key: cord-0878693-89zqgqx1 authors: Sethi, Sanjum S.; Zilinyi, Robert; Green, Philip; Eisenberger, Andrew; Brodie, Daniel; Agerstrand, Cara; Takeda, Koji; Kirtane, Ajay J.; Parikh, Sahil A.; Rosenzweig, Erika B. title: Right Ventricular Clot in Transit in COVID-19: Implications for the Pulmonary Embolism Response Team date: 2020-05-29 journal: JACC Case Rep DOI: 10.1016/j.jaccas.2020.05.034 sha: b4fe7209f1fe1cd59c4680cc3811c3fec9144911 doc_id: 878693 cord_uid: 89zqgqx1 Abstract Severe acute respiratory syndrome coronavirus 2 is associated with a prothrombotic state in infected patients. After presenting a case of right ventricular thrombus in a COVID-19 patient, we discuss the unique challenges in the workup and treatment of COVID-19 patients highlighting our COVID-19 modified pulmonary embolism response team (PERT) algorithm. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19related critical illness and multiorgan dysfunction in a subset of those infected. Given this increased potential for hypercoagulable events, yet being mindful of exposure risks and practical considerations in caring for COVID-19 patients, we present the first report of a COVID-19 patient with clot in transit, along with an algorithm for diagnosing and treating venous thromboembolism in COVID-19 patients. A 44-year-old man was admitted following 2 days of shortness of breath and nonproductive cough. Upon presentation, the patient had a temperature of 99.3 F, heart rate of 152 beats per minute, blood pressure of 102/84mmHg, and a respiratory rate of 44 breaths per minute. He was hypoxic with a peripheral oxygenation saturation (SpO2) of 86%, while breathing 6 liters per minute of supplemental oxygen via nasal canula with an additional 15 liters per minute applied by non-rebreather mask. His past medical history was notable only for obesity (body mass index 31) and type 2 diabetes mellitus. The primary differential diagnosis for the patient's presentation includes bacterial pneumonia, viral upper or lower respiratory infection, and pulmonary embolism. Given the patient's age, few medical comorbidities and the significant community spread of SARS-CoV-2 virus, COVID-19 illness was the most likely diagnosis. His chest radiograph revealed diffuse bilateral hazy opacities ( Figure 1 ). SARS-CoV-2 nasopharyngeal swab polymerase chain reaction test was positive. Initial venous blood gas was significant for a pH of 7.09, PaCO 2 41 mmHg, PaO2 33 mmHg with a lactate of 12 mmol/L. Following intubation, his arterial blood gas improved slightly to pH 7.14, PaCO2 53 mmHg, PaO2 193 mmHg with with a fraction of inspired oxygen (FiO2) of 100%. The PaO2:FiO2 (P:F) ratio of 193, along with his chest radiograph findings of diffuse bilateral hazy opacities, was consistent with moderate ARDS. (11) The patient's initial laboratory studies (Table 1) were most notable for a white blood cell count of 27.8x10 3 /µL and serum creatinine 1.88mg/dL. His high sensitivity troponin-T was initially 46 ng/L with a subsequent value of 154 ng/L, N-terminal Btype natriuretic peptide was 14,535 pg/mL, ferritin was 3,495 ng/L, and D-dimer was greater than 20µg/mL (upper limit of detection). TTE was obtained given severity of hypoxemia, hemodynamic instability, and elevated D-dimer out of concern for acute PE. TTE revealed a left ventricular ejection fraction of 45% with global hypokinesis, and moderate to severely dilated right ventricle with moderate to severely reduced right ventricular systolic function (Video 1). There was flattening of the interventricular septum throughout the cardiac cycle consistent with both pressure and volume overload of the right ventricle. Additionally noted was a 1.5cm x 1.7cm well circumscribed mobile echodensity attached to the right ventricular free wall concerning for clot in transit ( Figure 2 ). He was intubated for hypoxemic respiratory failure and admitted to the intensive care unit (ICU). During the patient's initial course in the ICU, he became progressively hypotensive over the course of the first 6 hours, requiring maximum doses of norepinephrine (40 mcg/min) and vasopressin (2.4U/hr). Given his progressive shock in the setting of high inflammatory markers, he was started on 1mg/kg of intravenous methylprednisolone per day. TTE was obtained with the resultant findings described above. Given these findings, the pulmonary embolism response team (PERT) was consulted and the patient was given 100 mg (over 2 hours) of tissue-type plasminogen activator (tPA) and systemic anticoagulation with unfractionated heparin once the tPA infusion was complete. The patient was started on a dobutamine infusion for inotropic support and considered for venoarterial extracorporeal membrane oxygenation (ECMO) in case his hemodynamic condition worsened. After administration of tPA, the patient was weaned off pressors within 24 hours. He was subsequently weaned off inotropic support over the ensuing 3 days. His repeat TTE revealed normal left ventricular systolic function, mild dilation of the right ventricle with preserved right ventricular systolic function. The previously seen clot in transit was no longer visualized and the right ventricular function was improving (Video 2). Bilateral lower extremity venous doppler ultrasounds were negative for deep vein thrombosis. The patient had no immediate bleeding complications following administration of tPA. The usual risk stratification schema for acute pulmonary embolism rely on a combination of hemodynamic clinical parameters, such as hypoxemia, tachycardia, and hypotension along with serum biomarkers, such as troponin or brain natriuretic peptide followed by confirmatory imaging tests. (12) An