key: cord-0922946-uysnlxtr authors: Hirschbaum, Julian H; Bradley, C Pierce; Kingsford, Philip; Mehra, Anilkumar; Kwan, Wilson title: Recurrent massive pulmonary embolism following catheter directed thrombolysis in a 21-year-old with COVID-19: a case report date: 2021-04-30 journal: Eur Heart J Case Rep DOI: 10.1093/ehjcr/ytab140 sha: 73241db75c4160c5d3468f5a39d1716b8178def2 doc_id: 922946 cord_uid: uysnlxtr BACKGROUND: Coronavirus Disease-2019 (COVID-19) has been associated with increased incidence of pulmonary embolism (PE), even among patients at low risk for venous thrombo-embolic (VTE) events. CASE SUMMARY: We present the case of a 21-year-old male, with no previous medical history, who presented with cough, fevers, shortness of breath, pleuritic chest pain, and 1 day of dizziness with near syncope as well as acutely worsened dyspnoea. He was subsequently diagnosed with COVID-19 and massive PE. He underwent successful catheter-directed thrombolysis (CDT), and his clinical status improved. One day following initial CDT, he developed acute respiratory failure and hypotension and was diagnosed with recurrent massive PE. He was treated with repeat CDT and extracorporeal membrane oxygenation (ECMO) to provide time for right ventricular recovery. The patient was able to be weaned off ECMO after 9 days and was eventually extubated and discharged to an acute rehabilitation facility. DISCUSSION: Beyond COVID-19, no hypercoagulable risk factors were identified despite thorough investigation. This case highlights the thrombogenic potential and morbid sequelae of SARS-CoV-2 infection, even in young patients. It also highlights the use of CDT and ECMO among patients with massive PE and COVID-19. To date, this is the youngest reported patient to develop massive PE in the setting of COVID-19. • Pulmonary embolism (PE) is associated with Coronavirus Disease-2019 (COVID-19) and should be suspected in any patient with haemodynamic collapse regardless of their age, clinical trajectory, or anticoagulation status. • Careful attention should be paid to initiation and dosing of anticoagulation in patients with COVID-19. This is particularly true of obese patients. • Catheter-directed thrombolysis and extracorporeal membrane oxygenation should be considered in critically ill patients with massive PE and COVID-19. Since the emergence of Coronavirus Disease-2019 , an association between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coagulopathy has been noted. 1 Pulmonary embolism (PE) is widely described in this context, even among patients at low risk for venous thromboembolic (VTE) events. 2 We illustrate the case of a 21-year-old male, who presented with COVID-19 and a sub-massive PE with later development of massive-PE requiring catheter directed thrombolysis (CDT), extracorporeal membrane oxygenation (ECMO), and repeat CDT for recurrent massive PE. An obese 21-year-old male with no other past medical history presented to the emergency department (ED) with 3 days of cough, fevers, shortness of breath, pleuritic chest pain, and 1 day of lightheadedness with near syncope as well as acutely worsened dyspnoea. He denied contact with sick persons, exertional chest pain, weight loss, night sweats, abdominal pain, changes in bladder or bowel habits, and recent travel, surgery, or prolonged immobilization. Upon arrival, he was febrile (38.9 C), tachycardic (121 beats per minute), normotensive (104/66 mmHg), and hypoxic saturating 82% on room air, however, improved to 100% with non-rebreather mask at 15 L/min. Obesity: body mass index (BMI) 37. This patient's presentation with chest pain, dyspnoea, and near syncope preceded by cough and fever in the midst of a global pandemic raised concerns for COVID-19 and community-acquired pneumonia as well as pneumothorax and pulmonary embolism. Severe Acute Respiratory Syndrome Coronavirus 2 nasopharyngeal qualitative polymerase chain reaction (PCR) was positive. electrocardiogram (ECG) demonstrated evidence of right heart strain as well as S wave in lead I, Q wave and inverted T wave in lead III (S1Q3T3), a pattern associated with acute PE (Figure 1 The patient was admitted to the intensive care unit (ICU) on highflow nasal cannula and intravenous (IV) unfractionated heparin (UFH) infusion (goal PTT 60-80 s) with stable vital signs. Twelve hours after initial presentation, the patient became increasingly hypoxic and persistently hypotensive with systolic blood pressure <90 mmHg. At this point, he was presumptively diagnosed with massive PE, and urgently underwent CDT of the bilateral pulmonary