Recurrent, Acute Limb Ischemia Secondary to Arterial Thrombosis: A Devastating Complication in the Setting of Severe COVID-19 Infection

Abstract

Background

COVID-19 infection, particularly with the Delta variant, has been associated with a heightened risk of thromboembolic events due to a profound hypercoagulable state. While venous thrombosis is more commonly reported, arterial thrombosis—including acute limb ischemia—has emerged as a serious complication with significant morbidity and mortality.

Case Presentation

We report the case of a 53-year-old man with severe COVID-19 pneumonia who developed recurrent acute limb ischemia secondary to an aortic mural thrombus. Despite therapeutic anticoagulation and multiple surgical interventions—including thrombectomy, angioplasty, and stenting—the patient experienced repeated episodes of arterial thrombosis. His clinical course was further complicated by pneumothorax and hemothorax, ultimately resulting in cardiopulmonary arrest and death.

Conclusion

This case highlights the aggressive and resistant nature of arterial thrombosis in the setting of severe COVID-19. Recurrent arterial thrombosis in severe COVID-19 underscores the need for early recognition and aggressive anticoagulation strategies. Further research is warranted to establish protocols for thromboembolic prevention in this high-risk population.

Background

Blood hypercoagulability is a typical feature of COVID-19 pneumonia, placing patients at a high risk of thromboembolic events.^1,2 While pulmonary embolism is the most common thrombotic manifestation of COVID-19,² cases of arterial thrombosis causing large vessel strokes,^3,4 clot formation in the abdominal aorta,^5,6 mesenteric ischemia,⁷ and acute limb ischemia^8–10 have also been reported. While the exact causal mechanism is not yet known, the severe inflammation in COVID-19 and the direct infection of endothelial cells likely contribute to this hypercoagulable state, increasing the risk of clot formation, which can affect any organ system.¹¹ To illustrate this potentially devastating effect of COVID-19, we highlight a unique case of acute limb ischemia secondary to the formation of an aortic mural thrombus. Additionally, we urge clinicians to recognize the rapid and resistant clot formation that can occur in this setting as our patient required multiple surgical interventions for recurrent arterial thromboses of his left lower extremity despite being on therapeutic doses of heparin for anticoagulation.

Case Presentation

A 53-year-old man with a history of hypertension presented to the emergency department with fever, chills, shortness of breath, and pleuritic chest pain. The patient was hypoxic on admission and tested positive for COVID-19 infection. He initially required 6 liters of oxygen via nasal cannula but was then placed on a nonrebreather mask for further management of his severe COVID-19 pneumonia. His inflammatory markers were significant for elevated C-reactive protein, D-dimer, lactate dehydrogenase, and ferritin. An initial computed tomography (CT) angiogram of the chest demonstrated multifocal patchy airspace opacities but was negative for pulmonary emboli or aortic thrombi (Figure 1: Left). The patient was therefore started on daily subcutaneous enoxaparin for deep vein thrombosis (DVT) prophylaxis. For COVID-19 pneumonia, the patient was treated with intravenous (IV) remdesivir, IV ceftriaxone, IV azithromycin, low dose IV dexamethasone, and inhaler therapy with tiotropium and albuterol.

Figure 1.

(Left) A computed tomography of the chest with intravenous administration of iopamidol 76 mL showed no thrombi. (Right) A computed tomography aortogram showed the aortic mural thrombus.

The patient’s hospital course was unremarkable until day 4, when he experienced a sudden onset of severe pain upon passive manipulation of his left foot. His physical examination was notable for significant pallor and discoloration amid sensory deficits over the mid-dorsal aspect of his left foot. The dorsalis pedis and the posterior tibialis pulses were neither palpable nor obtainable via bedside doppler. The patient was immediately started on a therapeutic heparin drip after a bolus of weight-based heparin. A CT angiogram of the aorta with runoff demonstrated a new extensive thrombotic burden extending distally from the descending thoracic aorta, mid-distal left external iliac, and the femoral and mid-distal portion of the left popliteal arteries (Figure 1; Right). There was accompanied poor filling of the infrapopliteal vessels, including the posterior tibialis, concerning for distal thrombo-emboli. The patient underwent an emergent bilateral common femoral artery exploration with endarterectomy, patch angioplasty, and stenting. A penumbra thrombectomy was performed at the level of the popliteal, which allowed for reconstitution of the laminar flow. There were still some residual clots noted in the distal popliteal artery, as well as its trifurcation. An open thrombectomy was then performed upon which the patient had complete laminar flow to the anterior tibial and the peroneal arteries. He was transferred to the intensive care unit (ICU) on a therapeutic heparin drip and intubated for possible take-back.

