with the prothrombin 20210G-A mutation.
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Thrombosis occurs in 20 to 30% of patients with Behcet's disease (BD), but the precise pathogenic mechanism underlying the thrombotic tendency in these patients is not well known. Venous thromboses are commonly located in the lower extremities, but right intracardiac thrombi are extremely rare. We report for the first time on a young patient with BD associated the 20210G-A prothrombin gene mutation and right intracardiac thrombosis. We suggest that the association of BD with this newly recognized prothrombotic genetic mutation may have contributed to the development of the thrombotic event in this patient. (+info)
Identification of coronary thrombus with a IIb/IIIa platelet inhibitor radiopharmaceutical, technetium-99m DMP-444: A canine model.
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BACKGROUND: A diagnostic test that could distinguish between stable and unstable coronary atherosclerotic plaques would be useful. We tested the ability of a new glycoprotein IIb/IIIa platelet inhibitor DMP-444, labeled with technetium (Tc)-99 m, to identify platelet-rich thrombus by nuclear imaging in a canine model. METHODS AND RESULTS: Combinations of a flow-limiting stenosis and 0 to 15 minutes of endothelial electrical stimulation at a site in the left anterior descending coronary artery were used to induce varying amounts of thrombus formation. In 10 animals with markedly positive nuclear images after the injection of Tc-99m DMP-444, the presence of platelet-rich thrombus was confirmed postmortem by gross appearance, high nuclear counts, and abundant platelets on electron microscopy. The 10 animals with negative images had lower counts, smaller thrombus weights (P<0.05 for each), and fewer platelets by electron microscopy. CONCLUSIONS: Activated platelets participating in acute thrombus formation can be accurately detected by nuclear imaging using Tc-99 m DMP-444. (+info)
Noninvasive, transthoracic, low-frequency ultrasound augments thrombolysis in a canine model of acute myocardial infarction.
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BACKGROUND: Limitations of coronary thrombolysis include the time to reperfusion, patency rate, and bleeding. We evaluated the use of noninvasive transcutaneous ultrasound to augment coronary thrombolysis. METHODS AND RESULTS: In 24 dogs, a thrombotic occlusion of the left anterior descending coronary artery was induced and documented by 12-lead ECG and coronary angiography. After >/=60 minutes of occlusion, tissue-type plasminogen activator (t-PA; 1.42 mg/kg) was given intravenously over 90 minutes. A total of 12 of the 24 dogs had concomitant transcutaneous application of low-frequency ultrasound (27 kHz) over the chest. At 90 minutes, the mean TIMI grade flow in the t-PA alone group was 0.92+/-1.4 compared with 2. 42+/-1.9 in the t-PA plus ultrasound group (P=0.006). TIMI 2 to 3 flow was present in 4 of 12 cases receiving t-PA alone compared with 10 of 12 cases receiving t-PA plus ultrasound (P=0.003). At 180 minutes, mean TIMI grade flow was 0.75+/-1.4 in the t-PA alone group versus 2.58+/-0.9 in the t-PA plus ultrasound group (P=0.001). Pathological examination confirmed the angiographic patency rate and did not reveal injury secondary to ultrasound in the skin, soft tissues, heart, or lungs. CONCLUSIONS: In vivo, the noninvasive transthoracic application of low-frequency ultrasound (1) greatly augments the efficacy of t-PA-mediated thrombolysis, (2) seems safe, and (3) has substantial potential as a noninvasive adjunct to improve coronary patency without increasing the risk of bleeding. (+info)
Multivessel coronary thrombosis, acute myocardial infarction, and no reflow in a patient with essential thrombocythaemia.
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Essential thrombocythaemia (ET) has been reported rarely to cause coronary thrombosis, but the management is still undefined. A 63 year old woman with multivessel coronary thrombosis, acute myocardial infarction (MI), and no reflow in reperfused coronary artery in association with ET is presented. The patient's platelet count was only moderately raised at the onset of MI, but peripheral blood smear and bone marrow evaluation revealed clumping giant platelets and numerous large hyperploid megakaryocytes. Long term prophylaxis with antiplatelet agents in patients with ET is recommended, even if the platelet count is not largely raised. Cytoreductive treatment may also be effective for secondary prevention when thrombotic complications occur. (+info)
Active remodeling of the coronary arterial lesions in the late phase of Kawasaki disease: immunohistochemical study.
