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Mayo Clin Proc. 2009 October; 84(10): e1–e4.
PMCID: PMC2755811

57-Year-Old Woman With Acute Lower Extremity Pain and Swelling

A 57-year-old postmenopausal woman presented to our emergency department with a 1-day history of left leg pain, redness, and swelling. She reported no chest pain or shortness of breath. During the previous week, she made several car trips, each lasting 3 hours. Her medical history was remarkable for a left femoral and popliteal deep venous thrombosis (DVT) after breast reduction surgery during the previous year, which was treated with 1 week of subcutaneous low-molecular-weight heparin therapy and 6 months of oral warfarin therapy. She also had a history of hyperlipidemia, allergies, gastroesophageal reflux, and depression. She denied using tobacco or illicit drugs. Breast, cervical, and colon cancer screening were current and unremarkable. Daily oral medications were atorvastatin, sertraline, montelukast, and pantoprazole. She reported no family history of DVT.

On arrival at the emergency department, the patient's vital signs were as follows: temperature, 36.8°C; blood pressure, 150/77 mm Hg; heart rate, 71 beats/min; respiratory rate, 18 breaths/min; and room air oxygen saturation, 93%. Physical examination revealed erythema, warmth, tenderness, and swelling of the entire left leg with intact distal pulses (Figure 1). The right leg was unaffected. Laboratory tests revealed the following: white blood cell count, 9.3 × 109/L; hemoglobin, 14.7 g/dL; platelets, 321 × 109/L; creatinine, 0.7 mg/dL; activated partial thromboplastin time, 23 seconds; and international normalized ratio, 0.9.

