What to Do When They’re Eating for Two? A Case of Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism in Pregnancy

A 33-year-old G7P0 female at 8 weeks gestation presented to the emergency department (ED) following a syncopal episode. She complained of chest pain and dyspnea, and had hemodynamic instability, which responded to intravenous fluids. Continued fluid resuscitation, supplemental oxygen, as well as therapeutic dose low molecular weight heparin (LMWH) were administered in the ED. Computed tomography (CT) pulmonary angiogram confirmed saddle pulmonary embolism (PE). After 12 h of continued chest pain and high oxygen requirements, a decision was made to use catheter-directed thrombolysis (CDT) involving alteplase with manual thrombus maceration in bilateral pulmonary arteries. There were no immediate hemorrhagic complications and follow-up fetal ultrasound demonstrated a normal viable intrauterine pregnancy. She clinically improved and was discharged on LMWH. Cesarean section was scheduled, and the patient delivered a healthy term infant at 37 weeks gestation without complications. Our case demonstrates that CDT may be a safe and effective treatment for submassive PE in pregnancy. RÉSUMÉ Une femme âgée de 33 ans et enceinte de huit semaines (G7P0) se présente aux urgences à la suite d’un épisode syncopal. Elle se plaint de douleurs thoraciques et de dyspnée et présente une instabilité hémodynamique qui répond aux solutés intraveineux. Une réanimation liquidienne continue, une oxygénothérapie ainsi qu’une dose thérapeutique d’héparine de faible poids moléculaire sont administrées aux urgences. L’angiographie pulmonaire par tomodensitométrie confirme une embolie pulmonaire en selle. Après 12 heures de douleurs thoraciques continues et de besoins élevés en oxygène, on décide d’utiliser la thrombolyse dirigée par cathéter (TDC) à l’aide de l’altéplase avec macération manuelle du thrombus dans les artères pulmonaires bilatérales. Il n’y a pas eu de complications hémorragiques immédiates et le suivi échographique du fœtus a démontré une grossesse intra utérine normale et viable. Son état clinique s’est amélioré et elle a obtenu son congé sous héparine de faible poids moléculaire. Une césarienne a été planifiée et la patiente a accouché d’un enfant à terme et en bonne santé à 37 semaines de grossesse, sans complications. Notre cas démontre que la TDC peut être un traitement sûr et efficace de l’embolie pulmonaire submassive en cours de grossesse. C a n a d i a n J o u r n a l o f G e n e r a l I n t e r n a l M e d i c i n e 24 V o l u m e 1 6 , I s s u e 1 , 2 0 2 1 Case Reports and Clinical Images CJGIM_4_WKBK.indd 24 3/19/21 5:36 PM Case Report A 33-year-old female, 8 weeks pregnant (Gravida 7, Para 0), with past medical history significant for hypothyroidism, uterine leiomyomas, and seven spontaneous abortions (all <20 weeks’ gestational age) presented to the emergency department (ED) with chest pain, right upper quadrant abdominal pain, and dyspnea. She had reported a brief syncopal episode on ambulation earlier that day. Medications included levothyroxine and prenatal vitamins. Family history was significant for systemic lupus erythematosus (SLE). In the ED, she was neurologically intact, appeared diaphoretic, and had an increased work of breathing. Vital signs demonstrated hypotension (88/66 mmHg), tachycardia (126 beats per minute), and tachypnea (36 breaths per minute). Intravenous fluids were administered with an increase in systolic blood pressure to 100 mmHg, and 100% oxygen by facemask was applied, which improved the hypotension and hypoxia; however, tachycardia persisted. Initial investigations included an electrocardiogram (ECG) demonstrating sinus tachycardia, S1Q3T3 phenomenon, and evidence of right heart strain (Figure 1). Initial high-sensitivity troponin I was 126 ng/L (normal < 30 ng/L), and bedside point of care ultrasound demonstrated right ventricular (RV) dysfunction. A computed tomography (CT) scan of the thorax demonstrated a pulmonary embolism (PE) with a large clot burden involving distal left and right main pulmonary arteries, and extending into the lobar arteries (Figure 2). Formal transthoracic echocardiogram demonstrated severe RV enlargement, moderately to severely impaired RV systolic function, and akinesia of the RV free wall. RV systolic pressure (RVSP) was 29 mmHg and left ventricular ejection fraction (LVEF) was 60–65%. The diagnosis of submassive