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COVID-19: Acute limb ischemia

COVID-19: Acute limb ischemia
Literature review current through: Jan 2024.
This topic last updated: Jul 31, 2023.

INTRODUCTION — Coagulation defects have been described with respiratory viruses including severe acute respiratory syndrome coronavirus 1 (SARS CoV-1), Middle East respiratory syndrome coronavirus [MERS-CoV], and severe acute respiratory virus syndrome coronavirus 2 [SARS-CoV-2] [1-7]. Findings suggest that endothelial dysfunction, inflammation, cytokine release, hypercoagulability, and hypoxia contribute to thrombosis [2,8-10]. Thrombotic complications in patients with coronavirus disease 2019 (COVID-19) present in a variety of ways, most commonly with venous thromboembolism, but also with ischemic complications related to thrombosis of extremity, cerebral, coronary, and visceral arteries. Early recognition of acute limb ischemia (ALI), which is a sudden decrease in the perfusion to an extremity, and intervention, when possible, can help reduce mortality in these very ill patients and maximize the chance for limb salvage.

Risk factors for COVID-19 associated ALI and management are reviewed. Other clinical features and the diagnosis of COVID-19 and coagulation disorders associated with COVID-19 are reviewed separately. (See "COVID-19: Clinical features" and "COVID-19: Hypercoagulability".)

INCIDENCE AND DISTRIBUTION — The data available on the incidence and characteristics of arterial thromboembolic complications in patients with COVID-19 come from a handful of case series and individual case reports. Early in the experience of COVID-19, the reported incidence of ALI in patients with COVID-19 who required hospitalization ranged from 3 to 15 percent [11-13]. Later literature suggested that the incidence of ALI in these patients was lower than reported in the beginning of the pandemic. In a meta-analysis of 15 studies (37,217 patients), the incidence of ALI was 0.3 percent in all hospitalized COVID-19 patients [14]. It is observed to be higher in critically ill patients. Another systematic review of five cohort studies reported a 2.5 prevalence of ALI in critically ill patients with COVID-19 [15].

By comparison, the rate of ALI in the general population is approximately 10 to 15 per 100,000 per year (about 30,000 to 50,000 cases) and includes embolic, thrombotic, and traumatic etiologies [16]. Risk factors for ALI (in general) include atrial fibrillation and other cardiac sources of thromboembolism, trauma, dissection, peripheral artery disease (PAD), and hypercoagulability related to inherited or acquired conditions and malignancy. Among patients with PAD, ALI is reported to occur in approximately 1.7 to 7 percent (data collected before the COVID-19 pandemic) [17,18]. (See "Clinical features and diagnosis of acute lower extremity ischemia", section on 'Etiologies' and "Overview of upper extremity ischemia", section on 'Incidence and etiologies'.)

Etiology and anatomic distribution — In patients with COVID-19, ALI is predominantly due to large or medium artery thrombosis and embolism, although other etiologies can also occur. As with ALI in the general population, the lower extremity is affected more commonly than the upper extremity [11-13,19,20]. In the largest case series, which included 42 patients with ALI, the distribution of ischemic events included [12]:

Lower extremity – 71 percent

Upper extremity – 14 percent

Cerebral ischemia – 10 percent

Bowel ischemia – 4 percent

Multiple locations occurred – 12 percent

Concomitant deep vein thrombosis – 16 percent

Patient characteristics — Based on several case series (table 1), patients with COVID-19 associated ALI were, on average, over 60 years of age with body mass index >25 and had typical cardiovascular risk factors including hypertension, PAD, and diabetes [12,13,19-21]. Several meta-analyses reported higher prevalence of ALI in men [15,22]. The incidence of PAD and diabetes in these reviews has varied, ranging from 4 to 37.6 and 15 to 53 percent, respectively. It is important to note that COVID-19 associated ALI can occur in young, otherwise healthy individuals. About 20 percent of patients are young with no significant medical history and do not exhibit typical risk factors for arterial disease. This observation is based on several case reports and small case series, but there are no large, population-based studies to confirm it [23-28].

In a review of cases from a New York hospital, the median age for hospitalized patients with ALI was 64 [21]. On multivariate analysis, age, male sex, Hispanic ethnicity, history of myocardial infarction, coronary artery disease, and elevated D-dimer level at hospital presentation were significantly associated with an increased risk of developing an arterial thrombotic event leading to stroke, myocardial infarction, ALI, or acute mesenteric ischemia. The risk was highest in patients ≥75 years of age (hazard ratio 2.71, 95% CI 1.65-4.43).

