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Venous Thrombosis in Rare or Unusual Sites: A Diagnostic Challenge Antonio Girolami, MD1 Bruno Girolami, MD2
Martina Treleani, MD1
Emanuela Bonamigo, MD1
1 Department of Medicine, University of Padua Medical School,
Padua, Italy 2 Division of Medicine, Padua City Hospital, Padua, Italy
Valentina Tasinato, MD1
Address for correspondence Antonio Girolami, MD, Department of Medicine, University of Padua Medical School, Padua, Italy (e-mail: [email protected]).
Abstract
Keywords
► ► ► ► ►
thrombosis venous rare unusual site diagnosis
Venous thrombosis usually involves the veins of the limbs, most frequently the leg veins. All other venous districts may sometimes be affected by the thrombotic process. Sometimes, the thrombotic occlusion of the veins of a given region show typical signs and symptoms. In other cases, the picture may not be clear and a high degree of clinical suspicion is needed for a correct approach to patient diagnosis and management. Thrombosis of retinal and jugular veins, right heart thrombosis including thrombosis of coronary sinus and thrombosis of the azygos system may be included in this group. In addition, thromboses of umbilical, renal, ovarian, spermatic, and iliac veins also require attention. Finally, the dorsal veins of the penis may also be affected by thrombotic events. The main clinical features of these thromboses are reviewed herein with suggestions for a correct diagnostic approach. The importance of sonography and of other imaging techniques is emphasized. A prompt diagnosis is of paramount importance as most of these thromboses in rare or unusual sites may still cause severe systemic complications (pulmonary embolism, sepsis, and heart failure).
The commonest sites of venous thromboses are the superficial or deep veins of lower limbs. However, it has to be remembered that every venous district may be involved in a thrombotic process.1 A second group of relatively rare venous thrombosis is represented by those affecting cerebral sinuses, the splanchnic system and the upper limbs. The thrombosis of hepatic veins is usually dealt together with the splanchnic vein thrombosis. Less frequent but potentially unrecognized and probably underdiagnosed or diagnosed only after a long investigation are the thromboses involving the internal jugular vein, the brachiocephalic vein (BCV), or innominate vein, the azygos vein, the coronary sinus, right heart, iliac veins, the renal veins, the ovarian or testicular veins, the dorsal veins of the penis, the umbilical vein, and sometimes, even the retinal veins. Actually, retinal vein thromboses are frequently encountered in ophthalmological practice but this occurs only after a general practitioner or an internist has referred the patient for a consultation for undiagnosed and generic “visual disturbances or partial visual loss.”
The purpose of this review is to deal with these peculiar clinical entities in an attempt to stimulate clinical suspicion and suggest suitable diagnostic and therapeutic procedures.
published online December 17, 2013
Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
Issue Theme Hot Topics V; Guest Editor, Emmanuel J. Favaloro, PhD, FFSc (RCPA).
Retinal Vein Thrombosis Retinal vein occlusion (RVO) is the second most frequent vascular lesion of the retina, after diabetic retinal disease. Indeed, the condition is much more frequent than commonly thought, especially among elders.2–4 RVO is usually divided into three types, namely branch retinal vein occlusion, central retinal vein occlusion (CRVO), and hemiretinal vein occlusion (HRVO). The merger of the superior and inferior branch occurs either before or after the lamina cribrosa. The central retinal vein drains into the cavernous plexus via the inferior ophthalmic vein. Several variants in the branching have been reported.4 The most frequent causes of retinal vein thrombosis are listed in ►Table 1.5,6 Congenital thrombophilia does not appear among the most frequent causes. This may be due
DOI http://dx.doi.org/ 10.1055/s-0033-1363471. ISSN 0094-6176.
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Semin Thromb Hemost 2014;40:81–87.
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Table 1 Main causes of retinal vein occlusiona • • • • • • • • • • • • • • a
Hypertensions Old age Diabetes Dyslipidemia Smoking Drugs (clomiphene citrate, oral contraceptives) Glaucoma Thrombophilia Congenital malformation Myeloproliferative disease Chronic renal failure Bechet disease Vasculitis Sarcoidosis
Causes listed according to prevalence.
in part to the fact that a thrombophilic screening is seldom performed in these patients. However, occasional cases apparently because of congenital thrombophilia have been described.7 The clinical picture is variable according to the extension and the site of occlusion. Variable vision loss is the hallmark symptom. CRVO is characterized by a sudden and painless loss of vision. Retinal veins are enlarged and occasional hemorrhages may be found near the dilatated vein. Several degenerative changes may occur in the retina if occlusion is not suddenly resolved. HRVO is characterized by loss of vision in the upper or lower part of visual field. Because of the anatomic variability and anastomosis, the pattern may not be so clear cut. If the merger of the superior and inferior retinal branch vein occurs after the lamina cribrosa, the loss of vision is present both in the superior and inferior parts of the visual field.4 Branch occlusion may be asymptomatic or cause some blurring of vision in the corresponding quadrant of the field. The management of RVO is still controversial. The majority of physicians tend to treat it as another venous thrombosis, using mainly heparin and Coumadin. Needless to say, the presence of associated risk factors should be immediately eliminated if possible (e.g., oral contraceptives).
Internal Jugular Vein Thrombosis Internal jugular vein thrombosis was first described in 1936 by Lemierre,8 explaining why this thrombotic event is also known as Lemierre syndrome.9–15 The condition usually involves young adults in good general condition after a pharingotonsillitis. The condition is actually a thrombophlebitis with clear signs of inflammation and infection.8 The main signs and symptoms are recent history of oral cavity infections, pain and tenderness in the lateral side of the neck, local swelling, dysphagia, malaise, and fever. The germ most frequently recovered is Fusobacterium necrophorum (gram-negative obligate anaerobic germ).12 The septic thrombophlebitis may be complicated by multiple embolic abscesses that involve mainly lungs and joints.11,12 Neurological complications may also occur. Other germs may be Seminars in Thrombosis & Hemostasis
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implicated and the condition has been observed even after infectious mononucleosis. It is usually monolateral. Diagnosis must be prompt and based on clinical suspicion, cultural swabs, and echographic demonstration of the thrombus in jugular vein. Thrombosis of the jugular vein may occur also without infection. In this case catheters, underlying neoplasia and thrombophilia are the main causes. In recent years, several cases have been described in women after assisted contraception therapy.9,10 A few cases totally or partially due to congenital thrombophilia, namely protein S deficiency or factor V Leiden have been described.13 In some cases, both a congenital and an acquired thrombotic condition may be present. In the postinfection cases, treatment must be immediate.14 Usually, penicillin derivatives with βlactamase inhibitors are effective. Low-molecular-weight heparin (LMWH) should be given particularly when local signs of inflammation are not marked. Removal of catheter and persistent anticoagulation with heparins and coumadin are indicated in the other cases.
