**2. Etiology and incidence**

The majority of undesirable material presenting in the major venous circulation have their origins in the lower extremity veins. Deep venous thrombosis has an estimated annual incidence of over 2 million cases in the United States (Hirsh & Hoak, 1996), and accounts for approximately 600,000 hospitalizations per year (Schreiber, 2010). The genesis of venous thrombosis continues to be aptly characterized by the observations of Virchow in 1856 (Virchow, 1998, as cited in Lopez et al., 2004), who is credited with associating the triad of (1) venous stasis, (2) endothelial injury and (3) hypercoagulability with the formation of intravascular clot. The incidence of pulmonary embolism is closely tied to the occurrence of deep venous thrombosis, so much so that the complex of deep venous thrombosis and pulmonary embolism is defined by the term "venous thromboembolism". It is estimated that approximately 50% of patients with deep venous thrombosis have detectable pulmonary emboli (Hirsh, 1996). Lower extremity deep venous thrombosis in the distal vessels, e.g. calf vein thrombosis, has commonly been held to be relatively benign, and mostly asymptomatic; however, some studies have shown that propagation of calf vein clot above the popliteal level occurs in approximately 15% of patients (Lohr et al., 1991). Upon propagation to the popliteal vein, the risk of measurable pulmonary embolism increases to approximately 40% (Kakkar et al., 1969, as cited in Hirsch & Hoak, 1996).

Risk factors for venous thromboembolism are associated with conditions that alter elements of Virchow's triad. These include increasing age, surgery, trauma, hospital or nursing home

Application of a Novel Venous Cannula for

thromboembolism patients (Campbell et al., 2007).

**3. Therapeutic history** 

or intravenous fibrinolysis.

**3.2 Surgical therapy** 

**3.1 Medical therapy** 

En-Bloc Removal of Undesirable Intravascular Material 129

Medical treatment of venous thromboembolism was instituted in 1960 with the first randomized clinical trial evaluating the efficacy of anticoagulation in patients with pulmonary embolism (Barrett & Jordan, 1960). Anticoagulation therapy does not resolve existent thrombus, but prevents its propagation, and significantly reduces the mortality rate of pulmonary embolism. Untreated pulmonary embolism carries a mortality rate of approximately 30%; this is reduced to approximately 8% when anticoagulation is instituted (Banovac et al., 2010). The typical therapeutic approach involves intravenous infusion of unfractionated or low molecular weight heparin, followed by oral anticoagulation with warfarin , which is continued for a period of several months. It has been suggested that little benefit is gained by extending anticoagulation therapy from three to six months in venous

Fibrinolytic agents provide active dissolution of clot; they were introduced into clinical treatment of venous thromboembolic disease in the 1970s (Tibbutt et al., 1974). Streptokinase, urokinase, and recombinant tissue plasminogen activator (rTPA) are compounds available for fibrinolytic therapy. All three agents convert plasminogen to plasmin, with subsequent enzymatic degradation of fibrin clot. Studies on the efficacy of the three available fibrinolytic agents demonstrate no difference in clot resolution after twentyfour hours (Almoosa, 2002). The positive effect of thrombolytic agents is partially offset by their potential for major bleeding complications, including intracerebral hemorrhage. The risk of hemorrhage during fibrinolytic therapy varies between 6 – 20% (Harris & Meek, 2005). A meta-analysis of nine randomized, controlled clinical trials comparing anticoagulation alone to anticoagulation plus thrombolysis demonstrated no difference in overall mortality between the two treatment regimes in non-selected patients with acute pulmonary embolism (Thabut, G. et al., 2002). Therefore, fibrinolytic therapy is indicated for patients with massive pulmonary embolism characterized by hypotension, or potentially for normotensive pulmonary embolism patients demonstrating right heart dysfunction, as this subgroup of patients has been associated with a higher risk of mortality in previous studies (Goldhaber, 1993, as cited in Harris & Meeks, 2005). Fibrinolytic agents may be delivered intravenously, or selectively into the pulmonary artery at the site of occlusion. A prospective, multi-center trial comparing intrapulmonary fibrinolytic infusion with intravenous fibrinolytic administration found no significant benefit with intrapulmonary catheter therapy (Verstraete et al., 1988). Instead, a prolonged intravenous thrombolytic infusion over seven hours appeared to yield a superior benefit to a single infusion over two hours. Direct insertion of an infusion catheter into the substrate of the embolus has been suggested as a more efficacious method of fibrinolytic delivery. Insufficient clinical data is available at this time to establish superiority of intra-embolic infusion over intrapulmonary