Several retrospective studies from France and Italy reported a similar incidence of COVID-19 associated ALI (0.6 to 2.4 percent) in patients receiving thromboprophylaxis or therapeutic anticoagulation [20,29,30]. In contrast, a randomized control trial conducted in 34 centers in the United States showed that full-dose anticoagulation reduced thrombotic complications as compared with standard-dose prophylactic anticoagulation [31].

ALI can develop in those without typical risk factors for thrombosis. None of four patients in one review had any history of thromboembolism or risk factors that could justify their ischemia [32]. Three patients developed unsalvageable lower limb ischemia due to partial to complete occlusion of infrarenal aorta. Another developed acute upper limb ischemia due to complete occlusion of the axillary and brachial artery.

CLINICAL PRESENTATIONS AND DIAGNOSIS — ALI is defined as an acute decrease in limb perfusion, usually producing new or worsening symptoms or signs, and often threatening limb viability. The classic clinical features of ALI include the 6 Ps (pain, pallor, poikilothermia, pulselessness, paresthesia, and paralysis). A detailed discussion of the clinical examination is provided separately. (See "Clinical features and diagnosis of acute lower extremity ischemia", section on 'Six Ps' and "Overview of upper extremity ischemia", section on 'Six Ps of acute ischemia'.)

The presence and degree of sensorimotor deficits and Doppler findings determine the severity of ALI as described by the Society for Vascular Surgery/International Society for Clinical Vascular Surgery (SVS/ISCVS; ie, Rutherford) classification ranging from a viable, not immediately threatened limb (stage I) to a profoundly ischemic limb with irreversible damage (stage III) [33-36]. The severity of ALI determines the urgency and type of diagnostic evaluation and course of treatment. (See 'Diagnostic evaluation' below and 'Approach to limb management' below.)

Acute limb ischemia presentations — While ALI is a complication of hospitalized patients with severe COVID-19, it can occur in patients with mild symptoms of COVID-19, and moreover ALI can be the primary presenting symptom of COVID-19 even in the absence of respiratory symptoms [11-13,19-21] (table 1). In addition, ALI can occur concurrently with ischemic symptoms in other vascular beds (arterial, venous) and has also been reported in association with vaccine-induced immune thrombocytopenia and thrombosis (VITT). Some studies described that 12 to 18 percent of patients developed thrombosis in multiple arterial locations, including extremities, visceral, cerebral, and coronary arteries [12,15,25,26,37]. In another study, 16 percent of patients with ALI also had a concomitant deep vein thrombosis [38].

ALI with mild or no symptoms of COVID-19 — Infected patients with minimal or no symptoms of COVID-19 can develop a prothrombotic state, and reports have described patients complaining predominantly of acute extremity pain that was associated with mild respiratory symptoms or other symptoms associated with COVID-19, but in some cases ALI has been the sole clinical manifestation of COVID-19 [12,23,39-53]. ALI has also been described following recovery from a mild cases of COVID-19 [37,54,55].

In a review of 49 patients of COVID-19-associated ALI, acute arterial ischemia was the initial presentation in 22 (45 percent) patients; COVID-19 was subsequently diagnosed on laboratory testing [12]. In a review from Italy, among patients presenting to the emergency room with ALI, 15 of 32 patients were positive for COVID-19 on admission or shortly thereafter [56].

ALI in hospitalized patients — Among hospitalized patients, case reports and case series describe the occurrence of ALI at variable times during the hospitalization, either as isolated large/medium vessel thrombosis or concurrently with thrombosis in other vascular beds (arterial or venous) [12,57-60], but often heralded by increasing D-dimer levels [11,13,23,61-69]. Thrombosis of large (eg, aorta, iliac, subclavian, axillary) and medium-sized (superficial femoral, brachial) arteries of the upper and lower extremities are more commonly reported compared with other arterial sites (see 'Etiology and anatomic distribution' above) [32,70-81]. Thrombosis of prior vascular reconstruction including stents and bypass grafts have also been reported [82,83].

Among 49 patients diagnosed with COVID-19 related ALI, 27 (55 percent) developed ischemia during hospitalization [12]. In a retrospective review of all adult patients with a confirmed diagnosis of COVID-19 admitted to a tertiary care hospital over a three-month period, 6 of 638 (0.9 percent; median age 62 years) developed ALI, all of whom were receiving low-molecular-weight heparin when ALI developed [61]. The median of duration between COVID-19 diagnosis and ALI symptom onset was 13 days. In another review, thrombotic events in the setting of COVID-19 infection occurred at a median of 11 (5 to 20) days after the first symptoms of infection [11].

