**1. Introduction**

Venous thromboembolism (VTE) manifesting as deep vein thrombosis(DVT) or pulmonary embolism (PE), is one of the most common complications of hospitalization and is associated with short and long-term morbidity, mortality and resource expenditure. Routine use of thromboprophylaxis reduces adverse patient outcomes while at the same time decreasing overall costs. Almost all hospitalized patients have at least one associated risk factor for VTE, and approximately 40% have three or more risk factors **(Table 1)**(1).

Surgery **Trauma (major trauma or lower-extremity injury)**  Immobility, lower-extremity paresis **Cancer (active or occult)**  Cancer therapy (hormonal, chemotherapy, angiogenesis inhibitors, radiotherapy) **Venous compression (tumor, hematoma, arterial abnormality)**  Previous VTE **Increasing age**  Pregnancy and the postpartum period **Estrogen -containing oral contraceptives or hormone replacement therapy**  Selective estrogen receptor modulators **Erythropoiesis-stimulating agents**  Acute medical illness **Inflammatory bowel disease**  Nephrotic syndrome **Myeloproliferative disorder**  Paroxysmal nocturnal hemoglobinuria **Obesity**  Central venous catheterization **Inherited or acquired thrombophilia** 

Table 1. Risk Factors for VTE

Approaching Venous Thrombosis in General Surgery Patients 183

**Optimal duration of** 

Continue until discharge for the majority of patients. Selected patients may benefit from postdischarge prophylaxis.

Minimum of 10 days and

Continue until discharge for the majority of patients. Prophylaxis should be continued for the inpatient rehabilitation period.

Duration appropriate for the specific patient risk

group.

up to 35 days.

**prophylaxis** 

Not applicable.

**thromboprophylaxis** 

Low-molecular-weight

Low-molecular-weight heparin Fondaparinux Rivaroxaban or dabigatran Warfarin (target INR 2-3)

Low-molecular-weight heparin Combinations of a mechanical method and an

Mechanical method of

prophylaxis (GCS, PCD, VFP) Consider anticoagulant prophylaxis when bleeding

GCS indicates graduated compression stocking; PCD, pneumatic compression device, VFP, venous foot

Table 3. Risk stratification, recommended thromboprophylaxis and optimal duration of

The *high-risk* group are patients over 60, candidates for major surgery, with associated risk factors. The prevalence of DVT is 20%–40%; proximal DVT 4%–8%, clinical PE 2%–4% and fatal PE 0.4%–1%. Higher doses of LMWH or LDUH should be used, together with 1 PC

anticoagulant

risk decreases

Low-dose heparin Fondaparinux Combinations of a mechanical method and an anticoagulant

No prophylaxis Early and frequent ambulation

**options\*** 

heparin

**Patient groups Recommended** 

**Low VTE Risk:** 

factors

surgery

•Medical - fully mobile, brief admission, no additional risk factors • Surgical - procedure < 30 minutes, patient mobile, no additional risk

**Moderate VTE Risk:**  •Acute medical illness •Major general surgery •Major gynecologic surgery " Major urologic

•Thoracic surgery •Bariatric surgery

**High VTE Risk:** 

**High VTE Risk:** 

spinal cord injury)

**High bleeding risk** 

pump.

devices and ES.

•Hip or knee arthroplasty •Hip fracture surgery

•Major trauma, (including

prophylaxis by patient group.

Without thromboprophylaxis, the incidence of objectively confirmed, hospital-acquired DVT is approximately 10 to 40% among medical or general surgical patients and 40 to 60% following major orthopedic surgery **(Table 2)**(1-2).


\* Rates based on objective diagnostic: screening for asymptomatic DVT in patients not receiving thromboprophylaxis.

Table 2. Approximate Risk of DVT in Hospitalized Patients

Several hundred clinical trials of thromboprophylaxis, conducted over the past 50 years, have shown that the use of prophylaxis reduces the rates of deep vein thrombosis (DVT), proximal DVT, pulmonary embolism (PE), and fatal PE by more than 60% in a broad spectrum of hospitalized patients with a very low risk of adverse effects. Although effective strategies for the prevention of venous thromboembolism (VTE) are widely available and existence of several guidelines for individual risk assessments to determine thrombosis risk and prophylaxis, a significant number of patients still develop VTE because appropriate thromboprophylaxis is not correctly prescribed. Adapting evidence-based practice guidelines into existing local policies and protocols has been shown to significantly increase the proportion of at-risk patients receiving appropriate thromboprophylaxis.