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BACKGROUND: Remodeling of the coronary artery lesions in Kawasaki disease has been observed in longitudinal angiographic studies. However, mechanisms of such remodeling have not yet been elucidated. METHODS AND RESULTS: We examined formalin-fixed specimens of the coronary arteries immunohistochemically by using antibodies against vascular growth factors (GFs) and their receptors in 7 children with Kawasaki disease, 9 children with no coronary disease, and 3 adults with atherosclerosis. In the thickened intima at stenotic sites and at recanalized vessels with Kawasaki disease, extensive expression of vascular GFs, such as transforming GF-beta(1), platelet-derived GF-A, and basic fibroblast GF, was observed both within and surrounding smooth muscle cells. Vascular endothelial GF was observed within smooth muscle cells. Furthermore, all of these GFs were strongly expressed in the newly formed microvessels within the intima. In the thinned media, these GFs were focally and weakly expressed. In contrast, these GFs were expressed only in the media in the control children. In cases of adult atherosclerosis, GFs were expressed diffusely in the media but focally and weakly if at all in the intima. CONCLUSIONS: Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of luxuriant intimal proliferation and neoangiogenesis for several years after the onset of the disease. This process is distinct from adult-onset atherosclerosis. (+info)
BACKGROUND: Clinical studies have implicated preinfarct angina (brief antecedent ischemia/reperfusion [I/R]) as a predictor of more rapid thrombolysis and lower rates of reocclusion. However, the effects of antecedent ischemia on the efficacy of thrombolysis have not been rigorously assessed. Using a canine model of coronary thrombosis, we aimed to (1) reproduce these clinical findings and (2) determine whether release of adenosine (a potent inhibitor of platelet aggregation via stimulation of platelet A(2) receptors) during brief I/R contributes to this improved patency. METHODS AND RESULTS: To address our first objective, we compared the time required to achieve lysis with recombinant tissue plasminogen activator and patency during the first 2 hours after lysis in dogs in which 1-hour thrombotic occlusion was preceded by brief I/R (10-minute coronary occlusion/10-minute reperfusion) versus 20-minute uninterrupted perfusion (controls). Time to lysis was accelerated in the I/R group versus the control group (11+/-1 versus 35+/-6 minutes, P=0.004). In addition, the duration of subsequent reocclusion was reduced (17+/-12 versus 30+/-11 minutes), and the area of the flow-time profile (normalized to baseline flow x 120 minutes) was increased (64+/-12% versus 35+/-7%, P=0.04) in the I/R cohort. The protocol was then repeated, but all dogs were pretreated with the adenosine A(2)/A(1) antagonist CGS 15943 (CGS, 1.5 mg/kg). Time to lysis (38 versus 39 minutes) and subsequent patency were comparable in the CGS+control group versus the CGS+I/R group. CONCLUSIONS: Brief antecedent I/R enhances the efficacy of coronary thrombolysis in this canine model, which is due, at least in part, to an adenosine-mediated mechanism. (+info)
Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene is not associated with restenosis after coronary stent placement.
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BACKGROUND: The renin-angiotensin system is thought to play a role in coronary thrombosis and restenosis. Plasma angiotensin I-converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. The objective of this study was to test the hypothesis that the D allele of the ACE gene is associated with a higher risk for restenosis after coronary stent placement. METHODS AND RESULTS: This prospective study included 1850 consecutive patients with coronary artery disease who underwent intracoronary stent implantation. The adverse clinical events recorded were death, myocardial infarction, and target vessel revascularization. The primary end point of the study was restenosis (>/=50% diameter stenosis at follow-up angiography performed in 84% of the patients). The secondary end point was clinical outcome 1 year after the procedure. The restenosis rate at the 6-month angiographic follow-up was 32.8% in patients with the II genotype, 34.0% for patients with the ID genotype, and 31.2% for patients with the DD genotype (P=0.62). One-year event-free survival was 77.7% in patients with genotype II, 75.2% in patients with genotype ID, and 75.5% in patients with genotype DD (P=0.54). The lack of association was also present in the subgroup of patients with a low risk for restenosis: the restenosis rate was 21.7% in II carriers, 23.4% in ID carriers, and 19.7% in DD carriers (P=0.83). CONCLUSIONS: The ACE DD genotype or D allele does not influence the 1-year clinical and angiographic outcome of patients undergoing coronary stent placement. These data suggest that routine determination of the ACE genotype may not help identify patients who are at a higher risk of thrombotic and restenotic events after coronary stent placement. (+info)
PlA polymorphism of glycoprotein IIIa and risk of adverse events after coronary stent placement.
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OBJECTIVE: We designed this prospective study to test the hypothesis that platelet antigen (PlA) polymorphism of glycoprotein (GP) IIIa is associated with an increased risk for adverse events after coronary stent placement. BACKGROUND: Platelets play a central role in arterial thrombosis. The PlA polymorphism of GP IIIa, a constituent of the fibrinogen receptor, may influence the platelet function and, thereby, the early outcome of patients after coronary stent placement. METHODS: The study included 1,759 consecutive patients with stable or unstable angina and successful coronary stent placement. Platelet antigen genotypes were determined by allele-specific restriction enzyme analysis. The end point of the study was a composite of death, myocardial infarction and urgent revascularization during the first 30 days after stent placement. RESULTS: The PlA1 genotype of the patients included was: 70.2% were homozygous for platelet antigen 1 (PlA1), 2.6% homozygous for platelet antigen 2 (PlA1), and 27.2% were heterozygous (PlA1/A2). The incidence of the composite end point was 5.5% among PlA2 carriers and 5.4% in homozygous PlA1 subjects (p = 0.94). It was 5.4% in PlA1/A1 patients, 4.8% in PlA1/A2 patients and 13.0% in PlA2A2 patients (p = 0.06). The combined incidence of death or myocardial infarction was 4.3% in PlA1/A1 patients, 4.2% in PlA1/A2 patients and 13.0% in PlA2/A2 patients (p = 0.02). CONCLUSIONS: The isolated presence of the PlA2 allele in heterozygous patients is not associated with any detectable increase in the risk for an adverse 30-day outcome after coronary stenting. This study suggests also that an increased risk is likely to be present in homozygous carriers of the PlA2 allele, but this should be confirmed in a much larger series of patients. (+info)