COVID-Related Thrombosis and Overall Implications Related to Percutaneous Interventions

Abstract

The SARS-COV-2/ COVID-19 pandemic created unique, once in a lifetime challenges for healthcare workers across the globe. One of the challenges specific to interventional radiology was the increased incidence of vascular thrombosis leading to urgent and emergent clinical patient management issues. Limited healthcare resources and complex clinical presentations required innovative solutions, and workflows to manage the increased burden on the healthcare providers.

New York City was the epicenter of the SARS-CoV-2 COVID-19 pandemic in North America in early 2020. Despite broad access to vaccines and therapeutics resulting in lower numbers of infections and deaths, clinical practice in interventional radiology has been forever altered to reflect the new reality of patients with SARS-CoV-2 infection. The challenges of patient and staff safety combined with limited resources create unique challenges to diagnose, triage, and care for patients with peripheral vascular disease. ¹ The following sections will give clinically specific recommendations for the diagnosis and management of several manifestations of peripheral vascular disease.

Intermittent Claudication

Percutaneous interventional revascularization procedures for intermittent claudication (IC) are indicated in case of failure of a conservative approach by multidisciplinary consensus. ² During a peak surge of the pandemic, deferring these procedures is essential. Optimal medical therapy (OMT) should be continued in all patients with IC (Rutherford classification 0–3) regardless of their COVID-19 infection status. ² Close follow-up via remote monitoring or telehealth is recommended and any symptomatic deterioration of a peripheral arterial disease patient from IC to ischemic pain at rest or tissue loss should warrant an urgent reassessment.

Critical Limb Ischemia

According to current consensus guidelines, patients with ischemic pain at rest (Rutherford 4) and patients with minor (Rutherford 5) or major (Rutherford 6) tissue loss should undergo immediate imaging followed by an attempt at either endovascular or surgical revascularization. ² During a peak surge of the pandemic, a differentiated approach that considers the COVID-19 status as well as the specific PAD presentation should be applied. If tested negative, patients should undergo Doppler ultrasound (DUS), computed tomography angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography (DSA) followed by revascularization if indicated and if hospital resources allow. If tested positive for COVID-19, DUS or CTA should be performed to exclude absence of flow to the calf and foot and conservative treatment with OMT should be pursued. In case of persistent flow below the knee and the absence of imminent limb loss, revascularization should be postponed until 14 days after the positive SARS-CoV-2 polymerase chain reaction (PCR) test with 3 days of being afebrile (<100 °F) not on antipyretics and significant resolution of symptoms. In patients with Rutherford class 5 or 6, wound care is crucial, and close monitoring for progressive tissue loss, wet gangrene, and ascending cellulitis is mandated since these represent indications for immediate revascularization regardless of COVID-19 status.

Acute Limb Ischemia or Acute on Chronic Limb-Threatening Ischemia

In patients presenting with acute limb ischemia (ALI) or acute on chronic limb ischemia, treatment should be expedited regardless of COVID-19 status, and therapy should be applied according to current guidelines. ² In ALI stages I and IIa, endovascular intervention may be preferred over surgery to avoid overburdening hospital resources. Since catheter-directed thrombolysis (CDT) requires an intensive care unit (ICU) stay and repeat peripheral angiogram, mechanical thrombectomy may be preferred if local experience and expertise will allow. Recent advances in percutaneous thrombectomy technology have allowed for “single-session therapy” to manage acute thrombotic occlusions in the peripheral circulation resulting in ALI. This has the potential to avoid an overnight ICU stay entirely if there is adequate expertise in these emerging techniques. In the instance where local expertise in endovascular thrombectomy is not available or the clinical result is suboptimal, strong consideration should be given to convert to surgical therapy. Although reported in single cases, systemic thrombolysis as initial treatment of ALI in patients with severe COVID-19 cannot be recommended due to the lack of supporting evidence. ³ In patients with ALI stage III (non-salvageable limb), a decision on the timing of major amputation should be based on the severity of COVID-19 symptoms. ⁴

Venous Thromboembolism and Pulmonary Embolism

The exact incidence of venous thromboembolism (VTE) in hospitalized COVID-19 patients is currently unknown; reports range from as low as 1% in the medical wards to over 30% in ICUs. ^{5 6 7 8} The coagulopathic state associated with COVID-19 and the resultant increased thrombin generation can increase the risk of VTE, including pulmonary embolism (PE). COVID-19 hospitalized patients have a variety of usual factors that increase risk for VTE, including sepsis, immobilization, respiratory failure, mechanical ventilation , pharmacologic sedation and paralysis, vasopressor use, and central venous catheter use.