The American College of Chest Physicians (ACCP) sponsor and publish what are generally considered to be the most comprehensive and most commonly utilized of these guidelines(3). A summary of the 2008 ACCP Guidelines on the Prevention of VTE is presented in **Table 3**, (4).

The type and duration of surgery clearly influence the risk of DVT. Numerous efforts have been made to identify the patients most at risk for DVT and PE. The studies of this problem categorize risk levels as low, medium, high, and very high.

Patients at *low risk* are under 40 years of age contemplating minor surgery and with no associated risk factors. The incidence of DVT is less than 2%, proximal DVT 0.4%, PE at 0.2%, and fatal PE 0.02%. This group requires no special prophylaxis other than early ambulation.

Patients at *moderate risk* are those aged 40–50 who are undergoing major surgery, have no associated risk factors, and expect a prompt recovery. The frequency of DVT is 10%–20% proximal DVT, 2%–4%, clinical PE 1%–2%, and fatal PE 0%– 1.4%. This group will benefit from prophylactic treatment with LMWH, or LDUH and ES.

Without thromboprophylaxis, the incidence of objectively confirmed, hospital-acquired DVT is approximately 10 to 40% among medical or general surgical patients and 40 to 60%

\* Rates based on objective diagnostic: screening for asymptomatic DVT in patients not receiving

Several hundred clinical trials of thromboprophylaxis, conducted over the past 50 years, have shown that the use of prophylaxis reduces the rates of deep vein thrombosis (DVT), proximal DVT, pulmonary embolism (PE), and fatal PE by more than 60% in a broad spectrum of hospitalized patients with a very low risk of adverse effects. Although effective strategies for the prevention of venous thromboembolism (VTE) are widely available and existence of several guidelines for individual risk assessments to determine thrombosis risk and prophylaxis, a significant number of patients still develop VTE because appropriate thromboprophylaxis is not correctly prescribed. Adapting evidence-based practice guidelines into existing local policies and protocols has been shown to significantly increase

The American College of Chest Physicians (ACCP) sponsor and publish what are generally considered to be the most comprehensive and most commonly utilized of these guidelines(3). A summary of the 2008 ACCP Guidelines on the Prevention of VTE is

The type and duration of surgery clearly influence the risk of DVT. Numerous efforts have been made to identify the patients most at risk for DVT and PE. The studies of this problem

Patients at *low risk* are under 40 years of age contemplating minor surgery and with no associated risk factors. The incidence of DVT is less than 2%, proximal DVT 0.4%, PE at 0.2%, and fatal PE 0.02%. This group requires no special prophylaxis other than early ambulation. Patients at *moderate risk* are those aged 40–50 who are undergoing major surgery, have no associated risk factors, and expect a prompt recovery. The frequency of DVT is 10%–20% proximal DVT, 2%–4%, clinical PE 1%–2%, and fatal PE 0%– 1.4%. This group will benefit

the proportion of at-risk patients receiving appropriate thromboprophylaxis.

**Patient Group DVT Prevalence, %** 

Medical patients 10-20 General, surgery 15-40 Major gynecologic surgery 15-40 Major Urologic surgery 15-40 Neurosurgery 15-40 Stroke 20-50 Flip or knee arthroplasty, HFS 40-60 Major trauma 60-80 SCI 60-80 Critical care patients 10-80

following major orthopedic surgery **(Table 2)**(1-2).

Table 2. Approximate Risk of DVT in Hospitalized Patients

categorize risk levels as low, medium, high, and very high.

from prophylactic treatment with LMWH, or LDUH and ES.

thromboprophylaxis.

presented in **Table 3**, (4).


GCS indicates graduated compression stocking; PCD, pneumatic compression device, VFP, venous foot pump.

Table 3. Risk stratification, recommended thromboprophylaxis and optimal duration of prophylaxis by patient group.

