Case Review
Use of Thrombolytic Agents to Treat Pulmonary Embolism in Pregnancy Mohammad Yusuf Beebeejaun, MD, Olumayowa Adenugba, MD William Harvey Hospital, East Kent Hospital University Trust, Ashford, United Kingdom
Pulmonary embolism in pregnancy is a major cause of maternal mortality and morbidity. We describe the case of a 27-year-old pregnant woman who underwent successful thrombolysis. Our patient presented to the emergency department after a fainting episode and complaining of shortness of breath. A computed tomography pulmonary angiogram revealed a pulmonary embolism, which was found to be causing significant right ventricular strain. After examination by our gynecologic and medical teams, she underwent successful thrombolysis, made a successful recovery, and carried an uneventful pregnancy. [ Rev Obstet Gynecol. 2013;6(3/4):182-184 doi:10.3909/riog0206]
®
© 2014 MedReviews , LLC
Key words Pulmonary embolism • Pregnancy • Antithrombolytics
A
venous thromboembolic event (VTE) is one of the most common causes of maternal mortality in the United Kingdom and is believed to account for 11% to 20% of maternal deaths.1,2 Venous thrombosis and pulmonary embolism, therefore, need to be effectively prevented, and, if detected, managed adequately and safely.3 Because of the possible hemorrhagic and teratogenic effects of certain medications in pregnancy, the management of VTE can be quite difficult. We describe the case of a pregnant woman with
a pulmonary embolism who received successful thrombolytic therapy and continued an uneventful pregnancy. We also briefly review the literature on the management of pulmonary embolism in pregnancy.
Case Report
A 27-year-old woman (gravida 6, para 0+6) presented to the emergency department at 8 weeks of gestation with chest pain, shortness of breath, and acute collapse after feeling increasingly faint. The
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Use of Thrombolytic Agents to Treat Pulmonary Embolism in Pregnancy chest pain was central in nature and worse on inspiration. The shortness of breath had started a few hours prior to presentation and was not associated with any cough. Past medical history included five miscarriages, all terminating before 8 weeks of gestation, with the exception of a twin pregnancy, which miscarried at 12 weeks. On admission, the patient was dyspneic with a respiratory rate of 42 breaths per minute and an oxygen saturation of 96% on room air. The patient was also hypotensive (blood pressure 81/33 mm Hg) with a sinus tachycardia at 134 beats per minute. Respiratory and cardiovascular examinations were both unremarkable. On vascular examination, both legs appeared swollen and mild tenderness was elicited in the calves. On questioning, the patient stated that she first noticed her calves swelling and becoming increasing tender 2 days prior to presentation to the emergency department. A full blood count and pneumonic panel were ordered and bedside electrocardiography demonstrated supraventricular tachycardia with T waves inversion in leads V1, V2, and V3. With the clinical presentation highly suggestive of VTE, and in
Figure 1. Computed tomography pulmonary angiogram demonstrating a massive riding central pulmonary embolism with saddle embolus associated with right heart ventricle strain.
embolism with saddle embolus associated with right heart ventricle strain (Figure 1). The right and left pulmonary arteries and their segmental branches appeared fully occluded by the emboli. Due to the significant hemodynamic compromise caused by the embolus, a multidisciplinary decision between the emergency and obstetric teams was made to perform thrombolytic treatment. Thrombolysis with streptokinase was administered and the patient was admitted to the intensive care unit for regular monitoring following thrombolysis. Heparin therapy was also commenced after thrombolysis. Arterial blood gas monitoring was performed and assessed regularly. Supplemental oxygen
CTPA demonstrated a massive riding central pulmonary embolism with saddle embolus associated with right heart ventricle strain.
view of the calf tenderness and the chest pain, a working diagnosis of pulmonary embolism was made. The patient was informed of the diagnosis and her hemodynamic stability was monitored. The potential risks and benefits of computed tomography pulmonary angiogram (CTPA) with regard to both mother and fetus were eventually weighed and the patient gave her consent for the procedure. CTPA demonstrated a massive riding central pulmonary
was eventually discontinued and the tachycardia gradually resolved, proving that the patient had an excellent response to the thrombolytic therapy. The chest pain and shortness of breath also resolved. In view of the increased risk of miscarriage, the obstetrics team ordered regular pelvic examinations and ultrasound scans. A regular fetal heart rate was heard and no associated placental or fetal bleeding was reported. Reassuring views of the fetal heart and face were also
Figure 2. Repeat computed tomography pulmonary angiogram identified resolution of the embolism seen in Figure 1.
detected. A repeat CTPA identified resolution of the embolism (Figure 2). The patient was eventually discharged on low molecular weight heparin (enoxaparin) to be injected twice daily once the intravenous heparin therapy was completed. It was advised that she continued the enoxaparin therapy until she was in the postpartum period. Our patient had an uneventful pregnancy and a healthy baby girl was born at 39 weeks of gestation by an uncomplicated vaginal delivery. A repeated lung perfusion scan showed complete resolution of the emboli.