Thrombosis of Brachiocephalic (Innominate) Vein Isolated thrombosis of the BCV is rare but has been described in patients with neoplasia, indwelling catheter, strenuous exercise (especially in triathlon athletes), thoracic outlet malformations, and fibrotic bands.16–18 The innominate vein is a large but short vein that results from the merging of the subclavian and the internal jugular vein on each site of the body.17 The vein is 6-cm long on the left side and shorter (approximately 3.5 cm) on the right side. The merger of the two veins gives origin to the superior vena cava (SVC). Thrombosis usually involves the left side. Supraclavicular or upper chest pain and discomfort, monolateral jugular vein distention, swelling of the face, neck, and arm are the usual symptoms and signs. In long-standing cases, chylothorax may occur as the thoracic lymphatic duct ends at the origin of the left BCV.18 An important clinical sign is the presence of swollen, sometimes tender breast. This is because of the fact that the BCV receives the internal mammary vein. Swelling of the breast is not present in case of occlusions of the subclavian or axillary vein, as such occlusions do not interfere with the venous discharge from the breast. This is an important clinical sign. Diagnosis has to be confirmed by angio-computerized axial tomography (angio-CAT) or angio-magnetic resonance imaging (angio-MRI) techniques. Phlebography has also been used. Sonography may be useful but not sufficient to reach the diagnosis. The therapeutic approach is that of the deep vein thrombosis, namely heparin and coumadin.
Thrombosis of the Azygos Vein The azygos vein arises from the lumbar vein and it ascends to the posterior mediastinum on the right side of vertebral column to emerge in the SVC just before this enters the pericardium. During its course, it drains blood from the right intercostal veins and from the hemiazygos and the accessory
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hemiazygos vein. The hemiazygos arises from lumbar vein of the left side and then crosses over to join the azygos vein at the level of the body of the eighth thoracic vertebra. Along its course, it receives as tributaries the last intercostal veins. The accessory hemiazygos veins descend on the left side of the vertebral column receiving as tributaries the fourth to seventh intercostal veins and merges into the azygos vein by crossing to the right side at the level of the seventh thoracic vertebra. The first three intercostal veins on the left side form the superior intercostal vein which drains into the left anonymous or brachycephalic veins. Several variants and communications among these veins may exist. Thrombosis of the azygos vein is rare, but it has been described in literature.19–24 Furthermore, the recent use of the azygos system as a site for a permanent or temporary indwelling catheter placement in children or for dialytic purpose has increased the chance for thrombotic occlusions.20 Besides catheters, the main causes of thrombosis in the azygos vein are malformation (especially atresia of inferior vein cava with azygos continuation and aneurysms) and local tumors.21 The clinical picture is poor and ill defined. Vague abdominal pain, sometimes colicky in nature is the most important but nonspecific feature.23 Pulmonary embolism may occur. The diagnosis is usually made by angio-CAT or angio-MRI.24 In case of a thrombosis occurring in an aneurysmatic sac, the plain chest X-ray may reveal a right paratracheal mass. Transesophageal sonography may also be useful. The therapeutic approach is based on usual anticoagulant administration. Surgical approach is indicated in the presence of a thrombus in an aneurysm.19,22
Intracardiac Thrombosis Intracardiac thrombosis should be divided in the right-side or left-side heart thrombosis.25 Only the right heart may be included as part of the venous system and therefore we will deal only with this aspect in this review together with the coronary sinus. The right atrium is the third most frequent site of intracardiac thrombosis, the first one being the left atrium, and the second the left ventricle. Right ventricle thrombosis, on the contrary, is the rarest form of intracardiac thrombosis.25 Heart failure, invasive intracardiac procedures, and atrial fibrillation are the most frequent causes. Sometimes, the presence of a thrombus in the atrium may be secondary to thrombosis in the SVC. Thrombosis of coronary sinus may also protrude into the atrium. Right ventricle thrombosis is usually secondary to right atrium thrombosis. Symptoms and signs are vague and nonspecific: vague chest pain, arrhythmias, dyspnea, and cough if pulmonary embolization occurs, fever. An aggravation of preexisting cardiac condition is also a frequent pattern of presentation. Diagnosis is achieved by sonography, particularly by transesophageal sonography.26,27 Differential diagnosis has to take into account myxoma of atrium which may also give pulmonary arteria occlusion, when undergoing spontaneous fragmentation. The therapeutic approach depends on the size and aspect of the thrombus; fibrinolytic agents and heparins are the
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most widely used. Surgical removal of the thrombus is usually reserved for large clots.28–30 Fibrinolytic agents have been administrated both systemically and, more often, locally through a jugular vein catheter. Coronary sinus thrombosis can also be included within this section. The coronary sinus is a wide venous channel 2- to 3-cm long, located between the left atrium and left ventricle. It ends in the right atrium between the opening of the inferior vena cava and the atrioventricular orifice. Its opening displays a semilunar flap, the valve of coronary sinus. The sinus receives the three cardiac veins, great, small, and middle. Thrombosis of the coronary sinus has increased during the last decade because of the diffusion of right atrium invasive procedures (central veins catheters, ablations, etc.) although it remains often unsuspected. Coronary sinus thrombosis is sometimes associated with right atrium thrombosis.26–29 Patients present a precipitous clinical aggravation of preexisting cardiac condition (severe dyspnea, chest pain, and pericardial tamponade). Coronary sinus thrombosis is sometimes the cause of sudden death.30 Diagnosis is done almost always post mortem. Early diagnosis is essential. Any sudden modification of condition after a right atrium invasive procedure should raise the suspicion of coronary sinus thrombosis. Diagnosis is by arteriography. Spiral computed tomography and MRI may also supply useful information. The therapeutic approach involves heparin administration and also arthrographic invasive disobstruction.
