Aortic stent graft leak and aneurysm rupture after alteplase for stroke

Discussion

Endovascular therapies for the management of infrarenal abdominal aortic aneurysms are increasingly performed because of their favourable early safety profile, shorter hospital stays and decreased short-term mortality, when compared with open surgical repair.1^,2 However, long-term outcomes remain generally more favourable with open repair because of late complications associated with endovascular prosthesis.1^,2

The most important late complications are leaks, which have been described in 30.5% of patients after endovascular aortic repair procedures.3 Endoleaks are classified as 5 different types of endoleaks and endotension (Box 1). Endotension, sometimes referred to as type V endoleak, consists of increased expansion of the aneurysm sac with growth surrounding the stent graft but no actual leak identified. In most patients, endoleaks and endotension will be discovered on radiologic follow-up, while some will present with subacute progression of abdominal pain. Prompt radiologic evaluation will allow for timely intervention before aneurysm rupture. In a cohort of 39 966 Medicare beneficiaries who underwent endovascular aortic repair, aneurysm rupture occurred in 5.4% of patients over an 8-year follow-up.4 Risk factors for aneurysm rupture after endovascular aortic repair are the presence of an endoleak, stent migration and, potentially, the size of the underlying aneurysm.5 Aneurysm rupture occurs at a constant rate after endovascular aortic repair4 and delayed length of time since the original repair should not preclude the possibility of aneurysm rupture.

Thrombolytics are used frequently for various indications, including strokes, massive pulmonary embolism and limb ischemia. Multiple absolute and relative contraindications exist and must be systematically reviewed before those drugs are administered. Our case highlights a potential complication of the use of thrombolytics with aortic endovascular stent grafts, even when inserted months to years earlier (10 mo in our patient; even longer in other case reports).

Appendix 1 (available at at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.181698/-/DC1) summarizes some similar cases we identified in the medical literature, in which patients with aortic endovascular stent grafts developed acute endoleaks after administration of thrombolytic agents (altepase or urokinase) for stroke or lower-extremity limb ischemia, some requiring endovascular or surgical repair procedures. Of note, out of 178 reported adverse events associated with alteplase (most of those being intracerebral hemorrhagic complications or allergic reactions) in the Canada Vigilance Adverse Reaction Online Database (www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/adverse-reaction-database.html), only 3 are listed as intra-abdominal or peritoneal hemorrhage and none mention the presence of a stent graft. It has been proposed that stent grafts become more porous after exposure to thrombolytics, but dynamic changes in the integrity of wall thrombus may also play a role.6 The formation of normal wall thrombus after graft implantation is part of the graft’s integrity and impermeability, especially for type IV endoleak. It is plausible that thrombolytics may disrupt the integrity of normal wall thrombus and precipitate formation of new leaks. Systemic anticoagulation with warfarin, which causes less disruption of clot homeostasis than thrombolytics, has been shown to increase the risk of formation of all types of endoleak.7 However, it is unclear whether thrombolytics cause new leaks to form or if leaks are simply undiagnosed before administration of the agent.

In unrepaired aortic aneurysm, use of thrombolytics has been associated with leak of the aneurysm8 and dislodgement of thrombus with distal embolization.9 These reports suggest that unruptured arterial aneurysms maintain a fragile homeostasis from the balance of coagulation and innate fibrinolysis inside the mural thrombus. This homeostasis has been extensively studied,10^–11 but the impacts of thrombolytic drugs could be critical for patients with underlying aneurysmal vascular disease.

Current guidelines, including the American Heart Association/American Stroke Association12 and Canadian guidelines,13 do not include the presence of an aortic aneurysm or a prior aortic stent graft as a consideration before thrombolysis. As endoleaks are both common and associated with aneurysmal rupture after endovascular aortic repair, we believe those should be listed as relative contraindications for administration of thrombolytics, whether for stroke, myocardial infarction, pulmonary embolism or limb ischemia. If time permits, we suggest that patients with a known history of endovascular aortic repair undergo abdominal CT angiogram before administration of thrombolytics agents, to help identify patients at higher risk of aneurysm rupture. Because the absence of an endoleak does not preclude aneurysm rupture, we suggest that risks associated with administration of thrombolytics in the presence of an aortic aneurysm or stent graft be presented to the patient or substitute decision-maker when discussing the risks and benefits of this therapy. Balancing these risks and benefits is challenging, as the actual risk of rupture is unknown; we can assume the risk remains low, as only a few case reports of this complication have been published. This risk, however small, may help with making the decision in ambiguous cases (for example, stroke with minor deficits, or submassive pulmonary embolism). When evaluating risk and benefits, we suggest that the time delay between graft installation and presentation be noted, careful review of follow-up imaging be undertaken and, when in doubt, consultation with a vascular surgeon before administration be considered.