ABSTRACT
BACKGROUND: Clinical studies suggest that 10-50% of patients are resistant to clopidogrel therapy. ADP induced platelet aggregation, a widely used test to monitor clopidogrel therapy, is affected by aspirin and is not specific for the P2Y12 receptor inhibited by clopidogrel. OBJECTIVES: To develop a P2Y12-specific platelet aggregation test and to compare it with other methods used for monitoring clopidogrel therapy. PATIENTS/METHODS: Study population included 111 patients with the history of ischemic stroke being on clopidogrel monotherapy and 140 controls. The effect of clopidogrel was tested by a newly developed ADP(PGE1) aggregation test in which prostaglandin E1 treated platelets are used. Results of conventional ADP induced platelet aggregation, VerifyNow P2Y12 assay and ADP(PGE1) aggregation were compared to those obtained by flow cytometric analysis of vasodilator stimulated phosphoprotein (VASP) phosphorylation. Reference intervals for all assays were determined according to the guidelines of Clinical Laboratory Standards Institute. RESULTS: The P2Y12-specificity of ADP(PGE1) test was proven by comparing it with ADP aggregation in the presence of P2Y1 antagonist, adenosine 3', 5'-diphosphate. The method was not influenced by aspirin treatment. Approximately 50% of patients were clopidogrel resistant by conventional ADP aggregation and VerifyNow tests. The ADP(PGE1) method and the VASP phosphorylation assay identified 25.9% and 11.7% of patients as non-responders, respectively. ADP(PGE1) aggregation showed good correlation with VASP phosphorylation and had high diagnostic efficiency. CONCLUSION: The new ADP(PGE1) method is a reliable test for monitoring P2Y12 receptor inhibition by platelet aggregation. As a subset of patients are non-responders, monitoring clopidogrel therapy by adequate methods is essential.
Subject(s)
Platelet Aggregation/drug effects , Receptors, Purinergic P2Y12/metabolism , Stroke/drug therapy , Ticlopidine/analogs & derivatives , Adenosine Diphosphate/pharmacology , Adult , Aged , Alprostadil/pharmacology , Blood Platelets/drug effects , Blood Platelets/metabolism , Cell Adhesion Molecules/metabolism , Clinical Laboratory Techniques/methods , Clopidogrel , Female , Flow Cytometry , Humans , Male , Microfilament Proteins/metabolism , Middle Aged , Phosphoproteins/metabolism , Phosphorylation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Platelet Function Tests/methods , Purinergic P2Y Receptor Antagonists/therapeutic use , Reproducibility of Results , Stroke/blood , Ticlopidine/therapeutic useABSTRACT
The authors summarize the current knowledge on the types, prevalence, reasons, diagnosis and current therapy of arrhythmias occurring in patients with obstructive sleep apnea. Most of the patients with obstructive sleep apnea have nocturnal bradycardia (5-50%), paroxysmal tachyarrhythmia (atrial 35%; ventricular 0-15%), or both. The frequency of rhythm disturbances associated with the severity of the sleeping disorder. It is important to recognize the factors predisposing to arrhythmias and the early appropriate therapy of patients is essential, in order to protect patients from life threatening arrhythmias which may worsen the clinical outcome.
Subject(s)
Bradycardia/etiology , Bradycardia/therapy , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/therapy , Tachycardia/etiology , Tachycardia/therapy , Atrial Fibrillation/etiology , Atrial Fibrillation/therapy , Atrial Flutter/etiology , Atrial Flutter/therapy , Bradycardia/prevention & control , Cardiac Pacing, Artificial , Continuous Positive Airway Pressure , Electrocardiography , Electroencephalography , Humans , Risk Factors , Severity of Illness Index , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/prevention & control , Tachycardia/prevention & control , Tachycardia, Paroxysmal/etiology , Tachycardia, Paroxysmal/therapy , Tachycardia, Supraventricular/etiology , Tachycardia, Supraventricular/therapy , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/therapyABSTRACT
BACKGROUND AND PURPOSE: Clinically silent circulating microembolic signals (MES) can be identified by transcranial Doppler ultrasound (TCD). It is not yet clear whether their occurrence is always linked to the presence of embolic sources. METHODS: 24 terminally ill patients (7 women, 17 men; mean age 68 years) were investigated by TCD of the middle cerebral arteries. These findings were correlated with a complete post-mortem examination of potential embolic pathways. RESULTS: Four patients out of the 24 under investigation showed MES, 2 of them bilaterally. All these 4 MES-positive patients had a definite embolic source, i. e. bilateral carotid artery occlusive disease, endocarditis with thrombotic valvular adhesions and severe plaques in the aortic arch, dilated left atrium and a patent foramen ovale, or severe plaques in the aortic arch and a dilated left atrium, respectively. CONCLUSION: In the investigated patient group, we could demonstrate that MES can only be found when an embolic source is present. The finding of MES justifies an extensive clinical and laboratory search for potential embolic sources including extracranial and intracranial colour-coded duplex ultrasound, ECG, Holter-ECG, and TEE.