Renal Vein Thrombosis There are usually two renal veins one drains blood from the right kidney and the other from the left kidney. Smaller additional renal veins may also be present. Both renal veins receive the respective suprarenal vein. In addition, the left renal vein receives the left spermatic or ovarian vein. This discrepant anatomic condition plays an important role in clinical medicine. The main causes of renal thrombosis are renal tumors, nephrotic syndrome, external traumas, vena cava thrombosis, testicular tumors with spermatic vein thrombosis, antiphospholipids antibodies (APA) syndrome, lupus erythematosus systemicus, postrenal transplantation. Congenital thrombophilia may also play a role in some instances.31–38 The picture is insidious with lumbar area pain, renal colic, left side varicocele with or without thrombosis and scrotal swelling and pain. Pulmonary embolism may also occur.34,37 Proteinuria, enlarged kidney on sonography, variable renal insufficiency are also present. Renal scintiscan reveals a normal uptake but no or limited discharge curve. The management approach varies with the cause involved. In case of renal or suprarenal tumors, surgery is mandatory. In other cases, anticoagulant therapy may be established. Local fibrinolysis after percutaneous thrombectomy has also been proposed.35 In cases secondary to nephrotic syndrome with heavy proteinuria, antithrombin should be checked as it may be low because it is usually eliminated similar to albumin. This is particularly true if unfractionated heparin (UH) or LMWH are planned to be used. Seminars in Thrombosis & Hemostasis
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Venous Thrombosis in Rare or Unusual Sites
Venous Thrombosis in Rare or Unusual Sites
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Prognosis depends on the basic condition present. If the condition is due to chronic glomerular disease the prognosis depends on the evolution of the renal disease. A caval filter is sometimes needed.34 The forms secondary to thrombophilia or to APA syndrome usually respond to anticoagulant therapies.32 The prognosis of the cases secondary to tumors is frequently poor.39,40
Umbilical Vein Thrombosis There are, originally, two umbilical veins, right and left, but the right one disappears early and the left one remains as the single umbilical vein. The umbilical vein carries oxygenated blood from the placenta to the fetus. Thrombosis of the umbilical vein at birth is rare but is important because it is often the cause of portal vein thrombosis (PVT) in the neonate or child.41 Causes are ill defined. Traumas or congenital thrombophilia have been implicated. The insertion of catheters for fetal cells harvesting or the attempts at recanalization of the vein in childhood for therapeutic purposes have also been implicated.42–46 Because of the merger or communication of the umbilical vein with the left branch of the portal vein during fetal life, it has to be kept in mind that a thrombosis of the umbilical vein is to be considered an actual or potential cause of PVT, until proven otherwise.44,45
vena cava at the level of the 12th dorsal vertebra. The left one drains into the left renal vein. They may contain some valves, which are always present in spermatic or testicular veins. Ovarian veins thrombosis is rare but recently it has been diagnosed more frequently due to the use of multidetection computed tomography (MDCT), which allows the full visualization of the veins in almost all women. Ovarian vein thrombosis has been reported to occur primarily in early puerperal period, in pregnancy, but also in chronic pelvic inflammatory diseases, tumors or as a complication of surgery.54–56 There are no specific clinical signs or symptoms and it is widely assumed that in the past, many cases went undetected or misdiagnosed as abdominal colicky pain. Lower quadrant pain and tenderness, nausea, fever, and malaise are common. The pain is sometimes radiated to the back. Diagnosis requires demonstration of the presence of thrombosis occlusion of one of the ovarian veins. This is best achieved by CT or MRI or, as stated above, by MDCT.55 Sonography may also be useful, but it is usually incapable of visualizing the entire course of the vein. Management is conservative with bed rest and anticoagulant therapy. UH or LMWH for 15 to 20 days may be sufficient if in the meantime the cause has been eliminated. Associated use of antibiotics is indicated in cases of postpartum or postsurgery.
Isolated Iliac Vein Thrombosis Testicular Vein Thrombosis Testicular or spermatic veins arise from the pampiniform plexus of both sides of the scrota. On the right side, the vein drains into the vena cava; whereas on the left side, it drains into the left renal vein. This discrepant course has important pathophysiologic implications. For example, tumors of the left kidney may cause stasis and thrombosis of left spermatic veins. The same is not true for the right side. Other important causes are trauma, strenuous exercise, varicocele, Henoch–Schönlein purpura.39,40,47–52 The condition is rare and involves mainly the left side, probably because of more frequent stasis and varicocele present in this side because of hemodynamic reasons (longer course, rectangle merger with renal vein). Presentation is usually with testicular pain, scrotal swelling, and vague abdominal discomfort. The pain may radiate to the back. Pulmonary embolism has been reported.52 Differential diagnosis involves the following: incarcerated hernia, epididymitis, and spermatic cord tumors. Sonography or venography is diagnostic. When thrombosis involves the left side, diagnostic sonography procedure has to rule out left kidney pathology.53 Management is usually conservative with bed rest and anticoagulant therapy. Surgery is sometimes needed. Laparoscopy easily allows the identification and ligation of the thrombosed spermatic vein.
