Uterine leiomyomas, also known as uterine fibroids or myomas, are the most common tumors in the female reproductive system.¹ They affect at least 30% of women aged 25 to 45 years.² The total prevalence is difficult to estimate, because the proportion of asymptomatic uterine leiomyomas is not known.² Uterine leiomyomas are the most frequent indication for hysterectomy, accounting for a greater proportion of hysterectomies in black women (50%) than in white women (30%).² A myriad of symptoms are associated with these tumors, most often abnormal uterine bleeding, pelvic pain or pressure, abdominal distension, genitourinary dysfunction, or infertility. Rarely, lower-extremity edema, intestinal obstruction, or deep-vein thrombosis (DVT) can also occur. Only 8 cases of concurrent DVT and leiomyomata have been reported in the English medical literature. The following is the ninth case.

Case Presentation
A 27-year-old white woman presented to the emergency department with a complaint of left lower-extremity swelling and sudden pain and numbness in her left leg. About 10 days earlier she had discomfort in her left leg while at work. She denied any history of trauma, recent surgery, recent travel, or prolonged periods of inactivity. The patient also denied having fever, chills, nausea, shortness of breath, or chest pain. She had her menses at the time of presentation; they were regular and completely normal, with no history of menorrhagia or menometrorrhagia. She reported chronic lower back pain and denied melena, hematochezia, bright red blood per rectum, or hematuria. The patient had smoked for 1 year and quit 5 years ago. She denied use of alcohol, illicit drugs, or oral contraceptives. She had no family history of bleeding or clotting disorders. Her only medication was albuterol (AccuNeb, Proventil), which she rarely took.

Physical examination showed she was moderately overweight, with a body mass index of 29 kg/m². Her vital signs were stable and she was afebrile. Her abdomen was soft, nontender, and nondistended, with no organomegaly, but the left lower quadrant was firm on palpation, a chronic finding according to the patient. She had massive edema of the left lower extremity but no discoloration of either lower extremity. Marked tenderness over the left calf and medial thigh was evident. Distal pulses were good bilaterally; femoral pulses were difficult to palpate on the left lower extremity because of the swelling.

A test for serum beta-human chorionic gonadotropin was negative. A left lower-extremity venous Doppler showed DVT involving the entire deep-venous system, beginning in the common femoral vein and extending distally. Her coagulation profile was normal, but she was profoundly anemic, with hemoglobin, 5.5 g/dL; hematocrit, 17.1%; and mean corpuscular volume, 53.5 fL, suggestive of iron-deficiency anemia. She received transfusion with 5 units of packed red blood cells and was started on unfractionated heparin per DVT protocol. The next day, warfarin, 5 mg, was added.

Additional evaluation was done to determine the cause of her abdominal mass, anemia, and thrombosis. Test results for protein C, antithrombin III, factor V, homocysteine, lupus anticoagulants, and anticar­diolipin levels were within normal limits, as was the prothrombin gene study. The slightly diminished protein S level was attributed to consumption in the setting of an acute, very large DVT, which was to be rechecked after warfarin therapy was discontinued.

A pelvic sonogram showed a large solid intrauterine mass. Pelvic magnetic resonance imaging (MRI) revealed a 10 x 17 x 16-cm posterior uterine fundal mass consistent with a large intramural fibroid (Figure 1), extending out of the pelvis into the lower abdomen and compressing the distal inferior vena cava and iliac bifurcation. Extensive venous thrombosis was seen within the iliac vein, extending into the left common femoral vein (Figure 2). Human chorionic gonadotropin tumor marker and cancer antigen 125 levels were within normal limits.

Iron studies showed: iron, 16 µg/dL; total iron binding capacity, 264 µg/dL; ferritin, 8.7 µg/mL; transferrin, 222 µg/dL; transferrin saturation, 6.1%. The hematologist suggested that the anemia was caused by iron deficiency secondary to the uterine fibroid. The patient was started on oral ferrous sulfate, 324 mg 3 times daily, and was discharged after 1 week, with instructions to follow up with a gynecologic surgeon.

After discharge, the patient followed up with a surgical gynecologist and requested definitive treatment (ie, surgery) for her uterine leiomyoma. She was prescribed leuprolide acetate (Lupron Depot), 3.75 mg once monthly for 3 menstrual cycles, to shrink the fibroid.

A left lower-extremity venous Doppler done 1 month before surgery showed frank DVT, extending from the left iliac vein down to the distal left femoral vein and partial recanalization of the left popliteal femoral vein. The inferior vena cava was patent. The patient was started on enoxaparin sodium injection (Lovenox), 1 mg/kg twice daily, 6 days before surgery, overlapping with the warfarin, which was discontinued 72 hours before surgery. Two days before surgery, a Trap-Ease filter was placed at the L2 level. A simple hysterectomy was performed. The patient was restarted on heparin and was transitioned back to the warfarin.

At 2 years postoperatively, the patient is doing well. The recheck of the hypercoagulable disorder workup was unremarkable. The hematologist decided to continue the warfarin therapy until there was no evidence of a thrombus.

