80-year-old man with massive leg swelling.

An 80-year-old man was admitted to the hospital with a 2-month history of painful swelling of his right lower extremity. His medical history was remarkable for metastatic prostate cancer, radical prostatectomy, androgen deprivation therapy with goserelin acetate (a gonadotropin-releasing hormone analogue used to treat prostate cancer, breast cancer, and endometriosis), and radiation therapy for cancer recurrence with bony metastases. He had no history of claudication. The patient had undergone right total hip arthroplasty 6 months previously and lower back surgery 3 months later. Two months before admission, he noticed right leg swelling. Lower extremity ultrasonography (US) performed elsewhere reportedly showed right deep venous thrombosis (DVT). Anticoagulation was initiated with war-farin and low-molecular-weight heparin (LMWH) bridging. An international normalized ratio (INR) determination performed 6 weeks before the current admission revealed a value of 9.0; warfarin therapy was discontinued, and the patient was lost to follow-up. Physical examination on admission revealed the following: temperature, 36.8°C; heart rate, 70 beats/min and regular; blood pressure, 132/82 mm Hg; respiratory rate, 20 breaths/min; and oxygen saturation, 100% while breathing room air. The patient was in moderate distress from leg pain. Examination of the head, ears, nose, throat, heart, lungs, and abdomen yielded unremarkable findings. The patient’s right leg was markedly swollen, with edema extending from the groin to the foot. The skin was firm and warm to touch. Results of motor and sensory examinations were normal. Posterior tibial and dorsalis pedis arteries could not be palpated due to swelling. Palpation of the right groin disclosed a large, rock-hard mass that extended into the femoral triangle. Which one of the following tests should be performed for evaluation of this patient’s leg symptoms? Computed tomographic angiography (CTA) Magnetic resonance angiography (MRA) Lower extremity duplex US Serum D-dimer Serum prostate-specific antigen Computed tomographic angiography and MRA are used to assess the arterial system if occlusion is suspected. In this case, findings are inconsistent with arterial occlusion (erythematous extremity, skin warm to touch). Therefore, CTA and MRA should not be ordered. Even if arterial compromise secondary to elevated leg compartment pressures is a concern, CTA and MRA can miss obstruction of distal small vessels. Lower extremity duplex US allows noninvasive assessment of the venous system as well as visualization of enlarged lymph nodes and masses such as a Baker cyst. Because the patient’s symptoms suggest DVT, duplex US is the best initial screening examination. A serum D-dimer evaluation is most helpful in patients with a low pretest likelihood of DVT to determine whether further work-up with lower extremity US is needed. Because this patient has a high pretest likelihood of DVT, D-dimer testing would not add valuable information. The serum prostate-specific antigen level would be elevated in a patient with metastatic prostate cancer and would not provide information on the cause of leg swelling. Lower extremity duplex US was performed to determine the cause of the patient’s leg symptoms. Which one of the following diagnoses is most likely in this patient? May-Thurner syndrome Incipient phlegmasia cerulea dolens (PCD) Lymphedema secondary to local compression of the inguinal lymphatic system Bakers cyst Right-sided heart failure May-Thurner syndrome is characterized by an iliofemoral DVT on the left side secondary to compression of the left common iliac vein by the overlying right common iliac artery.1 It rarely could occur on the right side in patients with unusual anatomic variations. Incipient PCD is the most likely diagnosis in this patient. It is characterized by extensive thrombosis leading to obstruction of both deep and superficial veins resulting in tense swelling of the leg. Arterial perfusion is initially not compromised, but later in the disease course, increased intracompartmental pressure leads to distal extremity ischemia. Although this patient may have a component of lymphedema secondary to obstruction of the inguinal nodes, lymphedema usually causes painless swelling without plethora from venous engorgement. A Baker cyst only causes calf swelling up to the knee. In addition, patients often report a history of isolated swelling of the knee and pain with maximal intensity in the popliteal fossa. Right-sided heart failure is unlikely because it would lead to bilateral lower extremity swelling. Ultrasonography revealed extensive DVT extending from the right external iliac vein through the common femoral and popliteal veins all the way down into the deep veins of the calf. Acute venous thrombosis was also noted in the great