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ORIGINAL ARTICLE
Year : 2022 | Volume
: 9
| Issue : 4 | Page : 302-306
COVID-19 and clotting: A wave of acute limb ischemia
Rahul Agarwal, Viswanath Atreyapurapu, Pritee Sharma, Vamsi Krishna Yerramsetty, Chainulu Saripalli, K Santhosh Reddy, Gnaneswar Atturu, Prem Chand Gupta
Department of Vascular and Endovascular Surgery and Interventional Radiology, Care Hospital, Banjara Hills, Hyderabad, Telangana, India
Correspondence Address:
Prem Chand Gupta
Department of Vascular and Endovascular Surgery and Interventional Radiology, Care Hospital, Banjara Hills, Hyderabad, Telangana
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/ijves.ijves_47_22
Introduction: A surge in the number of patients with acute limb ischemia (ALI) was seen during the first and second waves of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This has been ascribed to the hypercoagulable state seen in COVID infections. The aim of this study is to report our experience and outcomes of ALI associated with SARS-CoV-2 infection. Materials and Methods: It was a single-center observational retrospective study from a prospectively maintained database of patients with SARS-CoV-2 infection presenting with ALI between July 2020 and December 2020 with 1-year follow-up. Results: Thirty-nine acutely ischemic limbs were treated in 32 patients including three upper limbs. The mean age of patients was 55.75 (range: 27–80). There were 23 (71.87%) males and 9 (28.12%) females. Majority of the limbs were in Class IIB of ALI, whereas 20.51% had irreversible ischemia. Of the 39 affected limbs in 32 patients, 22 limbs were revascularized, 9 had primary amputation, and 8 were managed conservatively with anticoagulation. The overall limb salvage was 26 out of 39 limbs (66.7%), whereas it was 81.8% for the limbs that had an intervention. The overall mortality was 9.4%. There was no further limb loss or mortality during 1-year follow-up. Interestingly, 15 patients did not have any symptoms suggestive of SARS-CoV-2 infection other than ALI. The severity of COVID infection did not correlate with the severity of ALI. Conclusion: COVID-19 infection can be associated with arterial thrombosis and ALI, which, if treated early with appropriate intervention, can result in a satisfactory limb salvage rate. Prophylactic anticoagulation in COVID-19-infected patients may not prevent arterial thrombosis, and the clinical severity of the COVID-19 infection is not a predictor of arterial thrombosis.
Keywords: Acute limb ischemia, COVID-19, pandemic
Acute limb ischemia (ALI) is a limb and life-threatening vascular emergency requiring prompt diagnosis and treatment.[1] Arterial thrombosis can be due to multiple factors including but not limited to atherosclerotic plaque,[1] hypercoagulable state,[2] and endothelial injury,[3] whereas embolism could be arterio-arterial or cardioembolic. While cardiac source is the most common cause, hypercoagulable state accounts for up to 40% of patients with ALI requiring revascularization.[4],[5]
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in December 2019 in Wuhan, China, and declared a pandemic in March 2020. As on July 15, 2022, over 43 million cases and more than half a million deaths have been attributed to COVID-19 in India and over 560 million cases with nearly 6.3 million deaths across the world.
The spectrum of the COVID-19 clinical presentation continues to evolve and ranges from common symptoms of fever, myalgia, cough, and dyspnea to less common headache, nausea, loose stools, loss of taste and smell to rare presentations of thrombosis and ALI. It is now known that this infection causes a state of excessive inflammation and can progress to cytokine storm[6] and/or a hypercoagulable state.[7]
At the peak of SARS-CoV-2 pandemic, patients presented with ALI with either recently diagnosed SARS-CoV-2 infection[8] or were diagnosed with SARS-CoV-2 infection at the time of presentation. Published data on the management of such patients is very limited.[9] The aim of this study is to report the presentation, clinical characteristics, treatment, and outcomes of the patients with SARS-CoV-2 infection and ALI.
Materials and MethodsIt is a single-center observational retrospective study from a prospectively maintained database of patients with SARS-CoV-2 infection presenting with ALI between July 2020 and December 2020. Data regarding patient presentation, comorbidities, SARS-CoV-2 infection status, radiological findings of chest computed tomography (CT), angiograms, diagnosis, class of the ischemia, outcome, and follow-up till 1 year were collected and analyzed using descriptive statistics and Kendall tau rank correlation. Approval for this study was taken from the institutional ethics committee.
