Platelet function analyzer (PFA)-100® closure time in the evaluation of platelet disorders and platelet function

BACKGROUND: Closure time (CT), measured by platelet function analyzer (PFA-100) device, is now available to the clinical laboratory as a possible alternative or supplement to the bleeding time test. AIM: On behalf of the Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (ISTH-SSC), a working Group was formed to review and make recommendations on the use of the PFA-100 CT in the evaluation of platelet function within the clinical laboratory. METHODS: The Medline database was searched to review the published information on the PFA-100 CT in the evaluation of platelet disorders and platelet function. This information, and expert opinion, was used to prepare a report and generate consensus recommendations. RESULTS: Although the PFA-100 CT is abnormal in some forms of platelet disorders, the test does not have sufficient sensitivity or specificity to be used as a screening tool for platelet disorders. A role of the PFA-100 CT in therapeutic monitoring of platelet function remains to be established. CONCLUSIONS: The PFA-100 closure time should be considered optional in the evaluation of platelet disorders and function, and its use in therapeutic monitoring of platelet function is currently best restricted to research studies and prospective clinical trials.     

Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients

Summary. A variety of definitions of major bleeding have been used in published clinical studies, and this diversity adds to the difficulty in comparing data between trials and in performing meta-analyses. In the first step towards unified definitions of bleeding complications, the definition of major bleeding in non-surgical patients was discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Arising from that discussion, a definition was developed that should be applicable to studies with all agents that interfere with hemostasis, including anticoagulants, platelet function inhibitors and fibrinolytic drugs. The definition and the text that follows have been reviewed and approved by the cochairs of the subcommittee and the revised version is published here. The intention is to also seek approval of this definition from the regulatory authorities.     

Diaphragm Pacing with a Quadripolar Phrenic Nerve Electrode: An International Study

We sought to determine the international experience with the quadripolar diaphragm pacer system and to test two hypotheses: the incidence of pacer complications would be (1) increased among pediatric as compared to adult patients; and (2) highest among active pediatric patients with idiopathic congenital central hypoventilation syndrome (CCHS). Data were collected via a questionnaire coupled with the Atrotech Registry data for a total of 64 patients (35 children and 29 adults) from 14 countries. Thoracic implantation of electrodes and bilateral pacer use each occurred in 94% of all subjects. Tetraplegic (vs pediatric CCHS) patients were more typically paced 24 hours/day (P = 0.001). Pacing duration averaged 2.0 ± 1.0 years among children and 2.2 ± 1.1 years among adults. Infections occurred among 2.9% of surgical procedures, all in pediatric CCHS patients (vs pediatric tetraplegic patients, P = 0.01). The incidence of mechanical trauma was 3.8%, without significant differences among patient groups. The incidence of presumed electrode and receiver failure were 3.1% and 5.9%, respectively, with internal component failure greater among pediatric CCHS than pediatric tetraplegic patients (P < 0.01). Intermittent or absent function of 0–4 electrode combinations occurred among 19% of all patients, with increased frequency among pediatric CCHS than pediatric tetraplegic patients (P < 0.03). Complication- free successful pacing occurred in 60% of pediatric and 52% of adult patients. In all, 94 % of the pediatric and 86% of the adult patients paced successfully after the necessary intervention. Although pacer complications were not increased among pediatric as compared to adult patients, the incidence of complications was highest among the active pediatric patients with CCHS. Longitudinal study of these patients will provide invaluable information for modification and improvement of the quadripolar system.     

Lead Extraction in Young Patients With and Without Congenital Heart Disease Using the Subclavian Approach

Pacemaker lead removal using interlocking stylets and dilator sheaths has greatly reduced the need for major surgical intervention when lead extraction is required. Previous reports have shown the utility of this method in older patients, most of whom have anatomically normal hearts. The purpose of this study is to report the results of this technique in young patients with and with-out congenital heart disease. There were 13 patients (M:F = 7:6) aged 9–26 years (median 13). Congenital heart disease was present in 8 of 13 patients. A total of 17 leads required removal; they had been implanted for 54 ± 24 months (range 19–94). Leads were removed from the left subclavian vein (13) or right subclavian vein (4) only. Seventeen of 18 leads were completely removed and one partially retained in the left subclavian vein. New leads were implanted from the same vein in 11 of 13 patients. Interlocking stylets and metal or flexible dilator sheaths were used in all cases except two. There was one surgical complication: a late wound dehiscence, which was easily managed. No patient required a transfusion, and there was no structural damage noted in any patient on the postoperative echocardiogram. We conclude that lead removal using interlocking stylets and dilator sheaths from the subclavian approach is an effective technique that can be used in young patients, including those with congenital heart disease.     

