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• W2022679300 abstract "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 warfarin 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. 1.Which one of the following tests should be performed for evaluation of this patient's leg symptoms? a.Computed tomographic angiography (CTA)b.Magnetic resonance angiography (MRA)c.Lower extremity duplex USd.Serum D-dimere.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. 2.Which one of the following diagnoses is most likely in this patient? a.May-Thurner syndromeb.Incipient phlegmasia cerulea dolens (PCD)c.Lymphedema secondary to local compression of the inguinal lymphatic systemd.Bakers cyste.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.1Moudgill N Hager E Gonsalves C Larson R Lombardi J DiMuzio P May-Thurner syndrome: case report and review of the literature involving modern endovascular therapy.Vascular. 2009; 17: 330-335Crossref PubMed Scopus (78) Google Scholar 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. 3.Which one of the following is the best definitive treatment for this patient's disorder? a.Intravenous unfractionated heparin (UFH)b.Subcutaneous LMWHc.Intravenous direct thrombin inhibitor (argatroban or lepirudin)d.Catheter-directed thrombolysise.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. 4.Which one of the following risk factors did not contribute to the development of DVT and incipient PCD in this patient? a.Androgen deprivation therapy with goserelinb.Immobilizationc.Metastatic prostate cancerd.Local compression by enlarged lymph nodese.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. 5.Which one of the following is the most appropriate management after successful thrombolysis in this patient? a.Oral dabigatranb.Oral aspirinc.Subcutaneous UFHd.Vena cava filtere.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.2Connolly SJ Ezekowitz MD Yusuf S et al.Dabigatran versus warfarin in patients with atrial fibrillation.N Engl J Med. 2009; 361: 1139-1151Crossref PubMed Scopus (8845) Google Scholar 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.3Schulman S Kearon C Kakkar AK et al.Dabigatran versus warfarin in the treatment of acute venous thromboembolism.N Engl J Med. 2009; 361: 2342-2352Crossref PubMed Scopus (2162) Google Scholar Clinical trials have also established its effectiveness in prevention of thrombosis after total hip or knee replacement.4Eriksson BI Dahl OE Rosencher N et al.Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial.Lancet. 2007; 370: 949-956Abstract Full Text Full Text PDF PubMed Scopus (1044) Google Scholar 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.5Grassi CJ Swan TL Cardella JF et al.Quality improvement guidelines for percutaneous permanent inferior vena cava filter placement for the prevention of pulmonary embolism.J Vasc Interv Radiol. 2003; 14: S271-S275Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar 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,6Lee AY Levine MN Baker RI et al.Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.N Engl J Med. 2003; 349: 146-153Crossref PubMed Scopus (2259) Google Scholar 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. Given its low incidence, PCD is encountered infrequently, and as a result, many clinicians have limited experience in diagnosing and managing this disease. Phlegmasia cerulea dolens is a life- and limb-threatening condition and therefore requires timely intervention. Because PCD is rare, treatment approaches have been investigated only in a few studies with low case numbers. Early involvement of specialist services such as vascular medicine or surgery and interventional radiology is of utmost importance because treatment decisions must be made with an orchestrated multispecialty approach. The current consensus is that a selected subset of patients might benefit from thrombus removal. The rationale behind this approach is aimed at quick relief of acute symptoms and outcome improvement by reducing the incidence of post-thrombotic syndrome and preventing the development of valvular incompetence.7Watson LI Armon MP Thrombolysis for acute deep vein thrombosis.Cochrane Database Syst Rev. 2004; : CD002783PubMed Google Scholar In addition, thrombus removal in extensive DVT involving the iliofemoral vein might reduce the incidence of recurrent venous thromboembolism (VTE).8Douketis JD Crowther MA Foster GA Ginsberg JS Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis?.Am J Med. 2001; 110: 515-519Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar Whereas patients with extensive DVT and large thrombus burden (iliofemoral DVT) benefit from this approach (75% of patients experience painful chronic edema and 40% experience venous claudication during treatment with anticoagulation alone9Kearon C Kahn SR Agnelli G Goldhaber S Raskob GE Comerota AJ Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).Chest. 2008; 133: 454S-545SCrossref PubMed Scopus (1872) Google Scholar), almost all patients with a smaller thrombus burden do not derive additional benefit because anticoagulation alone is effective. Generally accepted indications for DVT thrombolysis include extensive DVT involving the iliofemoral level, symptoms lasting less than 14 days for catheter-directed clot lysis or less than 7 days for operative venous thrombectomy, good functional status, and life expectancy greater than 1 year. Our patient proceeded with thrombolysis despite symptom duration of greater than 14 days because of worsening leg swelling and pain. Although the efficacy of clot lysis is highest in the first 14 days after symptom onset, thrombolysis can still be effective if treatment is instituted thereafter. High risk of bleeding is a contraindication. Available approaches are percutaneous venous thrombectomy, catheter-directed thrombolysis, systemic thrombolysis, and operative venous thrombectomy.10Tung CS Soliman PT Wallace MJ Wolf JK Bodurka DC Successful catheter-directed venous thrombolysis in phlegmasia cerulea dolens.Gynecol Oncol. 2007; 107: 140-142Crossref PubMed Scopus (27) Google Scholar, 11Vysetti S Shinde S Chaudhry S Subramoney K Phlegmasia cerulea dolens-a rare, life-threatening condition.Scientific World Journal. 2009; 9: 1105-1106Crossref Scopus (13) Google Scholar, 12Vedantham S Interventional approaches to acute venous thromboembolism.Semin Respir Crit Care Med. 2008; 29: 56-65Crossref PubMed Scopus (28) Google Scholar, 13Tardy B Moulin N Mismetti P Decousus H Laporte S Intravenous thrombolytic therapy in patients with phlegmasia caerulea dolens.Haematologica. 