Discussion
Thromboembolic disease is a major cause of death in pregnancy and any large thrombus in the pulmonary circulation can cause a reduction in cardiac output, resulting in potential organ hypoperfusion, multiorgan failure, and death. Any obstruction in the pulmonary system can facilitate the onset of pulmonary hypertension, which can cause further complications in pregnancy. The optimal management of pulmonary embolism in pregnant patients remains unclear, primarily due to the lack of any definitive study or national guidelines, and because of their varying presentations. Thrombolytic therapy is regarded as the standard first-line
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Use of Thrombolytic Agents to Treat Pulmonary Embolism in Pregnancy continued treatment in nonpregnant patients with VTE, but it has been found to be associated with some serious complications in pregnancy. Major complications associated with thrombolysis include pregnancy loss (5.8%), preterm delivery (5.8%), and hemorrhagic complications (8.1%).4 Thrombolysis via the use of streptokinase and recombinant tissue plasminogen activator (rt-PA) is, however, still preferred over heparin injection because it causes a quicker fragmentation of the emboli if administered within the first 24 hours when compared with heparin.3,5,6 Although no research has concluded which thrombolytic agent (streptokinase or rt-PA) is safest in pregnancy, the large size of rt-PA limits its crossing
the placenta and entry into the fetal circulation, giving it a theoretical advantage in pregnancy. Also, rt-PA has a short half-life, limiting its untoward effects, and it has not been found to be associated with any allergenic complications.7 The current limited literature does not justify withholding thrombolytic therapy from pregnant women in cases of life-threatening pulmonary embolism. Nonetheless, a personalized approach should be adopted with regard to any changing clinical situation, with the safety of the mother being the primary concern of any clinician. Other management options for a massive pulmonary embolism in pregnancy include surgical embolectomy and catheter-directed therapy.
References 1.
2.
3.
4.
5.
6.
7.
Clark SL, Belfort MA, Dildy GA, et al. Maternal death in the 21st century: causes, prevention, and relationship to cesarean delivery. Am J Obstet Gynecol. 2008;199:36.e1-36.e5. Benhamou D, Chassard D, Mercier FJ, et al. The seventh report of the confidential enquiries into maternal deaths in the United Kingdom: comparison with French data [article in French]. Ann Fr Anesth Reanim. 2009;28:38-43. Lonjaret L, Lairez O, Galinier M, Minville V. Thrombolysis by recombinant tissue plasminogen activator during pregnancy: a case of massive pulmonary embolism. Am J Emerg Med. 2011;29:694. e1-684.e2. Turrentine MA, Braems G, Ramirez MM. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. Obstet Gynecol Surv. 1995;50:534-541. Fasullo S, Scalzo S, Maringhini G, et al. Thrombolysis for massive pulmonary embolism in pregnancy: a case report. Am J Emerg Med. 2011;29:698.e1-698.e4. Capstick T, Henry MT. Efficacy of thrombolytic agents in the treatment of pulmonary embolism. Eur Respir J. 2005;26:864-874. Konstantinides S, Geibel A, Heusel G, et al; Management Strategies and Prognosis of Pulmonary Embolism-3 Trial Investigators. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002;347: 1143-1150.
Main Points • Venous thromboembolic events (VTEs) are among the most common causes of maternal mortality in the United Kingdom and are believed to account for 11% to 20% of maternal deaths. • Thrombolytic therapy is regarded as the standard first-line treatment in nonpregnant patients with VTE, but it has been found to be associated with some serious complications in pregnancy, including pregnancy loss, preterm delivery, and hemorrhagic complications. • Thrombolysis via the use of streptokinase and recombinant tissue plasminogen activator is preferred over heparin injection because it causes a quicker fragmentation of the emboli if administered within the first 24 hours.
