Introduction Venous thromboembolism (VTE) encompasses both pulmonary embolism (PE) and deep venous thrombosis (DVT) and is a grossly underdiagnosed disease spectrum associated with high mortality and morbidity. It is surprising that despite the vast advances in the interventional field, no significant changes have occurred on a wide scale in the approach to this entity over the last half century, with the mainstay of treatment remaining heparin and chronic warfarin therapy. We present a 52-year-old man with massive bilateral DVT extending into the inferior vena cava (IVC) who underwent rheolytic thrombectomy and power-pulse spray with local thrombolytic therapy, leading to rapid resolution of symptoms. Though this approach is not new, its use in DVT of this magnitude has not been previously reported. We would like to use this case to call for a “paradigm shift” in the approach to VTE amongst endovascular specialists, and recommend an early aggressive pharmacomechanical approach to its treatment. We hope that intervention in the venous system gains the long forgotten attention it deserves. Case Report A 52-year-old man was admitted to our institution with severe bilateral lower extremity pain, tenderness, and 4+ edema. He could hardly walk and was in severe distress, secondary to leg pain. Sixty days prior to admission he had fallen off a ladder, leading to fracture of 11 ribs on his right side with development of “flail chest,” requiring intubation and positive pressure ventilation for nearly 3 weeks. There was no perceived injury to his lower extremities. Due to prolonged immobility, an inferior vena cava Optease filter (Johnson & Johnson, Warren, New Jersey) was placed prophylactically. He was discharged to a rehabilitation facility after 3 weeks of his accident and was recovering well. Two weeks into his rehabilitation program, he developed progressive swelling in the left leg. A venous duplex evaluation, which was limited to the left lower extremity, revealed DVT involving the calf vessels which extended to the superficial femoral vein. No evaluation of pelvic veins or IVC was made at that time. He was placed on warfarin, but despite “therapeutic” international normalized ratio (INR) levels, he did not improve. His symptoms became bilateral and more severe. Two INR levels performed a week apart post initiation of warfarin were therapeutic, though the INR on admission was 1.5. He had no history of a hypercoagulable state or prior VTE. On admission, his blood pressure was 160 /90 mm Hg; pulse rate, 92; respiratory rate, 20; temperature, 37.8 Celsius. He was 187 cm and weighed 95 kg. His oxygen saturation and partial pressure of oxygen were normal. His lower extremities demonstrated significant tenderness from the calf area to the groin. Pedal pulses were reduced but palpable. His hemoglobin was 8.7 g/dL. A stat venous duplex demonstrated extensive fresh thrombi in both feet, extending to the iliac veins and into the inferior cava. The IVC filter was almost totally occluded with thrombus. The patient was heparinized using 80 units of heparin/kg bolus, followed by 18 units/kg as maintenance infusion and 325mg of chewable aspirin given. He was quickly taken to the cardiac catheterization laboratory. He was initially placed in the prone position, and using ultrasound guidance and a Micropuncture needle (Cook, Bloomington, Indiana) access to both popliteal veins was obtained. His left leg had more extensive thrombosis, and despite appropriate needle entry into the venous lumen, blood could not be aspirated. Injection of agitated saline verified appropriate endoluminal needle positioning under ultrasound guidance. Subsequently, 6-French (FR) sheaths were inserted in both popliteal veins. Venography demonstrated significant thrombus in both legs. The thrombosis extended from the popliteal veins into the superficial femoral veins (SFV), with almost no flow from the mid level of the SFV to the IVC filter (Figures 1 and 2). It was decided to proceed with power-pulse spray and rheolytic thrombectomy using the DVX AngioJet (Possis Medical, Minneapolis, Minnesota) device. Using the power-pulse spray technique, 15 mg of Alteplase (Genentech, South San Francisco, California) was administered in each leg, and subsequent rheolytic thrombectomy was performed 30 minutes later. The methodology for the pulse spray technique has been previously described.1 Substantial improvement in venous blood flow was noted, and blood could now be aspirated from the left popliteal vein. Significant thrombus burden was still present in the inferior vena cava and common iliac veins. The popliteal sheaths were removed and pressure dressing applied to both popliteal fossa. The patient was supinated and bilateral common femoral vein access obtained with placement of 7 Fr sheaths. It was decided to proceed with overnight local infusion of thrombolytic therapy. Using two separate infusion catheters, (Pulse Spray, Angiodynamics, Queensbury, New York) which extended into the IVC filter, an additional 26 mg of TPA (13 mg through each port) was delivered over 20 hours. Heparin was continued at 18 units/kg/hr, and achieved an adjusted PTT of 1.5 to 2 times normal. Repeat venography the following day demonstrated total resolution of thrombus on the right side, with significant improvement on the left (Figure 3). Some residual thrombus was still present in the left popliteal and distal part of the superficial femoral vein, which prompted further rheolytic thrombectomy with the DVX AngioJet device. The patient’s leg pain had resolved several hours after the initial operation, and by the following day, his lower extremity edema had disappeared on the right side and had been reduced to 1+ on the left. The patient was discharged on day 2 of admission on chronic warfarin therapy