key: cord-0771907-a48ksmrb
authors: Maurera, Annabella H.; Vu, Jonathan-Hien; Rehring, Thomas F.; Layman, Peter F.; Johnson, Stephen P.
title: Acute Limb Ischemia in Minimally Symptomatic SARS-CoV-2 Infection
date: 2020-08-13
journal: Journal of Vascular and Interventional Radiology
DOI: 10.1016/j.jvir.2020.08.009
sha: 285aa8610aba7dc75ed08d4c78d1b5d7ff877267
doc_id: 771907
cord_uid: a48ksmrb

nan

Patients with COVID-19 present with a wide spectrum of symptoms, but mounting experience is noted with an apparent pro-thrombotic state. In addition to microvascular thromboses, there are reports of macrovascular thrombotic events in critically ill patients infected with SARS-CoV-2 (1,2). However, acute limb ischemia is also seen in a patient only minimally symptomatic with SARS-CoV-2 infection and no other risk factor for embolus or thrombosis. This case report was approved by the Institutional Review Board.

The patient is a 60-year-old obese nonsmoker with hypertension presenting with a 10-day history of fever, sinus congestion, anosmia, ageusia and three days of new onset left foot aching pain and coolness, digital numbness, and the inability to bear weight. Cardiovascular examination demonstrated a normal sinus rhythm. Physical examination was consistent with acute limb ischemia (Rutherford IIa). An emergent arteriogram demonstrated thrombus in the distal left profunda femoris artery (Figure 1) , occlusion of the left popliteal artery (Figure 2 ), and thrombi throughout the left tibial arteries without flow into the left foot ( Figure 3 ). The patient received 100 units per kilogram of intravenous heparin. Mechanical thrombectomy of the anterior tibial and peroneal arteries, with 2 mg of intra-arterial tPA laced into the popliteal and anterior tibial arteries, was performed with a CAT5 Penumbra Indigo® catheter (Penumbra, Alameda, CA). An overnight dual level tPA infusion was started at 0.5 mg/hr each into a 10 cm MicroMewi infusion catheter (Metronic, Minneapolis, MN) that was placed into the anterior tibial artery and a CAT5 Penumbra catheter in the popliteal artery. Five hundred units of intravenous heparin was also administered through the sheath.

The patient clinically improved overnight without evidence for compartment syndrome. Followup angiography demonstrated residual thrombi in the anterior and posterior tibial arteries. The left peroneal artery had segmental occlusion and terminated just above the ankle (Figure 4 ). Vacuum-assisted thrombectomy of the anterior and posterior tibial arteries was performed with CAT6 Penumbra Indigo® catheter (Penumbra, Alameda, CA) and patency was restored to the level of the ankle; flow into the foot remained minimal via small plantar vessels. Catheterdirected thrombolysis was continued with 5 cm Uni-Fuse infusion catheter (Angiodynamics, Latham, NY) placed in the distal left popliteal artery at a rate of 0.75 mg/hr. A repeat angiogram on the third hospital day demonstrated patent anterior and posterior tibial arteries with restored perfusion into the left foot ( Figure 5 ). Catheter-directed thrombolytic therapy was discontinued.

No source of embolus was discovered on echocardiogram or CTA of the aorta. However, chest CT revealed scattered bilateral pulmonary ground glass opacities ( Figure 6 ). In-hospital SARS-CoV-2 testing was positive. A hypercoagulable panel was remarkable only for increased levels of anticardiolipin IgM (39; 0-12 MPL) and IgG (43; 0-14 GPL). Therapeutic intravenous heparin was continued during his hospitalization. The patient was transitioned to oral anticoagulation and discharged on hospital day six. At discharge, there was residual left foot swelling and superficial skin ischemia in the distal left first and fourth toes, and palpable pedal pulses. He was able to bear weight on his left foot and subsequently returned to work a month later. Post-intervention noninvasive vascular studies at one month demonstrated bilateral ankle-brachial indices were 0.98 and there was no hemodynamically significant stenosis in either lower extremity.

As the scientific community learns more about SARS-CoV-2, it is understood that the virus is capable of impacting multiple organ systems beyond its effect as a predominantly pulmonary J o u r n a l P r e -p r o o f pathogen. While the data highlighting abnormal coagulation factors in patients with SARS-CoV-2 has mostly been obtained from critically ill patients (3) , this case suggests that coagulopathy might exist in the absence of critical illness and may lead to large vessel occlusion. The mechanism for SARS-CoV-2 induced coagulopathy is complex and likely has multiple contributing factors. Vascular endothelium is critical for maintaining vascular homeostasis. The virus acts on vascular endothelium via ACE2 receptors and there is evidence of direct virus infection of the vascular endothelial cells, resulting in diffuse endothelial inflammation and procoagulant state (4). Antiphospholipid antibodies may play a role (1). Published case reports of treatment of ALI in COVID-19 patients have been largely limited to open surgical approach (2). Transluminal pharmaco-mechanical technique is an option in this vulnerable population. Anticoagulation appears to be associated with better prognosis in severe COVID-19 patients with coagulopathy (2, 4) . How long inflammation and thrombotic derangements last after recovering from the symptoms of COVID-19 remains unclear. Thus, extended post hospitalization anticoagulation, either with LMWH or oral anticoagulant, for 30 days to 6 weeks is currently empirical and long-term treatment may be considered.

Various immunologic factors appear to contribute to the development of microvascular and macrovascular thromboses in patients infected with SARS-CoV-2. Although a direct link remains unclear, SARS-CoV-2 infection can present with acute limb ischemia, even in those who are not critically ill and without prior cardiovascular disease. In selected patients, this may be managed successfully with percutaneous transluminal intervention. 

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan

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