2006; 91: 281-282PubMed Google Scholar Percutaneous venous thrombectomy alone is not recommended because recurrences are frequent. Catheter-directed thrombolysis can be used either alone or in conjunction with mechanical thrombus fragmentation (called pharmacomechanical thrombolysis) and is the recommended modality among the aforementioned approaches. Systemic thrombolysis and operative venous thrombectomy are second-line alternatives.9Kearon C Kahn SR Agnelli G Goldhaber S Raskob GE Comerota AJ Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).Chest. 2008; 133: 454S-545SCrossref PubMed Scopus (1872) Google Scholar In catheter-directed thrombolysis, a catheter is introduced into the popliteal vein or a lower calf vein to allow slow infusion of tissue plasminogen activator directly into the clot. Some catheters have side holes to allow greater distribution of the thrombolytic agent. As the clot dissolves, the catheter is advanced up the leg into new clot. Sometimes mechanical thrombectomy can be done with a catheter that emulsifies the clot and opens up a track. The process may take 1 to 2 days, and venographic images are obtained to confirm clot dissolution. Often on completion of thrombolysis, a vein stenosis may be apparent, for example at the common iliac level in the case of May-Thurner syndrome, requiring venous balloon angioplasty and stenting. After completion of thrombolysis, standard anticoagulation is continued with vitamin K antagonists (VKA) or LMWH. Phlegmasia cerulea dolens represents an emergency that can lead not only to loss of a limb but also to hypovolemic shock secondary to massive fluid sequestration. Therefore, responsibilities of the physician who performs the initial evaluation include fast recognition of the condition, initiation of anticoagulation, intravenous fluid resuscitation, adequate analgesia, and early involvement of the appropriate subspecialty service for expedited management. Phlegmasia cerulean dolens and compartment syndrome share a final common pathway: compression of arterial vessels secondary to increased pressure in the lower extremity compartment. Although in compartment syndrome, the compromised inflow is triggered by trauma (fracture, overuse), causing bleeding into the enclosed compartment and edema of the muscle, PCD results in inflow impairment by massive fluid extravasation into the tissue due to an extensive DVT obstructing venous outflow. A theoretical distinction (with questionable clinical importance) is made between phlegmasia alba dolens and PCD in that the former is caused by massive thrombosis of deep and superficial veins with preservation of collateral vessel patency. Patients characteristically present with limb pain, pitting edema, and blanching. The risk of severe complications like limb loss is low, although in about 50% of patients, phlegmasia alba dolens can precede PCD. In PCD, collateral vessels are also thrombosed, which results in severe pain, pitting edema, cyanosis, and, if untreated, venous gangrene with high risk of limb loss. Management of a DVT in the absence of PCD consists of anticoagulation alone. Vena cava filter insertion is reserved for patients who cannot receive anticoagulation therapy due to high bleeding risk. Lifelong therapy with VKA at an INR goal of 2.0 to 3.0 preceded by bridging with therapeutic doses of either intravenous UFH or subcutaneous LMWH is a correct approach for patients with a second episode of unprovoked DVT and should be considered in some patients with a first episode of unprovoked proximal DVT in whom risk factors for bleeding are absent and reliable anticoagulation monitoring can be ensured. Therapeutic-dose subcutaneous UFH is a viable option for the initial treatment of a newly diagnosed DVT. The DVT of our patient should be classified as a first event that propagated due to treatment discontinuation. Given the fact that he has an active metastatic malignancy, lifelong anticoagulation should be pursued. For long-term treatment, guidelines recommend only VKA or LMWH. Our patient's condition is unusual because of his medical history of active malignancy. For cancer patients, guidelines recommend lifelong anticoagulation with therapeutic-dose subcutaneous LMWH. The differing approach in the setting of active malignancy is based on the CLOT trial, which showed a reduction of recurrent VTE incidence in the LMWH group within the first 6 months.6Lee AY Levine MN Baker RI et al.Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.N Engl J Med. 2003; 349: 146-153Crossref PubMed Scopus (2259) Google Scholar These findings were recently confirmed by a meta-analysis that concluded that compared to VKA, LMWH reduced the incidence of recurrent VTE but not death.9Kearon C Kahn SR Agnelli G Goldhaber S Raskob GE Comerota AJ Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).Chest. 2008; 133: 454S-545SCrossref PubMed Scopus (1872) Google Scholar, 14Akl EA Barba M Rohilla S et al.Low-molecular-weight heparins are superior to vitamin K antagonists for the long term treatment of venous thromboembolism in patients with cancer: a Cochrane systematic review.J Exp Clin Cancer Res. 2008; 27: 21Crossref PubMed Scopus (51) Google Scholar A post-hoc analysis of the CLOT trial published in 200515Lee AY Rickles FR Julian JA et al.Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism.J Clin Oncol. 2005; 23: 2123-2129Crossref PubMed Scopus (455) Google Scholar concluded that, in patients with nonmetastatic solid tumors, LMWH was associated with improved survival compared to VKA. The survival benefit was not noted in patients with metastatic cancer. Clinicians should be cognizant of the disease entity PCD. A high level of suspicion guided by a combination of symptoms (sudden severe leg pain and in later stages cardi-ocirculatory instability) and physical examination findings (swelling, cyanosis, edema, skin firm to touch (Figure) and in later stages venous gangrene and arterial compromise) should prompt diagnosis of phlegmasia and expedite management including stabilization using intravenous UFH or subcutaneous LMWH, analgesia, and fluid resuscitation as well as immediate consultation of a vascular subspecialty service for evaluation of eligibility for catheter-based or surgical intervention." @default.
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• W2022679300 title "80-Year-Old Man With Massive Leg Swelling" @default.
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