Since the beginning of severe acute respiratory syndrome Coronavirus 2 pandemic, hypercoagulable states have been prevalent in the majority of individuals with Coronavirus (COVID-19) [1,2]. Patients suffering from severe acute respiratory distress syndrome in the intensive care unit are especially at risk for thrombosis during the acute phase [2-4]. This severe illness primarily affects the pulmonary system, and the associated coagulopathy significantly contributes to the high fatality rates [5,6].

Furthermore, thromboembolic complications have developed at significant rates in recovered and discharged patients [4,7,8]. We report a case of multiple arterial thrombosis in a 63-year-old female patient. These thrombotic events developed 20 days after her discharge from treatment in the intensive care unit for severe COVID-19 pneumonia and pulmonary embolism.

This case report was exempt from assessment by the institutional review board of the Atatürk University Medical Faculty, and informed consent was obtained.

A 63-year-old female patient was discharged after receiving treatment in the critical care unit for 2 months in another hospital owing to severe COVID-19 pneumonia (Fig. 1) and accompanying submassive pulmonary embolism (Fig. 2). She did not have a significant chronic disease, had no history of smoking, and had not yet received vaccination for COVID-19. Since her discharge, she has been taking rivaroxaban 20 mg and methylprednisolone 16 mg daily.

Figure 1. The patient’s computed tomography images of thorax. Severe COVID-19 pneumonia during her treatment in intensive care unit (A). Partially healed lung after discharge (B).

Figure 2. Images of the patient’s thorax and abdomen computed tomography. Right and left main pulmonary artery embolism (A). Celiac artery thrombosis extending into the aortic lumen (B). Superior mesenteric artery thrombosis hanging to aorta (C). Saddle embolism at aortic bifurcation (D) and the thrombus extending into the bilateral common iliac arteries (E). Left external iliac artery thrombosis (F). Arrows indicated the lesions.

However, 20 days after being discharged, the patient visited the emergency department with complaints of stomachache, weakness, and pain in her left lower limb. The patient was admitted to our clinic. On physical examination, mild tenderness in the abdomen, loss of pulse in the left lower extremity, and weakened pulse in the right lower extremity were noted. Additionally, increased respiratory rate with mild hypoxia (22 breaths/min, 89% in room air) and normal body temperature were detected. There was no evidence of deep venous thrombosis (DVT) in physical and Doppler ultrasound examinations. Laboratory testing revealed high aspartate aminotransferase and D-dimer levels, hyponatremia, and hypokalemia. Since the patient had been hospitalized for a long time and was in the critically-ill group, we thought that she was already at high risk for thrombosis. Also, the anticoagulant (AC) treatment would affect the hypercoagulability tests; therefore, hypercoagulability test was not conducted. We performed thorax and abdominal computed tomography (CT), which revealed thrombosis of the celiac artery (CA) and superior mesenteric artery (SMA), as well as a thrombus hanging in the aortic lumen. Saddle embolism of the aortic bifurcation and left external iliac artery thrombosis were also detected (Fig. 2).

The general surgery consultant did not deem emergency laparotomy necessary. Therefore, oral intake was discontinued, and the patient received medical-supervision to monitor potential signs of mesenteric ischemia. An electrocardiogram, which showed no signs of myocardial ischemia, revealed sinus rhythm. Transthoracic echocardiography also revealed no presence of cardiac thrombus.

The patient underwent bilateral femoral thromboembolectomy under local anesthesia. The bilateral common, deep, and superficial femoral arteries were explored. After heparinization, proximal and distal thrombectomy was performed separately with more than one pass. Abundant thrombus was evacuated from both proximal sides. No thrombus was observed in the femoropopliteal arteries, and strong pulsatile flow was achieved in the bilateral femoral arteries. Postoperatively, the patient was given intravenous 6×5000 IU/day unfractionated heparin, followed by subcutaneous low molecular weight heparin (LMWH) (enoxaparin 1 mg/Kg twice a day) on the 2nd postoperative day to discharge. The sample pathology report was acute arterial thrombus.

