Table 1.

Clinical summary of patients treated with low-dose alteplase for submassive pulmonary embolism

Case	Age (years) sex	Underlying conditions	Signs and symptoms	Imaging	Echocardiogram prior to tPA	Cardiac Biomarkersa	Thrombolytic therapy	Anticoagulantb	Outcome
1	42 M	Metastatic thymoma s/p left pneumonectomy in remote past and chemotherapy-induced cardiomyopathy; recent (<1 month) debridement diabetic leg ulcer	Dyspnea and SpO2 of 85% on room air	CTA: Large right main PA clot with numerous rightsided segmental and subsegmental emboli	Severe RV dilation with RV dysfunction present but not worse compared with baseline	NT-proBNP: 354 pg/ ml (0–92pg/ml); troponin I: normal	6 mg of tPA per day for 2 days via a central venous catheter (1 mg/h for 6 h)	UFH	48 h following the first dose of tPA, repeat CTA demonstrated a significant reduction in the right main PA clot that no longer extended into the upper and lower lobe branches. Discharged home on enoxaparin and did not require supplemental oxygen
2	86 F	Heparin-induced thrombocytopenia	Dyspnea and SpO2 of 86% on room air	V/Q: Mismatched perfusion defect of the entire LLL and 2 seqments of the RUL	Moderate RV dilation with RV dysfunction	NT-proBNP: 5889 pg/ml (0–623 pg/ml); troponin I: 0.506 ng/ml	6 mg of tPA per day for 2 days via a central venous catheter (1 mg/h for 6 h)	Argatroban	48 h following the first dose of tPA, repeat V/Q scan demonstrated improvement in perfusion of the RUL and one segment of the LLL; repeat TTE 12 days after tPA revealed decreased RV dilation, normal RV function, and a decrease in estimated RVSP from 81 to 58 mmHg. Discharged home on warfarin and did not require supplemental oxygen
3	75 F	Metastatic endometrial cancer, bilateral malignant pleural effusions on home oxygen (3 l/min)	Worsening dyspnea and SpO2 of 85% on 5 l/min O2	CTA: Large left main PA embolus with multiple bilateral filling defects	Mild RV dilatation with normal RV function	Not tested	6mg of tPA per day for 2 days via a central venous catheter (1 mg/h for 6 h)	UFH	48 h following the first dose of tPA, repeat CTA demonstrated reduction of RLL thrombus and multiple RUL thrombi; partial lysis of large left main PA thrombus with residual clot embolization of the LLL branch. Discharged home on enoxaparin and an increased amount of supplemental oxygen (SpO2 94% on 4 l/min)
4	41 F	Sickle cell anemia s/p failed HSCT, PH, and prior PE on enoxaparin at presentation	Dyspnea, pleuritic chest pain; SpO2 87% on room air	CTA: Extensive bilateral filling defects	Severe RV dilation with RV dysfunction	NT-proBNP: 4033 pg/ml (0–124 pg/ml); troponin: not tested	6 mg of tPA per day for 2 days via a central venous catheter (1 mg/h for 6 h)	UFH	48 h following first dose of tPA, repeat TTE showed restoration of RV function, but no change in RV dilation and estimated RVSP remained markedly elevated at 93 mmHg. TTE at 1 week showed slight improvement in RV size with preserved function, and a decrease in estimated RVSP to 48 mmHg. Discharged home on apixaban and did not require supplemental oxygen
5	46 M	Von Hippel–Lindau disease with a history of multiple surgeries for CNS hemangioblastomas and renal tumors; 3 weeks s/p ventriculoperitoneal shunt revision complicated by heparin-induced thrombocytopenia	Sudden onset tachypnea and SpO2 75% on room air	CTA: Large saddle embolus and multiple, bilateral filling defects	Moderate RV dilation with RV dysfunction	NT-proBNP: 62 pg/ml (0–124 pg/ml); troponin T: 0.039 ng/ml	2 mg of tPA administered by pulse spray catheter injection to right and left main PA followed by 6 mg of tPA via PA pigtail catheter (1 mg/ h for 6 h); interatrial defect noted incidentally during PA catheterization	Argatroban	Hypoxia resolved overnight. Repeat TTE demonstrated improved RV function 15 h following start of tPA and bubble study confirmed right to left interatrial shunting. Estimated RVSP was not measurable. Discharged home on rivaroxaban and did not require supplemental oxygen
6	78 M	Prostate cancer and recent LLE DVT	Sudden onset of dyspnea, SpO2 97% on 2–3 l/min O2	CTA: Extensive bilateral filling defects	Severe RV dilation with RV dysfunction	NT-proBNP: 8573 pg/ml (0–449 pg/ml); troponin T: 0.024 ng/ml	Days 1 and 2: 2 mg of tPA administered by pulse spray catheter injection to right and left main PA followed by 6 mg of tPA via PA pigtail catheter (1 mg/ h for 6 h); Day 3: 2 mg of tPA by pulse spray catheter injection to right and left main PA followed by 6 mg of tPA to LLE by pulse spray catheter injection; Day 4: 4 mg of tPA to DVT LLE via a LLE venous catheter (1 mg/h for 4 h)	UFH	6 h following the initiation of tPA, PA pressures decreased from 50/23 to 37/17 mmHg. After the first dose of tPA, CTA showed modest decrease in the extent of emboli. Repeat CTA 6 d following first tPA treatment showed marked improvement in right sided emboli and decreased emboli on the left side, but to a lesser extent. TTE 1 week after first tPA treatment showed reduced RV dilation and improved RV function, estimated RVSP decreased from 60 to 32 mmHg. Discharged home on enoxaparin and did not require supplemental oxygen
7	65 F	Sickle cell anemia, PH, history of catheter-associated DVT on warfarin, and on home oxygen (2 I/m in)	Dyspnea on exertion, SpO2 87% on 2 l/min O2; right scapular pain	V/Q: Mismatched segmental perfusion defects bilaterally and global decrease in lung perfusion	Severe RV dilation with RV dysfunction, both worse compared with baseline	NT-proBNP: 6239 pg/ml (0–124 pg/ml); troponin T: 0.021 ng/ml	6 mg/day of tPA for 3 days via central venous catheter (1 mg/h for 6 h)	UFH	72 h following presentation, repeat V/Q scan showed improvement in segmental defects bilaterally as well as improvement of global right lung perfusion. Discharged home on enoxaparin and baseline amount of supplemental oxygen (SpO2 95–100% on NC at 2 l/min O2)
8	52 F	Cushing’s syndrome POD 22 s/p laparoscopic right adrenalectomy	Dyspnea, SpO2 78% on room air and difficulty ambulating	V/Q: Numerous, bilateral mismatched segmental and subsegmental perfusion defects; Doppler US: Left LE DVT	Moderate RV dilation with RV dysfunction; McConnell’s sign noted	NT-proBNP: 2390 pg/ml (0–124 pg/ml); troponin T: 0.048 ng/ml	Day 1: 2 mg of tPA administered by pulse spray catheter injection to right and left main PA followed by 6 mg of tPA via PA pigtail catheter (1 mg/h for 6 h); Day 2: 0.5 mg of tPA to right PA and 0.5 mg tPA to left PA followed by 9 mg of tPA to LLE DVT by pulse spray catheter injections	UFH	6 h following initiation of tPA, PA pressures decreased from 59/29 to 39/18 mmHg. 72 h following presentation, repeat TTE demonstrated improved RV function. Discharged home on warfarin and did not require supplemental oxygen
9	29 M	Metastatic papillary renal cell carcinoma POD 2 s/p left total nephrectomy with RP and pelvic lymph node dissection complicated by aortic injury	Sudden onset of dyspnea, tachycardia, and SpO2 89% on 6 l/min O2	CTA: Right-sided segmental PE in the middle and lower lobes	Mild RV dilation with RV dysfunction	NT-proBNP: 1254 pg/ml (0–124 pg/ml); troponin T: 0.01 7 ng/ml	Day 1: 2 mg of tPA administered by pulse spray catheter injection to right PA followed by 4 mg of tPA via right PA pigtail catheter (1 mg/h for 4 h); Day 2: 6 mg of tPA via central venous catheter (1 mg/h for 6 h)	UFH	10 h following 1st tPA dose, PA pressures decreased from 58/20 to 39/22 mmHg and symptoms greatly improved; repeat TTE showed persistent RV dysfunction. 4 h following infusion of 2nd tPA dose, patient developed hypotension and abdominal distension/pain requiring emergent surgery for hemorrhage at the site of RP lymph node dissection. UFH was reversed with protamine. Subsequently received prophylactic dose UFH with no recurrence of PE and uneventful recovery. Discharged home on treatment dose enoxaparin and did not require supplemental oxygen