PE was confirmed. Therapeutic dose low molecular weight heparin (LMWH; dalteparin 200 IU/kg = 18,000 IU) was administered subcutaneously, and the patient was transferred to the intensive care unit (ICU). Repeat troponin rose Figure 1. Electrocardiogram demonstrating S1Q3T3, sinus tachycardia and right heart strain on initial presentation. Figure 2. CT PE at diagnosis demonstrating the clot burden. CT = computed tomography; PE = pulmonary embolism. C a n a d i a n J o u r n a l o f G e n e r a l I n t e r n a l M e d i c i n e V o l u m e 1 6 , I s s u e 1 , 2 0 2 1 25 R a d f o r d e t a l . CJGIM_4_WKBK.indd 25 3/19/21 5:36 PM to 1335 ng/L. Despite receiving multiple doses of morphine for analgesia, she continued to complain of abdominal pain, pleuritic chest pain, and dyspnea. Supplemental oxygen was titrated down from FiO2 100 to 40% by facemask to maintain SaO2 above 95%. Blood pressure remained stable at 100–110/80–90 mm Hg. On subsequent evaluation, her symptoms persisted despite initial treatment with anticoagulants. Weighing the persistence of symptoms in a patient with submassive PE against a low bleeding risk profile, the decision was made to proceed with catheterdirected thrombolysis (CDT). After obtaining informed consent outlining risks of mortality (1%), major bleeding (8–10%), and 5–10% risk of fetal loss, she underwent CDT on day one of her hospital admission. Through a 5F vascular sheath in the right common femoral vein, 5 mg of tissue plasminogen activator (tPA; Alteplase) was laced in each main pulmonary artery (total bolus of 10 mg) via a 5F pigtail catheter. The tPA sat within the thrombus for 5 min, followed by manual maceration of the thrombus. The pigtail was then pulled back into the main pulmonary artery for continuous tPA infusion of 1 mg/h (0.01 mg/h at 100 mL/h). Heparin was simultaneously infused at 500 IU/h (40 IU/mL at 12.5 mL/h) via the right common femoral vein sheath to prevent thrombus formation on the catheter and provide subtherapeutic anticoagulation. Efforts were made to limit the radiation dose to the fetus during the procedure by minimizing the angiographic runs, appropriate collimation, and decreasing the pulse rate of fluoroscopy to 2–3 pulses per second. After 7 h of tPA infusion, there was marked clinical improvement, with FiO2 requirements decreasing to 4L/min by nasal prongs, heart rate decreasing to 112 bpm, and resolution of the chest pain and dyspnea. The tPA infusion was discontinued, the catheter and sheath were removed and a therapeutic heparin infusion was initiated. There were no hemorrhagic complications. Symptoms of chest and abdominal pain resolved, and supplemental oxygen was discontinued. Fetal ultrasound on day 3 of admission demonstrated a single viable intrauterine pregnancy. Given the patient’s history of recurrent pregnancy loss, antiphospholipid antibody testing was ordered and returned negative (anti-cardiolipin IgG and beta2-gycloprotein IgG both < 5 units/mL), which supported the belief that her previous fetal losses were secondary to leiomyomas. She was transitioned to tinzaparin 18,000 IU SC daily and discharged home 7 days after her initial presentation with close follow-up arranged. She was followed throughout her pregnancy where she continued to be asymptomatic with no episodes of major bleeding, recurrent venous thromboembolism (VTE), or pregnancy complications. She remained on tinzaparin throughout the remainder of her pregnancy and planned delivery for 37 weeks gestation. Her last dose of tinzaparin was administered 24 h prior to delivery. She delivered a healthy baby boy by caesarian section without any immediate complications. Discussion VTE in pregnancy is one of the leading causes of maternal mortality with close to one in 10 maternal deaths attributed to antepartum and postpartum PE.1 The clinical presentation of PE is variable, and acute complications are similar to those seen in the nonpregnant population.2 In pregnancy, therapeutic dose LMWH is the standard of care for the management of VTE (acute submassive/low-risk PE and deep vein thrombosis).3 When patients present with massive PE (Table 1), or if anticoagulation alone fails to improve the patient’s condition, thrombolysis can be considered.4 Table 1. American Heart Association classification of pulmonary embolism Risk stratification of acute PE Criteria (1 or more) Massive • Sustained hypotension (systolic BP <90 mm Hg for 15 min or requiring ionotropic