Idiopathic bilateral ovarian vein thrombosis

Abstract

Ovarian vein thrombosis (OVT) is a condition most commonly associated with malignancy, hypercoagulable disorders, pelvic surgery, trauma, inflammatory bowel disease and the postpartum period. Idiopathic bilateral OVT is extremely rare. We report the case of a 30-year-old African-American woman who presented with bilateral lower pelvic pain and nausea. She had no recent pelvic infections nor a personal or family history of malignancy or thrombophilia. Workup results for a hypercoagulable state was negative. A CT scan of the abdomen and pelvis revealed bilateral OVT. Treatment included novel oral anticoagulants or warfarin, with comparison studies showing a similar risk–benefit ratio. Repeat imaging is recommended after 40–60 days to determine the necessity for further anticoagulation. Emphasis is placed on starting anticoagulation early in order to reduce the risk of extension of the thrombus into the inferior vena cava, conversion to pulmonary embolism or increase in the risk of infection.

Background

Ovarian vein thrombosis (OVT) is a rare but serious condition that is reported primarily in case studies and retrospective studies.¹ The occurrence of OVT with unidentified aetiology is extremely rare.² OVT is most commonly associated with malignancy or the postpartum state but can occur as a sequela to sexually transmitted diseases (STDs), urinary tract infections (UTIs), pelvic surgery, trauma or inflammatory bowel disease.^{1 3} Many studies have shown that OVT most commonly occurs in the right ovarian vein (46%–100%). The incidence of OVT in the left vein is 0%–37%. Bilateral OVT is very rare and accounts for only 11%–14% of all cases.^{1 4} In this study, we present the case of a 30-year-old African-American woman, G3P3A0 (Gravida, Para, Abortus), who experienced bilateral lower pelvic pain and nausea.

Case presentation

A 30-year-old African-American woman presented to the emergency department with bilateral lower pelvic pain and nausea for 2 days. She denied having fever or bowel or urinary symptoms.

The patient had a history of chlamydial infection in 2011 and a stable dermoid cyst sized 1.7×1.1×1.8 cm since 2014. She also had a history of three caesarean sections; last one was performed 7 years prior to this presentation.

She denied having any recent pelvic infection or any personal or family history of malignancy or thrombophilia. The family history was positive only for systematic lupus erythematous (SLE) in her father.

On physical examination, the patient was haemodynamically stable. Tenderness in the bilateral iliac fossae was noted on abdominal examination. Left adnexal fullness was also noted on gynaecological examination.

Laboratory investigations including hepatic, renal and pancreatic functions were normal. Urinalysis, β-human chorionic gonadotropin and ECG were unremarkable. Tumour markers including lactate dehydrogenase, cancer antigen (CA)-12, alfa-fetoprotein and CA-19-9 were negative. Chlamydia, gonorrhoea and vaginal swab cultures were also negative. Thrombophilia workup showed no evidence of a coagulation disorder. Ultrasound examination of the pelvis demonstrated an old left dermoid cyst. CT of the abdomen and pelvis demonstrated bilateral (b/L) OVT with no concerning masses indicating malignancy. CT examination of chest showed b/L mediastinal lymphadenopathy. Biopsy of the lymph nodes was negative for malignancy or inflammation.

Treatment

While awaiting results of thrombophilia evaluation, the patient was initially started on intravenous heparin, then bridged with enoxaparin to warfarin, with a target of international normalised ratio of 2–3, which represent therapeutic levels.

Outcome and follow-up

The patient was advised to continue anticoagulation therapy for an additional 3 months. She had improvement in her pelvic pain during this time period. We have recommended a follow-up CT scan of the pelvis after 3 months to evaluate for possible recanalisation and resolution of her thrombosis.

