ClearWay RX-Directed Combination Thrombolytic and Glycoprotein IIb/IIIa Therapy With Embolic Protection Device in an Acute Upper Extremity Occlusion

ABSTRACT: A 75-year-old patient with coronary artery disease, hypertension, and former tobacco use presents with acute left upper limb ischemia with rest pain, pallor, and partial paralysis for 3 hours. Duplex demonstrated occlusive thrombus in the distal brachial artery. The patient was successfully treated with a combined approach consisting of an embolic protection device, intralesion delivery of tissue plasminogen activator and glycoprotein IIb/IIIa inhibitor via a specialized catheter, and rheolytic thrombectomy. This novel approach of bolus combination anticoagulant therapy coupled with rheolytic thrombectomy may provide a unique endovascular solution as an alternative to traditional infusion catheter for a patient who could not be addressed by surgery in a timely way.

VASCULAR DISEASE MANAGEMENT 2013:10(7):E130-E134 

Key words: local drug delivery, thrombectomy, distal protection devices, critical limb ischemia,
thrombolytic therapy

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We present a patient who was successfully treated by an endovascular approach with a novel technique: a combined approach utilizing initial filter deployment, then bolus intra-lesion delivery of tissue plasminogen activator (tPA) and glycoprotein (GP) IIb/IIIa, followed by rheolytic thrombectomy (RT). This technique, to the best of our knowledge, is being described for the first time in treatment of brachial artery thrombosis.  

Case Report

A 75-year-old male 60-pack-year former smoker with history of hypertension and percutaneous coronary intervention to the left anterior descending artery in 2008 presented to a rural hospital within 3 hours of developing acute left hand pain and weakness. He gave no history of prior left hand pain. In addition, on arrival to the emergency department he began having chest pressure that was similar to his myocardial infarction in 2008. Physical exam demonstrated hand pallor, coolness, and weakness, as well as absent radial and ulnar pulses. The Arterial Duplex Doppler visualized acute thrombus formation within the distal brachial artery with involvement of the proximal radial and ulnar arteries (Figure 1). There was a trickle of blood flow extending towards the hand (Figure 2). The ulnar artery was never well visualized at the bifurcation, but monophasic blood flow was visualized at the wrist. Electrocardiogram and cardiac biomarkers were normal. 

The patient received a bolus of 5,000 units of IV heparin and was started on 1,000 units/hr while in the emergency department. Because the patient required urgent cardiac catheterization given his ongoing symptoms of chest pain and no board certified vascular surgeon was available within 180 miles, a percutaneous approach was planned for this patient’s acute upper limb ischemia. 

After discussion of risks, benefits, and alternatives to procedure, the patient was taken emergently to the catheterization lab for both coronary and peripheral angiography. 

Angiographic Findings

Upper-extremity angiography showed a patent axillary artery.  The proximal and mid brachial artery were patent but with slow flow. At the distal brachial artery, there was 100% occlusive thrombus extending into the proximal radial, with filling of the radial artery via small collateral from the brachial artery (Figure 3). There appeared to be only one-vessel radial run-off to the hand. There was almost absent flow to the wrist and hand. The ulnar artery was never visualized. Left heart catheterization showed patent left anterior descending stent and no other significant disease. 

Procedural Course

A 7 Fr 90 cm Flexor Shuttle guiding sheath (Cook Medical) was advanced into the distal axillary artery from a right femoral approach. The patient received IV unfractionated heparin for anticoagulation. A ViperWire with a 0.017˝ tip (CSI) was advanced into the radial artery. Then an Emboshield NAV6 filter (Abbott Vascular) was advanced and deployed to the proximal radial artery. Super selective delivery of 10 mg of tPA, weight-adjusted eptifibatide (15.8 mg), 200 mcg nitroglycerin, and 2.5 mg verapamil were delivered to the distal brachial artery via a 3 mm x 20 mm ClearWay RX catheter (Atrium Medical) placed at the site of the main thrombus (Figure 4). After 10 minutes, angiography demonstrated minimally improved thrombus burden, but now with contiguous slow flow via the brachial to radial artery. Ulnar flow remained absent. Rheolytic thrombectomy with a 4 Fr AngioJet (Bayer HealthCare) was then performed with four passes from the distal brachial artery to the proximal radial artery. With each RT pass, the retained contrast within the thrombus visually improved. 