in addition to aspirin. Follow-up with venous duplex in 1 month demonstrated resolution of DVT in the popliteal and supra-popliteal vessels. Infrapopliteal veins still had some residual thrombus. At 2-month follow up, there was total resolution of DVT in all venous segments. Discussion The incidence DVT alone is estimated at 1–2 per 1,000 persons per year.1 The incidence of PE has been estimated at 600,000 patients in the United States, with 150,000–200,000 annual deaths.2 VTE is a serious complication of patients undergoing major surgical procedures developing in 30% of such patients and accounting for approximately 60,000 annual deaths in the United States.3,4 DVT in iliofemoral segments is associated with significant complications.5 Of untreated patients, 50% develop PE, with a mortality rate of approximately 30%.6 Despite appropriate anticoagulation, PE can occur in as many as 21% patients with proximal DVT.7 Postthrombotic syndrome may occur in 60% of patients months to years after an acute episode of DVT, despite anticoagulation.6,8 The ensuing venous valvular reflux is the major cause of chronic venous insufficiency, leading to stasis dermatitis and chronic edema.9 Though infrequent, phlegmasia cerulea dolens and venous gangrene are devastating consequences of extensive DVT, with an overall mortality rate approaching 41%.10 Of those who survive this complication, the amputation rate may reach 50%.11 The mainstay of therapy for VTE over the last several decades has been the administration of heparin and warfarin. The optimal goals of therapy in patients with DVT should be: 1) restoration of normal venous flow; 2) prevention of PE; 3) preservation of venous valve function and elimination of postthrombotic syndrome; and 4) prevention of recurrent DVT. It is clear from current data that heparin and warfarin alone are not sufficient for achieving these goals. In patients with adequate systemic anticoagulation, recurrent DVT can occur in over 1/5 of the patients.7 Furthermore, postthrombotic syndrome is not obliterated with the use of anticoagulation.6,8 There are also many patients who may not achieve an adequate level of anticoagulation despite close monitoring, such as in this case. Despite substantial improvements in endovascular technology and operator experience, intervention in the venous beds is a relatively virgin terrain for cardiologists involved in peripheral interventions. Recent data, chiefly coming from surgical and radiological literature, has supported the efficacy of percutaneous mechanical and local direct thrombolysis for extensive DVT.1,4–13 Pharmacomechanical thrombectomy is associated with lower total hospital length of stay and costs, as compared to the local thrombolysis.12 AngioJet rheolytic thrombectomy has been successfully used in the treatment of DVT with promising results.1,13 The addition of power-pulse spray with various thrombolytic agents and utilizing the AngioJet has been proven to be highly successful in thrombus removal in both arterial and venous beds.1,14 There have been several case reports describing the efficacy of percutaneous thrombectomy in large PE.15–18 It has been life-saving in patients with hemodynamic instability and hypoxemia.15,17,18 This case highlights the importance of early percutaneous venous intervention in the treatment of extensive DVT. Whether or not the IVC filter initially caused development of DVT or prevented catastrophic PE is not clear. The patient’s initial venous duplex did not evaluate the pelvic veins or IVC. The patient, however, developed an aggressive form of DVT. The rapid progression of disease may have lead to venous gangrene and limb loss were it not for successful thrombus extraction. Warfarin alone was not enough to treat the patient’s DVT, as his disease rapidly progressed while on “therapeutic” doses of warfarin. No cause for his anemia could be documented, other than possible consumption of erythrocytes in the formation of extensive thrombus. Specifically, there was no substantial blood loss due to his injury or previous hospitalization. VTE is an underdiagnosed disease spectrum that we believe needs a paradigm shift in its diagnosis and treatment. The “treatment as usual” approach to VTE should be critically reassessed. In the current era of modern endovascular technology and skilled interventionalists, we recommend an aggressive percutaneous approach to this disease. The referring and emergency room physicians should be educated about VTE and have the endovascular specialist involved in the early stages of diagnosis. We recommend that any asymptomatic DVT involving the popliteal vein and above, with the presence of thrombus in more than 50% of the luminal area, and any symptomatic patient with any degree of luminal area involvement in the popliteal vein and above, be considered for percutaneous intervention. This recommendation is not based on any randomized data, simply because there are none; rather it is based on common sense and recognition of decades of underdiagnosis and undertreatment of this disease, leading to an epidemic of stasis dermatitis, which has been sadly accepted as an inevitable consequence! We further propose that large PE and those associated with hemodynamic instability or hypoxemia be highly considered for a similar approach. The existing pool of interventional cardiologists would specially be helpful in contributing to the necessary manpower to perform these procedures. We would also recommend formation of a registry to evaluate long-term results of percutaneous venous interventions for VTE. Acknowledgements The authors would like to thank Alan Poland and Tim Wheeler from Possis Medical for their input on the application of the Power Pulse Spray mode of Angiojet.
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