Discussion

OVT is an uncommon scenario. The greatest incidence of OVT is seen in postpartum women, with a rate of 0.05%–0.18% after vaginal deliveries and 1%–2% after caesarean sections.^{1 2} Other common conditions that increase the risk of OVT include malignancies, STD, UTI, pelvic surgery, trauma and inflammatory bowel disease.^{1 3} The most commonly associated cancers are ovarian cancer, followed by pancreatic and hepatic cancer.⁵ Hypercoagulable conditions such as SLE, antiphospholipid antibody syndrome, Factor V Leiden, paroxysmal nocturnal haemoglobinuria, hyperhomocysteinaemia, and protein C and S deficiencies are all risk factors for OVT.⁶

Idiopathic OVT is extremely rare. The pathophysiological state contributing to formation of OVT, in the above conditions, involve satisfying the criteria of Virchow’s triad: stasis (eg, enlarged uterus causing compression), hypercoagulability by increasing clotting factors and endothelial damage secondary to inflammation.¹

OVT most commonly occurs in the right vein rather than the left because the right vein unites directly with the inferior vena cava and has a longer length.^{1 4}

Patients with OVT usually present with abdominal pain, rarely pelvic pain, with or without flank pain and fever.^{1 3} Non-specific symptoms such as nausea or fever can occur in up to 80% of patients.^{2 3} In pregnant patients, fever is the most common symptom.^{1 4} Ninety per cent of postpartum patients present with symptoms within the first 10 days and up to 5 weeks after delivery.⁶

Given this clinical presentation, differential diagnosis should include pyelonephritis, renal colic, endometritis, ovarian torsion, pelvic inflammatory disease, and acute appendicitis.⁷

Ultrasound is usually a first-line imaging modality because it is inexpensive and does not require contrast enhancement. However, it has a sensitivity of only 56% for diagnosis of OVT.⁴ Body habitus, bowel gas and other structures usually limit the sensitivity of ultrasound.⁸ CT scans with contrast enhancement have the highest sensitivity (100%) and specificity (99%).^{1 4} CT scan usually demonstrates an enlarged ovarian vein with defined vessel walls and thrombus signified by a central hypodensity (figures 1 and 2). MRI can also be used, which has 92% sensitivity and 100% specificity, but is more expensive than CT.

Figure 1.

CT scan showing thrombosis of right ovarian vein.

Figure 2.

CT scan showing thrombosis of left ovarian vein.

Intravenous administration of antibiotics and anticoagulants are the mainstay of treatment for OVT.² Patients are often started on anticoagulants such as heparin and warfarin, which are often continued for 3–6 months.^{5 8 9} There is no evidence-based protocol for the duration of anticoagulation.² However, some reports suggest that pregnancy-related OVT will generally resolve with a short-term treatment of 3 months. Thrombus extension or positive thrombophilia evaluation generally requires treatment for at least 6 months or lifelong.⁸

Improvement of pain while on heparin can occur secondary to its anti-inflammatory properties, including binding to growth factors and tissue-destructive enzymes, which occurs apart from its role in anticoagulation.¹⁰ The actual time to resolution of pain from OVT can vary from 10 days to 4 months.¹

While earlier studies have mentioned no role of novel oral anticoagulants,⁴ there have been promising studies that have shown a similar risk–benefit ratio when comparing apixaban and rivaroxaban to warfarin and enoxaparin.¹¹ The outcomes of interest in these studies include thrombus resolution, recurrent thromboembolic events and 1 year cumulative incidence of clinically significant bleeding events.

The failure to identify OVT can lead to catastrophic consequences. Complications include pulmonary embolism (PE), which occurs in 25% of patients with postpartum OVT, and thrombus extension into the IVC and renal veins.^{1 3} Other serious complications include septic thrombophlebitis and even infectious emboli.⁹ Deaths have occurred mainly due to cancer complications (not the OVT itself) or PE.^{1 2 5}

Various studies have demonstrated the course of OVT. Factors involved include aetiology, side of occurrence of OVT, clinical presentation, diagnostic utility, treatment and complications. We searched PubMed and identified only 11 other case reports with idiopathic bilateral OVT. A comparison of other case reports versus our case report can be seen in table 1.