FIGURE 1.
Photograph of a 57-year-old woman with a 1-day history of left lower extremity pain, erythema, and swelling.
  1. Which one of the following is the most likely diagnosis in our patient?
    1. Deep venous thrombosis
    2. Muscle strain
    3. Superficial thrombophlebitis
    4. Ruptured Baker cyst
    5. Cellulitis
    Deep venous thrombosis is the most likely diagnosis given the prior DVT, recent car trips, and clinical findings. One can assess the probability of DVT by using the Modified Wells Clinical Score.1 One point each is given for clinical features, such as active cancer, paralysis or recent lower extremity immobilization, being bedridden for more than 3 days within the previous 4 weeks, localized tenderness along the deep venous system, whole leg swelling, calf swelling by more than 3 cm compared with the asymptomatic leg, pitting edema, collateral superficial veins, and previous DVT. Two points are subtracted when an alternative diagnosis is more likely than DVT. A score of 2 or more indicates that DVT is likely, whereas a score of 1 or less indicates that DVT is unlikely. Our patient's score was 2, indicating that DVT was likely.
    Muscle strain can mimic DVT; 40% of patients with suspected DVT but negative findings on contrast venography have muscle injury as the cause of lower extremity symptoms.2 Our patient, however, had not experienced a recent injury. Superficial thrombophlebitis (ie, acute inflammation of a superficial vein caused by a thrombosis) usually presents with a palpable cord, inconsistent with our patient's clinical findings. A ruptured Baker (popliteal) cyst can mimic DVT because it causes leg pain and swelling. However, a ruptured Baker cyst involves the popliteal fossa and distal lower extremity, not the entire limb as in our patient. Cellulitis typically presents with localized erythema, warmth, tenderness, edema, and constitutional symptoms such as fever and chills. Our patient's clinical findings were more consistent with DVT than cellulitis.
    In this setting, some clinicians might obtain a D-dimer test. D-dimer tests, however, should not be used to exclude DVT in patients like ours who have a high probability of DVT.1 However, in patients with low to intermediate probability, a D-dimer test might be helpful to rule out DVT. Nevertheless, the preferred diagnostic test for DVT is Doppler ultrasonography. Compared with contrast venography, which is considered the criterion standard, ultrasonography is 94% sensitive for detecting proximal DVT, 64% sensitive for detecting distal DVT, and 94% specific for both.3 However, ultrasonography is less invasive and does not employ radiocontrast dye.
    In our patient, color flow Doppler compression ultrasonography of the left lower extremity deep venous system revealed patent left common femoral and left popliteal veins; the thrombus was not visualized. However, waveforms lacked phasicity, and the left common femoral and popliteal veins were difficult to completely compress. These findings, in the absence of direct visualization of the thrombus, strongly suggested proximal venous obstruction. Notably, for identifying pelvic vein DVT, ultrasonography performs poorly, particularly in obese patients or when bowel gas is present.4
  2. In light of these findings, which one of the following is the best next diagnostic test?
    1. Impedance plethysmography
    2. Computed tomographic (CT) angiography
    3. Lymphoscintigraphy
    4. Positron emission tomography
    5. Genetic testing for inherited thrombophilia
    Impedance plethysmography is an indirect technique for diagnosing DVT; thromboses are not visualized. False positives occur in conditions that diminish arterial inflow and impede venous outflow. Findings on impedance plethysmography would likely be positive in our patient but would not shed light on the specific location or cause of the obstruction. Computed tomographic angiography is 100% sensitive and 96% specific compared with conventional venography in identifying DVT.5 Although contrast venography was commonly used in the past in patients suspected of having proximal venous obstruction, CT angiography is less invasive and provides more anatomic details of the pelvis. Thus, CT angiography is the best test for determining the cause of proximal venous obstruction in our patient. Lymphoscintigraphy is a nuclear medicine test used to diagnose lymphedema and would not identify the location or cause of the venous obstruction in our patient. Searching for malignancy may be indicated, but positron emission tomography is not likely to identify the location or cause of the venous obstruction. Finally, although genetic testing for inherited thrombophilia should be considered in patients with DVT, such testing would not identify the location or cause of the venous obstruction.
    In our patient, CT angiography of the abdomen and pelvis revealed an acute-appearing occlusive thrombus from the confluence of the internal and external iliac veins to the common femoral vein. No other anatomic abnormalities were seen. Given these findings, anticoagulation was indicated.
  3. Which one of the following is the best choice for initiating anticoagulation in our patient?
    1. Warfarin, 5 mg by mouth once daily
    2. Unfractionated heparin, intravenous infusion at 1000 U/h
    3. Unfractionated heparin, 5000-U intravenous bolus and then intravenous infusion at 1000 U/h
    4. Unfractionated heparin, 5000 U subcutaneously twice daily
    5. Unfractionated heparin, intravenous bolus and infusion in accordance with a weight-based dosing nomogram
    The objective of anticoagulation therapy for DVT is to stop thrombus propagation and formation. Although our patient will eventually require long-term warfarin anticoagulation, warfarin alone will not achieve immediate anticoagulation. In fact, shortly after its administration, warfarin transiently engenders a hypercoagulable state because of reduced plasma protein C levels. Instead, guidelines recommend initiating heparin anticoagulation immediately after establishing the diagnosis of DVT by imaging. If imaging is delayed and the suspicion for DVT is high, heparin anticoagulation should also be initiated.6