As with other critically ill patients, patients with COVID-19 may be treated with multiple vasopressor agents that can lead to small vessel thrombosis, acral ischemia, and digital gangrene (upper or lower extremities) [84-86].

ALI following vaccination — VITT is an extremely highly morbid but rare condition that has occurred following two adenoviral vector-based vaccines: the ChadOx1 nCoV-19/AZD1222 (AstraZeneca COVID-19 vaccine) and Ad26.COV2.S (Janssen COVID-19 vaccine, also referred to as the Johnson & Johnson vaccine) [87-91]. The risk for developing thrombosis associated with these vaccines, clinical features, and diagnosis are reviewed separately. (See "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)", section on 'Epidemiology' and "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)", section on 'Clinical features'.)

Venous thrombosis, and more rarely arterial thrombosis leading to ALI, has been reported. In a review of 170 definite and 50 probable cases of VITT, while cerebral vein thrombosis and deep venous thrombosis were most common, acute limb ischemia occurred in 26 patients (12 percent) of patients [87].

Diagnostic evaluation — Because arterial thrombosis can occur without the traditional risk factors associated with ALI, a high index of suspicion is necessary to recognize evolving ALI and to provide early, directed treatment, as indicated. The diagnosis of ALI is predominantly clinical based on physical examination findings, including measurement of extremity pressures (eg, ankle brachial index, wrist brachial index, if distal Doppler signals are present), in combination with the patient's history. Vascular imaging confirms the location and extent of arterial obstruction and aids with planning intervention. (See "Clinical features and diagnosis of acute lower extremity ischemia", section on 'Diagnosis' and "Overview of upper extremity ischemia", section on 'Diagnosis'.)

Duplex ultrasound and CT angiography are the most common confirmatory imaging modalities and help determine the anatomic location and extent of the arterial occlusion. CT angiography can be useful for identifying a proximal thromboembolic source [65]. The European Society for Vascular Surgery 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischemia in Light of the COVID-19 Pandemic recommend imaging with CT angiography from the aortic arch to the feet/hands in these patients [92]. This allows for exclusion of other thrombotic events that have been often reported to occur in combination with ALI. However, in the setting of the COVID-19 pandemic, the vascular imaging study used has depended upon the stability of the patient for transfer to the imaging suite, if needed, as well as consideration for allocation of resources. In a review of a small cohort of 16 patients with acute upper or lower extremity ischemia, only 8 patients underwent confirmatory imaging studies [20]. In general, for patients with viable or marginally threatened limbs, there is usually enough time to obtain vascular imaging prior to intervention. However, patients with an immediately threatened limb require more urgent evaluation, typically in an operating room setting. (See 'Approach to limb management' below.)

Obtaining a platelet count, D-dimer, fibrinogen, and the use of thromboelastography can be helpful for assessing the degree of hypercoagulability [3,93,94]. In critically ill patients, D-dimer, fibrinogen, and factor VIII are often elevated, and protein C, protein S, and antithrombin levels are decreased [95,96]. Antiphospholipid antibodies may also be present. The correlation between D-dimer levels and clinical outcomes is not clear. In a retrospective study from China, 46.4 percent of patients with COVID-19 had elevated D-dimer, and the elevation was more pronounced in severe cases [97]. Several studies have reported that increased D-dimer levels were significantly associated with increased mortality [3,93,98-100]. In a review of 183 patients with COVID-19, 21 (11.5 percent) patients died; 71 percent of patients who died had coagulation abnormalities compared with 0.6 percent of survivors [99]. However, a later meta-analysis that included 34 studies showed that increased D-dimer levels were not associated with death (odds ratio [OR] 1.17, 95% CI 0.36-3.76) or amputation (OR 2.0, 95% CI 0.33-11.97) [22]. Increasing D-dimer in hospitalized patients may also herald the occurrence of thrombotic events [11,101]. Other common laboratory abnormalities in patients with COVID-19 include lymphopenia, elevated lactate dehydrogenase, and increases in inflammatory markers such as C-reactive protein, ferritin, and interleukin-6.

Differential diagnosis — The differential diagnosis of ALI in patients with COVID-19 includes other conditions that present with extremity pain or neurologic abnormalities and conditions that mimic the appearance of ischemia, which may or may not be associated with COVID-19. (See "Clinical features and diagnosis of acute lower extremity ischemia", section on 'Differential diagnosis' and "Overview of upper extremity ischemia", section on 'Differential diagnosis'.)

