Discussion
Mortality intermediate PE remains exceedingly high despite thrombolytic and anticoagulation therapy. At present, clinical effectiveness of fibrinolysis on mortality has not been clearly established beyond 90 days [2]. Despite initial encouraging results, thrombectomy and CD thrombolysis have not been considered as the first choice of treatment in the current European Guidelines for high risk PE, even in cases of major contraindication to thrombolysis [3]. Given the variability in PE mortality, risk stratification of low, intermediate, and high risk PE has been adopted by all major guideline committees including the American College of Cardiology. Risk stratification is used to navigate treatment modalities. Patients with low risk PE (normotensive, normal biomarkers) are typically treated with direct oral anticoagulants in the outpatient setting. High risk PE (hypotension with systolic blood pressure <90 mmHg for >15 minutes, syncope, cardiac arrest) warrant immediate thrombolytic therapy, with or without mechanical hemodynamic support. Intermediate risk PEs can present in a normotensive patient with imaging indicative of RV strain, elevated biomarkers, Pulmonary Embolism Severity Index (PESI) class III-IV and its simplified version, sPESI >1. Systemic thrombolysis, CD therapy, and surgical embolectomy with mechanical support, plus anticoagulation are all considered in the treatments for both high and intermediate risk PE.
Systemic thrombolysis for intermediate risk PE has shown to reverse hemodynamic compromise by improving RV dilatation, PA pressure and pulmonary perfusion [4]. Unlike high risk PE, systemic thrombolytic therapy in intermediate risk PE has not shown to reduce mortality and recurrence [5]. Given the risks of systemic thrombolysis including major bleeding and intracranial hemorrhage (ICH), CD approaches are used in patients with relative contraindications to thrombolytic therapy. CD delivery of fibrinolytic agents or mechanical fragmentation of a thrombus have lower risk of ICH (0.35%) when compared to systemic thrombolysis (3%) [6]. Surgical embolectomy is an option after failed thrombolytic therapy or absolute contraindications to thrombolytics. In recent years, the perioperative mortality for surgical embolectomy has decreased from 29% to 3.6% [7]. In cardiogenic shock or refractory PE, mechanical circulatory support is considered to decrease RV afterload and improve RV function [8].
First-line treatment for high risk PE has been systemic thrombolysis due to more than 90% of patients responding within 36 hours [9]. In comparison, CD thrombolysis also showed a reduction in the mean RV distention within 48 hours. For CD therapy, the rates of major bleeding ranged from 0% to 4%, and less than 1% experienced ICH [10]. The rate of major bleeding from systemic thrombolysis was 19%, and 5% was intracranial [11]. In general, bleeding rates vary among studies, and the rates comparing interventional bleeding risk after 48 hours are lacking in literature. Considering our patient presented 5-days after symptom onset, systemic heparinization was initiated as the benefits and risks were similar to systemic thrombolysis after one week of onset [12]. Additionally, the patient’s PESI score was 69 (Class II low risk) and sPESI was 0, which supported use of heparin over thrombolysis in the setting of intermediate risk PE. Due to ongoing dyspnea, CD thrombolysis was performed after platelets recovered. The ULTIMA trial compared CD thrombolysis plus anticoagulation and anticoagulation alone which showed improvement of RV distension in the former; thus supporting a hemodynamic benefit in the CD therapy group [13].
The presence of HIT antibodies and decrease of more than 50% in platelet count warranted cessation of heparin and initiation of argatroban. Platelet count of 100,000/L was considered adequate for thrombolysis as indicated by Srinivias et. al. in a study comparing thrombolysis and anticoagulation in management of DVT [14]. Small studies have shown success with CD thrombectomy for high risk PE [15]. One common theme shared with the management of intermediate risk PE was that CD thrombectomy was an option only when systemic thrombolysis was contraindicated. With more advancement in the field, CD therapy could become first-line treatment for intermediate PE.