Discussion
Thromboembolism is a known complication of gynecologic surgery, in particular hysterectomy. DVT complicating leiomyoma uteri is rare. Most cases reported a history of menorrhagia or menometrorrhagia. Similar to most patients with uterine leiomyomas, this patient denied any problems with her menses. She had not seen a physician in years. The differential diagnosis of anemia, thrombosis, and abdominal mass was complicated because she had not had a regular gynecologic exam in at least 5 years. Regular medical care might have identified the leiomyoma earlier. Early diagnosis and appropriate medical therapy could have decreased the size of the fibroid. Common medical therapy involves progestins or gonadotropin-releasing hormone (GnRH) analogs.

A Medline search using the terms “uterine leiomyoma, fibroid complications, and DVT” resulted in a total of 12 cases of uterine leiomyoma associated with DVT, 3 of which were foreign-language publications. There have been only 6 English-language articles (this is the seventh) and 9 cases, including this one, describing this complication (Table), with age ranging from 27 to 51 years.^3-8 All the reports involved DVT with a large leiomyomatous uterus. Three patients had pulmonary embolism associated with leiomyoma and DVT.^3,6 Management of all patients consisted of hysterectomy after anticoagulation. In all cases, the patients recovered uneventfully, and the DVT linked to leiomyoma uteri occurred without polycythemia. Although an unusual complication, polycythemia has been reported in women with myomas. The myometrium has the ability to produce erythropoietin, and excess erythropoietin has been measured in patients with polycythemia.

The Virchow’s triad-stasis, hypercoagulability, and endothelial disruption-is recognized as a risk factor for developing DVT. The main cause for venous thrombosis in this patient was the left lower-extremity venous stasis secondary to compression of the inferior vena cava by the leiomyomatous uterus. Unlike the other patients, she did not have any other risk factors for thrombosis.

In the previously reported cases, the diagnosis of DVT-associated uterine leiomyoma was made by use of abdominal computed tomography in conjunction with venous Doppler and pelvic sonogram. In this case, diagnosis was made by lower-extremity venous Doppler, pelvic sonogram, and MRI. This is the fourth reported case of unilateral lower-extremity DVT secondary to leiomyoma; the other reports involved bilateral DVT. In all but 1 case, a vena cava filter was used in the surgical management.

For women who are not candidates for surgery or who want to preserve their fertility, alternative treatments are available. Myomectomy, GnRH agonists/antagonists, or waiting for menopausal regression of the leiomyoma are all options for decreasing the size of the uterus and, thereby, the compression of the pelvic veins. Medical management is contraindicated in women with a history of thromboembolism.

Conclusion
Leiomyomatous uterus causing DVT is a rare event. In this case, the large posterior uterine fibroid obstructing blood flow from the lower extremity was the sole identifiable risk factor for the development of DVT; this supports the correlation suggested by previous reports between large uterine leiomyomas complicated by lower-extremity venous stasis and thrombosis. It further demonstrates the benefit of adjunctive imaging in the diagnosis of this condition.

This report is only the fourth case of unilateral lower-extremity DVT associated with uterine leiomyoma. This is also the only patient who did not have a history of menorrhagia or other problems with her menses. An annual pelvic examination and good monitoring of the growth of the leiomyoma could potentially prevent such cases.

Acknowledgments
The author wishes to express her gratitude to Michael Wolkomir, MD, and Timothy Cooney, MS, for their review, comments, encouragement, and support.

References
1. Montemagno U, De Placido G, Colacurci N, et al. Uterine fibroids: protocols of integrated medical/surgical treatment. Clin Exp Obstet Gynecol. 1993;20:167-172.

2. Matchar DB, Myers ER, Barber MW, et al. Evidence Report/Technology Assessment: Number 34. Management of Uterine Fibroids. Volume 1, Evidence Report. Rockville, Md: Agency for Healthcare Research and Quality; 2001. Publication 01-E051. Available at www.ncbi.nlm.nih.govbooks/bv.fcgi?rid=hstat1.chapter.47755.

3. Tanaka H, Umekawa T, Kikukawa T, et al. Venous thromboembolic diseases associated with uterine myomas diagnosed before hysterectomy: a report of two cases. J Obstet Gynaecol Res. 2002;28:300-303.

4. Dekel A, Rabinerson D, Dicker D, et al. Thrombosis of the pelvic veins associated with a large myomatous uterus. Obstet Gynecol. 1998;92:646-647.

5. Chong YS, Fong YF, Ng SC. Deep vein thrombosis in patients with large uterine myomata. Obstet Gynecol. 1998;92:707.

6. Nishikawa H, Ideishi M, Nishimura T, et al. Deep venous thrombosis and pulmonary thromboembolism associated with a huge uterine myoma-a case report. Angiology. 2000;51:161-166.

7. Phupong V, Tresukosol D, Taneepanichskul S, et al. Unilateral deep vein thrombosis associated with a large myoma uteri. A case report. J Reprod Med. 2001;46:618-620.

8. Stanko CM, Severson MA II, Molpus KL. Deep venous thrombosis associated with large leiomyomata uteri. A case report. J Reprod Med. 2001;46:405-407.