Dermatologic conditions associated with COVID-19 are increasingly recognized [102,103] and these may mimic the appearance of ischemia (eg, acute chilblains). (See "COVID-19: Cutaneous manifestations and issues related to dermatologic care".)

MANAGEMENT — Timely vascular surgery consultation is critical in the management of patients with COVID-19 associated ALI [13,104].

Initiate anticoagulation — For patients with ALI, we initiate therapeutic anticoagulation with intravenous unfractionated heparin (bolus followed by continuous infusion), which should be provided once a diagnosis of ALI is established, unless there are significant contraindications such as active or serious bleeding in the prior 24 to 48 hours, recent surgery, or contraindications to the use of heparin (eg, history of heparin-induced thrombocytopenia [HIT] or suspected HIT). There are no data to suggest superiority of any type of anticoagulant, such as unfractionated heparin, low molecular weight heparin, or oral anticoagulants [105]. (See "COVID-19: Hypercoagulability", section on 'Resources and other guidance'.)

It is important to recognize that patients with COVID-19 can have a variety of abnormal coagulation patterns that may inhibit adequate therapeutic anticoagulation.

Heparin resistance, which is overall rare, has been observed [101]. Heparin resistance is defined as failure to achieve the desired activated clotting time after a full dose, or the need for high-dose unfractionated heparin of more than 35,000 international units/day to achieve the target-activated partial-thromboplastin time ratio [106-108]. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Heparin resistance/antithrombin deficiency' and "Antithrombin deficiency".)

HIT has also been reported in patients with COVID-19 [109,110]. (See "Management of heparin-induced thrombocytopenia (HIT) during cardiac or vascular surgery".)

New thromboembolic events have occurred despite apparently adequate anticoagulation in patients with COVID-19 [104].

Approach to limb management — Limb viability is classified and managed using the Society for Vascular Surgery/International Society for Clinical Vascular Surgery (Rutherford) classification [34-36,111].

Marginally threatened limbs (class IIa) are salvageable if treated promptly. There is minimal pain and minimal (toes only) or no sensory loss, and no muscle weakness; arterial Doppler signals are often inaudible, but venous Doppler signals are audible.

Immediately threatened limbs (class IIb) are salvageable with immediate revascularization. Sensory loss involves more than the toes and may be associated with rest pain in the foot (not just confined to toes). There is mild-to-moderate muscle weakness, arterial Doppler signals are usually inaudible, and venous Doppler signals are audible.

Irreversible ischemic (nonviable; class III) limbs have a severe and permanent nerve deficit. Sensory loss is profound, muscle weakness is profound with paralysis and possible rigor, and arterial and venous Doppler signals are inaudible. If the affected limb is nonviable at presentation, primary amputation will be required.

Based on the patient's overall stability, degree of ischemia, and limb viability, a determination needs to be made whether intervention is appropriate, and if so, whether an endovascular or open approach should be used. It is crucial to consider the severity of systemic illness when considering intervention. Because of the severe pulmonary complications associated with COVID-19, critically ill patients may not be candidates for revascularization. Similar to damage control in trauma patients, the principle of "life over limb" is justified. Based on published case series, less than half of patients with COVID-19 associated ALI underwent attempts at limb salvage; up to 15 percent required primary amputation (table 1). In one series of 49 patients, revascularization was performed in 13 (27 percent) patients, primary amputation in 5 (10 percent), 28 (57 percent) were treated with systemic anticoagulation only, and 3 (6 percent) received systemic administration of tissue-plasminogen activator [12]. The rate of limb loss was 18 percent. Twenty-one patients (46 percent) died in the hospital. In a systematic review that included 199 patients, 58 percent underwent revascularization procedures with a 23 percent pooled amputation rate and 31 percent pooled mortality rate [22]

VASCULAR INTERVENTION

Options for revascularization — Options for revascularization include the following:

Surgical revascularization for ALI consists of open thrombectomy, although other adjuncts may be required, including endarterectomy/patch angioplasty and/or surgical bypass. (See "Lower extremity surgical bypass techniques" and "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization".)

Endovascular revascularization may include catheter-directed thrombolysis or percutaneous mechanical thrombectomy. (See "Intra-arterial thrombolytic therapy for the management of acute limb ischemia" and "Endovascular techniques for lower extremity revascularization" and "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization".)

