Anaphylaxis Following Angioplasty of the Superficial Femoral Artery with Paclitaxel-Coated Balloon: A Case Report

Background: Paclitaxel-coated Drug coated balloons have been shown to reduce restenosis rates. Severe hypersensitivity reactions to systemic infusions of paclitaxel are well described. Notwithstanding, hypersensitivity reactions to DCBs are extremely rare when used as angioplasty devices. Methods: A 79-year-old woman presented to our institution with rest pain (Rutherford IV) afflicting her right leg on a background of a progressive claudication over the previous 6 months. She was a current smoker with chronic airways disease in the context of 50-pack year history. In addition, her background included dyslipidemia, hypertension, and osteoporosis. There was no history of diabetes. She was receiving lipid-lowering (atorvastatin), antihypertensive (irbesartan, and hydrochlorothiazide), and dual-antiplatelet (aspirin and clopidogrel) medications. She had known allergies to nonsteroidal anti-inflammatory drugs (skin rash), penicillins (skin rash), and sulfonylureas (skin rash). Two months previously, she had undergone successful angioplasty of a stenosed left external iliac artery (EIA) and an occluded left superficial femoral artery with two paclitaxel-coated Ranger DCB (2.0 μg/mm²; Boston Scientific, Marlborough, MA, USA). There were no procedural complications and she had no symptoms postoperatively. Preoperatively, she had palpable femoral pulses bilaterally with absent popliteal and pedal pulses on the right side and was Buerger's positive on the right with chronic trophic changes and prolonged capillary refill. Arterial duplex ultrasound imaging revealed a near-occlusion of the right SFA with a reduced ankle-brachial pressure index of 0.49. The patient underwent an SFA angioplasty procedure under local anesthetic and sedation. An “up and over approach” was taken with a retrograde puncture of the left common femoral artery (CFA) and placement of a 6F Britetip sheath into the right CFA (Cordis, Johnson and Johnson, Warren, NJ, USA). 7000 units of intravenous heparin was administered in total during the case (weight 70 kg). Digital subtraction angiography (DSA) confirmed a >20 cm SFA occlusion. The lesion was re-canalized for 10 cm before the wire passed into the subintimal plane. No re-entry was possible into the true lumen at the distal target from an antegrade approach. Subsequently, a retrograde puncture was made of the right dorsalis pedis artery with successful passage of a through and through “flossing' wire.” The lesion was pre-dilated with a 3 mm × 200 mm conventional Armada balloon followed by a 5 mm × 150 mm conventional Armada balloon (Abbott Vascular, Abbott Park, IL, USA) taken down from above through the 6F sheath. Residual dissection of the mid-SFA was treated with a 5.5 mm × 180 mm Supera bare-metal stent (Abbott Vascular, Abbott Park, IL, USA). Given the residual disease beyond the stent and to improve patency of the site of treatment, a 5 mm × 150 mm Ranger DCB with paclitaxel coating (2.0 μg/mm²; Boston Scientific, Marlborough, MA, USA) was deployed across the distal SFA and popliteal artery and inflated to nominal pressure in accordance with manufacturer recommendations. On inflation of the DCB, the patient became abruptly and hemodynamically unstable with hypotension (noninvasive blood pressure 60/30 mmHg) and tachycardic (heart rate 150 bpm) with warm peripheries and flushed skin changes. ST-elevation was noted on cardiac telemetry. The DCB was deflated and immediately removed from the patient. She was promptly intubated and ventilated and noted to have bronchospasm with reduced airway compliance. She was given a total of 70 mcg adrenaline together with crystalloid resuscitation. A urinary catheter and right radial arterial line were placed. The left groin sheath was removed with manual compression for closure. The patient was stabilized in theater with attainment of normal vital parameters and resolution of the cardiorespiratory and electrocardiographic abnormalities noted earlier. She was extubated and transferred to the coronary care unit for observation on telemetry and treated empirically with heparin infusion (APTT target 45–90) and regular dual anti-platelet therapy. Transthoracic echocardiography (TTE) and coronary angiography revealed no significant anomalies. Serial troponin (ng/L) results at t = 0, 4, 12, and 24 h postevent were 199, 67, 66, and 59, respectively. Serial tryptase (μg/L) results at t = 0, 