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Pulmonary Embolism due to Popliteal Vein Aneurysm during Pregnancy Induced by In Vitro Fertilization
Case Report Pulmonary Embolism due to Popliteal Vein Aneurysm during Pregnancy Induced by In Vitro Fertilization Gianfranco Varetto, Claudio Castagno, Matteo Ripepi, Ugo Bertoldo, Paolo Garneri, Valentina Molinaro, Simone Quaglino, and Pietro Rispoli, Turin, Italy
Popliteal vein aneurysms (PVAs) are rare but may cause severe and even fatal complications, such as pulmonary embolism (PE). A woman at the eighth week of pregnancy came to our attention because of a thrombosis of a previously undetected left PVA, diagnosed after a PE episode. Surgery was delayed until after delivery and breastfeeding, during which anticoagulant therapy was established.
Popliteal vein aneurysms (PVAs) are rarely observed but may cause severe and even fatal complications including pulmonary embolism (PE). We report the case of an almost certain episode of PE caused by a thrombosed left PVA (diameter, 3 cm) in a woman at the eighth week of pregnancy.
CASE REPORT A 43-year-old woman at the eighth week of pregnancy after in vitro fertilization (IVF) was admitted to our emergency department because of acute dyspnea and left lower limb pain. Her past medical history and previous oral contraceptive therapy were unremarkable, and no familiarity for venous diseases was reported. Her pregnancy precluded thoracic computed tomography angiography (CTA), and she declined magnetic resonance imaging (MRI). Ultrasound revealed a thrombosed PVA (diameter, 3 cm); the remaining femoroiliac tract was patent without thrombi. The D-dimer level was 17.1 mg/mL and echocardiography showed right ventricular dilatation and Division of Vascular Surgery, University of Turin, Turin, Italy. Correspondence to: Pietro Rispoli, MD, PhD, Division of Vascular Surgery, University of Turin, Molinette Hospital, Corso A. M. Dogliotti 14, Torino, Italy; E-mail: [email protected] Ann Vasc Surg 2014; -: 1–4 http://dx.doi.org/10.1016/j.avsg.2014.02.012 Ó 2014 Elsevier Inc. All rights reserved. Manuscript received: November 3, 2013; manuscript accepted: February 3, 2014; published online: ---.
overcharge, making the strong clinical suspicion of PE almost certain. The patient was hospitalized. Initial treatment was with unfractionated heparin for 3 days then switched to therapeutic doses of low-molecular-weight heparin (LMWH), which was continued because she refused having surgery until delivery. Thrombophilic screening tests were negative. Repeat echo color Doppler sonography performed 4 months later showed complete recanalization of the thrombosis, with a persistent PVA (diameter, 3 cm). After delivery, oral anticoagulation with warfarin (International Normalized Ratio target between 2 and 3) was started and surgery was again delayed until the end of breastfeeding. Preoperative CTA obtained for planning the surgical approach confirmed the presence of the left PVA (32 mm) with slight residual thrombotic stratification on the vessel wall (Fig. 1). At 7 months after delivery, the patient underwent surgery. A posterior approach was performed with the patient in prone position under spinal anesthesia. An S-shaped incision was placed in the popliteal fossa, and the aneurysm was isolated while respecting the tibial nerve. The aneurysm appeared to have a bilobed morphology, with a saccular portion arising from a fusiform dilatation (Fig. 2). Two small tributary vessels of the aneurysm were ligated and divided. The vessel was then clamped proximally and distally, and the aneurysm was opened through a longitudinal venotomy; no wall ulcerations or residual unstable thrombus were noted. The saccular portion was then tangentially clamped, and aneurysmectomy with polypropylene 7/0 mattress sutures (Fig. 3) was performed, as previously described by Aldridge.1
1
2 Case Report
Annals of Vascular Surgery
Fig. 3. Aneurysmectomy and lateral venorrhaphy of the saccular part.