The patient did not experience any gastrointestinal symptoms during the two days without oral intake. Subsequently, oral feeding was initiated with a liquid feeding regimen; however, the patient developed a recurrence of abdominal pain. CT angiography was renewed and interventional procedure was deemed necessary. Thrombi hanging in the CA, SMA, and aorta were still present. The patient was taken to the angiography unit, where femoral and brachial interventions were performed. Abdominal aortography was performed using brachial access. A thrombus protruding from the aorta was observed at the SMA entrance (Fig. 3A). Since the SMA orifice was not seen angiographically, the inferior mesenteric artery (IMA) was cannulated by coronary right diagnostic catheter (Boston Scientific) through brachial approach, and retrograde injection was performed to determine the SMA entry. The SMA stump identified by retrograde injection was attempted to be accessed through the femoral route but without success (Fig. 3B). IMA was re-cannulated with right guiding catheter (Boston Scientific). A 0.014-inch Choice Floppy Guide wire (Boston Scientific) was passed to the SMA with the support of a 2.5×15 mm balloon (Boston Scientific) that was advanced to the tip of the catheter (balloon-assisted tracking) (Fig. 4). After a small amount of retrograde thrombus was aspirated using the right guiding catheter, a coronary chronic total occlusion wire (HI-TORQUE PILOT 200 Guide wire, Abbott Vascular Inc.) was advanced into the distal cap of the SMA thrombus and subsequently migrated into the abdominal aorta with the assistance of a coronary micro-support catheter (Boston Scientific). The retrograde wire in the aortic lumen was grasped and externalized with a gooseneck EV3 snare (Medtronic) inserted through the femoral route, and subsequently, the system was converted to antegrade (Fig. 5). Antegrade mechanical thrombus aspiration was performed by passing the SMA thrombus area with an 8F SL1 (Abbott Vascular) supported right guiding catheter, which is preferred in neurovascular interventions (Fig. 6A), and then, a 0.035-inch stiff guide wire (Abbott Vascular) was placed in the SMA, and predilatation was performed with a 4.0×40 mm balloon (Abbott Vascular) (Fig. 6B). After balloon dilatation, it was observed that the flow was restricted due to dissection. Subsequently, a 6.0×29 mm balloon-expandable stent (Abbott Vascular) was implanted, and complete patency of the SMA was achieved (Fig. 7). The mesenteric network blood supply and retrograde CA blood supply were found to be good, and after the procedures, all distal arterial branches were checked and no distal embolization was observed.

Figure 3. (A) Abdominal aortography performed via the brachial access showing thrombosis of the celiac and superior mesenteric artery inlets, and these arteries are filled retrogradely through the riolan arch. (B) Since antegrade intervention carries a risk of distal thromboembolism and superior mesenteric artery and the inlet is not seen angiographically, the inferior mesenteric artery was cannulated and retrograde angiography was performed to determine the superior mesenteric artery access and to perform retrograde thrombus aspiration.

Figure 4. (A, B) The guide wire is passed from the inferior mesenteric artery to the superior mesenteric artery area with the balloon-assisted tracking method. The arrows show the guide wire reaching the superior mesenteric artery and continuing distally.

Figure 5. (A) 8F SL1 catheter extended to the superior mesenteric artery via femoral access (arrow). (B) The snare (arrow), advanced by the right guiding catheter in the SL1 sheath, captures the guide wire, which is dropped retrograde into the aortic lumen from the superior mesenteric artery, and then the wire is externalized.

Figure 6. (A) The system was turned to antegrade and the thrombus was aspirated from the superior mesenteric artery via right guiding catheter supported with SL1 sheath. (B) Balloon predilatation of the superior mesenteric artery.

Figure 7. (A) A balloon-expandable stent was implanted in the superior mesenteric artery. (B) Imaging of final flow after stent placement in the superior mesenteric artery.

After the intervention, the patient was followed up for additional 2 days. The pain in the abdomen and lower extremities was resolved, and she was discharged with dual antiplatelet agents (100 mg/day of aspirin and 75 mg/day of clopidogrel) and AC (rivaroxaban 20 mg/day). The patient was well at the 6th, 12th, and 18th months follow-up and had no additional problems.

The COVID-19 pandemic affected almost every age group. Many cases have been reported with an increased propensity for coagulopathy [1-3]. Thrombotic events include microvascular thrombosis, demonstrated by autopsy in multiple vascular beds, including the pulmonary, hepatic, and renal systems [8-10]. Macrovascular thrombosis has also been frequently observed in patients across different risk groups, resulting in impaired organ function in instances such as diffuse DVT, myocardial infarction (MI), stroke, or lower extremity ischemia [8-10]. Notably, 25% of all COVID-19 patients admitted to the critical care unit have developed acute DVT, which has been associated with an unfavorable prognosis [2]. Furthermore, it has been reported that patients with active COVID-19 infection may exhibit antiphospholipid antibodies, contributing to hypercoagulopathy and thrombotic microangiopathy [2]. Elevated D-dimer levels have been demonstrated in hospitalized patients with severe COVID-19, and many early reports have linked higher D-dimer levels to worse outcomes [2-4,8,10-12].