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Use of Thrombolytic Agents to Treat Pulmonary Embolism in Pregnancy Mohammad Yusuf Beebeejaun, MD, Olumayowa Adenugba, MD William Harvey Hospital, East Kent Hospital University Trust, Ashford, United Kingdom
Pulmonary embolism in pregnancy is a major cause of maternal mortality and morbidity. We describe the case of a 27-year-old pregnant woman who underwent successful thrombolysis. Our patient presented to the emergency department after a fainting episode and complaining of shortness of breath. A computed tomography pulmonary angiogram revealed a pulmonary embolism, which was found to be causing significant right ventricular strain. After examination by our gynecologic and medical teams, she underwent successful thrombolysis, made a successful recovery, and carried an uneventful pregnancy. [ Rev Obstet Gynecol. 2013;6(3/4):182-184 doi:10.3909/riog0206]
®
© 2014 MedReviews , LLC
Key words Pulmonary embolism • Pregnancy • Antithrombolytics
A
venous thromboembolic event (VTE) is one of the most common causes of maternal mortality in the United Kingdom and is believed to account for 11% to 20% of maternal deaths.1,2 Venous thrombosis and pulmonary embolism, therefore, need to be effectively prevented, and, if detected, managed adequately and safely.3 Because of the possible hemorrhagic and teratogenic effects of certain medications in pregnancy, the management of VTE can be quite difficult. We describe the case of a pregnant woman with
a pulmonary embolism who received successful thrombolytic therapy and continued an uneventful pregnancy. We also briefly review the literature on the management of pulmonary embolism in pregnancy.
Case Report
A 27-year-old woman (gravida 6, para 0+6) presented to the emergency department at 8 weeks of gestation with chest pain, shortness of breath, and acute collapse after feeling increasingly faint. The
182 • Vol. 6 No. 3/4 • 2013 • Reviews in Obstetrics & Gynecology
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Use of Thrombolytic Agents to Treat Pulmonary Embolism in Pregnancy chest pain was central in nature and worse on inspiration. The shortness of breath had started a few hours prior to presentation and was not associated with any cough. Past medical history included five miscarriages, all terminating before 8 weeks of gestation, with the exception of a twin pregnancy, which miscarried at 12 weeks. On admission, the patient was dyspneic with a respiratory rate of 42 breaths per minute and an oxygen saturation of 96% on room air. The patient was also hypotensive (blood pressure 81/33 mm Hg) with a sinus tachycardia at 134 beats per minute. Respiratory and cardiovascular examinations were both unremarkable. On vascular examination, both legs appeared swollen and mild tenderness was elicited in the calves. On questioning, the patient stated that she first noticed her calves swelling and becoming increasing tender 2 days prior to presentation to the emergency department. A full blood count and pneumonic panel were ordered and bedside electrocardiography demonstrated supraventricular tachycardia with T waves inversion in leads V1, V2, and V3. With the clinical presentation highly suggestive of VTE, and in
Figure 1. Computed tomography pulmonary angiogram demonstrating a massive riding central pulmonary embolism with saddle embolus associated with right heart ventricle strain.
embolism with saddle embolus associated with right heart ventricle strain (Figure 1). The right and left pulmonary arteries and their segmental branches appeared fully occluded by the emboli. Due to the significant hemodynamic compromise caused by the embolus, a multidisciplinary decision between the emergency and obstetric teams was made to perform thrombolytic treatment. Thrombolysis with streptokinase was administered and the patient was admitted to the intensive care unit for regular monitoring following thrombolysis. Heparin therapy was also commenced after thrombolysis. Arterial blood gas monitoring was performed and assessed regularly. Supplemental oxygen
CTPA demonstrated a massive riding central pulmonary embolism with saddle embolus associated with right heart ventricle strain.
view of the calf tenderness and the chest pain, a working diagnosis of pulmonary embolism was made. The patient was informed of the diagnosis and her hemodynamic stability was monitored. The potential risks and benefits of computed tomography pulmonary angiogram (CTPA) with regard to both mother and fetus were eventually weighed and the patient gave her consent for the procedure. CTPA demonstrated a massive riding central pulmonary
was eventually discontinued and the tachycardia gradually resolved, proving that the patient had an excellent response to the thrombolytic therapy. The chest pain and shortness of breath also resolved. In view of the increased risk of miscarriage, the obstetrics team ordered regular pelvic examinations and ultrasound scans. A regular fetal heart rate was heard and no associated placental or fetal bleeding was reported. Reassuring views of the fetal heart and face were also
Figure 2. Repeat computed tomography pulmonary angiogram identified resolution of the embolism seen in Figure 1.
detected. A repeat CTPA identified resolution of the embolism (Figure 2). The patient was eventually discharged on low molecular weight heparin (enoxaparin) to be injected twice daily once the intravenous heparin therapy was completed. It was advised that she continued the enoxaparin therapy until she was in the postpartum period. Our patient had an uneventful pregnancy and a healthy baby girl was born at 39 weeks of gestation by an uncomplicated vaginal delivery. A repeated lung perfusion scan showed complete resolution of the emboli.