At times, a combination of open and endovascular techniques may be needed. As an example, in a case of ALI due to extensive thrombosis of an aortic aneurysm, iliac arteries, and infrainguinal arteries, thrombolytic therapy restored patency of the aortoiliac occlusion, and bilateral open thrombectomy of the infrainguinal vessels restored distal perfusion [80].

There are no high-quality data to inform the choice for open versus endovascular intervention for COVID-19 associated ALI. Both have been associated with successful limb salvage, and both have also been associated with high rates of mortality and morbidity. The choice is likely influenced by specific anatomic considerations (eg, presence of atherosclerotic plaque, aneurysm), operator preference, and institutional resources.

Postprocedural anticoagulation — Following intervention for ALI, based on general treatment outcomes in patients with ALI, patients with COVID-19 should be maintained on therapeutic anticoagulation and transitioned to oral anticoagulation (eg, warfarin, direct oral anticoagulants [DOACs], or low molecular weight heparin, with or without an antiplatelet agent [eg, aspirin]). Oral anticoagulation is an established therapy following intervention for ALI with subsequent reduction in recurrent ischemic limb events and amputation [112].

Data specific to postprocedural anticoagulation in patients with COVID-19 associated ALI are sparse. In one Italian review, 17 of 20 patients with ALI underwent revascularization, which was successful in 12 patients [13]. While successful revascularization was not significantly associated with the postoperative use of intravenous heparin, no patient who received postoperative anticoagulation required reintervention. Two patients required reintervention because of a recurrent thrombotic occlusion within the first 48 hours. The use of continuous postoperative heparin was associated with increased survival. The authors concluded that prolonged systemic heparin might improve surgical treatment efficacy, limb salvage, and overall survival. Additional data on anticoagulation management for COVID-19 related ALI are anticipated [113].

LIMB OUTCOMES AND MORTALITY — Overall, the mortality rate of COVID-19 for those who require hospitalization is over 20 percent [114]. In most cases, the cause of death has been attributed to respiratory failure, sepsis, cardiac failure, kidney injury, or the consequences of coagulation abnormalities [115]. Among patients who develop ALI, mortality rates are as high as 50 percent (table 1) [13,19,20]. In a review of 571 COVID-19 patients, the risk of death was nearly three-fold higher in patients who had arterial thrombotic events (hazard ratio 2.96, 95% CI 1.4-4.7) [11]. A meta-analysis of 11 studies showed a significantly higher probability of death in COVID-19 patients with ALI compared with nonCOVID-19 patients with ALI (odds ratio [OR] 4.71, 95% CI 1.11-19.99) with an overall mortality rate of 33 percent in ALI patients who were COVID-19 positive [116].

Amputation — The rate of major amputation (eg, below-knee amputation, above-knee amputation) is higher than that associated with other vascular conditions and is required in 7 to 35 percent of patients with COVID-19 associated ALI (table 1) [12,13,19,20]. In the general population, in the absence of COVID-19, rates of major amputation following intervention for ALI are between 6 and 23 percent, depending on etiology and comorbidities [117-119]. As examples, in a single-institution series of 74 patients with ALI and cancer, the amputation rate was 11 percent [120]. In a pharmacologic trial that included patients with symptomatic peripheral artery disease, the rate of major amputation in those who developed ALI was 16 percent [117]. In addition, because patients with COVID-19 are commonly severely deconditioned from often prolonged illness with COVID-19, recovery and rehabilitation following amputation may be prolonged.

Recurrent arterial thrombosis — Some patients with COVID-19 related acute limb ischemia develop recurrent thrombosis after invasive interventions (eg, thrombectomy, thrombolysis) that were initially technically successful. One review reported a 17 percent rate of rethrombosis after revascularization in patients with COVID-19, with a significantly higher probability of rethrombosis as compared with a patient without COVID-19 (OR 2.65, 95% CI 1.34-5.23) [116]. There have been reported cases of successful limb salvage following recurrent arterial thrombosis. In some cases, the patient's clinical condition may have deteriorated such that further attempts to salvage the limb are no longer feasible. For others, the inability to clear outflow vessels may severely limit any meaningful attempt at salvage, and limb amputation may become a necessary lifesaving procedure [24]. In either case, limb amputation may become a necessary lifesaving procedure.