The incidence of venous thromboembolism (VTE) after COVID-19 disease is generally well-defined and has reported high rates ranging from 7.8% to 31.3% [13,14]. Conversely, the incidence of arterial thromboembolic events (ATEs) has generally been found to be lower. In a meta-analysis of 35 observational cohort studies involving 9,249 patients hospitalized with COVID-19 in the early period of the pandemic, the pooled incidence for VTE was 18.4% (12.0-25.7). The incidence of acute coronary syndrome/MI, ischemic stroke, systemic arterial embolism, mesenteric and limb ischemia was 3.3% (0.3-8.5), 1.8% (1.3-2.4), 1.6% (0.4-3.6), 1.4% (0.2-3.5) and 1.1% (0.1-3.0) respectively [15]. Additionally, Tan et al. [14] reported the incidence of ATE as 3.9% (95% confidence interval [CI], 2.0-3.0) in 16 studies involving 7,939 patients. In a recent meta-analysis, Candeloro and Schulman [16] reported ATE in 2,641 (2.6%) of a cohort of 100,949 patients. This pooled incidence of ATE included 0.8% (95% CI, 0.1-8.1) acute MI, 0.9% (95% CI, 0.3-2.9) acute ischemic stroke, 0.2% (95% CI, 0.0-4.2) acute limb ischemia, and 0.5% (95% CI, 0.1-3.0) other ATE [16].

Although this prothrombotic state in COVID-19 patients has been well-documented and boardly acknowledged, a standardized protocol has not yet been determined regarding the necessity for patients to use ACs, the specific type, and the duration of treatment. Bannazadeh et al. [4] reported four patients with symptomatic acute lower extremity DVT who returned to the emergency room within 7 days after being discharged following previous COVID-19 disease. Moreover, Borrelli et al. [8] submitted three patients presented with delayed ATE around 30 days after the diagnosis of COVID-19, even though they had tested negative for COVID-19 on a nasopharyngeal swab. The duration and incidence of post-discharge thromboembolic events in some studies ranged from 0.2% to 30.7% in an average of 23-90 days [17]. These difference in rates was associated with whether the patients in the study population possessed risk factors for thromboembolic events, such as advanced age, history of malignancy, diabetes, and intensive care unit treatment [17].

The patient we are presenting was admitted to the intensive care unit due to severe COVID-19 pneumonia for 3 weeks during her previous hospitalization in another hospital. While in the intensive care unit, she developed pulmonary embolism and remained hospitalized for an extended period of over 3 months. She received AC therapy with LMWH during hospitalization and switched to rivaroxaban after discharge. However, three weeks after being discharged, she returned to the emergency room again with acute CA, SMA, aortic bifurcation, and left external iliac artery thrombosis. This result emphasizes that in some patients with severe COVID-19 illness, the prothrombotic state may persist long after the acute symptomatic phase. Furthermore, in a community-based study, Knight et al. [18] reported that the incidence of vascular events after COVID-19 infection remained high up to 49 weeks. After the intervention, we added dual antiplatelet medications in addition to rivaroxaban as we thought that only anticoagulation would be insufficient for the patient, and we could reach an effective therapeutic outcome with the additional agents.

In conclusion, this case suggests that the prothrombotic condition may endure long after the onset of COVID-19 infection. Although thrombi formation in the aortic lumen and its main branches is rare, an increase in such cases has been noted during the pandemic. It is evident that extensive research is required to fully comprehend the role of coagulopathy and AC medications in the treatment of patients with COVID-19.

None.

The authors have nothing to disclose.

Concept and design: FB, GC, ESÇ. Analysis and interpretation: FB, ESÇ. Data collection: GC, ESÇ, IJ, HU. Writing the article: ESÇ, IJ. Critical revision of the article: FB, ESÇ, IJ. Final approval of the article: all authors. Statistical analysis: none. Obtained funding: none. Overall responsibility: ESÇ.