The therapeutic approach to massive pulmonary embolism (PE) becomes even more challenging when it gets complicated by resistance to intervention by substitute decision-makers along with comorbidities such as traumatic hemorrhagic brain contusions, history of anticoagulant use, and acute on chronic renal impairment. Massive PE is a life-threatening condition, often requiring systemic thrombolysis. However, the presence of significant contraindications necessitates individualized decision-making. According to current guidelines thrombolysis is the treatment of choice for massive PE, however; the decision to provide thrombolysis is subject to a lot of debates when a complicated case with multiple contraindications is encountered [1]. Additionally, to date, there is no high-quality evidence regarding dosing and infusion rates of thrombolytic agents to treat acute PE. Evidence is now emerging that lower-dose thrombolytic administered through a peripheral vein is efficacious in accelerating thrombolysis.

We encountered a 65-year-old man presented to our tertiary care hospital with a history of syncopal attack at home followed by fall and head injury. The patient was known to be diabetic and hypertensive, and there was a history of deep venous thrombosis and PE on regular warfarin. In the emergency department, the patient was drowsy but responsive, having severe respiratory distress, tachypnea, and tachycardia.

In view of severe respiratory distress and worsening hemodynamic status, he was intubated, and vasopressor commenced after fluid resuscitation. Computed tomography brain, chest and abdomen without contrast were done in view of high creatinine which revealed hemorrhagic brain contusion in the right posterior parietal and left higher parietal lobes. Two-dimensional echocardiography revealed severely dilated right atrium and right ventricle, jerky inter-ventricular septum with shift toward left ventricle, severe right ventricular dysfunction, and normal left ventricular systolic function (Figures 1-3). The lower extremity venous doppler showed evidence suggestive of thrombosis in bilateral superior femoral veins and left popliteal vein. Arterial blood gas analysis revealed nearly compensated metabolic acidosis with high lactate and hyperglycemia. On admission, lab include D-dimer of >20,000 ng/ml, serum creatinine 2.3 mg/dl, white blood cell counts 13,600 per microliter with normal hemoglobin and platelets counts, prothrombin time (PT) 23.1 seconds, international normalized ratio 1.7, and activated partial thromboplastin time (aPTT) 59.5 seconds. Liver function test revealed mildly elevated alanine transaminase and aspartate transferase (161 and 137 unit, respectively).

Angiography and endovascular thrombectomy was first advised by the treating team after taking in consideration concomitant hemorrhagic contusion, acute on chronic kidney injury and warfarin use, but refused by the substitute decision makers. Despite high vasopressor support, blood pressure was deteriorating rapidly, he was anuric for more than 2 hours and on high ventilator settings. His blood pressure continued to worsen despite multiple inotropic and vasopressor agents and reached 40 mm Hg systolic. Eventually, as lifesaving approach 10 mg alteplase was given through peripheral canula. The patient showed dramatic improvement in his hemodynamic parameters and systolic blood pressure increased to 110 mm Hg with in next 1–2 hours. Unfractionated heparin infusion started on the second day of admission with dose titrated according to aPTT level.

During the subsequent course, the patient showed gradual improvement. On discharge from intensive care unit, the patient was conscious and oriented, hemodynamically, and vitally stable, able to take orally after tracheostomy tube decannulation and no longer requiring renal replacement therapy. According to 2019 European Society of Cardiology guidelines, systemic thrombolysis is the main stay of treatment for high risk hemodynamically unstable PE [1]. Other modality of treatment like thrombectomy are reserved for thrombolysis-nonresponsive patients and patients with contraindications and at high risk of bleeding from systemic thrombolysis. Contraindications to thrombolytics can be divided into absolute and relative contraindications, but according to many authors, even the absolute contraindications can be considered as relative in very critical situations [2].

In our case the patient encountered recent head trauma with hemorrhagic brain contusion, and he was on oral anticoagulant (warfarin) with PT 23.1 seconds. Both conditions put him at high risk of intracranial bleeding from thrombolytic therapy. Moreover, acute on chronic renal impairment is not a classic exclusion criterion, but still contributes to the risk of bleeding due to the possibility of platelet dysfunction.

Based on the high risk of bleeding, it was decided to provide endovascular treatment, but that was refused by the patient relatives. This put us in a challenging situation of rapidly collapsing patient with severe obstructive shock and right ventricular dysfunction. Thus, left with no option, it was decided to give alteplase 10 mg (one tenth of recommended dose) to save the life of the patient that showed a good response in terms of improving the patient’s hemodynamic parameters within few hours and allowed us to taper and stop vasopressors.

The use of reduced dose of alteplase has not reached the level of recommendation till now due to the lack of randomized controlled trials with large sample size, despite some suggestions that it might reduce the risk of bleeding in lower body-weight patient with equivalent efficacy compared to 100-mg dose [3]. In one meta-analysis on reduce dose of alteplase in the acute PE, authors concluded that low dose had similar efficacy but safer than normal dose of alteplase. Additionally, in comparison to heparin, low dose was not associated with increased risk of significant bleeding for eligible PE patients [4]. In another meta-analysis, authors concluded that lower than standard dose alteplase may be an efficacious and safe management option for massive PE, especially in those who are at a high risk of bleeding [5]. However, the dose compared was standard 100 mg versus 0.6 mg/kg with a maximum dose of 50 mg unlike our patient where the dose given was 10 mg.

We believe an individual and case-specific approach should be followed in massive PE, and the treatment plan should be tailored to the patient's risk factors and severity level until clear guidelines regarding the dose of thrombolytics in venous thromboembolic disease become available.

This study did not require institutional review board approval, as it did not involve human participants as part of a research activity and did not include identifiable patient information. Written informed consent for publication was obtained from the patient’s legal guardian.