Fig. 1. Preoperative three-dimensional computed tomography angiography showing aneurysm of the popliteal vein.
Fig. 4. Final result of popliteal vein reconstruction.
Fig. 2. Intraoperative image showing the bilobed morphology of the aneurysm.
At this point, the procedure could have been considered technically completed, although leaving the vein still a bit dilated. However, we felt that, also because of the pathologic characteristics of the resected tissue, a more accurate reshaping of the vein profile and diameter, by resection and repair of the fusiform part of the aneurysm, would provide better blood flow velocity and longerlasting prevention against recurrences. Therefore, a second venotomy on the fusiform part of the aneurysm was done. Reconstruction entailed further aneurysmectomy and repair with continuous polypropylene 7/0 suture (Fig. 4). No adverse events occurred during hospitalization. The patient was discharged home on the third postoperative day.
Postsurgical treatment included twice daily LMWH, gradually switched to warfarin, and grade 2 elastic compression stockings. Histologic findings showed deposition of mixoid material and fibrosis on the vein wall (Fig. 5). Echo color Doppler ultrasonography at 1, 3, 6, and 9 months showed patency of the repair, without any signs of vein dilatation, stenosis or thrombosis (Fig. 6). The patient is well at 11 months of follow-up.
DISCUSSION Venous aneurysms are relatively uncommon. They usually arise in the lower limbs and the popliteal vein is the most frequently involved vessel.2 The first case of PVA was described by May and Nissel in 1968.3 A relationship between their recurrence and PE was first reported 8 years later by Dahl.4 They may represent the most severe complication of PVA, as almost half are incidentally diagnosed after an episode of PE. Most PVAs are congenital in origin, whereas the remaining arise after trauma or infections. No
Vol.
-,
No.
-, -
2014
Fig. 5. Histologic sample of the resected aneurysm.
Fig. 6. Postoperative echo color Doppler showing normal vein patency and diameter.
specific etiology could be identified in our patient. She had undergone IVF a few months before the presenting event. Although no relationship has been demonstrated between IVF (IVF) and vein wall degeneration, Horka et al. recently found significantly higher serum matrix metalloprotease 9 (MMP-9) levels were in women undergoing successful IVF compared with nonpregnant or healthy pregnant controls.5 Furthermore, Irwin et al.6 observed a higher concentration of metalloproteases, including MMP-9, in histologic samples of venous aneurysms, 5 of which were PVAs. Metalloproteases are common markers of inflammation. It is still unknown whether these enzymes are the manifestation of inflammation or, indeed, the cause of vein wall degeneration and dilatation. The mixoid materials and fibrosis found at histology of resected tissue from our patient could have been the expression of a high concentration of matrix metalloproteases, which, unfortunately, we were
Case Report 3
unable to assay. Finally, a recent study found a strong correlation between IVF and PE during the first trimester of pregnancy7 but did not mention PVA as a possible source of emboli. PVAs are often incidentally detected at echo color Doppler examination, particularly in the first-line approach in suspected pulmonary thromboembolism. To obtain better imaging of the aneurysm, we also performed preoperative CTA that revealed the bilobed morphology of the aneurysm not seen on the previous duplex scans. Surgery is mandatory in symptomatic cases to prevent aneurysm recurrence; some authors also recommend surgery in asymptomatic patients.8 Because of her pregnancy and wish to breastfeed, our patient preferred delaying surgery. Given these circumstances, our only option seemed to be temporary anticoagulant therapy. However, warfarin is contraindicated in pregnancy as it crosses the placental barrier and may cause fetal bleeding, spontaneous abortion, neonatal death, preterm birth, and congenital abnormalities. This left LMWH as the only acceptable therapy until delivery. After