arteries utilizing the EKOS TM Endowave Infusion Catheter System (1 mg/h tissue plasminogen activator (tPA) per side over 6 h). Intravenous heparin infusion was continued (goal PTT 40-60 s during tPA infusion, 60-80 s post-tPA infusion). Following CDT, the patient improved clinically and was transferred to the general medicine floor on hospital Day 3 with minimal supplemental oxygen and plan to discharge with oral anticoagulation. On hospital Day 4, the patient was initially normotensive with blood pressure 114/64 mmHg and saturating 99% on 2 L/min of oxygen via nasal cannular when he developed acute respiratory failure with oxygen saturation of 65% requiring non-re-breather mask and hypotension with blood pressure 70/30 mmHg. The patient was subsequently intubated and developed cardiac arrest regaining spontaneous circulation after two rounds of cardiopulmonary resuscitation and one electrical shock. Vasopressor support was initiated with Over the next 48 h, ventilation parameters improved, and vasopressors were discontinued. Repeat pulmonary angiography demonstrated significant improvement in the right central pulmonary embolism, with residual obstruction of the left central pulmonary artery (Figure 4) . Venous duplex ultrasound was then performed demonstrating non-occlusive thrombus of the right femoral vein and right popliteal vein. An inferior vena cava filter was placed, and the patient's anticoagulation regimen was transitioned from UFH to low-molecular-weight heparin (LMWH) (Enoxaparin, 1 mg/kg every 12 h) due to concern for failure of anticoagulation. Hypercoagulable workup consisting of Beta-2 Glycoprotein, Cardiolipin, and Phospholipid Antibodies as well as Prothrombin A and Factor V Leiden gene mutations was unremarkable. The patient was successfully weaned from ECMO on hospital Day 10 and extubated on hospital Day 31. The remainder of the hospital course was notable for septic shock treated with broad spectrum antibiotics and development of a right thigh haematoma and compartment syndrome requiring surgical debridement on hospital Day 40. Postoperatively, the patient was transitioned to rivaroxaban 15 mg twice daily for 21 days and 20 mg once daily thereafter. On hospital Day 52, the patient was discharged to an acute rehabilitation facility. The patient returned home 67 days after admission and was able to perform activities of daily living independently. The patient remained anticoagulated on rivaroxaban 20 mg daily and had no major adverse events 4 months following discharge. Massive PE is increasingly recognized as a significant cause of mortality in COVID-19. One systematic review estimates the incidence and mortality rate of PE in COVID-19 patients to be as high as 15% and 45%, respectively. 3 A study involving postmortem examination of COVID-19 patients demonstrated that massive PE was the cause of death in 33% (4/12), with thrombi originating from lower extremity. 4 Notably, all four patients who died were markedly obese (BMI 34. 4-38.8) . The frequency of thrombosis and PE in patients with COVID-19 highlights the need for early and appropriate anticoagulation. A retrospective analysis of 4400 adults with COVID-19 demonstrated that prophylactic and therapeutic anticoagulation was associated with a roughly 50% reduction in mortality when initiated within 48 h of admission, compared to no anticoagulation. 5 For COVID-19 patients, the International Society on Thrombosis and Haemostasis (ISTH) currently recommends standard dose prophylaxis for all admitted patients, intermediate dose prophylaxis for critically ill patients and those with acute respiratory distress syndrome, and therapeutic dose anticoagulation for patients with confirmed or presumed venous thromboembolism. The ISTH cautions that for obese patients, the standard doses of UFH and LMWH are likely insufficient, and a 50% dose increase for thromboembolic prophylaxis should be considered. 6 However, treatment failure and recurrence of venous thromboembolism despite anticoagulation appears to be common. One single-centre case series of COVID-19 patients admitted to the ICU identified PE in 22 (20.6%). At the time of diagnosis, 20 of the 22 were receiving appropriate antithrombotic treatment with UFH or LMWH. 7 At present, there are no large-scale studies to guide management of PE in COVID-19. Case reports have yielded mixed results with varying approaches including mechanical thrombectomy, CDT, systemic thrombolysis, and anticoagulation alone. [8] [9] [10] Massive PE in the setting of COVID-19 represents a unique and challenging clinical entity which may benefit from therapies such as CDT and/or ECMO. The role and efficacy of CDT in treating massive PE is an area of ongoing debate, while the use of ECMO in the setting of COVID-19 continues to evolve. 