Thrombus Aspiration and Local Fibrinolytic Therapy for Acute Pulmonary Thromboembolism

Case Report. A 52-year-old Caucasian female presented with increased shortness of breath and transient collapses over a 2-day period. Her medical history included pulmonary embolism in 1998 and deep vein thrombosis in 1996, 2000 and 2003. She discontinued oral anticoagulation therapy (OAT) in 2005. She had no history of thrombophilia. Physical examination revealed an obese woman weighing 82 kg, with a blood pressure of 120/85 mmHg, a pulse of 85/minute, and a respiratory rate of 24/minute. The patient was afebrile. Her venous pressure was elevated. Heart sounds were dual with no murmurs. Electrocardiography showed a heart rate of 88/minute with an S-wave in limb lead I, a Q-wave in limb lead III, and T-wave inversion in limb lead III. The patient’s chest X-ray showed a widened mediastinum on a mobile supine film. Her oxygen saturation on room air was 88%. Transthoracic echocardiography (TTE) revealed a small left ventricle with normal systolic function. The right ventricle was dilated with diffuse wall motion abnormalities and mildly depressed systolic function. There was grade 2/4 tricuspid regurgitation with an estimated right ventricular systolic pressure of 45 mmHg. On spiral thorax computed tomography, a significant thrombus in the proximal left pulmonary artery and small thrombi in the periphery of the right pulmonary artery were visible. Serum creatine kinase and cardiac troponin I levels were normal; the homocysteine level was borderline (14 micro g/l).
The patient was given 10,000 U of unfractionated heparin. An activated partial thromboplastin time (aPTT) goal of 80–100 seconds was used as a guide to continue the heparin infusion (18 U/kg/hour). Venography showed a chronic occlusion of the left common iliac vein with well developed collaterals to the inferior vena cava. There was no evidence of thrombus in the inferior vena cava or right common femoral and iliac veins. Pulmonary angiography revealed total occlusion of the left lower lobe pulmonary artery (Figure 1) and segmental branches of the left upper lobe and right middle- and lower-lobe pulmonary arteries. Her pulmonary artery pressure (PAP) was 45/22 mmHg (mean 32 mmHg). Systemic pressure was 118/78 mmHg. Thrombus aspiration was performed using an 11 Fr Aspirex catheter, which is designed for aspiration of emboli in lager vessels (Figure 2). A subsequent pulmonary angiogram showed partial recanalization of the thrombus (Figure 3). Following aspiration, a lysis catheter was placed within the left lower-lobe pulmonary artery; local lysis was initiated by administration of urokinase 36,000 U as a bolus administered over 10 minutes. Upon completion of the intervention, PAP was reduced to 36/19 mmHg and systemic pressure increased to 126/82 mmHg. Urokinase was continued at an infusion rate of 36,000 U/hour for 24 hours. Heparin infusion was discontinued during fibrinolysis. A duplex study of both legs revealed no evidence of deep vein thrombosis. Pulmonary angiography 24 hours after thrombus aspiration and fibrinolytic therapy showed almost complete resolution of the thrombus in the left lower-lobe artery, but only partial resolution in other branches (Figure 4). Her PAP was 32/19 mmHg (mean 24 mmHg) and her systemic pressure was 130/82 mmHg. TTE after 1 week revealed a normal size and function of the right ventricle without wall motion abnormality. Heparin was infused (18 U/kg/hour) with aPTT control (80–100 seconds) for 7 days after fibrinolysis and overlapped with coumadin to reach the goal INR of 2.0–3.0. The patient was discharged on lifelong OAT and folic acid.