Preoperative evaluation
All patients presenting with ALI were admitted, and preoperative baseline investigations including complete blood counts, renal function test, chest X-ray, electrocardiography, 2D echo, random blood sugars, and blood grouping were done. All patients underwent high-resolution CT (HRCT) chest as an evaluation for COVID-19 signs as reverse transcription–polymerase chain reaction (RT-PCR) was not available to us in the initial phase of the pandemic. A patient was considered to have SARS-CoV-2 infection if the HRCT chest showed bilateral and multifocal ground-glass opacities predominating in the peripheral, posterior, and basal parts of the lungs.[10] We used the molecular test for the diagnosis of SARS-CoV-2 infection once it was permitted by the government later during the pandemic. Imaging of limbs was done with CT angiogram or magnetic resonance (MR) angiogram (time of flight sequence) in majority of the patients.
Operative technique
Revascularization methods included transfemoral or transpopliteal balloon catheter thrombectomy, over-the-wire (OTW) balloon catheter thrombectomy, catheter-directed thrombolysis, and hybrid procedure (thrombectomy, along with angioplasty and stenting). Fasciotomy was performed with revascularization when clinically indicated or to check muscle viability before primary amputation.
Hybrid or endovascular options were reserved for patients who were considered noninfective since the hybrid suite in our hospital was not approved for patients who had transmissible SARS-CoV-2 infection.
Postoperative
Postoperatively, patients were isolated in SARS-CoV-2-designated intensive care units (ICUs) and provided full anticoagulation with enoxaparin, IV hydration, antibiotics, and analgesics as required. Oxygen support and other therapies for the viral infection were provided as per hospital protocol. Enoxaparin was continued for 2 weeks and patients then received direct-acting oral anticoagulants for at least 6 months.
ResultsStudy population
Thirty-two patients with ALI and SARS-CoV-2 infection were treated and included in the study, of which 29 patients had lower-limb ischemia and 3 upper-limb ischemia. Seven patients had involvement of bilateral lower limbs making it a total of 39 limbs that were treated [Table 1].
The mean age of patients was 55.75 (range: 27–80). There were 23 (71.87%) males and 9 (28.12%) females. Two patients were diabetic, 22 were hypertensive, 7 had coronary artery disease, 2 had a past history of deep venous thrombosis, and 3 had chronic kidney disease.
Most patients presented to emergency with symptoms of sudden-onset pain, paresthesia and sensory and motor loss in the limb. Some patients under treatment for SARS-CoV-2 infection at another hospital developed symptoms of acute ischemia and were referred to our center for management. Seventeen patients came with ischemia symptoms directly to our hospital emergency or to the vascular surgery outpatient department, whereas 15 were under treatment for COVID-19 infection at home or in hospital and were referred to us when they developed symptoms of limb ischemia.
Twenty (62.5%) patients presented within a week of onset of ALI and others reached the hospital after a week, with one patient presenting after 45 days.
All patients were evaluated in the emergency department by a physician, screened for SARS-CoV-2 infection by HRCT chest and/or RT-PCR test, if not already done.
More than half the limbs had ischemia Class IIB [Table 2]. Upper-limb ischemia included one of Class IIA and two of Class IIB.
Of the 32 patients, 18 underwent CT angiography and 6 had MR angiography. Four patients had only duplex ultrasound. Imaging was not done for four patients. Of the 24 patients with angiography, 8 patients were found to have nonoccluding aortic thrombus as the possible source of distal embolism [Figure 1].
Figure 1: MIP of CT angiography showing intraluminal nonocclusive thrombus in abdominal aorta (white arrow). Possible source of arterio-arterial embolism, MIP: Maximum intensity projection, CT: Computed tomographyOut of 39 affected limbs in 32 patients, 22 limbs were revascularized, 9 had primary amputation (2 with thrombectomy to improve stump vascularity), and 8 were managed conservatively with anticoagulation [Table 3]. Five limbs needed hybrid procedures. Common femoral artery was exposed surgically and OTW thrombectomy done. Endovascular component included popliteal angioplasty, tibial angioplasty and superficial femoral artery angioplasty and stenting for one limb each. Two limbs were subjected to iliac angioplasty and stenting. Five patients required general anesthesia for the procedures, whereas the rest were performed under regional or local anesthesia.
In our study, 15 patients did not have any symptoms suggestive of SARS-CoV-2 infection other than ALI. Eight patients had mild upper respiratory symptoms, four had hypoxia and required oxygen, four patients required ICU admission due to severe symptoms, and only one patient required ventilatory support at the time of SARS-CoV-2 infection diagnosis. The severity of COVID infection as graded in [Table 1] had no correlation with the severity of ischemia using Kendall tau rank correlation (P = 0.628). In patients with bilateral lower-limb ALI, the worse limb class was used for analysis.