RESEARCH INITIATIVES — There is an need for high-quality research on the impact of COVID-19 on patients with preexisting vascular disease, those with COVID-19 related vasculopathy, and delivery of care [121]. The Vascular Surgery COVID-19 Collaborative (VASCC) is an international registry collecting deidentified patient data from a wide variety of clinical practices with the aim of evaluating the effects of COVID-19 on vascular practice patterns as well as studying vascular manifestations and outcomes in patients with COVID-19 [122,123]. Ongoing research regarding the thrombotic vascular complications of COVID-19 aims to:

Identify key components of the diagnostic work-up

Describe surgical, endovascular, and non-operative management

Investigate various perioperative and postoperative anticoagulation strategies

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: COVID-19 – Index of guideline topics".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: COVID-19 overview (The Basics)" and "Patient education: COVID-19 and pregnancy (The Basics)" and "Patient education: COVID-19 and children (The Basics)" and "COVID-19: Vaccines" and "Patient education: COVID-19 vaccines (The Basics)")

SUMMARY AND RECOMMENDATIONS

Acute limb ischemia – Thrombotic complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection present in a variety of ways. Acute limb ischemia (ALI), the sudden decrease in perfusion to an extremity, is a dramatic clinical event more typically reported in association with severe infection; however, it has been reported in patients with few or none of the respiratory symptoms associated with coronavirus disease 2019 (COVID-19). While ALI can occur due to embolic or thrombotic etiologies, a thrombotic etiology predominates in patients with COVID-19. (See 'Incidence and distribution' above.)

Clinical features of ALI associated with COVID-19 – The classic clinical features of ALI include the 6 Ps (pain, pallor, poikilothermia, pulselessness, paresthesia, and paralysis). Clinical features of COVID-19 associated ALI include the following (see 'Clinical presentations and diagnosis' above):

The lower extremity is affected more commonly (about 70 percent) compared with the upper extremity.

Risk factors for ALI in patients with COVID-19 infection include older age, obesity, and cardiovascular comorbidities.

Patients without risk factors can develop ALI.

ALI can develop in patients with COVID-19 even when receiving thromboprophylaxis.

Elevated D-dimer levels occur in most patients who develop ALI, and a sudden increase in D-dimer may herald the acute thrombotic event.

ALI more typically affects patients with severe COVID-19, occurring five to seven days after respiratory decompensation.

About 20 percent of patients who present with COVID-19 related ALI have few or no respiratory symptoms. Furthermore, ALI can occur during the recovery phase following infection of any severity.

Thrombosis of large (eg, aorta, iliac, subclavian, axillary) or medium-sized (eg, superficial femoral, brachial, tibial) arteries have all been reported. Small vessel thrombosis leading to digital gangrene is often associated with the administration of vasopressor agents.

Thrombosis of prior vascular reconstruction including stents and bypass grafts can also occur.

Diagnostic evaluation – The diagnosis of ALI is predominantly clinical, and vascular imaging (duplex ultrasound, computed tomographic angiography) confirms the location and extent of arterial obstruction. The selection of vascular imaging studies in patients with COVID-19 associated ALI may be dictated by available resources and the stability of the patient to undergo the study. Limb viability is classified by the Society for Vascular Surgery/International Society for Clinical Vascular Surgery (ie, Rutherford) classification based upon the presence and degree of sensorimotor deficits and Doppler findings. The severity of ALI determines the urgency and type of diagnostic evaluation and course of treatment. (See 'Diagnostic evaluation' above and 'Management' above.)

Anticoagulation

Therapeutic anticoagulation should be initiated once a diagnosis of ALI is established. Patients with COVID-19 can have a variety of abnormal coagulation patterns that may inhibit adequate therapeutic anticoagulation such as heparin resistance or heparin-induced thrombocytopenia. Thromboembolic events can occur despite apparently adequate anticoagulation. (See 'Initiate anticoagulation' above.)

Following successful intervention for ALI (endovascular, surgical), patients with COVID-19 are maintained on therapeutic anticoagulation and transitioned to oral anticoagulation (eg, warfarin, direct oral anticoagulants [DOACs] or low molecular weight heparin, with or without the addition of an antiplatelet agent [eg, aspirin]) to reduce the incidence of recurrent ischemic events. (See 'Postprocedural anticoagulation' above.)

Vascular intervention – It is important to consider the severity of systemic illness when considering whether to perform an intervention in patients with COVID-19. Many patients with severe respiratory manifestations of COVID-19 are not candidates for limb salvage. Despite attempts at revascularization (endovascular, open surgical), ALI associated with COVID-19 has high mortality and high rates of limb loss. Major amputation (eg, below-knee amputation, above-knee amputation) is required in up to a third of patients. (See 'Vascular intervention' above and 'Limb outcomes and mortality' above.)

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Topic 128913 Version 14.0

References

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