Hemodynamic Deterioration Following Radiofrequency Ablation of the Atrioventricular Conduction System

Radiofrequeucy ablation of the atrioventricular conduction system (ACS) has become an estoblished theTapy for patients with drug refroctory atrial fibrillation. We observed eight patients with hemodynamic deterioration ofteT radiofrequency oblotion of the otTioventTicular conduction system. As we found hemodynamic deterioration related to worsening mitral regurgitation, we compared the clinical history, eiectrophysiologicai, ond echocardiographic dato from the patients with hemodynamic deteriorotion and worsening mitral regurgitation (group 1) to those without hemodynamic deterioration and stable mitral regurgitation after the procedure (group 2). Eight out of 108 patients (7.4%) undergoing ablation of the ACS deteriorated hemodynamically with acute pulmonary edema in three and congestive heart failure in five patients occurring at a mean of 3 and 8 weeks, respectively, after the procedure. Three of these patients were referred for mitral valve surgery. Two patients underwent ablation using a left-sided approach. A right-sided approach was used in five patients. In one patient, a left- and right-sided approach was used. Compared to group 2 patients, group 1 patients had significantly higher left ventricular end-diastolic diameters (64 ± 6 mm vs 56 ± 9 mm) at baseline despite similar fractional shortening (32%± Il% vs 34%± 13%), left ventricular end-systolic diameters (43 ± 9 mm vs36 ± 7 mm) and degree of mitral regurgitation (1.4 ± 1.1 vs 1.4 ±0.7) on echocardiographic analysis. Thus, hemodynamic deterioration together with progression of mitral regurgitation is a potential complication of ablation of the ACS (up to 7.4%). Patients with high left ventricular end-diastolic diameters ond moderate mitral regurgitation at baseline seem prone to this complication.     

U.S. Experience with the AddVent VDD(R) Pacing System

The AddVent pacemaker generator and model 1328C AV single-pass lead is a new pacemaker system capable of VDD or VDDR modes. The purpose of this study was to present the initial experience with AddVent in the United States and Canada. Between May 10, 1995 and May 3, 1996, 53 devices were implanted in 52 patients and followed for a mean of 217 (±39) days. At the predischarge, 1-, 3-, and 6-month follow-up evaluations, atrial sensing thresholds and ventricular sensing and capture thresholds were measured in the supine, sitting, and standing positions to evaluate stability of atrial sensing with respect to body posture at rest. At the 1-month follow-up, a treadmill exercise test was performed to evaluate atrial sensing during exercise and to evaluate two new features of the AddVent called "sensor-mediated rate smoothing" and "preferential P wave sensing." Atrial sensing thresholds were not significantly different (P > 0.05) among body postures for any follow-up period or among follow-up periods for each posture. At rest, the percentage of appropriately tracked P waves observed was > 99% at each follow-up period. During treadmill exercise, the percentage of appropriately tracked P waves was > 98.7%. Appropriate preferential P wave sensing and sensor-mediated rate smoothing (VDDR mode) was observed. The AddVent pacing system provides safe and effective pacing therapy. Several features of VDDR pacing offer advantages over standard VDD pacing.     

Submammary Pacemaker Implantation: A Unique Tunneling Technique

Submaminary pacemaker implantation offers women a cosmetically acceptable alternative to the standard pectoral implant. We present a novel method of submammary implantation performed on ten women aged 13–54 years. The lead electrodes are tunneled from the infraclavicular to the inframammary incision using a long needle, guidewire, and introducers/dilators in a manner analogous to the retained guidewire technique used for standard lead insertion. The procedure can generally be performed under local anesthesia. All patients tolerated the procedure well without acute complications. Over 2- to 23-month follow-up, there were no lead dislodgments. No patients developed mastitis or incisional complications, and all have been extremely satisfied with the cosmetic results. With proper technique, submammary pacemaker implantation can be performed under local anesthesia with minimal patient discomfort and optimal cosmesis.     

Prothrombotic gene variation and new vascular events after cerebral ischemia of arterial origin

Summary. Background: Several genetic variants involved in hemostasis have been associated with ischemic stroke or myocardial infarction (MI). Stroke patients who carry a prothrombotic genotype may also be at increased risk for subsequent vascular events. Patients and methods: We included 887 patients with non‐disabling cerebral ischemia of arterial origin, who were referred to the University Medical Center Utrecht in the Netherlands between 1995 and 2005 and followed them for the occurrence of ischemic stroke, MI or death. The primary outcome was a composite of death from all vascular causes, non‐fatal ischemic stroke, non‐fatal MI, whichever happened first. We selected 22 prothrombotic variants in 14 genes that were previously associated with ischemic stroke or MI or had evidence of functionality. Results: During a 4.6‐year mean follow‐up period new vascular events occurred in 135 patients (annual event rate 3.3%). None of the 22 variants was associated with the occurrence of new vascular events. Eight additional analyses with secondary outcomes or among subgroups revealed four associations that were likely to be false positive after accounting for multiple testing. Conclusions: In this cohort, prothrombotic genetic variants do not affect the risk of new vascular events after cerebral ischemia of arterial origin. This study does not support the use of prothrombotic genetic variants to identify stroke patients at increased risk for new vascular events or to guide antithrombotic treatment.