    Several effective heparin anticoagulation treatment options for acute DVT exist, including low—molecular-weight heparin and unfractionated heparin.6 An optimal dosing regimen of unfractionated heparin shortens the time to adequate anticoagulation and decreases the risks of excessive anticoagulation. Intravenous unfractionated heparin at 1000 U/h without a bolus will not achieve adequate and sufficiently quick anticoagulation. Although commonly used in the past, 5000 U of intravenous unfractionated heparin given as a bolus and followed by a continuous infusion at 1000 U/h may or may not achieve adequate and sufficiently quick anticoagulation and, in some patients, may result in overanticoagulation and risk of bleeding. Subcutaneous unfractionated heparin at a dose of 5000 U given twice daily is prescribed for DVT prophylaxis in hospitalized patients, not for treating acute DVT. Of the choices listed, the best is intravenous unfractionated heparin given as a bolus and then as a continuous infusion using a weight-based dosing nomogram (80-U/kg bolus, followed by an infusion of 18 U/kg/h).6 Patients treated using this nomogram are more likely to achieve adequate anticoagulation quickly and less likely to experience recurrent thromboembolism compared with patients treated with a 5000-U bolus followed by an infusion of 1000 U/h.7 Subcutaneous low-molecular-weight heparin can also be used to treat acute DVT6; however, discussion of its use in this setting is beyond the scope of this article.
    Our patient was treated with intravenous unfractionated heparin using a weight-based nomogram.
  4. Given the location and the recurrence of our patient's DVT, which one of the following is the most likely underlying cause?
    1. Chronic heart failure
    2. Budd-Chiari syndrome
    3. Ovarian cancer
    4. Abdominal aortic aneurysm
    5. May-Thurner syndrome
    A diagnosis of DVT should prompt consideration of potential predisposing factors, particularly in cases of recurrent DVT. Although patients with chronic heart failure are at increased risk of DVT, our patient had no findings suggestive of this diagnosis. Budd-Chiari syndrome is caused by obstruction of hepatic venous outflow and presents with abdominal pain, ascites, and hepatomegaly, none of which were present in our patient. Malignancy should always be considered in patients with DVT, especially pelvic malignancy in patients presenting with iliofemoral DVT. However, our patient had no evidence of malignancy. Abdominal aortic aneurysm has been associated with iliofemoral DVT.8 In this setting, DVT results from compression of the inferior vena cava or iliac veins by the aneurysm. However, our patient showed no signs of abdominal aortic aneurysm.
    Our patient's findings are consistent with May-Thurner syndrome, which is the constellation of repetitive injury to the left iliac vein caused by the overlying pulsating right iliac artery compressing the vein against the underlying lumbar vertebrae. Persons with this anatomic configuration and the consequent vascular injury are predisposed to DVT (Figure 2).9 Notably, CT angiography did not reveal this configuration in our patient. However, contrast venography, done as part of a later therapeutic procedure, established the diagnosis of May-Thurner syndrome.
    FIGURE 2.
    May-Thurner syndrome: the pulsating right iliac artery compresses the left iliac vein against the underlying vertebrae. Persons with this anatomic configuration and vascular injury are predisposed to left lower extremity deep venous thrombosis. IVC = ...
    After systemic anticoagulation, most patients with popliteal-tibial DVT experience complete recanalization. However, 6 months after anticoagulation, 88% of patients with iliofemoral DVT have moderate to severe venous obstruction.10 Failure to recanalize correlates with future postthrombotic syndrome. Indeed, most patients with iliofemoral DVT treated with anticoagulation alone develop chronic venous insufficiency, and many develop venous claudication and stasis ulcers.10-13 These data prompted us to consider treatments in addition to anticoagulation alone for our patient.
  5. In addition to anticoagulation, which one of the following is the best treatment for addressing our patient's current findings and preventing postthrombotic complications?
    1. Percutaneous catheter-directed thrombolysis, thrombectomy, and stent placement
    2. Systemic thrombolysis with tissue-type plasminogen activator
    3. Inferior vena cava filter
    4. Compression stocking
    5. Early ambulation
    In patients with iliofemoral DVT, treatments that remove the thrombus and maintain venous patency resolve symptoms such as edema and prevent chronic venous insufficiency syndromes.6,10,11,13,14 Guidelines recommend percutaneous catheter-directed pharmacothrombolysis with mechanical thrombectomy in selected patients with acute iliofemoral DVT to reduce new symptoms such as pain and edema and prevent postthrombotic morbidity. Notably, no randomized trials have compared percutaneous mechanical thrombectomy alone with other catheter-based or non-catheter-based therapies for DVT. After removal of the thrombus, angioplasty and stent placement to correct underlying venous lesions should also be considered.6 Indeed, some authors specifically recommend stent placement in patients with May-Thurner syndrome to treat the compressed right iliac vein, ensure long-term venous patency, and prevent chronic venous insufficiency syndromes.13,15,16
    Although systemic thrombolysis is superior to anticoagulation alone in resolving thrombus, it carries the risk of major bleeding. However, observational data suggest that catheter-directed thrombolysis is more effective and less risky than systemic thrombolysis.6,11 An inferior vena cava filter was unnecessary in our patient because she had no contraindications to systemic anticoagulation. Neither a compression stocking nor early ambulation would have resolved the iliofemoral DVT or the underlying May-Thurner syndrome. However, compression stockings may decrease lower extremity swelling, and early ambulation is advised to maintain mobility and prevent further thrombosis.6
    We arranged for our patient to undergo catheter-directed pharmacothrombolysis, mechanical thrombectomy, and stent placement. During the procedure, however, our interventionist determined that catheter-directed thrombolysis was unnecessary and, as such, only catheter-directed mechanical thrombectomy and stent placement were performed. The day after the procedure, the patient's leg pain, erythema, and swelling had completely resolved.
    Given our patient's relatively young age and recurrent DVT, a thrombophilia panel (activated partial thromboplastin time, prothrombin time, fibrinogen, mixing studies, factor V Leiden, prothrombin 20210, proteins S and C, and antithrombin III activity) was obtained, with unremarkable findings. The patient was treated with intravenous unfractionated heparin until she was adequately anticoagulated with oral warfarin.

