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.