Ovarian Vein Thrombosis Similarly to what seen for spermatic or testicular veins there are two ovarian veins. The right one drains into the inferior Seminars in Thrombosis & Hemostasis
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The common iliac vein is formed by the merge of the internal and external iliac vein, on each side of the body, at the level of the sacroiliac joint. The right common iliac vein, shorter than the left, is nearly vertical whereas the left is more oblique. The two common iliac veins merge at acute angle to form the inferior vein cava at the level of the body of the fifth lumbar vertebra. Isolated thrombosis of the iliac vein is rare as in most cases it is associated with femoral vein thrombosis. It has been described in pregnancy, because of compression from the right iliac artery, during oral contraception, after lithotripsy, after renal transplant, after strenuous exercise (cyclist, marathon runners), and in other rare conditions. A special mention is due to the left leg iliac vein thrombosis seen in pregnancy. The majority of thrombosis in pregnancy involves the left leg. This has been claimed to be related to the compression exercised by the enlarged uterus but also to the right iliac artery encroaching on the left iliac vein against the fifth lumbar vertebra.53,57–59 The condition is known as May– Thurner syndrome or Cockett–Thomas syndrome and it has been maintained to be a potential cause of left leg vein thrombosis even in nonpregnant women and in men.53,57–63 On clinical grounds, abdominal, lumbar, or flank pain accompanied by swelling of the leg are the most important findings. Compression sonography of the leg vein is negative and this may be surprising in view of the swollen leg and create diagnostic difficulties. Venous pletsigmography may be useful in suspecting intraluminal vein obstruction, but it is seldom used. Abdominal sonography may be suggestive, but MRI is the best diagnostic tool available for a definitive diagnosis.59
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Venous Thrombosis in Rare or Unusual Sites
Table 2 Potential complications of venous thrombosis in rare or unusual sites Retinal vein thrombosis
Suddenly reduced vision, blindness, extension to cavernous plexus
Jugular vein thrombosis
Generalized sepsis, endocarditis
Right heart thrombosis
Pulmonary embolism, intracardiac thrombosis
Coronary sinus thrombosis
Aggravation of pre-existing heart condition, severe arrhythmias, heart failure, pulmonary embolism
Isolated iliac vein
Pulmonary embolism
Renal vein thrombosis
Pulmonary embolism, nephrotic syndrome
Ovarian or testicular veins
Pulmonary embolism, renal vein thrombosis on left side
Dorsal veins of penis
Priapism
Thromboses of Dorsal Vein of Penis The drainage of blood from the penis occurs mainly through superficial and deep dorsal veins. The superficial vein is located in the subcutaneous tissue and is clearly visible, particularly when the penis is erected; it drains into the external pudendal vein, a tributary of the great saphenous vein. The deep vein lies underneath the superficial fascia, within the fibrous envelope (tunica albuginea). It divides at the end into two branches, which enter the prostatic plexus often communicating, below the symphysis pubis, with the internal pudendal vein. The deep vein drains most of the corpora cavernosa, whereas the superficial vein drains the skin and the glans. Thrombosis in the superficial or deep vein of the penis is caused by trauma, excessive sexual activity, infections, pelvic trauma, and surgical procedures (subinguinal varicocelectomy, hernia repairs, etc.).64–67 If only the superficial vein is involved, the condition is also known as Mondor disease of penis.65,67 The clinical picture is characterized by local swelling, variable priapism, pain, and tenderness on palpation. The picture is more severe if both systems, superficial and deep, are involved. In this case, priapism is usually persistent. Diagnosis is easy if one takes into account the setting in which signs and symptoms appear. Plain or color sonography of the penis is needed to establish the exact site of the thrombotic occlusion. Angiography is also sometimes needed.66 Anti-inflammatory drugs, local measures, and abstinence from sexual activity are usually sufficient. The use of anticoagulant (LMWH) may be needed. If conservative and anticoagulant therapies fail, then surgery is occasionally needed.
Funding The study was supported in part by the Associazione Emofilica ed altre Coagulopatie delle Tre Venezie.
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Conclusions Taken together these peculiar and rare venous thromboses may constitute only approximately 10% of all venous thrombosis. However, they are equally important as they may cause pulmonary embolism (testicular, ovarian, renal veins, and right heart thrombosis). They may also indicate hidden or unknown neoplasia (renal vein thrombosis). Vein thrombosis has also a peculiar relation with nephrotic syndrome. In fact, it may be both a cause and/or the complication of a primary form of nephrotic syndrome. These peculiar and rare venous thromboses may also be a cause and/or the result of sepsis (jugular vein thrombosis). Retinal vein thrombosis may extend to a thrombosis of the cavernous sinus with the consequent neurological involvement. Finally, thrombosis of the dorsal vein of penis may be the cause of priapism. The variable clinical picture seen in these peculiar and rare venous thromboses involving many vascular districts underlines the importance of a careful clinical evaluation, once the suspicion has arisen (►Table 2).
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The therapeutic approach is based on UH or LMWH and coumadin as for any deep vein thrombosis. Insertion of caval filters may sometimes be indicated.
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secondary to membranous glomerulonephritis treated with percutaneous catheter thrombectomy and localized thrombolytic therapy. Indian J Nephrol 2010;20(3):152–155 Chaturvedi S, Brandao L, Geary D, Licht C. Primary antiphospholipid syndrome presenting as renal vein thrombosis and membranous nephropathy. Pediatr Nephrol 2011;26(6):979–985 Skalova S, Minxova L, Lukes A, Dedek P, Tousovska K, Podhola M. Renal vein thrombosis with pulmonary embolism: first manifestation of lupus nephritis. J Paediatr Child Health 2011;47(5):315–316 Freitas C, Fructuso M, Rocha MJ, et al. Late venous thrombosis of renal allograft: two cases with different treatment and outcome. Nefrologia 2011;31(1):115–117 Mabjeesh NJ, Bar-Yosef Y, Schreiber-Bramante L, Kaver I, Matzkin H. Spermatic vein tumor thrombus in renal cell carcinoma. ScientificWorldJournal 2004;4(Suppl 1):192–194 Shinsaka H, Fujimoto N, Matsumoto T. A rare case of right varicocele testis caused by a renal cell carcinoma thrombus in the spermatic vein. Int J Urol 2006;13(6):844–845 Avagliano L, Marconi AM, Candiani M, Barbera A, Bulfamante G. Thrombosis of the umbilical vessels revisited. An observational study of 317 consecutive autopsies at a single institution. Hum Pathol 2010;41(7):971–979 Rubabaza P, Persadie RJ. Two cases of umbilical vein thrombosis, one with associated portal vein thrombosis. J Obstet Gynaecol Can 2008;30(4):338–343 Vanrykel K, Bruneel E, Van Hoestenberghe MR, Buekenhout L, Gyselaers W, Theyskens C. Neonatal disseminated intravascular coagulation after thrombosis of a fetal