**3. Pathogenesis and risk factors**

The traditional Virchow's triad of hypercoagulability, Stasis of the venous stream and vessel wall (endothelial) trauma is still the basis of description of the pathophysiology of DVT.

One or more of these three factors may explain DVT in patients with radical pelvic surgeries. The risk factors and the underlying pathogenetic mechanisms of DVT are shown in table (1).

A major factor is immobilization (prolonged bed rest), which can impair venous drainage from the lower limb with subsequent venous stasis (Clark & Cotton, 1968).

The other reasons that can induce venous stasis as well as other risk factors for DVT/PE are enlisted in table (1).

over years (Silverstein et al., 1998). However, the incidence of DVT and PE may be underestimated because of the missed diagnosis, absence of pertinent symptoms or the absence of laws to permit routine autopsies in sudden post-operative mortalities in most centers (Dalen & Alpert, 1975; Clagett, 1994). Furthermore, unexplained DVT may be the first presentation in some malignancies, such as prostate, colorectal and bladder (Monreal &

In a series of 2373 patients, the incidence of DVT was 0.87% after urologic surgeries for prostate and bladder tumors, 2.8% in general surgery and 2% in gynecological surgeries

The incidence of DVT may be as low 2% after radical cystectomy (Ali-El-Dein et al., 2008; Ghoneim et al., 2008), or as high as 40% following prolonged gynecological or obstetrical surgery (Walsh et al., 1974; Clarke-Pearson et al., 1983). Patients undergoing large bowel surgery also have a considerable risk of DVT and pulmonary embolism. The incidence of DVT following radical cystectomy in our hospital is 2% to 2.6% and PE following DVT or without prior DVT has long been a leading cause of post-operative death (Ali-El-Dein et al., 2008; Ghoneim et al., 2008). In patients undergoing surgery or radiotherapy for treatment of localized prostate cancer the incidence of DVT was 2% for pelvic lymphadenectomy alone and 1.9% following prostatectomy, while fatal PE occurred in 2 patients (3.7%) after

The incidence of DVT after gynecologic and obstetrical surgeries varies according to the presence or absence of the known risk factors among patients and according to the methods of diagnosis. It has been reported that this incidence is 14% after benign gynecological surgeries (Walsh et al., 1974), while the rate has been higher (38%) for patients undergoing surgery for gynecological tumors (Crandon & Knotts, 1983). In addition, among all causes of death following gynecologic surgeries, PE has been a leading cause of postoperative mortality in high risk women with gynecologic malignancy (Clarke-Pearson et al., 1983). Following laparoscopic radical hysterectomy for cervical carcinoma the incidence of DVT

In the study of yang et al. on 3645 patients undergoing surgery for colorectal cancer, 31 (0.85%) developed symptomatic venous thromboembolism or VTE (Yang et al., 2011).

The traditional Virchow's triad of hypercoagulability, Stasis of the venous stream and vessel wall (endothelial) trauma is still the basis of description of the pathophysiology of DVT.

One or more of these three factors may explain DVT in patients with radical pelvic surgeries. The risk factors and the underlying pathogenetic mechanisms of DVT are shown

A major factor is immobilization (prolonged bed rest), which can impair venous drainage

The other reasons that can induce venous stasis as well as other risk factors for DVT/PE are

from the lower limb with subsequent venous stasis (Clark & Cotton, 1968).

Prandoni, 1999).

(Scarpa etal., 2007).

prostatectomy (Bratt et al., 1994).

has been 3% (Chen et al., 2008).

in table (1).

enlisted in table (1).

**3. Pathogenesis and risk factors** 


Table 1. Risk factors in DVT following radical pelvic surgeries

Deep Venous Thrombosis After Radical Pelvic Surgery 177

The majority of cases of DVT/PE have one or more risk factor. Many cases of DVT/PE are asymptomatic. Suspected pulmonary embolism is a medical emergency and can be fatal. In symptomatic DVT cases, the patient may present with lower limb pain, unilateral leg swelling, redness and sometimes prominent superficial veins. A tender calf, especially with dorsiflexion (Homan's sign) and rarely a palpable venous cord are among the possible physical signs. However, the presence of these manifestations is nonspecific, because in more than 50% of the cases presenting with these symptoms, DVT is absent (Dainty et al., 2004). Therefore, diagnosis of DVT based on symptoms only is problematic and proper hospital assessment and further diagnostic tools are needed for accurate diagnosis. Similarly, most of the symptoms and signs of PE are nonspecific and simulate post-surgery pulmonary complications. However, physicians should maintain a high degree of suspicion if the patient is complaining of pleuritic

The use of a simple prediction tool, together with the laboratory tests of D-dimers and arterial blood gases (ABG) in cases of suspected PE are useful tools to exclude or prove DVT (Crisan et al., 2011). D-dimers are fibrinogen degradation products which are generally