Discussion
Thromboembolic disease is a major cause of death in pregnancy and any large thrombus in the pulmonary circulation can cause a reduction in cardiac output, resulting in potential organ hypoperfusion, multiorgan failure, and death. Any obstruction in the pulmonary system can facilitate the onset of pulmonary hypertension, which can cause further complications in pregnancy. The optimal management of pulmonary embolism in pregnant patients remains unclear, primarily due to the lack of any definitive study or national guidelines, and because of their varying presentations. Thrombolytic therapy is regarded as the standard first-line
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Use of Thrombolytic Agents to Treat Pulmonary Embolism in Pregnancy continued treatment in nonpregnant patients with VTE, but it has been found to be associated with some serious complications in pregnancy. Major complications associated with thrombolysis include pregnancy loss (5.8%), preterm delivery (5.8%), and hemorrhagic complications (8.1%).4 Thrombolysis via the use of streptokinase and recombinant tissue plasminogen activator (rt-PA) is, however, still preferred over heparin injection because it causes a quicker fragmentation of the emboli if administered within the first 24 hours when compared with heparin.3,5,6 Although no research has concluded which thrombolytic agent (streptokinase or rt-PA) is safest in pregnancy, the large size of rt-PA limits its crossing
the placenta and entry into the fetal circulation, giving it a theoretical advantage in pregnancy. Also, rt-PA has a short half-life, limiting its untoward effects, and it has not been found to be associated with any allergenic complications.7 The current limited literature does not justify withholding thrombolytic therapy from pregnant women in cases of life-threatening pulmonary embolism. Nonetheless, a personalized approach should be adopted with regard to any changing clinical situation, with the safety of the mother being the primary concern of any clinician. Other management options for a massive pulmonary embolism in pregnancy include surgical embolectomy and catheter-directed therapy.
References 1.
2.
3.
4.
5.
6.
7.
Clark SL, Belfort MA, Dildy GA, et al. Maternal death in the 21st century: causes, prevention, and relationship to cesarean delivery. Am J Obstet Gynecol. 2008;199:36.e1-36.e5. Benhamou D, Chassard D, Mercier FJ, et al. The seventh report of the confidential enquiries into maternal deaths in the United Kingdom: comparison with French data [article in French]. Ann Fr Anesth Reanim. 2009;28:38-43. Lonjaret L, Lairez O, Galinier M, Minville V. Thrombolysis by recombinant tissue plasminogen activator during pregnancy: a case of massive pulmonary embolism. Am J Emerg Med. 2011;29:694. e1-684.e2. Turrentine MA, Braems G, Ramirez MM. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. Obstet Gynecol Surv. 1995;50:534-541. Fasullo S, Scalzo S, Maringhini G, et al. Thrombolysis for massive pulmonary embolism in pregnancy: a case report. Am J Emerg Med. 2011;29:698.e1-698.e4. Capstick T, Henry MT. Efficacy of thrombolytic agents in the treatment of pulmonary embolism. Eur Respir J. 2005;26:864-874. Konstantinides S, Geibel A, Heusel G, et al; Management Strategies and Prognosis of Pulmonary Embolism-3 Trial Investigators. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002;347: 1143-1150.
Main Points • Venous thromboembolic events (VTEs) are among the most common causes of maternal mortality in the United Kingdom and are believed to account for 11% to 20% of maternal deaths. • Thrombolytic therapy is regarded as the standard first-line treatment in nonpregnant patients with VTE, but it has been found to be associated with some serious complications in pregnancy, including pregnancy loss, preterm delivery, and hemorrhagic complications. • Thrombolysis via the use of streptokinase and recombinant tissue plasminogen activator is preferred over heparin injection because it causes a quicker fragmentation of the emboli if administered within the first 24 hours.
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