Which Are the Best Techniques for Reducing the Incidence of Postoperative Deep Vein Thrombosis?

INTRODUCTION

Venous thromboembolism (VTE) is a major public health issue. VTE remains one of the main causes of mortality. It is also associated with considerable morbidity because nonfatal pulmonary embolism (PE) and deep vein thrombosis (DVT) induce short- and long-term complications. ^, In addition, anticoagulant treatment, although effective, may be a potential source of iatrogenic complications.

Nevertheless, the benefit/risk ratio of widespread postoperative prophylaxis is highly positive, at least in patients at moderate or high risk for DVT. Furthermore, the global VTE rate has been continuously decreasing since the early 1970s as a result of prophylaxis; the development of day surgery, fast-track procedures, and related improvements in the rehabilitation processes; and major progress in surgical and anesthetic techniques. ^, As an example, currently, less than 0.5% of patients undergoing major orthopedic surgery will develop a symptomatic VTE event. The PE rate is well below 0.2%, and the fatal PE rate is much lower than 0.05% in this setting.

Although the likelihood of a fatal PE episode in a patient with a hip fracture is now very low, this is not the case in other surgical settings such as thoracic or bariatric surgery. In addition, an increasing number of elderly patients with severe risk factors are undergoing major surgical procedures. Therefore many questions still need to be answered. New controversial data have recently been published on mechanical prophylaxis and are causing much debate. The direct oral anticoagulants (DOACs) are an issue of interest in that their high efficacy rate may be offset by an increase in bleeding risk. Last but not least, aspirin is coming back.

PATHOPHYSIOLOGY AND RISK

Postoperative thromboembolic risk includes both patient-related risk and surgical risk.

Patient-related risk increases linearly with age, becoming more marked after 40 years of age and even more so after 60 years. Obesity is responsible for an increased risk for thrombosis as a result of longer immobilization and decreased fibrinolytic activity. Cancer, especially lung, pancreas, colon, or pelvic cancer, increases thromboembolic risk, although surprisingly metastases do not. Cancer-related risk is independent of age. Several other important factors that increase perioperative VTE risk have been reported ( Box 46.1 ).

BOX 46.1

Patient-Related Risk Factors for Thrombosis ^,

Age older than 40 years
Obesity (body mass index >30)
Cancer and cancer treatment (hormones, chemotherapy, radiotherapy)

and
History of venous thromboembolism
Idiopathic or acquired thrombophilia
Acute medical illness
Active heart or respiratory failure
Severe infection
Estrogen-containing contraception or hormone replacement therapy
Selective estrogen response modifiers
Inflammatory bowel disease
Immobilization, bed rest, limb paralysis
Nephrotic syndrome
Myeloproliferative syndrome
Paroxysmal nocturnal hemoglobinuria
Smoking
Varicose veins
Central venous catheter

The surgical risk is usually well established and ranges from low or absent (e.g., hand surgery or osteosynthesis device removal) to high (e.g., surgery for hip fracture or pelvic surgery for cancer; Table 46.1 ). Nevertheless, the risk may also be uncertain in instances, such as in laparoscopy. Although the minimally invasive nature of laparoscopy might be thought to reduce risk, other aspects—the reverse Trendelenburg position, gas insufflation (vena cava compression with impaired venous return), and a longer operative time—might increase the risk. In addition, more and more complicated oncologic procedures are performed under laparoscopy, complicating the risk assessment.

TABLE 46.1

Risk Categories for Venous Thromboembolism Surgery

Examples of Surgical Procedures	Risk Category
Varicose vein	Low
Minor abdominal surgery	Low
Knee arthroscopy	Low
Trauma to knee without fracture	Low
Endoscopic prostate surgery	Low
Percutaneous kidney surgery	Low
Diagnostic laparoscopy (<30 mm)	Low
Minor abdominal surgery with extensive and/or bloody dissection, very long operative time or emergency	Moderate
Fracture of lower extremity	Moderate
Laminectomy	Moderate
Vaginal hysterectomy	Moderate
Breast cancer surgery	Moderate
Major abdominal surgery (even in the absence of cancer)	High
Bariatric surgery	High
Total hip or knee replacement	High
Hip fracture	High
Open kidney surgery	High
Open prostate surgery	High
Prolapse surgery	High
Uterine and ovarian surgery for cancer	High
Lung resection by thoracotomy	High
Intracranial neurosurgery	High