Repeat angiography after filter retrieval demonstrated 60% resolution of thrombus in the distal brachial artery. There was robust flow in the distal brachial artery, radial artery, and palmar arch (Figure 5). The patient had 2+ capillary refill and positive radial pulse, with return of normal skin color and resolution of pain and weakness. The ulnar artery was not visualized before or after successful treatment of the brachial artery. But because the patient’s clinical condition was effectively treated by reestablishing flow from the brachial to radial artery, the procedure was concluded. The femoral artery was treated with a collagen-based device for vessel closure. 300 mg of clopidogrel was administered and the patient was transferred to a telemetry floor. There the patient was monitored for signs of compartment syndrome or reocclusion. Because the patient presented within 3 hours of symptom onset and his pain resolved completely with intervention, he was deemed low risk for compartment syndrome. An indwelling infusion catheter with an overnight stay in the intensive care unit was not required. At our institution this approach of ClearWay bolus lytic therapy, as opposed to overnight continuous lytic therapy through a traditional catheter, results in less expense (despite the endovascular equipment) because the intensive care unit stay is not necessary. Intravenous heparin was continued until INR reached 2.0, at which time the patient was discharged on clopidogrel, atorvastatin, and warfarin. An echocardiogram demonstrated a normal ejection fraction and moderate left atrial dilation. Given his moderate left atrial enlargement and atherosclerotic heart disease, the cause of the embolism was presumed to be atrial fibrillation or atheroma of the ascending aorta. Regardless of the cause, the patient was discharged on warfarin and statin therapy. 

Left upper extremity arterial duplex Doppler ultrasound was performed approximately 2 months later, confirming normal triphasic waveforms, with previously noted brachial artery thrombosis absent. There was normal triphasic flow in the radial artery. The ulnar artery at wrist level had triphasic flow.

Discussion

Severe acute limb ischemia is a vascular emergency that threatens the viability of the limb and requires urgent revascularization.¹ Acute lower-limb ischemia occurs four to five times as often as upper limb ischemia.² Surgical embolectomy has traditionally been advocated for management of acute upper-extremity ischemia due to its simplicity and effectiveness. It has been the gold standard since the advent of the Fogarty catheter in 1962.³ However, significant incidence of perioperative events and morbidity and mortality exist. Hernandez-Richter et al examined 283 thromboembolectomies over a period of 20 years with a mean age of 70.³ Of the surgeries performed, 89.4% were done under local anesthesia. Postoperative general complications including cardiac failure and cerebral events occurred in 7.2% of patients. Local complications such as wound infection, persistence of ischemia or hematoma transpired in 20.3%. Reocclusion occurred in 8.8% of patients. The affected extremity required amputation in 2.0%, and 5.6% of patients died in the postoperative phase.³ Surgical success for upper-extremity ischemia was achieved in 95% of patients, demonstrating surgery is an effective first option in skilled hands.³ 

Licht et al presented 148 patients with upper-limb ischemia with similar results.⁴ Re-embolectomy was needed in 5% of patients, and 2 patients required amputation. The 30-day mortality rate was 9%, mostly from cardiovascular or cerebrovascular complications. Surgical success was obtained in 93% of patients. There is a paucity of outcomes data with percutaneous catheter-based treatment of acute upper-limb ischemia. But there likely is a role for both options depending on the clinical situation.¹ In this case, given the concern for unstable angina and lack of vascular surgery, a percutaneous approach was an acceptable alternative. 

However, in acute lower-limb ischemia, studies have demonstrated comparable results with percutaneous catheter-based approach versus open surgery.¹ The focus of many acute lower-limb ischemia trials has been on endovascular revascularization with urokinase or other lytic-based therapy. The Thrombolysis or Peripheral Artery Surgery Trial (TOPAS) compared recombinant urokinase or primary surgery. After 1 year of follow-up, amputation-free survival and mortality of thrombolysis vs surgery were similar in both groups (65% vs 70%, 20% vs 17% respectively).⁵ However, the thrombolytic patients had mean duration of infusion of >24 hours to achieve flow. Utilizing this modality, the patients require close monitoring in an intensive care unit, followed by increased length of hospital stay.⁵ In addition, long thrombolytic infusion times increases the rate of bleeding complications. Of patients in TOPAS, 12% experienced major hemorrhage, and less than 3% experienced an intracranial hemorrhage.⁵ Nevertheless, the fundamental limitation of reperfusion via passive thrombolysis technique is the risk of bleeding and embolic complications, as well as delay in reperfusion.^6-9 

Intralesion delivery of a lytic agent using ClearWay RX, as used in this case, is a novel mechanism for local bolus delivery at the site of the thrombus, which may confer some important advantages for treatment of acute limb ischemia. The ClearWay RX catheter is an infusion catheter with a thin, microporous PTFE balloon that delivers thrombolytic agents in a nontraumatic fashion. High drug concentrations can be achieved through the balloon’s unique methodology of occlusion, containment, and selective intralesion infusion.¹⁰ This mitigates the need for a temporary infusion catheter and subsequent long thrombolytic infusions in an intensive care unit setting. 

