Commentary: Dethrombosing Strategies and Endopharmacologic and Mechanical Techniques


Submitted on Fri, 09/05/2008 - 16:36

David E. Allie, MD

In this issue of VDM, Shammas has presented several algorithms regarding treatment of the spectrum of acute and chronic lower extremity ischemia with the emphasis refreshingly placed primarily on thrombus, platelets and “clot” management. I have referred to this as “endopharmacotherapy” in treating critical limb ischemia (CLI), and consider this tool just as important in achieving limb salvage as any of the recent novel device technologies we are now adding to our CLI “toolbox”.1 Endopharmacotherapy may even be more important when considering that ultimate limb loss often starts or ends up as minor distal tissue loss due to distal “infrapedal” digital vascular thrombosis and microvascular platelet aggregation that is essentially untreatable with any of our current device platforms. Furthermore, the realization that certainly microembolization and possibly macroembolization of athero or thromboembolic debris occur with every vascular intervention (including guidewire manipulation), should mandate interventionalists to consider novel pharmaceutical anticoagulation and antithrombus strategies in treating infrainguinal arterial occlusive disease, at least until “capillary-sized” distal protection devices (DPD) become available, which I do not foresee anytime soon. The author nicely describes the acute, subacute, and chronic presentations of ischemia and algorithms for treatment. Considerable experience and expertise is generally required to optimize outcomes in these challenging patients with true CLI. Unfortunately, consensus definitions are still lacking today regarding the classification of lower-extremity ischemia, resulting in confusion and inconsistencies in treatments and the reporting of outcomes. Regardless, each algorithm appears to be well described and considered. The algorithm for acute limb ischemia (ALI) was built upon the platform of mechanical thrombectomy, utilizing the AngioJet system (Possis Medical Inc., Minneapolis, Minnesota) with or without the “Power-Pulse Spray” Technique, and is also our preferred method of treating ALI. There are a wealth of data supporting the safety and efficacy of utilizing the AngioJet in this setting, and advocating the concept of improved outcomes resulting from rapid removal of thrombus and return of flow in ischemic tissues.2,3 This is why we are proponents of treating the acutely ischemic leg like the acutely ischemic heart, hence the concept “treat ALI like ACS.” The authors have appropriately identified the need for an optimal anticoagulation foundation utilizing bivalirudin (Angiomax, The Medicines Company, Parsippany, New Jersey) in each algorithm and identified the significant limitations of unfractionated heparin (UFH), which are magnified in the hyperthrombotic peripheral vascular disease (PVD) patient. I am in general agreement with algorithm 3A and 3B as the authors attempt to differentiate treatment in “subacute vs. chronic” CLI patients, where most of the inconsistencies and confusion exist around clinical care. Our endopharmacotherapy strategy, however, in each of those subsets or patients would include optimal periprocedural platelet inhibition with GP IIb/IIIa inhibitors regardless of clopidogrel. Every case is accompanied with some degree of distal microembolization, and therefore needs maximal perioperative protection from platelet microaggregation. It is our policy to have these patients on clopidogrel 75 mg a day for a one-week preprocedure, or immediately with a preprocedural load of 375 mg. Several recent reports support the safety and feasibility of this strategy in treating CLI like ACS even though randomized data are lacking.1,4,5 It must be mentioned that the recent report of the results of the Bilateral Lower Arterial Stenting Employing Reopro (BLASTER) trial, showing no difference in outcomes with abciximab (ReoPro, Eli Lilly and Company, Indianapolis, Indiana) in treating infrainguinal disease, was designed primarily for SFA endpoints treated with nitinol stents and not primarily for true CLI patients suffering primarily from severe infrapopliteal disease.6 These ACS patients undergoing percutaneous coronary intervention (PCI) that are known to benefit from GP IIb/IIIa inhibition include those patient with diabetes, small vessels, visible thrombus and complex lesions.1 This describes almost exactly the CLI patient population, hence a solid reason to apply this PCI strategy to the infrapopliteal vessels. Even though we have reported on the safety of combining thrombolytics with GP IIb/IIIas during both the “Power-Pulse Spray” technique and continuous infusion, we utilize continuous thrombolysis only after exhausting all other reasonable endovascular thrombus removal strategies in the non-ALI patient with CLI, as invariably the need most often arises in the old, frail and high-risk-for-bleeding patient subset.7 The excimer laser (Spectranetics Corporation, Colorado Springs, Colorado) has known thromboablative as well as atheroablative properties, and we have been impressed with the laser’s ability to treat thrombus, especially fresh or recent thrombus. We have also used immediate preprocedural 64-channel computed tomography angiography (CTA) to help identify lesion morphology in an effort to identify thrombus in both chronic and more acute phases. Attention to clinical history and the onset of symptoms is also important in helping to predict thrombus, as noted by Shammas. We have found the combination of laser therapy and the endopharmacotherapy foundation of bivalirudin and postprocedural GP IIb/IIIas to be particularly efficient in dealing with difficult-to-treat infrapopliteal and infrapedal vessels. The 0.9 mm laser probe (soon to be available in 0.7 mm) is especially helpful in delivering athero- and thromboablation, even to 220,000 amputations yearly in the United States and Europe, and when faced today with a decision to primarily amputate versus endovascular revascularization, in 2006 we have many more tools to offer our patients and we must create pathways to limb salvage in each community.8–13 These dethrombosing strategies and tools should be considered to be on the top shelf of our CLI “toolbox,” as it would be wise to assume every CLI patient has existing thrombus.