delivery, oral anticoagulation was started and then switched again to LMWH 5 days before surgery, as usual. Surgical options include tangential aneurysmectomy with lateral venorrhaphy, resection and endto-end anastomosis, resection and autologous or alloplastic graft interposition, bypass with autologous saphenous vein, and ligation of the proximal and distal vein.9 The first strategy, which is the one most frequently performed by the majority of authors, is preferred in saccular aneurysm; the other options are more suitable for fusiform lesions. Although this was one of the options considered in the preoperative planning, we decided against venous bypass with an autologous thigh saphenous vein, which would have deprived the patient of part of her venous estate, reserving this option in case the first surgical attempt turned out unsuccessful. As far as a possible re-do surgery is concerned, this is surely a redoubtable surgical option even for skilled surgeons, but still, although very seldom, it has been reported, with good results, in the recent literature10,11 Because our patient had a bilobed aneurysm, with both saccular and fusiform morphologies, we elected tangential aneurysmectomy and lateral venorrhaphy for the saccular portion and a second aneurysmectomy and repair to normalize the lumen of the fusiform segment. Postoperative anticoagulant therapy is mandatory after popliteal vein reconstructions.2 LMWH and then warfarin therapy were prescribed and continued for at least 6 months also
4 Case Report
because of her previous PE. Use of grade 2 elastic compression stockings was recommended.8 Follow-up echo color Doppler imaging, which is both safe and noninvasive, was repeated at 1, 3, 6 and 9 months after surgery, and then annually thereafter. In conclusion, PVA is a rare condition that can lead to potentially severe complications, including PE. Surgical treatment is mandatory in symptomatic cases to avoid recurrences and prevent PE in asymptomatic patients. To the best of our knowledge, this is the first case of symptomatic PVA during pregnancy. There may be a correlation between IVF and vein dilatation, and this relationship may be explained by higher MMP activity induced by assisted reproduction techniques. REFERENCES 1. Aldridge SC, Comerota AJ, Katz ML, et al. Popliteal venous aneurysm: report of two cases and review of the world literature. J Vasc Surg 1993;18:708e15. 2. Sessa C, Nicolini P, Perrin M, et al. Management of symptomatic and asymptomatic popliteal venous aneurysm: a retrospective analysis of 25 patients and review of the literature. J Vasc Surg 2000 Nov;32(5):902e12. Review.
Annals of Vascular Surgery
3. May R, Nissel R. Aneuvrysma der vena poplitea. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1968;108: 402e3. 4. Dahl JR, Freed TA, Burke MF. Popliteal vein aneurysm with recurrent pulmonary thromboemboli. JAMA 1976;236: 2531e2. 5. Horka P, Malickova K, Jarosova R, et al. Matrix metalloproteinases in serum and the follicular fluid of women treated by in vitro fertilization. J Assist Reprod Genet 2012;29(11): 1207e12. http://dx.doi.org/10.1007/s10815-012-9853-4. Epub 2012 Sep 28. 6. Irwin C, Synn A, Kraiss L, et al. Metalloproteinase expression in venous aneurysms. J Vasc Surg 2008;48:1278e85. 7. Henriksson P, Westerlund E, Wallen H, et al. Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilisation: cross sectional study. BMJ 2013;346:e8632. http://dx.doi.org/10.1136/bmj.e8632. 8. Lutz HJ, Sacuiu RD, Savolainen H. Surgical therapy of an asymptomatic primary popliteal venous aneurysm. Ann Vasc Surg 2012;26(5):729.e7e9. 9. Fiori R, Chiappa R, Gaspari E, et al. A rare case of popliteal venous aneurysm. Case Rep Med 2010;2010:579256. http:// dx.doi.org/10.1155/2010/579256. Epub 2010 Mar 10. 10. Gasparis AP, Awadallah M, Meisner RJ, Lo C, Labropoulos N. Recurrent popliteal vein aneurysm. J Vasc Surg 2010;51(2): 453e7. http://dx.doi.org/10.1016/j.jvs.2009.06.065. Epub 2009 Oct 17. 11. Falls G, Eslami MH. Recurrence of a popliteal venous aneurysm. J Vasc Surg 2010;51(2):458e9. http://dx.doi.org/10. 1016/j.jvs.2009.07.122. Epub 2009 Oct 17.
