Hemostasis in the Era of the Chronic Anticoagulated Patient

Unique structure of polymer in the pGlcNAc patch.
Splenic injury cross section demonstrating the interaction of red blood cells with pGlcNAc. The pGlcNAc causes rapid red blood cell aggregation.
Scanning electron micrograph demonstrating platelets contacting the pGlcNAc patch fibers.
Fluorescence and phase micrograms demonstrating platelets binding to and activating on the pGlcNAc patch fibers.
GPIIb/IIIa complex assumes an activated conformation upon contact with NAG.
pGlcNAc activates a Ca signal in platelets.
 pGlcNAc induces surface exposure of PS.
Scanning electron microgram showing platelets on the pGlcNAc.

Bonnie Weiner, MD, *Thomas Fischer, PhD, †Sergio Waxman, MD

The rationale for the need for rapid and safe hemostasis occurs at three levels. The first level is the patient. Patients want to have the bleeding stopped, but they also want to minimize discomfort associated with sheath dwell time, compression time and bed rest. The second level is the physician. Physicians want adequate hemostasis to decrease vascular complications, reduce procedural times and time to hemostasis and gain expertise with new devices and techniques. On the third level, hospitals and catheterization laboratories want to achieve earlier ambulation and discharges, which in turn will free beds in observations units and hospital rooms and will lead to better utilization of resources and lower costs. Thus, there is a justifiable need at all three levels to improve or to facilitate hemostasis.
The first requisite of an ideal hemostatic device is the ability to achieve complete hemostasis regardless of the level of anticoagulation and other clinical factors, such as in patients with the presence of peripheral vascular disease, bioprosthetic devices or materials in their bodies and different body habitus. Ideally, the hemostatic device should have low complication rates and will not compromise the arterial lumen by either embolization or narrowing. In addition, it will produce minimal sequelae in the surrounding tissues of the arteries so the site can be accessed repeatedly if necessary. Added bonuses include low cost and the ability to ambulate early.
All hemostatic devices are compared with the time-tested standard of care, which is manual compression. Historically, manual compression consisted of 15-minute compression cycles at the arteriotomy sites with 6 to 8 hours of bed rest. This recommendation was based on empiric knowledge; there are no randomized trials to support this. There are, however, observational studies and registries of patients looking at shorter compression times or bedrest, depending on the sheath size. The complication rates for diagnostic procedures range from 0% to 1.1%, and for interventional procedures from 1.3% to 5.9%, depending on the level of anticoagulation and sheath sizes.
Hoffer and Bloch2 reviewed 31 studies reported in the literature that measured efficacy rates of arterial closure devices (VasoSeal, Datascope Corporation, Mahwah, New Jersey; Angio-Seal, St. Jude Medical, Minnetonka, Minnesota; Duett, Vascular Solutions, Inc., Minneapolis, Minnesota; and Perclose, Abbott Vascular Devices, Redwood City, California). They reported success rates above 90%, hemostasis rates between 90% and 95% and failure rates around 5%. The major complication rates of arterial closure devices ranged from 3% to 4%, from 0.5% in the lowest to almost 10% in the highest. The major complications with any of these devices are not trivial; they can be life or limb threatening on occasion. The same report compared arterial closure devices with manual compression and found that there was no difference between the devices and manual compression. Therefore, it is justifiable to evaluate less invasive technologies that utilize the principle of assisted, augmented, or accelerated compression that access the site with a topical patch. Limited clinical experience suggests that assisted compression with pGlcNAc can decrease compression time, can decrease time to ambulation and can be associated with low complication rates.
A study conducted by Khuri et al.3 addressed whether assisted compression with pGlcNAc can decrease compression times. They studied 33 patients who underwent diagnostic cardiac catheterizations, randomized to either placebo gauze pad (n = 17) or pGlcNAc (n = 16). They developed a clamp device to measure the pressure that was being applied with either test product. They applied 5-minute cycles of compression, comparing placebo with the pGlcNAc patch. They determined time to hemostasis was reduced with use of the pGlcNAc patch and were able to obtain adequate hemostasis at 10 minutes. There was no difference in hematoma formation.
Hirsch et al.4 conducted a randomized trial of 40 patients undergoing both diagnostic and therapeutic neurointerventional procedures. The standard of care was 15-minute cycles with additional 5 minutes as needed if bleeding persisted. The protocol with the pGlcNAc patch was 8-minute cycles with 4-minute repeated cycles as needed. The sheath sizes varied from 5 Fr to 7 Fr. With the pGlcNAc patch, hemostasis was achieved in 8 minutes in 19 out of 20 cases. With the standard of care, hemostasis was achieved in 15 minutes in 18 out of 20 patients. There was no difference in outcome with either 8-minute or 15-minute compressions, with pGlcNAc or with the standard of care. There was one hematoma in the standard of care cohort, and no complications in the pGlcNAc cohort.
A study by Shubrooks et al.5 examined early ambulation in 40 consecutive patients after diagnostic cardiac catheterization with sheath sizes from 6 Fr to 8 Fr. Assisted compression with pGlcNAc was utilized, and patients were ambulated at two hours. The groups were divided as follows: 20 patients were discharged home immediately after a 2-hour period and 20 patients were kept in observation for an additional four hours for close follow up in the hospital. There was no difference in either group as far as hemotoma formation or other vascular complications.
Palmer et al.6 studied 200 consecutive patients who underwent outpatient cardiac catheterization with 6 Fr sheaths. Heparin was given in about half (53%) of the patients, and assisted compression with pGlcNAc was applied for 15 minutes. The objective was to demonstrate that early ambulation was possible with assisted compression. Patients had one-hour bed rest and ambulated in one hour. One-hundred ninety six patients (98%) were discharged within three hours of the angiogram. There were no major adverse events; however, there were two small bleeds and two hematomas during the observation procedure. None of the events prevented the patients from going home within four hours.
Nader et al.7 reported their experience with 1,000 consecutive patients in the largest series of patients that has been reported to date with the use of assisted compression with pGlcNAc. There were 636 diagnostic procedures and 364 interventional procedures observed. Assisted compression was used for 10 minutes in the diagnostic group and for 20 minutes in the interventional group as long as the ACT was less than 300 seconds. Their endpoint was complication rates rather than compression times. In the interventional group, about 76% of patients had ACTs of 200 seconds or more. A significant number of patients were taking platelet inhibitors. The overall major complication rate was 0.1%, and the minor complication rate was 1.3%. These are observational cohorts. Divided by type of procedures, the major complication was a pseudoaneurysm, which occurred in the interventional group; there were no major complications in the diagnostic group. There were 4 minor complications in the interventional group (3 small hemotomas and one nuisance bleed) and 9 minor complications in the diagnostic group (4 small hemotomas, 5 nuisance bleeds), suggesting that assisted compression with the pGlcNAc patch has a benign complication profile based on this cohort of patients.

Clinical Overview

There is mounting clinical evidence that assisted or accelerated compression with pGlcNAc may be as effective as standard of care, if not superior, but there are no trials yet to prove this. Assisted compression is as effective as arterial closure devices; has low complication profiles; may decrease the sheath dwell times and compression times, which is an outcome that is important for patients; and enables early ambulation, which is important for catheterization laboratory staff.
Decreased sheath dwell time, decreased time to hemostasis or early ambulation are the most desirable outcomes when dealing with hemostasis. Assisted compression with pGlcNAc may help achieve these outcomes with the added benefit of lower complication rates and costs when compared with closure devices. The present data invites physicians to take pause when deciding the best and safest ways of achieving hemostasis and calls for additional studies of assisted compression.

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