Patients with massive venous thromboembolism and particularly those with contraindications to thrombolytic therapy are candidates for surgical thrombectomy and embolectomy. Pulmonary embolectomy is a substantial procedure, necessitating a median sternotomy and cardiopulmonary bypass, but without cardioplegic arrest. An arteriotomy in the main pulmonary artery is performed to allow instrumental extraction of thrombus

confinement, malignancy, paralytic neurologic disease, presence of an indwelling venous catheter or pacing lead, varicose veins, previous superficial vein thrombosis, pregnancy, and oral contraceptive use (Heit, 2002). The recurrence rate for patients with a single episode of venous thromboembolism is approximately thirty percent over ten years.

The incidence of pulmonary embolism in the U.S. is estimated to be 1.35 million cases per year (Banovac et al., 2010). Predicted outcomes for patients with pulmonary embolism vary greatly with the hemodynamic stability of the patient upon presentation. Patients with a systolic arterial blood pressure below 90 mm Hg are deemed to have massive pulmonary embolism, while patients with a systolic pressure equal to or above 90 mm Hg are categorized as having non-massive pulmonary embolism. In the International Cooperative Pulmonary Embolism Registry involving 2,342 patients, the vast majority (95.5%) had non-massive pulmonary embolism, while 4.5% had massive pulmonary embolism. Patients with massive pulmonary embolism had a 90 day mortality of 52.4%, compared with a 90 day mortality of 14.7% in patients with non-massive pulmonary embolism (Kucher et al., 2006). In hospital mortality for patients with pulmonary embolism rose from 8.1% in clinically stable patients to 25% in unstable patients, and increased to 65% in patients requiring cardiopulmonary resuscitation, in a separate study of 1,001 patients (Kasper et al., 1997).

Inferior vena cava thrombosis is also associated with deep venous thrombosis, although to a lesser extent than the tie between deep venous thrombosis and pulmonary embolism. The frequency of IVC thrombosis in patients with deep venous thrombosis is estimated to be between 4 - 15% (Fernandez & Geehan, 2008). Other causes of inferior vena cava thrombosis include malignancy, trauma, surgery, abdominal aortic aneurysm, and indwelling venous catheters. In one series, carcinoma of the kidney was the most common cause of IVC thrombosis, accounting for 31% of cases presenting over a 23 year period (Siqueira-Filho et al., 1976). The actual incidence of inferior vena cava thrombosis is difficult to cite, due to the variability of its presentation. It is estimated that in patients with IVC thrombosis, over onehalf remain asymptomatic until their initial presentation with pulmonary embolism. Iatrogenic causes of inferior vena cava thrombosis are also significant. IVC thrombosis maybe a complication of vena cava filter placement, in the treatment of or prophylaxis for pulmonary embolism. The occurrence of IVC thrombosis was 2.7% in a 26 year review of 1731 patients implanted with 1765 vena cava filters (Athanasoulis et al., 2000). Vena cava thrombosis may also be caused by indwelling intravascular devices such as pacemaker leads, parenteral nutrition catheters, or hemodialysis catheters (Krug & Zerbe, 1980; Mulvihill & Fonkalsrud, 1984; Gouge et al., 1988).

Masses presenting in the cardiac portion of the venous circulation are relatively rare. Most of such masses are primary atrial myxomas. A study of 33108 consecutive cardiac surgical patients found an incidence of right atrial myxoma to be 0.036%; this incidence represents less than 10% of all atrial myxomas, as most atrial myxomas are left sided. Thrombus formation on the tumor surface or dislodged tumor fragments may cause pulmonary embolism. Thrombus originating in the iliofemoral system or the inferior vena cava may propagate into the right atrium (Khurana & Tak, 2004). Once clot presents in the right atrium, the prognosis is poor without active thrombectomy. A review of the literature involving twenty patients with right atrial thrombus found that the condition was uniformly fatal without treatment, while a 50% mortality rate was observed when either anticoagulation or thrombolytic therapy was administered. When surgical extraction was performed, the mortality rate was reduced to 14% (Armstrong et al., 1985).