Popliteal vein aneurysms (PVAs) are rare but may cause severe and even fatal complications, such as pulmonary embolism (PE). A woman at the eighth week of pregnancy came to our attention because of a thrombosis of a previously undetected left PVA, diagnosed after a PE episode. Surgery was delayed until after delivery and breastfeeding, during which anticoagulant therapy was established.
Popliteal vein aneurysms (PVAs) are rarely observed but may cause severe and even fatal complications including pulmonary embolism (PE). We report the case of an almost certain episode of PE caused by a thrombosed left PVA (diameter, 3 cm) in a woman at the eighth week of pregnancy.
CASE REPORT A 43-year-old woman at the eighth week of pregnancy after in vitro fertilization (IVF) was admitted to our emergency department because of acute dyspnea and left lower limb pain. Her past medical history and previous oral contraceptive therapy were unremarkable, and no familiarity for venous diseases was reported. Her pregnancy precluded thoracic computed tomography angiography (CTA), and she declined magnetic resonance imaging (MRI). Ultrasound revealed a thrombosed PVA (diameter, 3 cm); the remaining femoroiliac tract was patent without thrombi. The D-dimer level was 17.1 mg/mL and echocardiography showed right ventricular dilatation and Division of Vascular Surgery, University of Turin, Turin, Italy. Correspondence to: Pietro Rispoli, MD, PhD, Division of Vascular Surgery, University of Turin, Molinette Hospital, Corso A. M. Dogliotti 14, Torino, Italy; E-mail: [email protected] Ann Vasc Surg 2014; -: 1–4 http://dx.doi.org/10.1016/j.avsg.2014.02.012 Ó 2014 Elsevier Inc. All rights reserved. Manuscript received: November 3, 2013; manuscript accepted: February 3, 2014; published online: ---.
overcharge, making the strong clinical suspicion of PE almost certain. The patient was hospitalized. Initial treatment was with unfractionated heparin for 3 days then switched to therapeutic doses of low-molecular-weight heparin (LMWH), which was continued because she refused having surgery until delivery. Thrombophilic screening tests were negative. Repeat echo color Doppler sonography performed 4 months later showed complete recanalization of the thrombosis, with a persistent PVA (diameter, 3 cm). After delivery, oral anticoagulation with warfarin (International Normalized Ratio target between 2 and 3) was started and surgery was again delayed until the end of breastfeeding. Preoperative CTA obtained for planning the surgical approach confirmed the presence of the left PVA (32 mm) with slight residual thrombotic stratification on the vessel wall (Fig. 1). At 7 months after delivery, the patient underwent surgery. A posterior approach was performed with the patient in prone position under spinal anesthesia. An S-shaped incision was placed in the popliteal fossa, and the aneurysm was isolated while respecting the tibial nerve. The aneurysm appeared to have a bilobed morphology, with a saccular portion arising from a fusiform dilatation (Fig. 2). Two small tributary vessels of the aneurysm were ligated and divided. The vessel was then clamped proximally and distally, and the aneurysm was opened through a longitudinal venotomy; no wall ulcerations or residual unstable thrombus were noted. The saccular portion was then tangentially clamped, and aneurysmectomy with polypropylene 7/0 mattress sutures (Fig. 3) was performed, as previously described by Aldridge.1
1
2 Case Report
Annals of Vascular Surgery
Fig. 3. Aneurysmectomy and lateral venorrhaphy of the saccular part.
Fig. 1. Preoperative three-dimensional computed tomography angiography showing aneurysm of the popliteal vein.
Fig. 4. Final result of popliteal vein reconstruction.
Fig. 2. Intraoperative image showing the bilobed morphology of the aneurysm.