DISCUSSION

In 1957, May and Thurner9 reported that 22% of the 430 cadavers examined in their study had obstructive lesions within the left iliac vein owing to chronic endothelial injury caused by compression of the vein by the overlying pulsating right iliac artery and underlying lumbar vertebrae. They speculated that persons with this anatomic configuration were predisposed to DVT. Indeed, left-leg DVT is 3 to 8 times more common than right-leg DVT.

May-Thurner syndrome affects women more than men.15 Patients with this syndrome commonly present with left-leg DVT but may also present with left-leg pain, edema, and venous insufficiency in the absence of DVT.5 Nearly 50% of patients with left iliofemoral DVT have May-Thurner syndrome.16

Iliofemoral DVT usually occurs in the setting of an underlying anatomic configuration that affects the inferior vena cava or iliofemoral veins, such as May-Thurner syndrome, presence of a pelvic mass, or pregnancy.15 Despite adequate anticoagulation, most iliofemoral thromboses do not completely recanalize, resulting in postthrombotic syndrome. As a result, endovascular treatment has emerged as an effective treatment for acute iliofemoral DVT.11 The 2008 American College of Chest Physicians guidelines recommend catheter-directed pharmacothrombolysis, mechanical thrombectomy, and stent placement or surgical thrombectomy in patients with iliofemoral DVT.6

In patients with iliofemoral DVT in the setting of May-Thurner syndrome who have undergone thrombus removal and stent placement, the ideal duration of warfarin anticoagulation is unclear. Guidelines recommend that patients with a transient risk factor for DVT, such as major surgery, be treated for 3 months. Patients with unprovoked DVT should be treated for a minimum of 3 months and then the risks vs benefits of long-term anticoagulation should be evaluated. Patients with a second unprovoked DVT should be treated indefinitely.6 Our patient was predisposed to DVT because of May-Thurner syndrome, and this abnormal anatomic configuration was corrected. Guidelines do not address duration of anticoagulation therapy for this specific scenario. We chose to treat this patient with warfarin anticoagulation for at least 3 months, after which her status was to be reviewed and the need for longer-term or even indefinite anticoagulation therapy was to be considered.

Notes

See end of article for correct answers to questions.

Correct answers: 1. a, 2. b, 3. e, 4. e, 5. a

REFERENCES

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13. Patel NH, Stookey KR, Ketcham DB, Cragg AH. Endovascular management of acute extensive iliofemoral deep venous thrombosis caused by May-Thurner syndrome. J Vasc Interv Radiol. 2000;11(10):1297-1302 [PubMed]
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