11, 12 At our centre, we have experienced favourable outcomes in treating massive PE with CDT in carefully selected patients. In addition, we have found that patient with massive PE occasionally require ECMO for temporary support while awaiting right ventricular recovery. Furthermore, we were aware that ECMO had been utilized with positive results in treating severe cases of COVID-19. These factors along with the patient's rapid deterioration following his first massive PE, guided the decision to choose CDT (with ECMO as a bailout option) over systemic thrombolysis. While there are no high-quality comparisons of systemic thrombolysis vs. CDT, multiple large-scale studies have demonstrated the efficacy and safety of CDT. 13, 14 Moreover, a large retrospective study showed that CDT was associated with decreased in-hospital mortality and intracranial Haemorrhage when compared to systemic thrombolysis. 15 Localized delivery of thrombolytic agents may help alleviate concerns about dosing adequacy, particularly in obese patients. This case highlights the thrombogenic potential and morbid sequelae of SARS-CoV-2 infection, even in young patients. To date, this is the youngest reported patient to develop massive PE in the setting of COVID-19. Despite the severity of his illness, the patient had an excellent clinical outcome, demonstrating that CDT and ECMO can be used effectively in carefully selected patients. Given the growing body of evidence suggesting that patients with COVID-19 are prone to thrombosis and recurrent thrombo-embolic events despite appropriate anticoagulation, more research is required to determine best clinical practices. Julian Hirschbaum is a 4th-year resident at LACþUSC Medical Center in Los Angeles completing his residency in the combined specialties of Internal Medicine and Pediatrics. He is interested in congenital heart disease and providing transitional care to underserved adolescents and young adults living with congenital heart disease. He plans to pursue a fellowship in Pediatric Cardiology followed by a focus in Adult Congenital Heart Disease. In addition to his interest in Cardiology, he is also focused on primary healthcare for underserved populations, global health, and improving access to healthcare in rural areas through the training of community health workers. Pulmonary embolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: a narrative review Sudden death due to acute pulmonary embolism in a young woman with COVID-19 Incidence and mortality of pulmonary embolism in COVID-19: a systematic review and meta-analysis Autopsy findings and venous thromboembolism in patients with COVID-19 Anticoagulation, mortality, bleeding and pathology among patients hospitalized with COVID-19: a single health system study ISTH interim guidance on recognition and management of coagulopathy in COVID-19 Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence Recurrent massive pulmonary emboli in a critically ill patient with COVID-19 Difficulties of managing submassive and massive pulmonary embolism in the era of COVID-19 Catheter-directed thrombolysis to treat acute pulmonary thrombosis in a patient with COVID-19 pneumonia Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension COVID-19) Treatment Guidelines. National Institutes of Health pulmonary embolism response to fragmentation, embolectomy, and catheter thrombolysis (PERFECT): initial results from a prospective multicenter registry SEATTLE II Investigators. A prospective single-arm, multicenter trial of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis for acute massive and submassive pulmonary embolism: the SEATTLE II study Utilization of catheter-directed thrombolysis in pulmonary embolism and outcome difference between systemic thrombolysis and catheter-directed thrombolysis We acknowledge and thank all the members of the healthcare teams that participated in the care of this patient. Supplementary material is available at European Heart Journal -Case Reports online.Slide sets: A fully edited slide set detailing these cases and suitable for local presentation is available online as Supplementary data. The authors confirm that written consent for submission and publication of this case report including images and associated text has been obtained from the patient in line with COPE guidance. Funding: None declared.