By postoperative day 4, the patient began showing signs and symptoms of recurrent acute limb ischemia with similar previous complaints. A repeat CT angiogram of the aorta showed complete occlusion of the left common femoral artery continuing through the superficial femoral artery with accompanied in-stent thrombosis. The patient underwent a repeat femoral artery exposure, open thrombectomy of the common femoral artery with Fogarty embolectomy, an incorporation of a new bovine patch into the previous regional patch, and a penumbra suction thrombectomy of the left posterior tibial and lateral tarsal artery with significant thrombus retrieval. Again, there was no significant residual thrombus remaining at the end of the operation. The patient remained intubated postoperatively with an increased rate in heparin drip.

Unfortunately, despite the above surgical interventions and appropriate continuous anticoagulation, the patient had developed yet another episode of recurrent acute limb ischemia. An arterial duplex study done at the bedside was significant for an occluded left posterior tibial artery, and the vascular surgeon had to perform another embolectomy. There was extensive clot burden throughout the patient’s lower extremity arterial vasculature, some of which was inaccessible to surgical intervention. The operation concluded with balloon angioplasty of the left dorsalis pedis and anterior tibial arteries with sequential inflations along the entire length of the 2 vessels. Concerned that the patient continued to develop clots despite being on a continuous therapeutic heparin drip, he was transitioned to an argatroban drip with a goal-activated clotting time of 250–300 s.

Unfortunately, the patient’s remaining ICU course was complicated by a right pneumothorax, likely from prolonged mechanical ventilation and barotrauma, prompting a chest tube placement, further complicated by anticoagulation-induced hemothorax. The medical team had a risks and benefits discussion with shared decision-making to continue anticoagulation for limb salvage, but the patient was hemodynamically unstable, requiring pressors for his ongoing blood loss. Overnight, he required CPR for pulseless electrical activity and asystole, with the eventual family decision to stop all interventions.

Discussion

The cytokine storm associated with the Delta-variant (B.1.617.2) COVID-19 infection has been associated with many thromboembolic complications. While venous thromboembolism has been commonly reported, recent research including multiple case reports and series has highlighted the increased incidence of arterial thrombosis in this patient population.^11–13 While each case is unique, almost all patients developed arterial thrombosis in the setting of acute hypoxic respiratory failure secondary to COVID-19 pneumonia. In our case report, we outline a similar presentation as our patient developed arterial thrombosis in the setting of bilateral multifocal air space opacities secondary to COVID-19. This implies that patients with severe COVID-19 pneumonia with extensive lung involvement are in a profound hypercoagulable state secondary to the cytokine storm. Thus, to prevent such complications, we highlight the need for therapeutic anticoagulation in critically ill COVID-19 patients. To support our contention, an open-label, adaptive, multiplatform-controlled trial has shown increased probability of survival to hospital discharge among patients with severe COVID-19 pneumonia treated with therapeutic anticoagulation on admission.¹⁴ Several cohort studies have also shown a favorable association between anticoagulant use and survival from COVID-19 despite lack of DVT or pulmonary embolism on imaging. More recently, the MICHELLE trial reported the benefits of rivaroxaban after hospitalization for COVID-19 without increasing the risk for bleeding.¹⁵ While these results are promising, there are no set guidelines on the prevention of thromboembolic complications for these patients.

Conclusion

Therapeutic anticoagulation should be regarded as a critical component of care in patients with severe COVID-19, given the demonstrated risk of recurrent arterial thrombosis despite standard interventions. The hypercoagulable state induced by SARS-CoV-2 demands heightened clinical vigilance and may warrant protocolized anticoagulation strategies tailored to inflammatory and thrombotic markers. Establishing evidence-based guidelines is imperative to reduce thromboembolic complications and improve outcomes in this high-risk population.