intra-abdominal umbilical vein varix. J Obstet Gynaecol 2010;30(3):315 Williams S, Chan AK. Neonatal portal vein thrombosis: diagnosis and management. Semin Fetal Neonatal Med 2011;16(6):329–339 Witters P, Reynaert N, Pattyn L, et al. Intrauterine thrombosis of the ductus venosus leading to neonatal demise. Arch Dis Child Fetal Neonatal Ed 2012;97(1):F17 Gharehbaghi MM, Nemati M, Hosseinpour SS, Taei R, Ghargharechi R. Umbilical vascular catheter associated portal vein thrombosis detected by ultrasound. Indian J Pediatr 2011;78(2):161–164 Diana A, Gaze H, Laubscher B, De Meuron G, Tschantz P. A case of pediatric Henoch-Schönlein purpura and thrombosis of spermatic veins. J Pediatr Surg 2000;35(12):1843 Gleeson MJ, McDermott M, McDonald G, McDermott TE. Spontaneous thrombosis of the left spermatic vein. Br J Urol 1992;70(5): 567 Hashimoto L, Vibeto B. Spontaneous thrombosis of the pampiniform plexus. Scand J Urol Nephrol 2006;40(3):252–254 Review Isenberg JS, Ozuner G, Worth MH, Ferzli G. Effort-induced spontaneous thrombosis of the left spermatic vein presenting clinically as a left inguinal hernia. J Urol 1990;144(1):138 Maas C, Müller-Hansen I, Flechsig H, Poets CF. Acute scrotum in a neonate caused by renal vein thrombosis. Arch Dis Child Fetal Neonatal Ed 2011;96(2):F149–F150 Castillo OA, Diaz M, Vitagliano GJ, Metrebian E. Pulmonary thromboembolism secondary to left spermatic vein thrombosis: a case report. Urol Int 2008;80(2):217–218 Barrellier MT, Lezin B, Monsallier JM. [Isolated iliac deep venous thrombosis. Study of 48 cases seen in 7 years among 18,297 echoDoppler evaluations of the lower limbs]. J Mal Vasc 2001;26(5): 290–298 Goodwin TM, Gazit G, Gordon EM. Heterozygous protein C deficiency presenting as severe protein C deficiency and peripartum thrombosis: successful treatment with protein C concentrate. Obstet Gynecol 1995;86(4 Pt 2):662–664 Karaosmanoglu D, Karcaaltincaba M, Karcaaltincaba D, Akata D, Ozmen M. MDCT of the ovarian vein: normal anatomy and pathology. AJR Am J Roentgenol 2009;192(1):295–299 Klima DA, Snyder TE. Postpartum ovarian vein thrombosis. Obstet Gynecol 2008;111(2 Pt 1):431–435
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57 Fraser DG, Moody AR, Martel A, Morgan PS. Re-evaluation of iliac
62 Merhi Z, Awonuga A. Acute abdominal pain as the presenting
compression syndrome using magnetic resonance imaging in patients with acute deep venous thromboses. J Vasc Surg 2004; 40(4):604–611 Peters M, Syed RK, Katz M, et al. May-Thurner syndrome: a not so uncommon cause of a common condition. Proc (Bayl Univ Med Cent) 2012;25(3):231–233 (Bayl Univ Med Cent) Wolpert LM, Rahmani O, Stein B, Gallagher JJ, Drezner AD. Magnetic resonance venography in the diagnosis and management of MayThurner syndrome. Vasc Endovascular Surg 2002;36(1):51–57 Brodmann M, Gary T, Hafner F, Tiesenhausen K, Deutschmann H, Pilger E. Massive pulmonary embolism caused by internal iliac vein thrombosis with free-floating thrombus formation in the inferior vena cava. Ann Vasc Surg 2012;26(3):e5–e7 Girolami A, Prandoni P, Zanardi A, Girolami B, Zanon E. Isolated iliac vein thrombosis durino oral contraceptive therapy in three “normal” women. Clin Appl Thromb Hemost 1997; 3:284–287
symptom of isolated iliac vein thrombosis in pregnancy. Obstet Gynecol 2006;107(2 Pt 2):468–470 de Perrot T, Righini M, Bounameaux H, Poletti PA. Contrastenhanced sonographic diagnosis of unsuspected internal iliac vein thrombosis. J Clin Ultrasound 2011;39(9):553–555 Arango O, Lorente JA, Nohales G, Rijo E, Bielsa O. Superficial dorsal penile vein thrombosis: a little-known complication of subinguinal varicocelectomy. BJU Int 2011;107(1):95–98 Han HY, Chung DJ, Kim KW, Hwang CM. Pulsed and color Doppler sonographic findings of penile Mondor’s disease. Korean J Radiol 2008;9(2):179–181 Kolbenstvedt A, Jenssen G, Hedlund H. Priapism of the glans and corpus spongiosum. Report of two cases with angiography. Acta Radiol 2003;44(4):456–459 Molina Escudero R, Cabello Benavente R, Monzó Gardiner JI, et al. [Mondor’s syndrome. Case review and bibliographic review]. Arch Esp Urol 2009;62(4):317–319
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Venous Thrombosis in Rare or Unusual Sites
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Venous Thrombosis in Rare or Unusual Sites: A Diagnostic Challenge Antonio Girolami, MD1 Bruno Girolami, MD2
Martina Treleani, MD1
Emanuela Bonamigo, MD1
1 Department of Medicine, University of Padua Medical School,
Padua, Italy 2 Division of Medicine, Padua City Hospital, Padua, Italy
Valentina Tasinato, MD1
Address for correspondence Antonio Girolami, MD, Department of Medicine, University of Padua Medical School, Padua, Italy (e-mail: [email protected]).
Abstract
Keywords
► ► ► ► ►
thrombosis venous rare unusual site diagnosis
Venous thrombosis usually involves the veins of the limbs, most frequently the leg veins. All other venous districts may sometimes be affected by the thrombotic process. Sometimes, the thrombotic occlusion of the veins of a given region show typical signs and symptoms. In other cases, the picture may not be clear and a high degree of clinical suspicion is needed for a correct approach to patient diagnosis and management. Thrombosis of retinal and jugular veins, right heart thrombosis including thrombosis of coronary sinus and thrombosis of the azygos system may be included in this group. In addition, thromboses of umbilical, renal, ovarian, spermatic, and iliac veins also require attention. Finally, the dorsal veins of the penis may also be affected by thrombotic events. The main clinical features of these thromboses are reviewed herein with suggestions for a correct diagnostic approach. The importance of sonography and of other imaging techniques is emphasized. A prompt diagnosis is of paramount importance as most of these thromboses in rare or unusual sites may still cause severe systemic complications (pulmonary embolism, sepsis, and heart failure).
The commonest sites of venous thromboses are the superficial or deep veins of lower limbs. However, it has to be remembered that every venous district may be involved in a thrombotic process.1 A second group of relatively rare venous thrombosis is represented by those affecting cerebral sinuses, the splanchnic system and the upper limbs. The thrombosis of hepatic veins is usually dealt together with the splanchnic vein thrombosis. Less frequent but potentially unrecognized and probably underdiagnosed or diagnosed only after a long investigation are the thromboses involving the internal jugular vein, the brachiocephalic vein (BCV), or innominate vein, the azygos vein, the coronary sinus, right heart, iliac veins, the renal veins, the ovarian or testicular veins, the dorsal veins of the penis, the umbilical vein, and sometimes, even the retinal veins. Actually, retinal vein thromboses are frequently encountered in ophthalmological practice but this occurs only after a general practitioner or an internist has referred the patient for a consultation for undiagnosed and generic “visual disturbances or partial visual loss.”
The purpose of this review is to deal with these peculiar clinical entities in an attempt to stimulate clinical suspicion and suggest suitable diagnostic and therapeutic procedures.
published online December 17, 2013
Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
Issue Theme Hot Topics V; Guest Editor, Emmanuel J. Favaloro, PhD, FFSc (RCPA).