At this point, the procedure could have been considered technically completed, although leaving the vein still a bit dilated. However, we felt that, also because of the pathologic characteristics of the resected tissue, a more accurate reshaping of the vein profile and diameter, by resection and repair of the fusiform part of the aneurysm, would provide better blood flow velocity and longerlasting prevention against recurrences. Therefore, a second venotomy on the fusiform part of the aneurysm was done. Reconstruction entailed further aneurysmectomy and repair with continuous polypropylene 7/0 suture (Fig. 4). No adverse events occurred during hospitalization. The patient was discharged home on the third postoperative day.
Postsurgical treatment included twice daily LMWH, gradually switched to warfarin, and grade 2 elastic compression stockings. Histologic findings showed deposition of mixoid material and fibrosis on the vein wall (Fig. 5). Echo color Doppler ultrasonography at 1, 3, 6, and 9 months showed patency of the repair, without any signs of vein dilatation, stenosis or thrombosis (Fig. 6). The patient is well at 11 months of follow-up.
DISCUSSION Venous aneurysms are relatively uncommon. They usually arise in the lower limbs and the popliteal vein is the most frequently involved vessel.2 The first case of PVA was described by May and Nissel in 1968.3 A relationship between their recurrence and PE was first reported 8 years later by Dahl.4 They may represent the most severe complication of PVA, as almost half are incidentally diagnosed after an episode of PE. Most PVAs are congenital in origin, whereas the remaining arise after trauma or infections. No
Vol.
-,
No.
-, -
2014
Fig. 5. Histologic sample of the resected aneurysm.
Fig. 6. Postoperative echo color Doppler showing normal vein patency and diameter.
specific etiology could be identified in our patient. She had undergone IVF a few months before the presenting event. Although no relationship has been demonstrated between IVF (IVF) and vein wall degeneration, Horka et al. recently found significantly higher serum matrix metalloprotease 9 (MMP-9) levels were in women undergoing successful IVF compared with nonpregnant or healthy pregnant controls.5 Furthermore, Irwin et al.6 observed a higher concentration of metalloproteases, including MMP-9, in histologic samples of venous aneurysms, 5 of which were PVAs. Metalloproteases are common markers of inflammation. It is still unknown whether these enzymes are the manifestation of inflammation or, indeed, the cause of vein wall degeneration and dilatation. The mixoid materials and fibrosis found at histology of resected tissue from our patient could have been the expression of a high concentration of matrix metalloproteases, which, unfortunately, we were
Case Report 3
unable to assay. Finally, a recent study found a strong correlation between IVF and PE during the first trimester of pregnancy7 but did not mention PVA as a possible source of emboli. PVAs are often incidentally detected at echo color Doppler examination, particularly in the first-line approach in suspected pulmonary thromboembolism. To obtain better imaging of the aneurysm, we also performed preoperative CTA that revealed the bilobed morphology of the aneurysm not seen on the previous duplex scans. Surgery is mandatory in symptomatic cases to prevent aneurysm recurrence; some authors also recommend surgery in asymptomatic patients.8 Because of her pregnancy and wish to breastfeed, our patient preferred delaying surgery. Given these circumstances, our only option seemed to be temporary anticoagulant therapy. However, warfarin is contraindicated in pregnancy as it crosses the placental barrier and may cause fetal bleeding, spontaneous abortion, neonatal death, preterm birth, and congenital abnormalities. This left LMWH as the only acceptable therapy until delivery. After delivery, oral anticoagulation was started and then switched again to LMWH 5 days before surgery, as usual. Surgical