Table 1.

Study	Aetiology	Side of OVT	Signs and symptoms	Diagnostic utility	Treatment	Complications
Labropoulos et al1	Post partum/trauma/cancer /IBD/thrombophilia/idiopathic	Left/right/bilateral	Abdominal pain/flank pain/both abdominal and flank pain	CT scan/ultrasound	Anticoagulation, type not specified	DVT/superficial thrombophlebitis/pelvic congestion syndrome
Khishfe et al2	Idiopathic	Unilateral	Colicky groin pain with nausea and point tenderness	Non-contrast-enhanced CT scan	Oral warfarin	None
Stafford3	Idiopathic	Right	Central abdominal and right iliac fossa pain with nausea.	CT scan	Anticoagulation, type not specified
Kodali et al4	Idiopathic	Right	Acute right lower quadrant pain	CT Scan	LMWH and then warfarin for 6 months	None None
Lenz et al5	Post partum/trauma/cancer/Iinflammatory bowel disease/thrombophilia/idiopathic	Left/right/bilateral	Symptoms based on pathology	CT scan/MRI/ultrasound/surgery laparoscopy	Anticoagulation with warfarin/LMWH/factor X inhibitors	Venous thromboembolism with DVT/PE/IVC thrombus.
Arkadopoulos et al6	Idiopathic	Right	Right lower quadrant abdominal pain and fever	CT scan of the abdomen	LMWH/acenocoumarol	None
Garcia et al7	Idiopathic	Bilateral	Left flank pain	CT scan of the abdomen and pelvis	Rivaroxaban	None
Rottenstreich et al8	Pregnancy/non-pregnancy related/active infection/postsurgical/trauma/cancer/idiopathic	Left/right/bilateral	Abdominal pain/nausea/vomiting	CT scan/Doppler ultrasound/MRI	Anticoagulation/antibiotics	Extension of the thrombus into IVC, renal vein, and iliac vein/nonfatal PE/splenic infarct/renal artery thrombosis
Harris et al9	Idiopathic	Right	Right flank pain	CT scan of the abdomen and pelvis	Anticoagulant/warfarin	None
Farid10	Idiopathic	Right	Lower abdominal pain	CT scan of the abdomen	Rivaroxaban/warfarin	None
Covut et al11	Malignancy/peripartum/recent surgery/OCP/chronic inflammatory disease/ thrombophilia	Right/left/bilateral	Fever/pelvic or abdominal pain	CT scan of the abdomen	Direct oral anticoagulants/warfarin/enoxaparin/	Bleeding
Our report	Idiopathic	Bilateral	Bilateral lower pelvic pain and nausea	CT scan of the abdomen and pelvis	Enoxaparin/warfarin	None

DVT, deep vein thrombosis; OCP, oral contraceptive; OVT, ovarian vein thrombosis; PE, pulmonary embolism; LMWH, low-molecular-weight heparin; IVC, inferior vena cava.

In conclusion, bilateral idiopathic OVT is a very rare disorder in which extensive hypercoagulability testing is usually negative and is usually not associated with the postpartum period, malignancy and surgical causes. The presentation can be variable, with features including abdominal or flank pain, nausea or vomiting. CT scan revealed bilateral OVT. Treatment includes novel oral anticoagulation or warfarin. Repeat imaging is recommended to assess for the recanalisation of veins and prevent complications including PE.

Learning points.

• Bilateral idiopathic ovarian vein thrombosis is a rare disorder that is not associated with post partum, malignancy or surgical causes.

• After an extensive negative workup and ruling out other possible causes, the diagnosis of idiopathic ovarian vein thrombosis should be considered, as seen in this case presentation.

• Emphasis should be placed on starting anticoagulation promptly in order to reduce the risk of extension of the thrombus into the inferior vena cava, conversion to pulmonary embolism, and along with the use of antibiotics in the postpartum period.

• Increasing data suggest that novel oral anticoagulants have a similar risk–benefit ratio as that of warfarin.