BNP, brain natriuretic peptide; CNS, central nervous system; CTA, computed tomography angiography; DVT, deep vein thrombosis; HSCT, hematopoietic stem cell transplant; LE, lower extremity; LLE, left lower extremity; LLL, left lower lobe; NC, nasal cannula; NT, not tested; PA, pulmonary artery; PE, pulmonary embolism; PH, pulmonary hypertension; POD, postoperative day; RLL, right lower lobe; RP, retroperitoneal; RUL, right upper lobe; RV, right ventricle; RVSP, right ventricular systolic pressure; SpO₂, pulse oximeter oxygen saturation; tPA, tissue plasminogen activator (alteplase); TTE, transthoracic echocardiogram; UFH, unfractionated heparin; V/Q, ventilation/perfusion scan.

^aNormal range for NT-proBNP changed with change in assay, normal range shown in (). The normal range for troponin I is 0–0.045 ng/ml and for troponin T is 0–0.009 ng/ml. The assay for cardiac troponin was changed from troponin I subtype to troponin T during the timeframe of these case presentations.

^bUnfractionated heparin was administered concomitant with alteplase with a target activated partial thromboplastin time (apt) of 50–70 s or a target anti-Xa level of 0.2–4 IU/ml. Argatroban was administered concomitant with alteplase with a target aPTT of 50–70 s.