Deep Vein Thrombosis and Pulmonary Embolism

Risk Factors

Perioperative thromboembolic disease and pulmonary embolism contribute to morbidity and mortality in urological patients. Venous thromboembolism is a multifactorial disease involving clinical risk factors as well as genetic and environmental interactions. It is uncommon in the young, but after 40 years of age the incidence doubles with each decade of life. Hereditary risk factors include factor V Leiden mutation, G20210A prothrombin gene mutation, and deficiencies in protein C, protein S, and antithrombin. Hereditary and/or acquired risk factors are hyperhomocysteinemia and elevated levels of factor I, VIII, and IX. Acquired risk factors include malignancy, hospitalization/immobili-ty, surgery, venous trauma, estrogen therapy, pregnancy, and the presence of antiphospholipid antibodies. Especially operations at the prostate activate the coagulation cascade. These patients are therefore prone to develop deep veins thrombosis and thrombosis in the pelvic vein bearing an increased risk of pulmonary embolism.

It is important to identify patients with risk factors for venous thromboembolism and pulmonary embolism and patients with contraindications for the regular prophylaxis, because routine surveillance and screening are not cost-effective in the perioperative setting, as they do not reduce symptomatic venous thromboem-bolism or fatal pulmonary embolism. In most cases, it is not necessary to initiate specific diagnostic procedures to identify the exact cause of the thrombophilia, but rather attach importance to a consequent perioperative antithrombotic strategy. Therefore, prevention using the standard protocol for prophylaxis is far more preferable. Anticoagulants are the first choice in the prevention of perioperative thromboembolic disease. There are widespread differences in the use of prophylaxis, however, although guidelines were published recently (Geerts et al. 2004).

One exception of the above-mentioned approach is a deficiency of antithrombin or protein C, which is usually known by the patient. After a targeted evaluation, a specific therapy with substitution of the deficient factor might by useful (Dempfle 2005).

According to a prospective study in 99 cancer patients by Sarig et al. (2005), F.V and F.VIII are elevated and can lead to acquired protein C resistance. These au-

Table B.B. Risk factors for thromboembolic complications

Hereditary

Factor V Leiden mutation

G20210A prothrombin gene mutation

Protein C deficiency

Protein S deficiency

Antithrombin III deficiency

Hereditary

Hyperhomocysteinemia

and/or

Anticardiolipin antibodies

acquired

Lupus anticoagulant

Elevation of F.I or F.VIII or F.IX

Acquired

Surgery requiring more than 30 min of anes

thesia, especially cancer surgery

Malignancy

Fracture of pelvis, femur, or tibia

Age > 40 years

History of venous thromboembolism

Obesity

Pregnancy or recent delivery

Estrogen therapy

Prolonged immobilization, nursing home

confinement

Cerebrovascular incident

Congestive heart failure

Permanent pacemaker, internal cardiac defi-

brillator

Chronic in-dwelling central venous catheter

Inflammatory bowel disease

Hypertension

Cigarette smoking

Long-haul air travel

Activated protein C resistance

Modified from Motsch et al. (2006)

Modified from Motsch et al. (2006)

thors assume that acquired protein C resistance can serve as a possible risk factor for thromboembolic complications in cancer patients, but this needs to be further evaluated. In general, cancer is a major risk factor for developing thromboembolic complications. Therefore from the surgeon's point of view, it has been raised that patients presenting with the first episode of thromboembolic disease should always be screened for cancer. It should always be kept in mind that patients with prostate cancer are at increased risk for thrombosis or Trousseau syndrome, which is a manifestation of a chronic disseminated intravascular coagulopathy and clinically presents as a migratory superficial phlebitis. Table 3.3 summarizes the risk factors for thromboem-bolic complications.

Medical History

To reveal an increased risk for thromboembolism, the examiner should pay special attention to the following conditions in the patient's medical history: deep venous thrombosis, thrombophlebitis, pulmonary embolism, myocardial infarction, angina pectoris, other signs of coronary disease, cardiac arrhythmias, occlusion of arterial vessels, embolic events, strokes, pro longed ischemic deficits, anticoagulatory therapy, unexpected or allergic reactions to anticoagulants, immobilization before surgery, influenza-like diseases, and other conditions that initiate an acute phase reaction. Additionally, the medical history of relatives is important in order to detect a thrombophilic disposition: venous thromboembolism, arterial occlusion, cerebral ischemia, transitional neurologic deficits, and relatives with continuous anticoagulatory medication.

3.2.3 Therapy

After careful evaluation of the individual patient, an individual assessment of the degree of risk for perioperative thromboembolic complications is applied. Based on this evaluation, the appropriate prophylaxis is selected.

The basic preventive perioperative therapy against thromboembolism consists of early mobilization and the use of graduated elastic compression stockings. However, the backbone of specific strategies for perioperative prevention of venous thromboembolism is treatment with anticoagulants. The old drug, unfracti-onated heparin, is characterized by serious adverse effects and by large interindividual variability necessitating close monitoring. The new anticoagulants have a more predictable action, higher efficiency and are easier to handle because they no longer require routine monitoring, but effective antagonists are mostly lacking.

Although there are widespread differences in the use of prophylaxis, the following recommendations, which are based on recently published guidelines can be suggested. According to these guidelines (Motsch et al. 2006), low molecular weight heparins (LMWH) <3,400 U once daily or unfractionated heparin (UFH) 5,000 U every 8 h should be administered to general surgery patients without any additional risk factors for venous thromboembolism. High-risk patients should receive LMWH >3,400 U daily. Cancer patients should be treated as patients at high risk. Therefore, LMWH greater than 3,400 U should be administered twice daily and continued for 28 days. For patients with prolonged postoperative intensive care unit treatment and with delayed recovery, a surveillance by venous ultrasonog-raphy should be considered, because of the high incidence of venous thrombosis in patients staying in intensive care units.

New agents, such as fondaparinux, idraparinux are superior to the standard treatment in the prevention of venous thromboembolism after high-risk major orthopedic surgery and for initial treatment of patients with venous thromboembolism. In orthopedic patients, the risk of venous thromboembolism was reduced by approximately 55%. Although major bleeding occurred

Table 3.4. Risk stratification and therapy recommendations in pulmonary embolism

Risk cate-

Hemodynamic function

Therapy recommendations

gory

1

Stable, no right ventricular dysfunction

Anticoagulation, using LMWH (or UFH) or fondaparinux

2

Stable, signs of right ventricular dysfunction

Anticoagulation, in some cases thrombolysis

3

Shock

Thrombolysis, except for strong contraindications

4

Cardiopulmonary resuscitation

Thrombolysis

Modified from Motsch et al. (2006)

Modified from Motsch et al. (2006)

more frequently, the incidence of critical bleeding was comparable to patients receiving LMWH (enoxaparin). Such superior prophylactic effects of fondaparinux could not be confirmed in 2,297 patients undergoing abdominal surgery when compared to dalteparin in a double-blind study. Data for prophylaxis in major uro-logic operations are lacking. Therefore, these new anticoagulants such as fondaparinux need to be evaluated for the perioperative urologic setting.

Inferior vena cava filters are not advisable for long-term treatment, because they pose a nidus for recurrent thrombi, but may be considered as temporary retrievable filters in selected cases, when patients cannot receive anticoagulation.

If pulmonary embolism is present, the therapy is stratified according to the severity of the disease, ranging from the use of anticoagulants to thrombolysis (see Table 3.4).

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