Follow-up
In the revascularization group (22 limbs), 4 major amputations (3 below the knee and 1 above the knee) in 3 patients were done within 2 weeks for sepsis or necrotic foot. The overall limb salvage was 26 out of 39 limbs (66.7%), whereas it was 81.8% for the limbs that had an intervention. Three out of 22 limbs (13.6%) needed a re-intervention, two in the upper limb within 24 h and one in the lower limb for re-thrombosis at 2 weeks. There was no further limb loss at 1 year in the intervention group and no revascularization-related mortality.
One patient who was managed conservatively died in the hospital due to severe SARS-CoV-2 infection.
In the primary amputation group, two patients died (one after bilateral above-knee amputation and one after unilateral above-knee amputation) due to systemic complications during the hospital stay. The overall mortality in our study was 3 out of 32 patients (9.4%).
DiscussionCOVID-19 disease is relatively a young disease with still much to explore and understand its pathogenesis and systemic effects. The clinical spectrum has been wide from nonspecific symptoms to mild or severe respiratory disease and immunothrombosis affecting the circulatory system.
Respiratory system is commonly affected by SARS-CoV-2 causing COVID-19 disease, but it is increasingly evident that it is a systemic disease that affects the cardiovascular, neurological, hematological, and also gastrointestinal systems,[11],[12],[13],[14] with reports on cardiac failure and thromboembolic disease.[15],[16]
Venous thromboembolism is seen in COVID-19 patients with an incidence of 25%–31%, higher than in the general ICU population,[17],[18],[19] and is associated with elevated D-dimer levels.[17],[18] Similarly, an Italian study reported an increased incidence of arterial thrombosis with ALI in COVID-19-infected patients.[8]
Studies indicate that SARS-CoV-2 disease can result in proinflammatory[6] and hypercoagulable states[7] and is associated with ICU admission, mechanical ventilation, and death.[12] Han et al.,[7] in their study, reported markedly elevated D-dimer, fibrin/fibrinogen degradation products, and fibrinogen levels in SARS-CoV-2-infected patients compared to healthy individuals. These findings suggest that COVID-19 infection is a hypercoagulable state.
After the pandemic was declared in March 2020, there was a lockdown in the country and patients had great difficulty in reaching the hospitals for any non-COVID medical services. Even after the lockdown period, patients did face difficulty in getting to the hospital since public transport was very limited and there was a fear of getting infected while transporting patients.
As SARS-CoV-2 entered the community transmission phase, we saw an increase in the number of COVID-19-infected patients presenting to emergency with ALI. However, many presented late due to delayed recognition of ALI in ICU patients, lack of adequate transport, and stigma associated with COVID-19 infection. This could be seen in the variation in the time of presentation in our patients, with one patient presenting after 45 days of the onset of ischemic symptoms. Interestingly, all hospitalized patients had been on a prophylactic dose of anticoagulation with low-molecular-weight heparin and developed ALI despite that.
In our study, none of the patients had a cardiac source of embolism. However, a probable arterial source of embolism was identified in 8 out of 32 patients and this would suggest that the COVID-19 infection can cause inflammation of arteries causing thrombosis and distal embolization.
Of the 32 patients, only 5 patients required ICU stay during their treatment for the COVID-19 infection, 15 patients were asymptomatic for SARS-CoV-2, while 12 had milder symptoms, with 4 requiring oxygen support. This finding indicates that arterial thrombosis occurs even in patients with mild or no symptoms of COVID infection. However, it is not possible for us to be sure that ALI in asymptomatic patients was a result of SARS-CoV-2 infection.
An overall limb salvage of 61.7% in our study indicates that acute ischemia in SARS-CoV-2 infection can be severe resulting in significant limb loss. Our results indicate that majority of the limbs can be salvaged if leg muscles are viable at presentation and that early and appropriate treatment can provide satisfactory outcomes despite an underlying hypercoagulable state.
ConclusionCOVID-19 infection can be associated with arterial thrombosis and ALI, which, if treated early with appropriate intervention, can result in a satisfactory limb salvage rate. Prophylactic anticoagulation in COVID-19-infected patients may not prevent arterial thrombosis, and the clinical severity of the COVID-19 infection is not a predictor of arterial thrombosis. After revascularization, all patients should be given full-dose anticoagulation for a duration that is not clear but possibly till resolution of hypercoagulable state and aortic plaques.
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Conflicts of interest
There are no conflicts of interest.
References
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