Retinal Vein Thrombosis Retinal vein occlusion (RVO) is the second most frequent vascular lesion of the retina, after diabetic retinal disease. Indeed, the condition is much more frequent than commonly thought, especially among elders.2–4 RVO is usually divided into three types, namely branch retinal vein occlusion, central retinal vein occlusion (CRVO), and hemiretinal vein occlusion (HRVO). The merger of the superior and inferior branch occurs either before or after the lamina cribrosa. The central retinal vein drains into the cavernous plexus via the inferior ophthalmic vein. Several variants in the branching have been reported.4 The most frequent causes of retinal vein thrombosis are listed in ►Table 1.5,6 Congenital thrombophilia does not appear among the most frequent causes. This may be due
DOI http://dx.doi.org/ 10.1055/s-0033-1363471. ISSN 0094-6176.
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Venous Thrombosis in Rare or Unusual Sites
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Table 1 Main causes of retinal vein occlusiona • • • • • • • • • • • • • • a
Hypertensions Old age Diabetes Dyslipidemia Smoking Drugs (clomiphene citrate, oral contraceptives) Glaucoma Thrombophilia Congenital malformation Myeloproliferative disease Chronic renal failure Bechet disease Vasculitis Sarcoidosis
Causes listed according to prevalence.
in part to the fact that a thrombophilic screening is seldom performed in these patients. However, occasional cases apparently because of congenital thrombophilia have been described.7 The clinical picture is variable according to the extension and the site of occlusion. Variable vision loss is the hallmark symptom. CRVO is characterized by a sudden and painless loss of vision. Retinal veins are enlarged and occasional hemorrhages may be found near the dilatated vein. Several degenerative changes may occur in the retina if occlusion is not suddenly resolved. HRVO is characterized by loss of vision in the upper or lower part of visual field. Because of the anatomic variability and anastomosis, the pattern may not be so clear cut. If the merger of the superior and inferior retinal branch vein occurs after the lamina cribrosa, the loss of vision is present both in the superior and inferior parts of the visual field.4 Branch occlusion may be asymptomatic or cause some blurring of vision in the corresponding quadrant of the field. The management of RVO is still controversial. The majority of physicians tend to treat it as another venous thrombosis, using mainly heparin and Coumadin. Needless to say, the presence of associated risk factors should be immediately eliminated if possible (e.g., oral contraceptives).
Internal Jugular Vein Thrombosis Internal jugular vein thrombosis was first described in 1936 by Lemierre,8 explaining why this thrombotic event is also known as Lemierre syndrome.9–15 The condition usually involves young adults in good general condition after a pharingotonsillitis. The condition is actually a thrombophlebitis with clear signs of inflammation and infection.8 The main signs and symptoms are recent history of oral cavity infections, pain and tenderness in the lateral side of the neck, local swelling, dysphagia, malaise, and fever. The germ most frequently recovered is Fusobacterium necrophorum (gram-negative obligate anaerobic germ).12 The septic thrombophlebitis may be complicated by multiple embolic abscesses that involve mainly lungs and joints.11,12 Neurological complications may also occur. Other germs may be Seminars in Thrombosis & Hemostasis
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implicated and the condition has been observed even after infectious mononucleosis. It is usually monolateral. Diagnosis must be prompt and based on clinical suspicion, cultural swabs, and echographic demonstration of the thrombus in jugular vein. Thrombosis of the jugular vein may occur also without infection. In this case catheters, underlying neoplasia and thrombophilia are the main causes. In recent years, several cases have been described in women after assisted contraception therapy.9,10 A few cases totally or partially due to congenital thrombophilia, namely protein S deficiency or factor V Leiden have been described.13 In some cases, both a congenital and an acquired thrombotic condition may be present. In the postinfection cases, treatment must be immediate.14 Usually, penicillin derivatives with βlactamase inhibitors are effective. Low-molecular-weight heparin (LMWH) should be given particularly when local signs of inflammation are not marked. Removal of catheter and persistent anticoagulation with heparins and coumadin are indicated in the other cases.
Thrombosis of Brachiocephalic (Innominate) Vein Isolated thrombosis of the BCV is rare but has been described in patients with neoplasia, indwelling catheter, strenuous exercise (especially in triathlon athletes), thoracic outlet malformations, and fibrotic bands.16–18 The innominate vein is a large but short vein that results from the merging of the subclavian and the internal jugular vein on each site of the body.17 The vein is 6-cm long on the left side and shorter (approximately 3.5 cm) on the right side. The merger of the two veins gives origin to the superior vena cava (SVC). Thrombosis usually involves the left side. Supraclavicular or upper chest pain and discomfort, monolateral jugular vein distention, swelling of the face, neck, and arm are the usual symptoms and signs. In long-standing cases, chylothorax may occur as the thoracic lymphatic duct ends at the origin of the left BCV.18 An important clinical sign is the presence of swollen, sometimes tender breast. This is because of the fact that the BCV receives the internal mammary vein. Swelling of the breast is not present in case of occlusions of the subclavian or axillary vein, as such occlusions do not interfere with the venous discharge from the breast. This is an important clinical sign. Diagnosis has to be confirmed by angio-computerized axial tomography (angio-CAT) or angio-magnetic resonance imaging (angio-MRI) techniques. Phlebography has also been used. Sonography may be useful but not sufficient to reach the diagnosis. The therapeutic approach is that of the deep vein thrombosis, namely heparin and coumadin.
