Zdrav Vestn Supl | Puerperal ovarian vein thrombosis accompanied by hydronephrosis I-39 1 Division of Urology, Department of Surgery, General Hospital Murska Sobota, Ulica dr. Vrbnjaka 6, 9001 Murska Sobota 2 Department of Radiology, General Hospital Murska Sobota, Ulica dr. Vrbnjaka 6, 9001 Murska Sobota Korespondenca/ Correspondence: doc. dr. Tine Hajdinjak, Urološka ambulanta, SB Murska Sobota, Rakičan, Ulica dr. Vrbnjaka 6, 9001 Murska Sobota, m: tine.hajdinjak@gmail. com Ključne besede: poporodno obdobje; venska tromboza; bolečina v trebuhu; faktorji strjevanja krvi; obstrukcija ureterja Key words: puerperal period; venous thrombosis; abdominal pain; blood coagulation factors; ureteral obstruction KLINIČNI PRIMER/CASE REPORT Puerperal ovarian vein thrombosis accompanied by hydronephrosis Poporodna tromboza ovarialne vene in hidronefroza Boštjan Šutar,1 Marija Šantl-Letonja,2 Tine Hajdinjak1 Izvleček Tri tedne po porodu je bila 22-letna ženska spre- jeta na urološki oddelek zaradi vročine in bole- čin ledveno ter v trebuhu. Z intravensko urogra- fijo je bila ugotovljena hidronefroza, ki smo jo drenirali z nastavitvijo notranjega drena (DJ), ter uvedeno antibiotično zdravljenje. Po treh dneh je prišlo do otekanja nog, kar je spodbudilo na- daljne preiskave. Računalniška tomografija (CT) je pokazala trombozo ovarijske vene kot vzrok za hidronefrozo in še trombozo votle vene v vi- šini vtoka ledvičnih ven, trombozo iliakalnih in proksimalnih globokih ven obeh spodnjih udov. Uvedeno antikoagulantno zdravljenje z nizko- molekularnim heparinom in kasneje trajno anti- koagulantno zdravljenje z varfarinom so omogo- čili pretežno rekanalizacijo s trombi utesnjenih ven. Bolnica je heterozigotna nosilka mutacij za fak- tor V Leiden in protrombin. Čeprav literatura v zadnjem času navaja zanemarljivo povečano tveganje za globoko vensko trombozo pri dvoj- nih heterozigotih, je bolnica imela več očitnih dejavnikov tveganja (spontani splavi, mirovanje, kajenje, debelost, krvna skupina ne-O ...). Vse to bi moralo spodbuditi podrobnejšo oceno tvega- nja za trombozo in razmislek o tromboprofilaksi. Na tromboflebitis ovarialne vene je potrebno pomisliti pri bolnicah v poporodnem obdobju z nepojasnjeno vročino in bolečino v trebuhu. Abstract Three weeks after delivery, a 22-year old woman presented to urology with fever, abdominal and right-sided flank pain. Hydronephrosis was di- agnosed with iv-pyelography and treated with JJ-stent drainage and antibiotics for suspected pyelonephritis. On the third day oedema of the right leg appeared, which prompted further in- vestigations. CT identified ovarian vein throm- bosis as a cause of hydronephrosis, and further thrombosis of the inferior vena cava, iliacal and deep veins of both upper legs. Anticoagulant treatment with low-molecular-weight-heparin and later warfarin resulted in partial recanalisa- tion of thrombi. The patient is double heterozygous for factor V Leiden and prothrombin mutation. Although recent literature negates this as a significant risk factor, presence of other, more obvious and eas- ily recognizable risk factors (previous spontane- ous abortions, smoking, bed rest, obesity, non-O blood group...) should have prompted detailed risk evaluation and consideration of thrombo- prophylaxis. Ovarian vein thrombophlebitis should be sus- pected in any postpartum patient with unex- plained fever and abdominal pain. I-40 Zdrav Vestn Supl | julij 2014 | Letnik 83 KLInIčnI PRIMER/CASE REPORT Citirajte kot/Cite as: Zdrav Vestn 2014; 83 supl: I-39–44 Prispelo: 15. jul. 2013, Sprejeto: 7. nov. 2013 Introduction Ovarian vein thrombosis can present as asymptomatic or severely symptomatic (acute abdomen) and can have–with deve- lopment of sepsis or progression of venous thrombus to pulmonary embolism–severe consequences.1-3 It is most often identified in the postpartum period, but can appear also with other precipitating factors such as thrombophilia, surgical procedures, mali- gnancies and inflammatory conditions.4 Key factors in the pathogenesis of throm- bosis (Virchow triad) are blood flow