4, 12, and 24 h postevent were 37.9, 25.6, 8.5, and 5.2, respectively. The patient made a good clinical recovery with a marked improvement in her symptoms over 24 h. Palpable pedal pulses were noted on bedside examination at the end of the case. Repeat arterial duplex imaging 48 h following the event revealed a patent SFA with ABPI 0.96. At this point, the patient was able to mobilize at her baseline and was discharged on her usual dual anti-platelet therapy. She was referred to a specialist allergy clinic for further investigation with her consent. Intradermal allergy testing at standard concentrations was performed at the clinic for substances used in the case, with positive and negative controls. This was done in accordance with ANZAAG published guidelines. Substances included propofol, fentanyl, chlorhexidine, povidone iodine, ultravist, visipaque, omnipaque, and paclitaxel. Testing with paclitaxel yielded a significantly positive result. All other agents tested negatively. Results: The majority of contemporary DCBs use paclitaxel to prevent restenosis of arterial lesions following angioplasty. The Transpax™ proprietary coating of the Ranger™ balloon provides a paclitaxel density of 2 μg/mm², a relatively low concentration compared with commercially available DCBs. The excipient is a citrate ester with both hydrophilic and hydrophobic properties and its purpose to support coating integrity and transfer of paclitaxel to the vessel wall during inflation. Anaphylaxis is an acute, potentially life-threatening hypersensitivity reaction resulting from the abrupt release of mast cell and basophil-derived mediators into the circulation. It is a clinical diagnosis supported by elevated levels of serum mast cell tryptase. The reported incidence of hypersensitivity following systemic infusions of paclitaxel is 1%–3%, even when administered with antihistamine and glucocorticoids as premedication. In addition, the concentrations of paclitaxel deployed in DCBs are at least several hundred-fold lower. This case presents the first known incident of anaphylaxis following inflation of a paclitaxel DCB in the peripheral circulation. Our patient exhibited an abrupt onset of cutaneous signs with respiratory compromise and hypotension, together with a significantly elevated serum tryptase and a confirmed diagnosis of paclitaxel allergy. There is insufficient evidence to mount a case for a primary coronary insult. Investigations including TTE and coronary angiogram showed no evidence of significant disease. Instead we believe rate-related ST elevation and elevated troponins occurred in the context of hypotension and tachycardia. Notably, the patient had undergone successful angioplasty of the contralateral EIA and SFA 2 months earlier using two separate Ranger™ DCBs, with no adverse event. The mechanisms responsible for anaphylaxis are complex; however, it is proposed the patient was immunologically sensitized to paclitaxel from this previous exposure. It is implausible to suggest either the DCB excipient or delivery system were involved in the event. The likelihood that two independent agents induced anaphylaxis simultaneously is also exceedingly small. At the time of writing, three DCBs (IN.PACT Admiral DCB, Lutonix DCB, and Stellarex DCB) have been approved by the FDA following RCTs. Two DCBs (SurVeil DCB and Ranger DCB) are still to be approved following completion of the trials. No drug hypersensitivity reactions have been reported. To our knowledge, there are no other reported cases of anaphylaxis to paclitaxel DCB when used as endovascular treatment for peripheral arterial disease. There is one case in the literature of acute hypersensitivity reaction following femoral-popliteal angioplasty with paclitaxel DCB. The patient developed a painful, erythematous rash of the thigh shortly after removal of the DCB with associated agitation, tachycardia and hypertension. However, the patient did not meet criteria for anaphylaxis. Another paper reported delayed hypersensitivity reaction manifesting as a vasculitic rash of the lower limb following femoral angioplasty of the symptomatic limb with a paclitaxel-coated balloon. Conclusion: There is evidence to support the use of DCBs in the treatment of peripheral arterial occlusive disease via improvements in vessel patency. We present a rare case of anaphylaxis following deployment with a paclitaxel DCB. Clinicians using these devices should be aware of such risk.

Publication History

Article published online:
26 April 2021