Diagnosis and Risk Stratification

Understanding of the exact relationship between VTE and COVID-19 is evolving. It is clear that a hypercoagulable state can be associated with COVID-19 infection. Clinical symptoms of PE may be confused with those of COVID-19 infection. All physicians evaluating patients with COVID-19 in any clinical setting should have a low threshold for considering concurrent PE.

The presence of PE complicating COVID-19 infection (or in a person under investigation) should be considered when a patient exhibits hemodynamic instability or poor gas exchange that is not fully explained or is out of proportion to the stage, duration, and rate of progression of COVID-19 infection. PE testing should be performed in a patient presenting with short-term symptoms and syncope, shock, acute respiratory failure , or signs of acute right ventricular (RV) overload. PE should be considered if a patient develops acute onset of dyspnea, hypoxia, hypotension, or tachycardia , especially if imaging or clinical findings are not consistent with worsening COVID-19 pneumonia. The occurrence of these changes should trigger the need for diagnostic testing.

The use of biomarkers such as D-dimer to help identify patients with COVID-19 at risk of developing VTE has been reported in several case series and cohort studies . ^{9 10 11} In a single-center cohort study of 198 patients, an elevated D-dimer was associated with a 50% increased risk of developing VTE. ¹²

Given the limited data to support the use of biomarkers to diagnose PE in patients with COVID-19, standard diagnostic testing should be considered. Concerns about staff exposure may result in CTA not being readily available in a timely manner. In this scenario, bedside echocardiogram and lower extremity ultrasonography can be important adjunct in establishing the diagnosis of PE. If evidence of RV dilatation or dysfunction, intracardiac thrombus , or clot-in-transit is noted, the patient should be presumed to have acute PE and treatment with full-dose anticoagulation should be initiated. Evidence of right-sided overload such as right-sided chamber dilatation, McConnell sign, or paradoxical septal movement, although nonspecific, can confirm the diagnosis. If deep vein thrombosis is identified, or is highly probable, the patient should be treated with full-dose anticoagulation. At times, a patient with COVID-19 may be unable to be evaluated by CTA, ultrasonography, or echocardiogram because of concerns of staff exposure to COVID-19 or cardiorespiratory instability. If the clinical presentation supports PE, the patient should be treated with full-dose anticoagulation, unless contraindicated, pending definitive diagnosis.

Percutaneous endovascular therapy has recently emerged as an alternative to systemic administration of a fibrinolytic agent or open surgical embolectomy. Endovascular treatment options include CDT, ultrasound-accelerated thrombolysis (USAT), and percutaneous mechanical thrombo-aspiration (PMT). ¹² While there is a great deal of evidence demonstrating the safety and efficacy of CDT and USAT, these treatments will typically utilize an ICU bed for delivery of the fibrinolytic agent and hemodynamic monitoring. PMT has recently been evaluated as an alternative to CDT and USAT and recent reports suggest that these PMT procedures may avoid an ICU stay in selective patients. This therapeutic strategy may be utilized preferentially during a peak surge of the pandemic, although PMT requires local experience and expertise to be successful.

Environmental Considerations for Endovascular Therapy

The safety of the healthcare providers should be of paramount concern during a pandemic. Adequate personal protective equipment (PPE) must be available and the treatment room or interventional lab must have adequate ventilation and air exchanges to minimize staff exposure. In the instance where a hospital or facility may have multiple treatment rooms, it is recommended to have a specific dedicated room for the treatment of patients with communicable diseases to minimize the risk of environmental exposure. All specialized equipment in such a room must also be protected from exposure if possible and the room and equipment must be appropriately disinfected after every patient visit. Scenario rehearsal is extremely helpful to ensure that staff understand how, where, and when to don and doff their PPE and how to protect the equipment when an infectious patient is being treated in the room. This may be quite time consuming and stressful for the staff and focusing this workflow in a dedicated location instead of the general high-traffic areas has the potential to limit staff exposure, reduce anxiety, improve morale, and provide higher quality care.

Summary

The SARS-COV-2 pandemic has created unique clinical situations related to high rates of thrombotic occlusion in patients with peripheral vascular disease. These patients represent high-intensity stressful encounters for the healthcare providers and the healthcare delivery system.

Proper procedural resource forecasting can lead to greatest clinical success rates and the greatest safety for the endovascular team. Environmental assessment and rehearsals are critical to ensure the safety of the staff and the patients. Procedural training and expertise especially in the use of modern percutaneous thrombectomy systems may provide rapid therapeutic care to patients while allowing the critically ill patients to receive the critical care resources without interruption.