saphenous vein. In addition, US showed abnormally enlarged lymph nodes in the right groin. Massive right lower extremity DVT, superficial vein thrombosis, and incipient PCD were diagnosed. Which one of the following is the best definitive treatment for this patient’s disorder? Intravenous unfractionated heparin (UFH) Subcutaneous LMWH Intravenous direct thrombin inhibitor (argatroban or lepirudin) Catheter-directed thrombolysis Open surgical thrombectomy Intravenous UFH should be instituted early to prevent thrombus extension and thromboembolism, but it does not lead to recanalization of the vessels; hence, this is not the best treatment. The same reasoning applies to LMWH. Direct thrombin inhibitor therapy should be started in patients with a previous diagnosis of heparin-induced thrombocytopenia, but like UFH and LMWH, it does not lead to vessel recanalization. Catheter-directed thrombolysis is the best definitive treatment for PCD. It involves use of a thrombolytic agent to dissolve the clot, sometimes with support of mechanical clot fragmentation. Open surgical thrombectomy is a valid option but should be considered a second-line choice. The patient underwent catheter-directed thrombolysis with alteplase plus UFH and was monitored in the medical intensive care unit. The right lower extremity swelling was managed with elastic wraps. Which one of the following risk factors did not contribute to the development of DVT and incipient PCD in this patient? Androgen deprivation therapy with goserelin Immobilization Metastatic prostate cancer Local compression by enlarged lymph nodes Recent orthopedic surgery Goserelin has not been associated with DVT or induction of a prothrombotic state. Immobilization is a recognized risk factor for development of DVT because the limited use of leg muscles predisposes to decreased venous blood flow and stasis. The underlying malignancy creates a prothrombotic state. Local compression of the external iliac vein disturbs blood flow, causes stasis, and creates turbulence, thereby inducing a supportive environment for clot formation. Recent orthopedic surgery predisposes to clot development by immobilization and induction of a prothrombotic state. The patient tolerated thrombolysis well. During follow-up, the swelling decreased to almost baseline. The leg became soft, and the skin color changed from erythematous to normal. The patient noted reduction in discomfort and return of full mobility. Which one of the following is the most appropriate management after successful thrombolysis in this patient? Oral dabigatran Oral aspirin Subcutaneous UFH Vena cava filter Therapeutic dose of subcutaneous LMWH for 6 months, converted to oral warfarin with goal INR of 2.0 to 3.0 Recently approved by the US Food and Drug Administration, dabigatran is a direct thrombin inhibitor used for thromboembolism prophylaxis in atrial fibrillation.2 Currently, it is not used in the treatment of DVT but might become an option in the future inasmuch as recent studies have documented its noninferiority to warfarin and its benefit of not requiring laboratory monitoring.3 Clinical trials have also established its effectiveness in prevention of thrombosis after total hip or knee replacement.4 For our patient, dabigatran is not appropriate because it lacks Food and Drug Administration approval for treatment of acute DVT, and no data comparing LMWH or warfarin with dabigatran in cancer patients with DVT are available. Aspirin plays a role in preventing platelet aggregation and thromboembolism in the arterial system. It is ineffective in prevention of venous thrombosis or DVT recurrence. Subcutaneous UFH has 2 major drawbacks: cumbersome administration (2-3 times daily) and unreliable absorption. Vena cava filter insertion is indicated in patients with contraindications to anticoagulation in the setting of acute pulmonary embolism or significant DVT, anticoagulation failure, or anticoagulation complications. In some patients, an inferior vena cava filter may be indicated for inferior vena cava/iliofemoral thrombus, free-floating thrombus and massive pulmonary embolism with residual DVT, and high risk of recurrent thromboembolism.5 Our patient has no indications for vena cava filter insertion. Treatment with LMWH for 6 months followed by indefinite warfarin therapy is the best management option in this case. The duration of initial treatment with LMWH is based on the CLOT trial,6 which showed decreased DVT recurrence in patients with active malignancies initially treated with LMWH as opposed to warfarin. There was also a survival benefit with LMWH, although only in the subgroup of patients with solid tumors that had not metastasized. The patient was discharged with a 6-month regimen of LMWH. Therapy was continued with warfarin after LMWH discontinuation. At 3-month follow-up, the patient was stable with no complaints.