Discussion. The principal criteria for categorizing PE as massive are arterial hypotension and cardiogenic shock. Our patient was not in cardiogenic shock, but she has a history of collapse and findings of right ventricular (RV) dysfunction, indicating that she had a submassive PE. Early mortality in patients with massive PE is at least 15%, but in patients with submassive PE with RV dysfunction, it is 8%, and the degree of hemodynamic compromise is the most powerful predictor of in-hospital death.¹
Immediate initial management. As soon as PE is suspected, high-dose unfractionated heparin should be administered in larger-than usual doses. Most patients should receive at least a 10,000-U bolus of heparin, followed by a continuous intravenous infusion of at least 1,250 U/hour, with a target aPTT of at least 80 seconds. Fibrinolysis. Systemic fibrinolysis is recommended as standard first-line treatment in patients with massive PE and can reduce the risk of death or recurrent PE by 55%. But in patients with submassive PE, this therapy is controversial. A recent randomized clinical trial by Konstantinides and colleagues² examined the role of thrombolysis in hemodynamically stable patients (defined as those with a systolic blood pressure >90 mmHg) with PE. These patients had documented RV dysfunction by echocardiography or evidence of pulmonary hypertension. They were randomized into two groups: the first group received heparin plus 100 mg of alteplase (R-tPA), and the other group received heparin plus placebo. Although there were no differences in mortality, PE recurrence, or major bleeding, there were significant differences in escalation of treatment and secondary thrombolysis favoring the thrombolysis group (10% vs. 25%, p = 0.004, and 7.6% vs. 23%, p = 0.001, respectively). More patients in the heparin-only group had hypotension/shock and worsening symptoms (0.8% vs. 5.5%, and 5.9% vs. 15%, respectively), and more patients in this group required intubation (0.8% vs. 2%). Despite these differences, a difference in mortality or PE recurrence rates favoring thrombolysis was not shown in this or in any randomized clinical trial since 1970, when the UPET trial was conducted.^3,4 At the present, however, PE thrombolysis based solely on the presence of RV dysfunction is controversial due to a paucity of data.
Open surgical embolectomy on a warm beating heart without aortic cross-clamping, cardioplegia, or fibrillatory arrest has been successfully done with an 89% survival rate in patients with cardiogenic shock. Catheter thrombectomy. When thrombolytic therapy fails or is contraindicated, the nonsurgical, less invasive option available for this group of patients with massive PE is percutaneous embolectomy and thrombectomy with the use of some of the mechanical devices.⁵ Different percutaneous devices are potentially useful or have been successfully used in the treatment of massive PE: the Greenfield embolectomy catheter,^6,7 balloon angioplasty, and stents;^8–11 the pigtail rotational catheter;¹² the Amplatz thrombectomy device (ATD);¹³ the hydrodynamic thrombectomy catheter device;^14,15 and the Aspirex PE thrombectomy catheter.¹⁶
Most of the current techniques do not totally eliminate the clots, but rather break down the thrombus in smaller fragments, which migrate peripherally in the pulmonary artery circulation, opening up the main pulmonary artery and improving perfusion.¹⁷ In this patient, who was not in cardiogenic shock but had signs of RV dysfunction and a history of collapse, we aspirated the obstructing thrombus with an Aspirex 11 Fr catheter and administered local fibrinolysis with a special lysis catheter to achieve rapid reperfusion and hemodynamic improvement. The pulmonary angiogram, hemodynamic data and echocardiography showed practical improvement.
The Aspirex device is a highly effective mechanical thrombectomy catheter specifically developed for the treatment of central PE.¹⁸ The Aspirex is an 11 Fr over-the-wire, single-use catheter compatible with a 0.035 inch Terumo guidewire. The system offers the following three functions: (1) permanent suction via a spiral catheter with a 40,000 rotations/minute and 180 ml/minute suction capacity; (2) fragmentation into extremely small particles by entry of the material into the L-slit at the top of the catheter; and (3) continuous transport of the debris out of the vessel into a waste bag. To minimize the risk of perforation or dissection, thrombectomy should be performed only in the main and lobar pulmonary arteries, not in the segmental pulmonary arteries.¹⁸ The device functions differently from the AngioJet (hydrodynamic thrombectomy catheter device), which uses the Venturi effect to perform thrombectomy with a double-lumen system. The smaller lumen of the AngioJet is made of fine metal tubing that conducts the high-pressure, high-velocity stream of saline fluid. The metal tubing makes a circle (ring) at the tip of the end hole of the catheter, and the jet is oriented backward in the direction of the main lumen of the catheter shaft to create a low-pressure area that promotes fragmentation and evacuation of the clots.^19,20 It has been used successfully in an animal model and in clinical cases as well.^21,22
Hybrid treatment using a combination of mechanical fragmentation, local fibrinolysis, and clot aspiration with an angioplasty guiding catheter for PE in 25 patients was reported with 100% success.²³ The percutaneous thrombus aspiration of the pulmonary artery with an Aspirex 11 Fr catheter as adjunctive therapy for local fibrinolysis to achieve rapid reperfusion in extensive PE is a feasible method. The limited available data do not support the use of intrapulmonary thrombolytic therapy (levels II and V evidence). Further research is needed to determine the role of local pharmacomechanical thrombolysis employing low doses of thrombolytic agents and percutaneous thrombus aspiration, especially in the treatment of patients with PE who are at high risk for bleeding complications.

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