Infrahepatic Inferior Vena Cava Agenesis with Bilateral Renal Vein Thrombosis Nedaa Skeik, Kelly K. Wickstrom, Clark W. Schumacher, and Timothy M. Sullivan, Minneapolis, Minnesota
Congenital anomalies of the inferior vena cava (IVC) are rare and are estimated to be present in 0.07e8.7% of the general population. IVC agenesis (IVCA) is found in approximately 5% of cases of unprovoked lower extremity deep vein thrombosis in patients <30 years of age. Renal vein thrombosis (RVT) is an extremely rare and unusual presentation of IVCA. We report a unique case of a 23-year-old previously healthy man presenting with infrahepatic IVCAinduced bilateral RVT with azygos and hemiazygos continuation. To our knowledge, this is the third reported case in the literature of IVCA-induced RVT and the first to affect the bilateral renal veins in the absence of any other thrombogenic risk factors or any lower extremity venous complications. We also present a literature review of IVCA-induced vein thrombosis and highlight the lack of literature to manage this condition.
CASE REPORT A 23-year-old white man presented with a 6-day history of right lower quadrant pain radiating to his flank. The pain began as a mild side ache and progressed beyond a tolerable intensity with associated chills and diaphoresis. He denied fever, painful urination, urine color change, nausea, vomiting, or changes in bowel habits. His medical history was unremarkable save for a reported similar episode of abdominal pain 2 years earlier; a radiograph of his abdomen at the time was unremarkable. He reported the occasional use of alcohol and denied ever using tobacco or illicit drugs. His family history included a father with hypertension who died of a myocardial infarction at 53 years of age, a mother with multiple sclerosis, and a sister with hypertension. He denied any family history of vein-related disorders, including venous thromboembolism, coagulopathy, or congenital anomalies. His vital signs were normal and the physical examination revealed right flank and lower quadrant tenderness to palpation with some guarding. The rest of the physical Abbott Northwestern Hospital, Minneapolis Heart Institute, Minneapolis, MN. Correspondence to: Nedaa Skeik, MD, FACP, FSVM, RPVI, Section Head, Vascular Medicine, Medical Director, Coagulation Clinic, Abbott Northwestern Hospital/Minneapolis Heart Institute, 800 East 28th Street, H2100, Minneapolis, MN 55407, USA; E-mail: [email protected]
allina.com Ann Vasc Surg 2013; 27: 973.e19e973.e23 http://dx.doi.org/10.1016/j.avsg.2012.10.030 Ó 2013 Elsevier Inc. All rights reserved. Manuscript received: July 20, 2012; manuscript accepted: October 14, 2012.
examination was unremarkable and did not reveal any superficial vein collaterals. Pertinent laboratory findings revealed a white blood cell count of 12,400/mm3, C-reative protein of 4 mg/ dL, creatine kinase of 339 IU/L, and a glucose measurement of 102 mg/dL. Additional laboratory work-up, including prothrombin time (PT), basic metabolic profile, and urinalysis were all unremarkable. Computed tomographic (CT) scans of the abdomen and pelvis with contrast revealed inferior vena cava agenesis (IVCA) below the infrahepatic segment with large retroperitoneal collateral veins draining into the azygos and hemiazygos systems; and a large, tortuous, thrombosed right renal vein that extended inferior to the kidney. Delayed images revealed a nonocclusive thrombus spanning the left renal vein (Fig. 1). Inferior vena cavagram confirmed IVCA below the infrahepatic segment with azygos and hemiazygos continuation of the inferior vena cava (IVC). The right and left common iliac veins and the renal veins drained into large retroperitoneal collaterals then into the azygos and hemiazygos systems (Fig. 2). No additional prominent collaterals were identified. Renal duplex ultrasound confirmed the previous findings. Based on the imaging findings, a thrombophilia work-up was performed and was negative for anticardiolipin antibodies, lupus anticoagulants, and beta 2 glycoprotein antibody. In addition, levels of proteins C and S and factors II and V Leiden gene mutations were unremarkable. As an inpatient, he was medically managed with therapeutic intravenous unfractionated heparin (UFH) that was changed to enoxaparin because of an allergic reaction. In addition, he was started on warfarin 2 days
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Fig. 1. (A) Contrast-enhanced coronal computed tomographic (CT) scan showing (1) the portal vein; (2) a dilated, tortuous, and thrombosed right renal vein; (3) a well developed retroperitoneal collateral vein draining into the azygos system; (4) a partially thrombosed left retroperitoneal collateral vein; and (5) right and left
common iliac veins draining into the retroperitoneal collateral vein then into the azygos system. (B) A contrast-enhanced coronal CT scan showing a dilated, tortuous, and thrombotic right renal vein. (C) A contrast-enhanced axial CT scan showing a nonocclusive thrombus in the left renal vein.