The *high-risk* group are patients over 60, candidates for major surgery, with associated risk factors. The prevalence of DVT is 20%–40%; proximal DVT 4%–8%, clinical PE 2%–4% and fatal PE 0.4%–1%. Higher doses of LMWH or LDUH should be used, together with 1 PC devices and ES.

Approaching Venous Thrombosis in General Surgery Patients 185

and is associated with worsened mortality (10-12). In addition, patients with cancer who suffer VTE have an increased risk of recurrent VTE, bleeding complications, morbidity, and utilization of health care resources(13,14). Finally, newer anticancer agents particularly antiangiogenic drugs, appear to be more thrombogenic than conventional chemotherapy (15,16). Selected cancer patients with established VTE will need extended treatment to prevent its recurrence. In addition, a number of new cancer therapies have been associated with a further increase in the risk of VTE, warranting primary prophylaxis. Given the high mortality rate for VTE in cancer patients, it is imperative to ensure that all health-care professionals become familiar with and utilize the latest guidelines and tools for timely and

A hypercoagulable state or low-grade DIC is common in patients with cancer. The results of laboratory tests indicate that a process of fibrin formation and removal is ongoing during the development of malignancy. Reported rates of venous thromboembolism (VTE) in patients with cancer range from 4% to 31%(19,23). Cancer alone elevates the risk of thrombosis 4-fold; chemotherapy increases the risk 6.5-fold(24,25). Patients who undergo cancer surgery have a higher risk of postoperative VTE than those who have surgery for a nonmalignant disease (26). VTE is the second leading cause of death in cancer patients, and the presence of VTE in patients with cancer has been reported to increase the likelihood of

Results of the FRONTLINE (Fundamental Research in Oncology and Thrombosis) survey underscored the need for development of clinical guidelines focusing on VTE in cancer patients: surgeons and medical oncologists reported that they used VTE prophylaxis in only about 50% and 5% of their patients, respectively(33). Two sets of guidelines devoted specifically to oncology patients are available to help guide clinicians: recommendations by the American Society of Clinical Oncology (ASCO) and by the National Comprehensive Cancer Network (NCCN) (34-35). Both sets of recommendations direct that all adults hospitalized with cancer receive prophylactic anticoagulation therapy in the absence of contraindications. However, a recent review of more than 70,000 hospitalized patients with cancer in whom an indication for thromboprophylaxis had been identified showed that the

Alcalay et al. was found VTE as a significant predictor of death within 1 year of colorectal cancer diagnosis, among the patients with local or regional stage disease, but not among the

Thromboembolic events are a major cause of morbidity and mortality in patients undergoing surgery. Cancer patients requiring curative abdominal surgery are considered to be at a particularly high risk for VTE, and thromboprophylaxis is strongly recommended (38). Studies of Western populations have shown that DVT rates range from 15% to 30% for cancer patients not receiving thromboembolic prophylaxis, and a meta-analysis by Colditz et al. estimated fatal PE rates of 0.1%–0.8% (39,40). Colorectal surgery is associated with a specific high risk of postoperative thromboembolic complications relative to other general surgery (41-43). The incidences of DVT and PE in colorectal cancer surgery patients who do not receive thromboembolic prophylaxis are approximately 40% and 5%, respectively (42- 43). Moreover, late VTE rates of 10%– 20% have been reported in patients who received

The randomized double-blind ENOXACAN II study, and the multicenter randomized Denmark/Norway study found that thromboprophylaxis for 4 weeks after abdominal or pelvic cancer surgery reduced the incidence of venographically demonstrated asymptomatic

evidence-based risk assessment, prevention, and treatment of VTE(17,18).

death by 2- to 8-fold (27-32).

rate of appropriate prophylaxis was only 27%(36).

LMWH thromboprophylaxis in the first postoperative week (44).

patients with metastatic disease(37).

In the *very-high-risk* group of patients with major trauma (multiorgan, spinal, pelvic, long bone fractures), intermittent compression devices and ES should be started as early as possible, and LMWH or LDUH initiated as soon as it is safe. In cases of major trauma, with absolute contraindications for anticoagulants, the prophylactic indication of an inferior vena cava (IVC) filter should be considered, especially in cases with duplex ultrasonography demonstration of DVT.