Thrombosis of the Azygos Vein The azygos vein arises from the lumbar vein and it ascends to the posterior mediastinum on the right side of vertebral column to emerge in the SVC just before this enters the pericardium. During its course, it drains blood from the right intercostal veins and from the hemiazygos and the accessory
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hemiazygos vein. The hemiazygos arises from lumbar vein of the left side and then crosses over to join the azygos vein at the level of the body of the eighth thoracic vertebra. Along its course, it receives as tributaries the last intercostal veins. The accessory hemiazygos veins descend on the left side of the vertebral column receiving as tributaries the fourth to seventh intercostal veins and merges into the azygos vein by crossing to the right side at the level of the seventh thoracic vertebra. The first three intercostal veins on the left side form the superior intercostal vein which drains into the left anonymous or brachycephalic veins. Several variants and communications among these veins may exist. Thrombosis of the azygos vein is rare, but it has been described in literature.19–24 Furthermore, the recent use of the azygos system as a site for a permanent or temporary indwelling catheter placement in children or for dialytic purpose has increased the chance for thrombotic occlusions.20 Besides catheters, the main causes of thrombosis in the azygos vein are malformation (especially atresia of inferior vein cava with azygos continuation and aneurysms) and local tumors.21 The clinical picture is poor and ill defined. Vague abdominal pain, sometimes colicky in nature is the most important but nonspecific feature.23 Pulmonary embolism may occur. The diagnosis is usually made by angio-CAT or angio-MRI.24 In case of a thrombosis occurring in an aneurysmatic sac, the plain chest X-ray may reveal a right paratracheal mass. Transesophageal sonography may also be useful. The therapeutic approach is based on usual anticoagulant administration. Surgical approach is indicated in the presence of a thrombus in an aneurysm.19,22
Intracardiac Thrombosis Intracardiac thrombosis should be divided in the right-side or left-side heart thrombosis.25 Only the right heart may be included as part of the venous system and therefore we will deal only with this aspect in this review together with the coronary sinus. The right atrium is the third most frequent site of intracardiac thrombosis, the first one being the left atrium, and the second the left ventricle. Right ventricle thrombosis, on the contrary, is the rarest form of intracardiac thrombosis.25 Heart failure, invasive intracardiac procedures, and atrial fibrillation are the most frequent causes. Sometimes, the presence of a thrombus in the atrium may be secondary to thrombosis in the SVC. Thrombosis of coronary sinus may also protrude into the atrium. Right ventricle thrombosis is usually secondary to right atrium thrombosis. Symptoms and signs are vague and nonspecific: vague chest pain, arrhythmias, dyspnea, and cough if pulmonary embolization occurs, fever. An aggravation of preexisting cardiac condition is also a frequent pattern of presentation. Diagnosis is achieved by sonography, particularly by transesophageal sonography.26,27 Differential diagnosis has to take into account myxoma of atrium which may also give pulmonary arteria occlusion, when undergoing spontaneous fragmentation. The therapeutic approach depends on the size and aspect of the thrombus; fibrinolytic agents and heparins are the
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most widely used. Surgical removal of the thrombus is usually reserved for large clots.28–30 Fibrinolytic agents have been administrated both systemically and, more often, locally through a jugular vein catheter. Coronary sinus thrombosis can also be included within this section. The coronary sinus is a wide venous channel 2- to 3-cm long, located between the left atrium and left ventricle. It ends in the right atrium between the opening of the inferior vena cava and the atrioventricular orifice. Its opening displays a semilunar flap, the valve of coronary sinus. The sinus receives the three cardiac veins, great, small, and middle. Thrombosis of the coronary sinus has increased during the last decade because of the diffusion of right atrium invasive procedures (central veins catheters, ablations, etc.) although it remains often unsuspected. Coronary sinus thrombosis is sometimes associated with right atrium thrombosis.26–29 Patients present a precipitous clinical aggravation of preexisting cardiac condition (severe dyspnea, chest pain, and pericardial tamponade). Coronary sinus thrombosis is sometimes the cause of sudden death.30 Diagnosis is done almost always post mortem. Early diagnosis is essential. Any sudden modification of condition after a right atrium invasive procedure should raise the suspicion of coronary sinus thrombosis. Diagnosis is by arteriography. Spiral computed tomography and MRI may also supply useful information. The therapeutic approach involves heparin administration and also arthrographic invasive disobstruction.
Renal Vein Thrombosis There are usually two renal veins one drains blood from the right kidney and the other from the left kidney. Smaller additional renal veins may also be present. Both renal veins receive the respective suprarenal vein. In addition, the left renal vein receives the left spermatic or ovarian vein. This discrepant anatomic condition plays an important role in clinical medicine. The main causes of renal thrombosis are renal tumors, nephrotic syndrome, external traumas, vena cava thrombosis, testicular tumors with spermatic vein thrombosis, antiphospholipids antibodies (APA) syndrome, lupus erythematosus systemicus, postrenal transplantation. Congenital thrombophilia may also play a role in some instances.31–38 The picture is insidious with lumbar area pain, renal colic, left side varicocele with or without thrombosis and scrotal swelling and pain. Pulmonary embolism may also occur.34,37 Proteinuria, enlarged kidney on sonography, variable renal insufficiency are also present. Renal scintiscan reveals a normal uptake but no or limited discharge curve. The management approach varies with the cause involved. In case of renal or suprarenal tumors, surgery is mandatory. In other cases, anticoagulant therapy may be established. Local fibrinolysis after percutaneous thrombectomy has also been proposed.35 In cases secondary to nephrotic syndrome with heavy proteinuria, antithrombin should be checked as it may be low because it is usually eliminated similar to albumin. This is particularly true if unfractionated heparin (UH) or LMWH are planned to be used. Seminars in Thrombosis & Hemostasis
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Venous Thrombosis in Rare or Unusual Sites
Venous Thrombosis in Rare or Unusual Sites
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Prognosis depends on the basic condition present. If the condition is due to chronic glomerular disease the prognosis depends on the evolution of the renal disease. A caval filter is sometimes needed.34 The forms secondary to thrombophilia or to APA syndrome usually respond to anticoagulant therapies.32 The prognosis of the cases secondary to tumors is frequently poor.39,40
Umbilical Vein Thrombosis There are, originally, two umbilical veins, right and left, but the right one disappears early and the left one remains as the single umbilical vein. The umbilical vein carries oxygenated blood from the placenta to the fetus. Thrombosis of the umbilical vein at birth is rare but is important because it is often the cause of portal vein thrombosis (PVT) in the neonate or child.41 Causes are ill defined. Traumas or congenital thrombophilia have been implicated. The insertion of catheters for fetal cells harvesting or the attempts at recanalization of the vein in childhood for therapeutic purposes have also been implicated.42–46 Because of the merger or communication of the umbilical vein with the left branch of the portal vein during fetal life, it has to be kept in mind that a thrombosis of the umbilical vein is to be considered an actual or potential cause of PVT, until proven otherwise.44,45
vena cava at the level of the 12th dorsal vertebra. The left one drains into the left renal vein. They may contain some valves, which are always present in spermatic or testicular veins. Ovarian veins thrombosis is rare but recently it has been diagnosed more frequently due to the use of multidetection computed tomography (MDCT), which allows the full visualization of the veins in almost all women. Ovarian vein thrombosis has been reported to occur primarily in early puerperal period, in pregnancy, but also in chronic pelvic inflammatory diseases, tumors or as a complication of surgery.54–56 There are no specific clinical signs or symptoms and it is widely assumed that in the past, many cases went undetected or misdiagnosed as abdominal colicky pain. Lower quadrant pain and tenderness, nausea, fever, and malaise are common. The pain is sometimes radiated to the back. Diagnosis requires demonstration of the presence of thrombosis occlusion of one of the ovarian veins. This is best achieved by CT or MRI or, as stated above, by MDCT.55 Sonography may also be useful, but it is usually incapable of visualizing the entire course of the vein. Management is conservative with bed rest and anticoagulant therapy. UH or LMWH for 15 to 20 days may be sufficient if in the meantime the cause has been eliminated. Associated use of antibiotics is indicated in cases of postpartum or postsurgery.