The overall risk, which combines patient-related risk and surgical risk, can be classified into three broad categories: low, moderate, and high; however, these categories have not been precisely quantified. The level of risk should be a consideration in the choice of prophylaxis, but if three moderate risks are summed (e.g., prolonged immobilization, obesity, and age older than 60 years), the crucial question is whether the overall risk is significantly increased. The Caprini score, popularized by a North American surgeon in 2001, helps to set the risk level into a minor, moderate, or major level. Nevertheless, pending the major decrease in the postoperative VTE risk, this score may be now rather pessimistic and should be recalculated taking into account day surgery and fast track procedures. Very quickly, any patient becomes automatically a high-risk patient. Therefore a new version should be developed.

The bleeding risk should also be considered. The clinical development of new antithrombotic agents during the last 20 years has focused on several intrinsic and extrinsic criteria that could increase the perioperative bleeding risk in anticoagulant-treated patients. Renal insufficiency, age older than 75 years, and a low body weight (<50 kg) represent the three major bleeding risk factors that can be summarized by the use of the Cockroft-Gault formula for the calculation of creatinine clearance. A patient with a clearance less than 30 mL/min has a definite increased risk for bleeding (but also an increased thrombotic risk). Other bleeding factors are shown in Box 46.2 .

BOX 46.2

Risk Factors for Bleeding

Active bleeding
Acquired bleeding disorders (such as acute liver failure)
Concurrent use of anticoagulants known to increase the risk for bleeding (such as warfarin with international normalized ratio higher than 2)
Lumbar puncture/epidural/spinal anesthesia expected within the next 12 hours
Lumbar puncture/epidural/spinal anesthesia within the previous 4 hours
Acute stroke
Thrombocytopenia (platelets less than 75 × giga/L)
Uncontrolled systolic hypertension (230/120 mm Hg or higher)
Untreated inherited bleeding disorders (such as hemophilia and von Willebrand disease)

OPTIONS

The first method of VTE prevention should be early mobilization and ambulation. This is not always possible, however, and other techniques are needed. Mechanical and pharmacologic prevention can be proposed either separately or concomitantly, even if chemical prophylaxis appears to be more effective than mechanical prophylaxis, which is usually the first-line approach.

EVIDENCE

Mechanical Prophylaxis

Two types of techniques are commonly used, but their level of efficacy is quite different.

Graduated compression stockings (GCS) have been popular for many years. Several very old nonrandomized studies showed a benefit in VTE prevention. A regular update of a Cochrane review points out that there is a reduction risk of 65% in surgical patients. Most of the included studies are very old, however, up to 1971, with limited populations (1681 patients as a total in 20 studies) and major biases. The only large randomized study published in the Lancet and showing negative results is not included in this analysis because it was conducted in stroke patients. The CLOTS trial 1 was an outcome-blinded, randomized controlled multicenter (n = 64) trial, with 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile. Patients were randomized to routine care plus thigh-length GCS (n = 1256) or to routine care plus avoidance of GCS (n = 1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at 7 to 10 days and, when practical, again at 25 to 30 days after enrolment. The primary outcome (symptomatic or asymptomatic DVT in the popliteal or femoral veins) occurred in 126 (10.0%) patients allocated to thigh-length GCS and in 133 (10.5%) allocated to avoid GCS, which was not significantly different. Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use. Therefore there is definitely no benefit for the use of GCS, and potential harm has been reported, including a “tourniquet effect” when these GCS are not correctly adjusted. The GAPS study has recently shown that the use of graduated compression stockings (GCS) did not offer any adjuvant benefit when pharmaco-thromboprophylaxis is used for VTE prophylaxis in patients undergoing elective surgery. In total, 1905 elective surgical inpatients (≥18 years) have been included in this open, multicenter, randomized, controlled, noninferiority trial and have been assigned (1:1) to receive low-molecular- weight heparin (LMWH) pharmaco-thromboprophylaxis alone or LMWH pharmaco-thromboprophylaxis and GCS. A primary outcome event occurred in 16 of 937 (1.7%) patients in the LMWH alone group compared with 13 of 921 (1.4%) in the LMWH and GCS group. Because the 95% confidence interval (CI) did not cross the noninferiority margin of 3.5% (P < .001 for noninferiority), LMWH alone was confirmed to be noninferior. These findings indicate that GCS might be unnecessary on top of pharmacologic prophylaxis in most patients undergoing elective surgery.