stasis, altered coagulation and intimal injury. After childbirth, blood flow in the ovarian veins rapidly decreases, leading to venous collapse and stasis. Hypercoagulability is present for 6 weeks postpartum. Furthermore, intrau- terine bacterial infection post partum may cause local sepsis, producing inflammation and leukocyte infiltration that result in ve- nous intimal injury.5 Thrombosis of the ovarian vein post-par- tum occurs most often on the right side.2 However, recent report of predominantly non-pregnancy-related causes found equal frequency of left and right sided cases.6 The most common presenting symptoms of ovarian vein thrombophlebitis include fever and lower abdominal discomfort.7 Frequency of ovarian vein thrombosis rela- ted to pregnancy is estimated to be around 0.04 %8 after vaginal birth or 0.1 % after ca- esarean section.2 A lot of cases go undetec- ted. The diagnostic method of choice is CT or MR imaging, ultrasound being appropri- ate for follow up of thrombosis which also extends in other veins.9,10 Most patients with post-partum ovarian vein thrombop- hlebitis can be treated with antibiotics and anticoagulation therapy. Case report A 22-year-old woman was admitted to urology with right-lower-quadrant abdo- minal pain, right flank pain and high-grade fever (39 degrees C) for suspected ureteroli- thiasis with pyelonephritis three weeks after her first, full term vaginal delivery of a he- althy infant. She was a smoker and moderately obe- se. Her blood group was B positive. There had been no complications during birth, but she was advised bed rest during the second half of pregnancy. Regarding family history, her father had cerebrovascular insult at the age of 44. The patient’s medical history was unremarkable, except for appendectomy five years earlier and two previous spontaneous abortions. Results of cardiorespiratory exa- mination were unremarkable. On pelvic examination, the cervix and uterus were non-tender. There was no calf or thigh swel- ling or tenderness. Laboratory evaluation showed a white blood cell count of 13.000/ uL, CRP of 171 mg/L. On urine sediment microscopy, 50 red blood cells, 25 white blood cells and few bacteria were found per high power field. An abdominal ultrasound examination revealed a right-sided hydro- nephrosis. Intravenous urography showed obstruction of the right ureter at L3/L4 level (Figure 1). Our initial diagnosis was a right- -sided ureterolithiasis with pyelonephritis. We drained the right kidney with a JJ stent. Insertion of the stent was unexpectedly smooth and without resistance. Blood and urine cultures were obtained and antibiotic treatment was started. On the third day we noticed oedema of the right leg. Colour-Doppler ultrasound examination revealed proximal femoral thrombosis on the right side. Anticoagu- lant therapy with low- molecular-weight heparin in a therapeutic dose (enoxapari- ne – Clexane 0.6/12h) was started. Blood and urine cultures remained sterile. Despite antibiotic treatment, the patient still had a high-grade fever, which followed a spiking pattern for more than one week. Therefore, a contrast-enhanced abdominal computed to- mography was performed. The examination revealed right ovarian vein thrombosis and obstruction of the right ureter at the level L3/ L4, where the right ovarian vein crosses the right ureter. The thrombus extended into the inferior vena cava up to the level of renal ve- ins, and down into the common iliac, exter- nal and internal iliac and femoral veins on both sides. All these veins were completely obstructed (Figure 2). The patient was ma- intained on enoxaparin 0.6 ml/12h and an- Zdrav Vestn Supl | Puerperal ovarian vein thrombosis accompanied by hydronephrosis I-41 KLInIčnI PRIMER/CASE REPORT Figure 1: Intravenous urography showing an obstruction at L3/L4 level on the right side. tibiotics (cefuroxime initially (500 mg/12h); after hydronephrosis was established, gen- tamicin was added and after the diagnosis of thrombophlebitis of the ovarian vein was established, metronidazole 400mg/8h was added). Fever subsided in 10 