Aortoiliac thrombosis in COVID-19 patients: A case series.

Severe acute respiratory syndrome coronavirus 2 infection has been associated with a prothrombotic state. Reports of arterial and venous thrombosis have emerged. Here, we report three cases of aortoiliac thrombosis presenting as mesenteric and lower extremity ischemia in coronavirus disease 2019 patients with no identifiable proximal embolic source or history of prothrombotic condition. Copyright:

INTRODUCTION

Acute arterial thrombosis is a vascular emergency as a sudden decrease in end-organ perfusion can cause a threat to its viability. It most commonly occurs secondary to an embolic or thrombotic event in the setting of atherosclerotic disease or prior vascular intervention.[1] Here, we report three cases of acute aortoiliac occlusion presenting as mesenteric or lower extremity ischemia in coronavirus disease 2019 (COVID-19) patients with no identifiable proximal embolic source or history of prothrombotic condition.

CASE REPORTS

Case 1

A 53-year-old Caucasian female with a history of hyperlipidemia presented to the emergency department (ED) with 5 days of fever and dyspnea. Initial vitals revealed blood pressure (BP) of 136/67 mmHg, pulse of 91 bpm, respiratory rate (RR) of 26 bpm with SaO2 of 84% on room air, and temperature of 97.2°F. She was in acute hypoxic respiratory failure due to COVID-19 pneumonia and was placed on high-flow nasal cannula. On hospital day 7, the patient experienced severe left buttock claudication and left foot numbness. Examination revealed a cyanotic, pulseless left lower extremity with numbness and reduced motor function consistent with acute ischemia. The contralateral limb had normal pedal pulses. D-dimer levels had increased from 0.43 μg/mL to 3.14 μg/mL. Computed tomography angiography with runoff (CTA-R) showed a near occlusive thrombus in the left common iliac artery [Figure 1].

Figure 1

(a) Computed tomography angiography with runoff showing near occlusive thrombosis in the left common iliac artery (white arrow). (b) Intraoperative angiogram showing luminal irregularities in the anterior tibial artery (top arrow) and a filling defect in the peroneal artery (bottom arrow)

Therapeutic heparin was started. Thromboembolectomy of the left iliac artery and catheter-directed thrombolysis of the anterior tibial and peroneal arteries were performed [Figure 1 and Table 1]. Embolic workup did not reveal any proximal source. The patient was discharged on postoperative day (POD) 8. On POD 25, she reported resolution of claudication and had intact pedal pulses. She is currently maintained on therapeutic apixaban.

Table 1

Summary of patient presentations, significant laboratories, imaging findings, and intervention (s)

	Presentation	Significant Labs	Findings on CTA-R	Intervention
Case 1	Sudden left buttock claudication and left foot numbness during admission for acute hypoxic respiratory failure	D-dimer increase from 0.43 ug/ml to 3.14 ug/ml	Near occlusive thrombus in the left common iliac artery	Left iliac thromboembolectomy with selective catheter directed thrombolysis of the anterior tibial and peroneal arteries
Case 2	Fever, lethargy, and confusion. Found to have advanced right lower extremity ischemia on examination	Lactate of 3.9 mmol/L, D-Dimer>10ug/ml	Occlusive thrombus at the right common iliac artery with no evidence of distal reconstitution	Intervention withheld due to patient age, comorbidities, and family discussion
Case 3	Sudden severe epigastric pain after recent hospitalization for 10-days due to acute hypoxic respiratory failure	Lactate of 2.5 mmol/L, WBC of 22ȕ10ȕ^3/uL	Eccentric thrombus in the infrarenal aorta with filling defects in the SMA	Percutaneous mechanical thrombectomy followed by exploratory laparatomy and jejunal resection

Case 2

A 92-year-old Hispanic male with a history of hyperlipidemia presented to the ED in an obtunded state after 14 days of fever and lethargy. Initial vitals revealed BP of 155/91 mmHg, pulse of 117 bpm, RR of 30 bpm with SaO2 of 98% on room air, and temperature of 98.9°F. Examination was consistent with advanced right lower extremity ischemia with motor and sensory loss. The contralateral limb had normal pedal pulses. He was positive for COVID-19. There was lactic acidosis (3.9 mmol/L) and an elevated D-dimer (>10 μg/mL). CTA-R showed an occlusive thrombus originating at the right common iliac artery with no distal reconstitution [Figure 2]. Based on patient age and presentation, surgical intervention was withheld [Table 1]. Due to the patient's poor response to medical management, he was placed on comfort measures and expired on hospital day 1.