postadmission with a goal international normalized ratio of 2e3 for at least 6 months based on the current evidence discussed below.
to unite do not, this may result in an anomaly of the IVC.1 The prevalence of azygos continuation of the IVC, often referred to as absence of the hepatic segment of the IVC with azygos continuation, is 0.5e2.1% in the general population.6,8 The anomaly is a direct result of the right subcardinal vein failing to develop, resulting in a lack of continuity between the hepatic and renal segments of the IVC.8 In a normally developed IVC, blood ascends through the thoracic cavity and drains directly into the right atrium. In contrast, with the typical presentation of absence of the hepatic segment of the IVC, blood from the renal veins enters the renal portion of the IVC which passes posteriorly to the diaphragmatic crura and enters the thoracic cavity as the azygos vein. When the azygos vein reaches the right paratracheal space, it anastomoses with the SVC and drains into the right atrium.6 A key diagnostic feature of this condition is an enlarged azygos vein
DISCUSSION The prevalence of congenital anomalies of the IVC is estimated to be 0.07e8.7%.1e4 Rare anomalies of the IVC include absence of a part of the IVC with azygos and/or hemiazygos continuation, a duplicated IVC, double superior vena cava (SVC) and/or IVC, hypoplasia or agenesis, and interruption of the IVC.5 During embryogenesis, the IVC is formed by a process involving the development, regression, and anastomosis of 3 sets of paired veins: the posterior cardinal, subcardinal, and supracardinal.1,5e8 The normal IVC is converted to a unilateral rightsided system consisting (from cranial to caudal) of the hepatic, prerenal, renal, and postrenal segments.1,7 If the paired structures that are meant
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Fig. 2. (A) Inferior vena cavagram showing (1) simultaneous injection of the infrahepatic inferior vena cava (IVC) and (2) the confluence of the common iliac veins showing total agenesis of the IVC below the infrahepatic segment. (B) Interrupted infrahepatic portion of
the IVC (1) and prominent retroperitoneal collateral veins with (2) azygos and (3) hemiazygos continuation. (C) Infrahepatic portion of the IVC (1) and prominent retroperitoneal collateral veins with (2) azygos continuation.
noted with cross-sectional imaging in 2 places: at the confluence with the SVC and the retrocrural space.6 Anomalies of the IVC result in increased venous pressure and stasis, and have therefore been recognized as one of the predisposing factors for lower extremity deep vein thrombosis (LE DVT), especially in young adults.1e4,7e9 In patients <30 years of age with unprovoked LE DVT, IVCA is found in approximately 5% of cases.2,4,7,9 A typical presentation of these patients is spontaneous, recurrent, bilateral, and progressive LE DVT.3 The DVT most frequently involves the distal IVC, common, internal, and external iliac and femoral veins.8 Additional common clinical characteristics of patients with IVCA-induced LE DVT include proximal involvement, male predominance, and occurrence before the fourth decade of life, mostly after a major physical exertion.9 Lambert et al.9 examined a total of 72 cases of IVCA-induced vein thrombosis (10 from their institution and 62 from a literature search). Of the 72 cases, 2 involved distal IVC, 5 involved pelvic, and the remaining cases involved LE veins.9 None of the reviewed cases involved a renal vein. DVT-induced pulmonary embolism (PE) is estimated to cause 200,000 fatalities annually.10 IVCA-induced DVT can lead to significant morbidities and can also lead to PE. Based on the same paper by Lambert et al.,9 6 of the 62 (9.6%) reviewed cases developed PE. To our knowledge, there had been 7 additional cases of PE associated with IVCA-induced DVT reported in the