Imaging for DVT includes B-mode duplex Doppler ultrasound, impedance plethysmography, contrast venography, and magnetic resonance venography (MRV). Doppler ultrasound is currently the most common technique for the diagnosis of symptomatic DVT. B-mode ultrasonography allows a bi-dimensional image of the vessels of the lower extremity and when compression techniques are used, a sensitivity of up to 90% and a specificity of 96% to 100% can be achieved in the detection of DVT (Cronan et al., 1987;

In duplex ultrasonography B-mode is combined with Doppler flow, therefore, providing information about flow velocity. When color Doppler flow is used with compression Bmode ultrasonography (color duplex ultrasonography), additional data on the direction of

Impedance plethysmography is a noninvasive diagnostic test that has a good accuracy in the detection of proximal DVT, when the results are analyzed in combination with positive clinical data (Kearon et al., 1998). However, false positive results may be obtained with this test and if the results of this test are non-diagnostic or not coping with the clinical data,

Contrast venography is still the gold standard for the diagnosis of DVT and is used by investigators as a reference standard for testing the new noninvasive diagnostic DVT

The technique is done as classically described (Rabinov & Paulin, 1972). A misdiagnosis is expected if all the deep veins from the leg up to the vena cava are not seen. When there is a persistent filling defect in the lumen of 2 or more veins, the diagnosis of DVT is confirmed

present at higher concentrations than normal in the blood of people with DVT.

chest pain, hemoptysis, dyspnea, tachycardia and tachypnea.

flow is gained (Cronan et al., 1987; O'Leary et al., 1988).

venography should be performed (Kearon et al., 1998).

**4. Diagnosis of DVT/PE** 

**4.1 Laboratory testing** 

**4.2 Imaging in DVT** 

O'Leary et al., 1988).

measures (Tapson et al., 1999).

Endothelial injury of the vessel wall may be induced by surgical dissection in various radical pelvic surgeries (e.g. radical cystectomy) or from infiltration of the vessel wall by the tumor. In addition, catheters placed distally or proximally in the venous system are among the risk factors (Evans et al., 2010). However, in this situation, the risk of DVT/PE is determined by multiple factors including catheter size (Evans et al., 2010), degree of vein trauma during catheter insertion and dwell and hypercoagulability of the patient' blood.

Hypercoagulability or thrombophilia or prothrombotic state is a blood coagulation disorder with a subsequent increase in the incidence of thrombosis (Heit, 2007). There are multiple genetic and acquired risk factors that influence thrombophilia. The presence of these inherited risk factors alone usually does not cause thrombosis unless an additional risk factor is present (Heit, 2007; Kyrle et al., 2010).

Antithrombin deficiency, which is the first major form of thrombophilia, was identified in 1965, while the most common defects, such as factor V Leiden mutation and prothrombin gene mutation G20210A were described in the 1990s (Dahlbäck, 2008; Rosendaal & Reitsma, 2009). The risk of developing DVT/PE increases significantly if one of these abnormalities is present in patients undergoing radical pelvic surgery.

There are various possibilities, which can induce a hypercoagulable state during major radical pelvic surgeries. These possibilities include decreased fibrinolytic activity associated with surgery (Egan et al., 1974), increased level of coagulation factors I, V, VIII, IX, X, and XI, the presence of activated intermediate coagulation products such as thrombinantithrombin III complexes and abnormalities of the platelets (Piccioli et al., 1996). In addition, the malignant cells may secrete a substance promoting coagulation, such as tissue factor and cancer procoagulant or factors that influence vascular endothelial permeability such as vascular endothelial growth factor and subsequently stimulate fibrin deposition (Goad & Gralnick, 1996).

In the prospective study of Duke University Medical Center 411 patients undergoing major abdominal and pelvic gynecologic surgery were evaluated for DVT and the related possible risk factors (Clarke-Pearson et al., 1987). In this study, the important factors, which maintained statistical significance in stepwise logistic regression model were age, edema of the ankle, type of surgery, nonwhite race, presence of varicose veins, history of radiation preoperatively, past DVT and duration of surgery.

It has been found that the risk factors for distal DVT are different from those of proximal DVT. In the national (France) multicenter prospective OPTIMEV study, out of 6141 patients with symptoms suggestive of DVT, diagnosis was objectively confirmed in only 1643 and isolated distal DVT was more common than proximal one (Galanaud et al., 2009). In this study, acute or transient risk factors, such as recent surgery, recent plaster immobilization and recent travel, were more frequently discovered in distal DVT. On the other hand, in proximal DVT chronic risk factors such as active cancer, congestive heart failure or respiratory insufficiency and age above 75 years were more frequent.

Active cancer and related chemotherapy can increase the incidence of DVT by multiple mechanisms. In chronic lymphocytic leukemia patients, studies showed a link between lenalidomide associated DVTs and inflammation, upregulation of TNFα and endothelial cell dysfunction (Aue etal., 2011).