Figure 2

(a) Computed tomography angiography with runoff showing complete thrombosis of the right iliac and (b) right femoral arteries. Dashed arrows show thrombosed vessels while white arrows show patent vessels

Case 3

A 63-year-old Caucasian female with a history of coronary artery disease, chronic kidney disease, and multiple prior abdominal surgeries was hospitalized for 10 days with COVID-19 pneumonia. Three days after discharge, she returned with 2 h of severe epigastric pain. Initial vitals revealed BP of 143/83 mmHg, pulse of 111 bpm, RR of 26 bpm with SaO2 of 90% on room air, and temperature of 98.1°F. Examination revealed a soft, nontender abdomen. Laboratory workup revealed lactic acidosis (2.5 mmol/L) and leukocytosis (22 ȕ 103/μL). CTA showed an eccentric thrombus in the infrarenal aorta with filling defects in the superior mesenteric artery (SMA) confirming acute mesenteric ischemia [Figure 3].

Figure 3

(a) Computed tomography angiography showing eccentric thrombus at the level of the infrarenal aorta (red arrow). (b) Filling defect in superior mesenteric artery branch (white arrow). (c) Angiogram showing superior mesenteric artery branch occlusion (white arrow)

After starting therapeutic heparin, she underwent percutaneous mechanical thrombectomy via left radial access to restore intestinal perfusion [Figure 3 and Table 1]. As her symptoms improved, her diet was advanced. However, on POD 8, she had recurrent abdominal pain. CTA revealed a patent SMA, but there was jejunal pneumatosis requiring urgent exploratory laparotomy and resection of necrotic jejunum. Since there was no evidence of distal embolization on completion angiography, bowel necrosis was likely due to the initial ischemic insult and its progression. Embolic workup did not reveal any proximal source. On postintervention day 21, she was tolerating a regular diet with normal bowel function and was discharged on therapeutic apixaban.

DISCUSSION

The cases above may have arisen spontaneously or secondary to COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a propensity to create a prothrombotic state in infected hosts.[2] The virus accomplishes this function via direct and indirect mechanisms. In the direct pathway, it enters cells by binding to angiotensin-converting enzyme II receptors and triggering inflammatory cascades. This leads to tissue factor upregulation and activation of the coagulation cascade.[3] Tissue-engineered arterial models have supported this mechanism.[2] Indirect mechanisms involve the systemic effects of the virus and its ability to induce proinflammatory cytokines which activate endothelial and mononuclear cells to promote platelet activation and coagulation.[4]

In our cohort, all patients had macrovascular thrombosis involving the aortoiliac segment. The index patients had no history of peripheral arterial disease, known prothrombotic condition, or any identifiable proximal embolic source. This suggests the possibility of native arterial thrombosis occurring secondary to SARS CoV-2's propensity to promote endotheliopathy and platelet dysfunction.[4] At present, clinical data on acute arterial ischemia secondary to COVID-19 are limited. Vulliamy et al. reported two cases of mesenteric and aortoiliac occlusion in patients with minimal risk for embolic disease and negligible calcific burden.[5] Bellosta et al. published a descriptive cohort study of twenty Italian patients with acute arterial ischemia. Their institutional experiences suggest a virus-related hypercoagulability as the likely etiology.[6]

There are some data supporting the significance of D-dimer elevation as a predictor of venous thromboembolism (VTE) and overall disease severity.[78] In a retrospective review, patients with fibrinolysis shutdown, as defined by elevated D-dimer and low LY30 on thromboelastography, had a significantly elevated risk of VTE.[8] Emerging guidelines recommend prophylactic dose anticoagulation for all hospitalized COVID-19 patients in the absence of contraindications.[7910] However, the role of therapeutic anticoagulation has yet to be established.

As COVID-19 cases rise globally, an increase in the number of patients presenting with arterial thrombosis and end-organ ischemia is expected. Because COVID-19 patients are sequestered under strict isolation protocols, it is important to remain vigilant for this complication that requires prompt intervention. Most COVID-19 patients with arterial thrombosis may be successfully treated with anticoagulation and urgent intervention. The duration of anticoagulation therapy to prevent re-thrombosis remains to be determined.

Consent

Written consent was obtained in cases 1 and 3. Surrogate written consent was obtained from the patient's family in case 2.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients (cases 1 and 3) and patient's guardian (case 2) have given their consent for the images and other clinical information to be reported in the journal. The patients (cases 1 and 3) and patient's guardian (case 2) understand that the names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Research quality and ethics statement

This case series did not require approval by the Institutional Review Board/Ethics Committee. The authors followed applicable EQUATOR (http://www.equator-network.org/) network guidelines, specifically the CARE guideline, during the conduct of this research project.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.