literature.11e17 It is proposed that PE occurs less frequently in these patients because thrombus may become entrapped in the azygos/hemiazygos system, preventing it from reaching the pulmonary circulation.9 Although the risk of these patients developing PE is relatively low, it is not inconsequential. Renal vein thrombosis (RVT) is an extremely unusual and unique presentation of IVCA. To our knowledge, there are only 2 case reports of RVT associated with IVCA in the literature. One report described a 16-day-old male infant who presented with gross hematuria, proteinuria, and a palpable right-sided abdominal mass. A diagnosis of right RVT was made, and the patient was treated with intravenous hydration and alkalization, which led to resolution of symptoms. However, 1 year later, the patient presented with rapid-onset hypertension when he was discovered to have absence of the hepatic portion of the IVC via magnetic resonance imaging. He was managed with a right nephrectomy, which led to the resolution of his hypertension.18 The second case of IVCA-associated left RVT was diagnosed in a 26-year-old man. It occurred in conjunction with retroaortic left renal vein and absence of the suprarenal portion of the IVC. The RVT resolved after 6 months of anticoagulation with heparin.8 In general, isolated RVT is most commonly observed in neonates,19,20 where it is often associated with coagulopathy, maternal diabetes, sepsis, shock, acute blood loss, diarrhea, dehydration, birth
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asphyxia, neonatal infection, and the placement of umbilical catheters.19 In the adult population, renal malignancy, nephrotic syndrome, infection, inflammatory bowel disease, hormonal therapy, congenital hypercoagulable disorders, and retroaortic renal vein have all been associated with RVT.20e22 Because the incidence of IVCA-induced RVT is extremely rare, there are no consensus guidelines for management of this disorder. The recommendations for the management of this condition may be based on case reports and clinical experience with IVCA-induced DVT at other locations. Despite that IVCA-induced DVT is relatively well documented in the literature, there are no consensus guidelines to address the management of this condition.2 Based on the current literature from previous case reports, the common practice for managing IVCA-induced LE DVT has been long-term anticoagulation therapy and use of elastic stockings.9 Lambert et al.9 suggests indefinite oral anticoagulation therapy, based on the idea that IVCA-induced LE DVT in young people may be a source of lifelong concern and discomfort. A more conservative approach is taken by Chee et al.,2 who recommend discontinuing oral anticoagulation therapy at 6 months. In addition, patients with IVCA should be advised to avoid strenuous muscular exercise, long periods of inactivity,8 and hormonal contraceptive use.9 One author recommends starting UFH or lowe molecular weight heparin (LMWH) to bridge to warfarin as soon as the diagnosis of isolated RVT is made.20 Catheter based thrombolysis or thrombectomy may be indicated in some cases involving renal transplant or solitary kidney.20 We did not consider this option in our patient because he was clinically stable with noncompromised renal function. In addition, a procedure such as this one might cause more complications in a patient with unusual anatomy. The same author based the long-term outcomes on the underlying etiology; and favored long-term anticoagulation therapy for a minimum of 1 year.20 Outcomes for idiopathic RVT are not as well documented in literature because of its low prevalence.20 Guidelines for treating isolated RVT in neonates are provided by The 2012 American College of Chest Physician. However, they did not provide guidance for managing RVT in the adult population.23 For unilateral RVT in the absence of renal impairment or extension into the IVC, they suggest 2 options: supportive care with radiologic monitoring for thrombus extension (if extension occurs, they suggest anticoagulation therapy) or immediate anticoagulation therapy with doses of UFH or LMWH for a total duration of 6 weeks to 3 months. For
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unilateral RVT extending into the IVC, they suggest anticoagulation therapy with UFH or LMWH for a total duration of 6 weeks to 3 months. For bilateral RVT with evidence of renal impairment, they suggest anticoagulation therapy with UFH/LMWH or initial thrombolytic therapy with tissue plasminogen activator followed by anticoagulation therapy with UFH/LMWH.23 To our knowledge, our case is the third reported case in the literature of IVCA-induced RVT and the first to affect bilateral renal veins in the absence of any other thrombogenic risk factors, or any lower extremity venous complications. In contrast to the other 2 reported cases, it represents a total agenesis of the IVC below the infrahepatic segment. It also led to bilateral RVT in otherwise young healthy man. In addition, he did not have any LE venous complications including stasis or DVT.