options include tangential aneurysmectomy with lateral venorrhaphy, resection and endto-end anastomosis, resection and autologous or alloplastic graft interposition, bypass with autologous saphenous vein, and ligation of the proximal and distal vein.9 The first strategy, which is the one most frequently performed by the majority of authors, is preferred in saccular aneurysm; the other options are more suitable for fusiform lesions. Although this was one of the options considered in the preoperative planning, we decided against venous bypass with an autologous thigh saphenous vein, which would have deprived the patient of part of her venous estate, reserving this option in case the first surgical attempt turned out unsuccessful. As far as a possible re-do surgery is concerned, this is surely a redoubtable surgical option even for skilled surgeons, but still, although very seldom, it has been reported, with good results, in the recent literature10,11 Because our patient had a bilobed aneurysm, with both saccular and fusiform morphologies, we elected tangential aneurysmectomy and lateral venorrhaphy for the saccular portion and a second aneurysmectomy and repair to normalize the lumen of the fusiform segment. Postoperative anticoagulant therapy is mandatory after popliteal vein reconstructions.2 LMWH and then warfarin therapy were prescribed and continued for at least 6 months also
4 Case Report
because of her previous PE. Use of grade 2 elastic compression stockings was recommended.8 Follow-up echo color Doppler imaging, which is both safe and noninvasive, was repeated at 1, 3, 6 and 9 months after surgery, and then annually thereafter. In conclusion, PVA is a rare condition that can lead to potentially severe complications, including PE. Surgical treatment is mandatory in symptomatic cases to avoid recurrences and prevent PE in asymptomatic patients. To the best of our knowledge, this is the first case of symptomatic PVA during pregnancy. There may be a correlation between IVF and vein dilatation, and this relationship may be explained by higher MMP activity induced by assisted reproduction techniques. REFERENCES 1. Aldridge SC, Comerota AJ, Katz ML, et al. Popliteal venous aneurysm: report of two cases and review of the world literature. J Vasc Surg 1993;18:708e15. 2. Sessa C, Nicolini P, Perrin M, et al. Management of symptomatic and asymptomatic popliteal venous aneurysm: a retrospective analysis of 25 patients and review of the literature. J Vasc Surg 2000 Nov;32(5):902e12. Review.
Annals of Vascular Surgery
3. May R, Nissel R. Aneuvrysma der vena poplitea. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1968;108: 402e3. 4. Dahl JR, Freed TA, Burke MF. Popliteal vein aneurysm with recurrent pulmonary thromboemboli. JAMA 1976;236: 2531e2. 5. Horka P, Malickova K, Jarosova R, et al. Matrix metalloproteinases in serum and the follicular fluid of women treated by in vitro fertilization. J Assist Reprod Genet 2012;29(11): 1207e12. http://dx.doi.org/10.1007/s10815-012-9853-4. Epub 2012 Sep 28. 6. Irwin C, Synn A, Kraiss L, et al. Metalloproteinase expression in venous aneurysms. J Vasc Surg 2008;48:1278e85. 7. Henriksson P, Westerlund E, Wallen H, et al. Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilisation: cross sectional study. BMJ 2013;346:e8632. http://dx.doi.org/10.1136/bmj.e8632. 8. Lutz HJ, Sacuiu RD, Savolainen H. Surgical therapy of an asymptomatic primary popliteal venous aneurysm. Ann Vasc Surg 2012;26(5):729.e7e9. 9. Fiori R, Chiappa R, Gaspari E, et al. A rare case of popliteal venous aneurysm. Case Rep Med 2010;2010:579256. http:// dx.doi.org/10.1155/2010/579256. Epub 2010 Mar 10. 10. Gasparis AP, Awadallah M, Meisner RJ, Lo C, Labropoulos N. Recurrent popliteal vein aneurysm. J Vasc Surg 2010;51(2): 453e7. http://dx.doi.org/10.1016/j.jvs.2009.06.065. Epub 2009 Oct 17. 11. Falls G, Eslami MH. Recurrence of a popliteal venous aneurysm. J Vasc Surg 2010;51(2):458e9. http://dx.doi.org/10. 1016/j.jvs.2009.07.122. Epub 2009 Oct 17.