Although the ClearWay RX approach has not been studied in the upper extremity, there are some limited studies of its use in acute lower-limb ischemia. Began et al evaluated 7 patients treated with catheter-directed thrombolysis with urokinase and 14 patients treated with ClearWay directed therapy (CWT) with urokinase. Both arms utilized 50 IU/kg bolus of unfractionated heparin followed by manual aspiration thrombectomy prior to being assigned to treatment strategy. The acute limb salvage rate after recanalization was 90.4% (83% vs 93%, respectively). The limb salvage rate was 88.2% of all cases. However, the dose of urokinase was lower in the CWT arm (82,000 units/cm of occluded artery vs 260,000 units/cm, P=5.16) without major bleeding complications. Additionally, the average length of stay in the intermediate care unit and the hospital stay duration were significantly shorter in the CWT arm (1.1 days vs 3.9 days, P=.0016; 7.1 days vs 18 days, P=.0145, respectively).¹¹ Further, Selvaraj et al in the LIBRA (Lytic Infusion Versus Bolus Therapy for Peripheral Arterial Thrombosis Management) study showed a statistically significant reduction in average ICU stay (4 days vs 0 days), hospital stay (6 days vs 2 days), and total hospital cost ($21,588 vs $11,728) utilizing CWT with provisional RT vs traditional infusion catheter therapy.¹² There was no bleeding in the CWT arm, and one intracranial hemorrhage in the CDT arm requiring transfer to another hospital. Although this study did not have sufficient numbers to conclusively demonstrate lower bleeding rates, it has been established that longer transfusion times have increased major bleeding complications.^1,6-9

In this case, adjunctive use of a GP IIb/IIIa antagonist was administered via CWT to further maximize thrombus resolution. Glycoprotein antagonism blocks the final common pathway of platelet-induced thrombus and induces dissolution of platelet-rich clot by disrupting fibrinogen-platelet interaction (dethrombosis).¹³ The available evidence to support GP IIb/IIIa with catheter-directed thrombolysis for acute arterial thrombosis is limited and inconclusive and has not been studied with ClearWay technology.¹³ Studies do appear to corroborate that the combination of lytic therapy plus IIb/IIIa can accelerate reperfusion, reduce distal embolization, shorten thrombolysis times, and reduce reinterventions.^13-15 Intralesion dual anticoagulant therapy via CWT with low pressure inflation may provide maximum thrombus disruption, thus facilitating RT removal of the pharmacologically and mechanically altered thrombus. In this particular patient, the method was successful in restoring hand reperfusion. 

Any catheter-directed therapy or mechanical thrombectomy device carries the risk of embolization, which may lead to a lower rate of limb salvage, patency, and freedom from recurrent symptoms. The incidence of permanent embolization with loss of angiographic runoff during catheter-directed thrombolysis has been reported as between 7% and 12%.^16,17,18  The adjunctive use of an embolic protection device, as used in this case, was attempted to prevent that complication and protect this patient’s one-vessel radial artery run-off. 

Conclusion

We present a ClearWay RX-directed combination thrombolytic and GP IIb/IIIa therapy with RT and an embolic protection device to successfully treat acute upper-limb ischemia in a patient. Early and sufficient resolution of thrombus is one of the most important goals in treating patients with acute thrombosis. This case demonstrates viability of an endovascular technique for acute upper-extremity ischemia threatening a limb that uses a minimally invasive strategy demonstrated to safely and expeditiously treat lower-limb ischemia. We present it as an alternative to surgery for acute upper-limb ischemia when vascular surgery is not immediately available.

Acknowledgements: The authors wish to thank the DeBakey Heart Institute catheterization lab nurses and radiology technicians, nurse practitioners, and cardiac progressive care unit nurses and support staff. In addition, the authors would like to thank the Hays Medical Center radiology department and ultrasonographers.

Editor’s Note: Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Markiewicz reports prior membership of the 2012 Abbott OTW Coronary Advisory Board. Dr. Dave reports speaking and physician training for Abbott Vascular and Atrium Medical. Mr. Colby reports no conflicts of interest related to the content of this manuscript.

Manuscript received March 5, 2013; provisional acceptance given April 8, 2013; final version accepted April 22, 2013.

Address for correspondence: Dr. Richard J. Markiewicz, MD, DeBakey Heart Institute, Hays Medical Center, 4411 Newton Circle, Hays, KS 67601, USA. Email: rickjm99@gmail.com

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