Intermittent pneumatic compression (IPC) devices appear to be much more effective than GCS. Numerous studies, either in medical and surgical patients, have demonstrated a real efficacy with a reduction of VTE close to 60%. As an example, Lacut et al. have randomly allocated patients with a documented intracerebral hemorrhage (ICH) to GCS alone or combined with IPC. The primary outcome was a combined criteria assessed at day 10, including a symptomatic and well-documented VTE, or a death arising before day 10 and related to PE or an asymptomatic DVT of the lower limbs detected by compression ultrasonography (CUS). Outcome assessment was blinded. Fourteen asymptomatic DVTs were detected: 3 (4.7%) in the GCS and IPC group (all distal) and 11 (15.9%) in the GCS group (3 proximal and 8 distal). GCS combined with IPC was associated with a reduced risk for asymptomatic DVT compared with GCS alone (relative risk [RR] 0.29).

The CLOTS trial 3 was a multicenter parallel group randomized trial assessing IPC in immobile patients with acute stroke. In total, 2876 patients were enrolled in 94 centers from day 0 to day 3 of admission and allocated via a central randomization system (ratio 1:1) to receive either IPC or no IPC. To be included in the trial, patients had to be admitted to hospital within 3 days of acute stroke and be immobile (i.e., could not mobilize to the toilet without the help of another person). A technician who was blinded to treatment allocation did a CUS of both legs at 7 to 10 days and, wherever practical, at 25 to 30 days after enrolment. The primary outcome (DVT in the proximal veins detected on a screening CUS or any symptomatic DVT in the proximal veins, confirmed on imaging, within 30 days of randomization) occurred in 8.5% of patients allocated to IPC and 12.1% of patients allocated to no IPC. Excluding the 323 patients who died before any primary outcome and 41 without any screening CDU, the adjusted odds ratio (OR) for the comparison was 0.65. Deaths in the treatment period occurred in 11% of patients allocated to IPC, and 13% of patients allocated to no IPC died within the 30 days of treatment period (p = .057); skin breaks on the legs were reported in 3% of patients allocated to IPC and in 20 of patients allocated to no IPC ( p = .002). IPC was effective in reducing the risk of DVT and possibly improving survival in patients who were immobile after stroke.

A Cochrane review on the benefit of combining pharmacologic prophylaxis with IPC provides a moderate-quality evidence that suggests that combining IPC and pharmacologic prophylaxis, compared with IPC or pharmacologic prophylaxis alone, decreases the incidence of DVT compared with compression and incidence of PE compared with anticoagulation.

In contradistinction, a recent study by Arabi et al. randomly assigned patients within 48 hours after admission to an intensive care unit (ICU) to receive either IPC for at least 18 hours each day in addition to pharmacologic thromboprophylaxis with unfractionated heparin or LMHW or pharmacologic thromboprophylaxis alone. Proximal DVT occurred in 3.9% of patients in the IPC group and in 4.2% of patients in the control group (difference not significant). The rates of VTE (PE or DVT) did not differ either. IPC did not result in a significantly lower incidence of proximal DVT than pharmacologic thromboprophylaxis alone. This may probably be explained by the anticoagulant treatment, whose potency erased the potential effect of IPC, as in the GAPS study.

As a summary, IPC is widely used in the United States and Canada, and probably a little less in Europe. It is effective when used alone and should be proposed to patients with a high bleeding risk in the operating room, on supine patients undergoing long procedures, and in ICU patients with contraindications to anticoagulant agents (neurosurgery for instance).

Pharmacologic Prophylaxis

Three types of anticoagulants—vitamin K antagonists, heparins (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], and fondaparinux) and direct oral antithrombotic agents (anti-IIa and anti-Xa) are currently being used or are under clinical development for VTE prophylaxis. Aspirin also develops a VTE prophylaxis effect.

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