Isolated Iliac Vein Thrombosis Testicular Vein Thrombosis Testicular or spermatic veins arise from the pampiniform plexus of both sides of the scrota. On the right side, the vein drains into the vena cava; whereas on the left side, it drains into the left renal vein. This discrepant course has important pathophysiologic implications. For example, tumors of the left kidney may cause stasis and thrombosis of left spermatic veins. The same is not true for the right side. Other important causes are trauma, strenuous exercise, varicocele, Henoch–Schönlein purpura.39,40,47–52 The condition is rare and involves mainly the left side, probably because of more frequent stasis and varicocele present in this side because of hemodynamic reasons (longer course, rectangle merger with renal vein). Presentation is usually with testicular pain, scrotal swelling, and vague abdominal discomfort. The pain may radiate to the back. Pulmonary embolism has been reported.52 Differential diagnosis involves the following: incarcerated hernia, epididymitis, and spermatic cord tumors. Sonography or venography is diagnostic. When thrombosis involves the left side, diagnostic sonography procedure has to rule out left kidney pathology.53 Management is usually conservative with bed rest and anticoagulant therapy. Surgery is sometimes needed. Laparoscopy easily allows the identification and ligation of the thrombosed spermatic vein.
Ovarian Vein Thrombosis Similarly to what seen for spermatic or testicular veins there are two ovarian veins. The right one drains into the inferior Seminars in Thrombosis & Hemostasis
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The common iliac vein is formed by the merge of the internal and external iliac vein, on each side of the body, at the level of the sacroiliac joint. The right common iliac vein, shorter than the left, is nearly vertical whereas the left is more oblique. The two common iliac veins merge at acute angle to form the inferior vein cava at the level of the body of the fifth lumbar vertebra. Isolated thrombosis of the iliac vein is rare as in most cases it is associated with femoral vein thrombosis. It has been described in pregnancy, because of compression from the right iliac artery, during oral contraception, after lithotripsy, after renal transplant, after strenuous exercise (cyclist, marathon runners), and in other rare conditions. A special mention is due to the left leg iliac vein thrombosis seen in pregnancy. The majority of thrombosis in pregnancy involves the left leg. This has been claimed to be related to the compression exercised by the enlarged uterus but also to the right iliac artery encroaching on the left iliac vein against the fifth lumbar vertebra.53,57–59 The condition is known as May– Thurner syndrome or Cockett–Thomas syndrome and it has been maintained to be a potential cause of left leg vein thrombosis even in nonpregnant women and in men.53,57–63 On clinical grounds, abdominal, lumbar, or flank pain accompanied by swelling of the leg are the most important findings. Compression sonography of the leg vein is negative and this may be surprising in view of the swollen leg and create diagnostic difficulties. Venous pletsigmography may be useful in suspecting intraluminal vein obstruction, but it is seldom used. Abdominal sonography may be suggestive, but MRI is the best diagnostic tool available for a definitive diagnosis.59
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Venous Thrombosis in Rare or Unusual Sites
Table 2 Potential complications of venous thrombosis in rare or unusual sites Retinal vein thrombosis
Suddenly reduced vision, blindness, extension to cavernous plexus
Jugular vein thrombosis
Generalized sepsis, endocarditis
Right heart thrombosis
Pulmonary embolism, intracardiac thrombosis
Coronary sinus thrombosis
Aggravation of pre-existing heart condition, severe arrhythmias, heart failure, pulmonary embolism
Isolated iliac vein
Pulmonary embolism
Renal vein thrombosis
Pulmonary embolism, nephrotic syndrome
Ovarian or testicular veins
Pulmonary embolism, renal vein thrombosis on left side
Dorsal veins of penis
Priapism
Thromboses of Dorsal Vein of Penis The drainage of blood from the penis occurs mainly through superficial and deep dorsal veins. The superficial vein is located in the subcutaneous tissue and is clearly visible, particularly when the penis is erected; it drains into the external pudendal vein, a tributary of the great saphenous vein. The deep vein lies underneath the superficial fascia, within the fibrous envelope (tunica albuginea). It divides at the end into two branches, which enter the prostatic plexus often communicating, below the symphysis pubis, with the internal pudendal vein. The deep vein drains most of the corpora cavernosa, whereas the superficial vein drains the skin and the glans. Thrombosis in the superficial or deep vein of the penis is caused by trauma, excessive sexual activity, infections, pelvic trauma, and surgical procedures (subinguinal varicocelectomy, hernia repairs, etc.).64–67 If only the superficial vein is involved, the condition is also known as Mondor disease of penis.65,67 The clinical picture is characterized by local swelling, variable priapism, pain, and tenderness on palpation. The picture is more severe if both systems, superficial and deep, are involved. In this case, priapism is usually persistent. Diagnosis is easy if one takes into account the setting in which signs and symptoms appear. Plain or color sonography of the penis is needed to establish the exact site of the thrombotic occlusion. Angiography is also sometimes needed.66 Anti-inflammatory drugs, local measures, and abstinence from sexual activity are usually sufficient. The use of anticoagulant (LMWH) may be needed. If conservative and anticoagulant therapies fail, then surgery is occasionally needed.
Funding The study was supported in part by the Associazione Emofilica ed altre Coagulopatie delle Tre Venezie.
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Conclusions Taken together these peculiar and rare venous thromboses may constitute only approximately 10% of all venous thrombosis. However, they are equally important as they may cause pulmonary embolism (testicular, ovarian, renal veins, and right heart thrombosis). They may also indicate hidden or unknown neoplasia (renal vein thrombosis). Vein thrombosis has also a peculiar relation with nephrotic syndrome. In fact, it may be both a cause and/or the complication of a primary form of nephrotic syndrome. These peculiar and rare venous thromboses may also be a cause and/or the result of sepsis (jugular vein thrombosis). Retinal vein thrombosis may extend to a thrombosis of the cavernous sinus with the consequent neurological involvement. Finally, thrombosis of the dorsal vein of penis may be the cause of priapism. The variable clinical picture seen in these peculiar and rare venous thromboses involving many vascular districts underlines the importance of a careful clinical evaluation, once the suspicion has arisen (►Table 2).
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