CONCLUSION In summary, at present there are no guidelines or recommendations for the management of IVCAinduced RVT. The current literature is based on very few case reports and clinical experience with IVCA-induced LE DVT. Our paper highlights the lack of knowledge regarding the management of IVCA-induced vein thrombosis and calls for more research to help address this condition. REFERENCES 1. Obernosterer A, Aschauer M, Schnedl W, Lipp RW. Anomalies of the inferior vena cava in patients with iliac venous thrombosis. Ann Intern Med 2002;136:37e41. 2. Chee YL, Culligan DJ, Watson HG. Inferior vena cava malformation as a risk factor for deep venous thrombosis in the young. Br J Haematol 2001;114:878e80. 3. Atmatzidis K, Papaziogas B, Pavlidis T, Paraskevas G, Mirelis C, Papaziogas T. Surgical images: soft tissue. Recurrent deep vein thrombosis caused by hypoplasia of the inferior vena cava. Can J Surg 2006;49:285. 4. Clayburgh DR, Yoon JD, Cipriani NA, Ricketts PA, Arora VM. Clinical problem-solving. Collateral damage. N Engl J Med 2008;359:1048e54. 5. Kapetanakis S, Papadopoulos C, Galani P, Dimitrakopoulou G, Fiska A. Anomalies of the inferior vena cava: a report of two cases and a short review of the literature. Folia Morphol (Warsz) 2010;69:123e7. 6. Bass JE, Redwine MD, Kramer LA, Huynh PT, Harris JH Jr. Spectrum of congenital anomalies of the inferior vena cava: crosssectional imaging findings. Radiographics 2000;20:639e52. 7. Dudeck O, Zeile M, Poellinger A, Kluhs L, Ludwig WD, Hamm B. Epidural venous enlargements presenting with intractable lower back pain and sciatica in a patient with absence of the infrarenal inferior vena cava and bilateral deep venous thrombosis. Spine 2007;32:E688e91. 8. Cizginer S, Tatli S, Girshman J, Beckman JA, Silverman SG. Thrombosed interrupted inferior vena cava and retroaortic
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left renal vein mimicking retroperitoneal neoplasm. Abdom Imaging 2007;32:403e6. Lambert M, Marboeuf P, Midulla M, et al. Inferior vena cava agenesis and deep vein thrombosis: 10 patients and review of the literature. Vasc Med 2010;15:451e9. Lane DA. Congenital hypoplasia of the inferior vena cava: an underappreciated cause of deep venous thromboses among young adults. Mil Med 2005;170:739e42. Iwakura T, Yoshida S, Koyama T, et al. Acute pulmonary thromboembolism in polysplenia syndrome [in Japanese]. Kyobu Geka 2009;62:1065e7. Kitaguchi S, Miyara T, Ueda T, et al. A case of acute pulmonary thromboembolism accompanied by anomalous inferior vena cava with azygous continuation [in Japanese]. Nihon Kokyuki Gakkai Zasshi 2006;44:957e61. Tanju S, Dusunceli E, Sancak T. Placement of an inferior vena cava filter in a patient with azygos continuation complicated by pulmonary embolism. Cardiovas Intervent Radiol 2006;29:681e4. Miyasita K, Yamada N, Yazu T, et al. Azygos continuation of inferior vena cava as a sourse of acute massive pulmonary thromboembolism [in Japanese]. Nihon Naika Gakkai Zasshi 2000;89:765e7. Sadler RB, Fitzgerald G. Interruption of the inferior vena cava with azygos continuation and pulmonary embolus. Calif Med 1973;119:69e72.
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16. Castro FJ, Perez C, Narvaez FJ, et al. Congenital absence of the inferior vena cava as a risk factor for pulmonar thromboembolism [in Spanish]. An Med Interna 2003;20: 304e6. 17. Hyun DH, Seo JB, Chae EJ, et al. Pulmonary embolism associated with inferior vena cava interruption: multidetector computed tomography findings. J Thorac Imaging 2010;25: W131e2. 18. Lash C, Radhakrishnan J, McFadden JC. Renal vein thrombosis secondary to absent inferior vena cava. Urology 1998;51:829e30. 19. Kraft JK, Brandao LR, Navarro OM. Sonography of renal venous thrombosis in neonates and infants: can we predict outcome? Pediatr Radiol 2011;41:299e307. 20. Bashir R, Tinkel J, Malhotra D. Renal vein thrombosis: a case report. Angiology 2007;58:640e3. 21. Rooke TW, Sullivan TM, Jaff MR, Society for Vascular Medicine and Biology. Vascular Medicine and Endovascular Interventions. Malden, MA: Blackwell Futura: 2007. 22. Skeik N, Gloviczki P, Macedo TA. Posterior nutcracker syndrome. Vasc Endovascular Surg 2011;45:749e55. 23. Guyatt GH, Akl EA, Crowther M, et al. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians EvidenceBased Clinical Practice Guidelines. Chest 2012;141: 7Se47S.