days. Labora- tory parameters: WBC normalized, CRP first increased to 202 mg/L on day 12 and then started to decrease (96 mg/L on day 17). The patient was referred to the Clinical Department of Vascular Diseases for further investigation. Genetic analysis documented a prothrombin and coagulation factor V Le- iden heterozygous gene mutations. A life- -long anticoagulant therapy was advised and oral anticoagulation with warfarin instituted before discharge. Two months later we removed the JJ stent. One week after JJ stent removal, all ve- ins were still partially obstructed, but there was no hydronephrosis. After two years, veins are patent, but re- sts of thrombi are still seen in the iliac and femoral veins. The patient works as waitress, has no pain or swelling and has (against ad- vice) stopped using elastic stockings. Howe- ver, she is on oral anticoagulant treatment with INR strictly controlled between 2 and 3. Discussion The differential diagnosis of ovarian vein thrombophlebitis includes endometritis, appendicitis, pyelonephritis, ureterolithi- asis, adnexal torsion and tubo-ovarian ab- scess. A suspicion of the condition should arise when fever, which usually follows a spiking pattern, fails to respond to standard broad-spectrum antibiotic therapy. Blood cultures provide identification of a micro- organism in less than 35 % of cases.11,12 In the event of extension of thrombus to other veins, respective symptoms appear. The di- agnosis is best confirmed by abdominal CT with contrast, but can be detected by MRI or, in the case of thrombus extending to other veins, ultrasound studies. Thrombosis may extend into the vena cava5 or other veins, for example the renal vein on the left.13,14 The incidence of pulmonary embolism has been reported to be from 13 % to 33 %. Of these cases, 4 % are fatal.5,11 The described case is among more serious presentations of ovari- an vein thrombophlebitis. Flank pain from hydronephrosis was a result of obstruction caused by the thrombosed ovarian vein at the level where it crosses the ureter. Such presentations are very rare and always sur- prising. We found three reports of hydro- nephrosis as a result of ovarian vein throm- bosis in the recent literature.15-17 Regarding treatment, in mild cases, some observational studies questioned the effica- cy of anticoagulation therapy, like Brown and associates who prospectively randomi- zed 14 patients to receive either antimicro- bial therapy or antimicrobial therapy plus heparin. The duration of fever and hospital stay was similar in both groups. Further- more, neither thromboembolic events nor reinfection were reported.18 In cases with extensive thrombosis, anticoagulation is not questionable, however, the optimal duration I-42 Zdrav Vestn Supl | julij 2014 | Letnik 83 KLInIčnI PRIMER/CASE REPORT Figure 2: Cross sectional computed tomographic scan of the abdomen shows a filling defect in the right ovarian vein and in the inferior vena cava. Behind the ovarian vein is the right ureter, which contains a JJ stent. of anticoagulation is unknown, but with the thrombus in the vena cava it should last for at least 6 months.8 Historically, treatment was surgical. In 1951, Collins proposed a pathogenic model for suppurative pelvic thrombophlebitis and advocated ligation of the inferior vena cava and ovarian veins. He published his experi- ence with 202 women who underwent sur- gical intervention and reported a 90 % su- rvival rate.12 Such treatment was frequently associated with significant complications (postoperative oedema, recurrent throm- bophlebitis, leg ulcers, stasis dermatitis and venous claudication). The introduction of antibiotics, heparin and oral anticoagulation therapy into the treatment regimen led to a dramatic shift from surgical to pharmacolo- gical management. This approach has pro- duced post-treatment outcomes and long- -term results equivalent or better compared to those of surgery. Surgical treatment, whi- ch consists of insertion of a vena cava filter, open ligation of vein or thrombectomy, is generally reserved for patients in whom