extremity duplex ultrasound examination and TTE may even be performed by the same clinical provider in the same clinical setting using a portable or handheld device as a bedside screen to limit exposure and PPE use. Both troponin and N-terminal B-type natriuretic peptide may be elevated in the setting of severe COVID-19 illness. D-Dimer elevations are also common, but have also been associated with a high prevalence of underlying venous thromboembolism. (14) Another potential risk stratification tool would be the sepsis-induced coagulopathy (SIC) score, which uses common clinical and laboratory values to identify higher risk patient subsets. A SIC score >4 has an association with worse outcomes at 28 days. (15) Diagnostic CTA remains the gold standard for the diagnosis of acute pulmonary embolism. Nonetheless, exceptional circumstances specific to the COVID-19 pandemic, such as potential infection of clinical or ancillary staff by a patient with poorly controlled cough and refractory hypoxemia limiting patient transport may make empirical anticoagulation preferable to CTA or V/Q scanning. The clinical team should always carefully balance the risks and benefits of empiric anticoagulation without objective imaging. CTA should be performed at the discretion of the treating team and if needed after discussion with the PERT team so that considerations can be made based on feasibility and safety of performing the confirmatory test versus the risk of empiric treatment under these conditions. Patients admitted to the hospital with COVID-19 critical illness should be given VTE prophylaxis as standard of care, unless contraindicated. Retrospective, observational data suggests a possible benefit to more intensive anticoagulation, however, this association should be verified in prospective randomized controlled trials prior to changing treatment algorithms given the known risks associated with therapeutic anticoagulation. (16) The preferred anticoagulation for hemodynamically stable COVID-19 positive patients with proven VTE is enoxaparin 1 mg/kg SQ twice daily (based on total body weight; max 196 kg). Using low molecular weight heparin (LMWH) will reduce the use of PPE as routine monitoring with activated partial thromboplastin time or heparin assay is not necessary. Dose adjustment or the use of unfractionated heparin should be considered for those with reduced kidney function. The roles for systemic thrombolysis, catheter or surgical thrombectomy, and ECMO are as yet undefined. We propose an algorithm that outlines our approach for testing and treatment for VTE in the setting of COVID-19 (Figure 3 , Disclaimer: This algorithm is not a societal guideline, but a product of consensus of PERT members at our institution). Systemic thrombolysis remains a Class I recommendation for hemodynamically unstable PE. (17) However, the hemodynamic effect of the underlying PE must be clinically distinguished from the systemic vasodilatory effects that may accompany COVID-19. In the setting of right heart strain, there have been limited anecdotal reports of success with catheter-based treatments. However, caution must be advised with regards to resource utilization, including PPE, ICU beds, cardiac catheterization laboratories and operating rooms. Similar considerations must be made for the use of ECMO in properly equipped centers. In our case, the patient had severe right ventricular dysfunction with a large clot in transit. While surgical or catheter-based options were considered, the hemodynamic profile and low bleeding risk suggested that systemic thrombolysis would be the optimal approach. This led to dramatic improvement in the patient's hemodynamic profile. We used the standard dose of 100 mg due to the significant right ventricular strain suggesting concomitant PE, the patient's critical illness, and the low bleeding risk. Because a confirmed VTE was visualized on echocardiogram, tPA was a reasonable therapy. Right ventricular dysfunction in the absence of confirmed VTE is clinical conundrum which requires careful balancing of the risks and benefits of systemic thrombolysis prior to use but is generally discouraged. On post-tPA day 5, the patient was noted to have bleeding within the oropharynx, which ultimately required compression packing to allow for continued systemic anticoagulation, which has since been removed. He remains off of vasoactive medications, and is making progress towards extubation. The patient remains hospitalized as of this writing, but the plan is to continue oral anticoagulation for at least 3-6 months after discharge. In summary, we present the first reported case of a clot in transit during COVID-19 critical illness. COVID-19 appears to be associated with an increased propensity for thromboembolic disease. Heightened suspicion is necessary to clinically detect VTE in this disease and treat accordingly, while mindful of the inherent risks to healthcare workers and resources available, depending on the level of crisis, in the overall health system. 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JACC: Case Reports Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia Incidence of thrombotic complications in critically ill ICU patients with COVID-19 Acute respiratory distress syndrome: the Berlin Definition Diagnosis, Treatment and Follow Up of Acute Pulmonary Embolism: Consensus Practice from the PERT Consortium American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology After treatment with the tissue plasminogen activator (tPA), the right ventricular thrombus is no longer visible. The right ventricle function has improved and the right ventricle size has decreased