an- ticoagulation is contraindicated, for those who have recurrent pulmonary emboli de- spite medical management, complications related to medical management, and for pa- tients with a free-floating thrombus.5,19,20 With such serious cases, the need for se- arch and identification of risk factors and prevention of venous thromboembolism is obvious. Looking retrospectively, it is now easy to see a number of risk factors that our patient presented with. Three are universal- ly recognized and could be easily identified: immobilization during pregnancy, smoking and obesity.21 The question of thrombophilia risk fac- tors is less clear. First, it is not clear whether one should screen for them or not, and se- cond, the role of “double heterozygosity” was questioned. It seems guidelines do not advise screening for thrombophilia in pre- gnant women without previous venous thromboembolism.22,23 However, our pa- tient had family history of embolic event (brain stroke, father at age 44) and she had two previous miscarriages (three should prompt for antiphospholipid antibody scre- ening)22 – should this not, in combination with three established risk factors, prompt screening for thrombophilia? If it would– double heterozygosity (factor V Leiden and prothrombin) – would be found. Is this im- portant? Although each heterozygosity itself increases the risk, recent analyses, show do- uble heterozigosity by itself not being a very strong risk factor.24,25 However, our patient had an additional, only recently recognized as relatively stronger compared to factor V Leiden, but very easily identified genetic risk factor – her blood group was B (non-O).26 It was recently found that non-O blood group presents further risk in addition to factor V Leiden and prothrombin.27 According to present knowledge and gu- idelines, due to three classical risk factors (obesity, immobilization and smoking) this patient would be considered for prophylaxis with low-molecular-weight heparin.21 However, most probably she would only re- ceive 7 days of prophylaxis and this would be probably not enough. If her genetic risk fac- tors were known, she would be considered for longer time and higher dose prophylaxis. But–it is estimated that general screening for thrombophilia is not advised.22,23 Per- haps women with presence of two or more established risk factors in combination with non-O blood group (blood group is known in all pregnant women) represent a group at higher risk, where detailed evaluation of risk and screening for thrombophilia would be justified and would improve chances to prevent such serious cases, as described in this report. Zdrav Vestn Supl | Puerperal ovarian vein thrombosis accompanied by hydronephrosis I-43 KLInIčnI PRIMER/CASE REPORT Early diagnosis and treatment of po- stpartum ovarian vein thrombosis is impor- tant to prevent progression of thrombosis with potentially disastrous consequences, but requires a high degree of suspicion, as many other, more straightforward reasons for abdominal pain and fever seem more obvious. Strict evaluation of every woman during pregnancy and at the time of deli- very for risk of thrombosis with application of thromboprophylaxis, as required by gu- idelines, may significantly reduce risk for the occurrence of serious cases and prevent most of them. Perhaps new, only recently re- cognized genetic risk factor – blood group status, which is easily available, should also be taken into account and used to help de- tecting women at risk, who would benefit from thrombophilia screening. References 1. Graupera B, Pascual MA, Garcia P, Di Paola R, Ubeda B, Tresserra F. Atypical ultrasonographic presentation of ovarian vein thrombosis. Eur J Gynaecol Oncol 2011; 32(4): 439–40. 2. De Stefano V, Martinelli I. Abdominal thrombo- ses of splanchnic, renal and ovarian veins. Veno- us Thromboembolism Adv Controv 2012; 25(3): 253–64. 3. Heavrin BS, Wrenn K. Ovarian vein thrombosis: a rare cause of abdominal pain outside the peripar- tum period. J Emerg Med 2008; 34(1): 67–9. 4. 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