Fig. 10.1
A CT scan of the chest with PE protocol of a healthy 50-year-old patient who underwent elective orthopedic surgery and presented 1-week postoperatively with a massive PE. She had no risk factors other than the use of a topical vaginal estrogen ointment
There are varying types of ultrasound, which include compression ultrasound (B-mode imaging), Doppler waveform imaging, and color Doppler imaging. B-mode imaging creates images of the vessels that can be analyzed for alteration of blood flow around a filling defect or echogenic material within the lumen, and compression is added to evaluate the amount of compressibility of the vein (decreased if a thrombus is present) (Figs. 10.2, 10.3, 10.4, and 10.5). Both Doppler waveform and color Doppler imaging use sound or color, respectively, to better identify vessels and look for changes or absence of blood flow. Duplex ultrasound is the combination of compression ultrasound with either color or Doppler waveform imaging. The sensitivity and specificity of ultrasound depend on the form of ultrasound used, the location of the thrombus, and whether the patient is symptomatic or not [78]. A meta-analysis of studies using various ultrasound methods to detect DVT in asymptomatic patients found a pooled sensitivity of 62 % and specificity of 97 % [71]. Proximal DVT was significantly better with a sensitivity of 95 % and specificity of 100 % [71]. A meta-analysis that looked at studies with only symptomatic patients found a pooled sensitivity of 89.7 % for detecting any DVT, 94.2 % for proximal DVT, and 63.5 % for distal DVT [23]. In a high-risk postoperative patient with concern for DVT but a negative ultrasound, venography or serial ultrasounds may need to be considered. The diagnostic criteria for a DVT on ultrasound are displayed in Table 10.1.
Fig. 10.2
Compression ultrasound (B-mode imaging) showing (a) the vein with an open lumen and (b) full compression of the vein, indicating absence of thrombus
Fig. 10.3
Echogenic material within the vein demonstrating a thrombus
Fig. 10.4
Color Doppler imaging showing (a) color flow in the lumen, (b) absence of color flow in the lumen suggesting a clot, (c) an example of venous and arterial Doppler with a flow in both, and (d) image showing a flow in the artery, but not in the vein, indicating a clot
Fig. 10.5
Diagram for reporting DVT found on ultrasound examination
Table 10.1
Ultrasound diagnostic criteria for DVT
B-mode/compression imaging | Color/waveform Doppler imaging |
|---|---|
Intraluminal echogenic material | Absent intraluminal signal (no flow) |
Blood flow around intraluminal filling defect | Color flow around an intraluminal filling defect |
Partially compressible or non-compressible vein | Diminished or absent flow response with augmentation maneuvers (squeezing distal portion of the vein) |
Increase in vein diameter | Non-phasic, continuous flow (with respirations) |
No change or reflux with Valsalva maneuver |
10.4 Risk Factors
Multiple risk factors, both patient and procedure specific, may affect a patient’s overall risk for developing VTE.
10.4.1 Patient-Specific Factors
Patient-specific risk factors include age, gender, previous history of VTE, oral contraceptives or hormone replacement therapy, varicose veins, smoking, obesity, history of malignancy, pregnancy, and an inherited or acquired thrombophilia.
Increasing age is considered an independent risk factor for VTE [8, 24, 31], and multiple studies show a positive correlation between increasing age and incidence of DVT [36, 45, 46, 63, 65, 67, 77]. One study indicated that hazard ratio for VTE after knee arthroscopy increased by 34 % for every 10-year increase in age [48].
A number of studies have analyzed gender as a risk factor for VTE after knee arthroscopy or ACL reconstruction. The overwhelming consensus appears to be that there is no difference in incidence between males and females [13, 36, 45, 46, 67]. Only one study found a higher risk of DVT in female patients, but their female population had a higher age than their male counterparts [77].
Another factor that can affect the gender divide is the use of oral contraceptives (OCP) or hormone replacement therapy (Fig. 10.1). While the use of these in general is considered to be an independent risk factor for VTE, the literature with respect to knee arthroscopy and ACL reconstruction is more conflicting [24, 31]. Two studies found no association between the use of OCPs and incidence of DVT postoperatively [12, 65], while a third retrospective study found that there was a higher incidence of DVT in patients who had received or refilled a prescription for OCP in 4 months leading up to knee arthroscopy surgery [45]. They found the odds of developing a DVT, adjusted for age, were 2.54 times higher if the patient was taking OCPs [45].
Most studies did not find obesity (typically defined as BMI >30) alone related to increased incidence of DVT [48, 61, 65, 67]. One study did find that in the presence of at least two other patient-specific risk factors, a BMI >30 contributed to an increased incidence of DVT [12].
The presence of varicosity or chronic venous insufficiency was not found to be associated with DVT incidence in two studies [12, 65], but was the only statistically significant risk factor in another study [61].
A personal history of previous VTE has long been associated with an increased risk of a recurrent VTE. One study confirmed it as an independent risk factor with a relative risk of 8.2 for the development of DVT [12]. However, two other studies did not find an association between increased incidence of DVT post-arthroscopy and a previous history of VTE [13, 65].
Smoking is not frequently assessed in the literature, though is considered a classic risk factor for DVT [24]. One study found no correlation with incidence of DVT [46], while another found that it contributed to an increased incidence of DVT when in combination with one or more other patient-specific risk factors [12].
Another risk factor associated with developing DVT is air travel, though it has not been specifically evaluated after knee arthroscopy or ACL reconstruction. Recent studies have shown a two- to fourfold increased risk [42]. Several underlying causes have been identified including immobilization and hypoxia [6]. Air travel appears to be an especially strong risk factor for those with a genetic or acquired hypercoagulability [7]. However, even in the healthy population, some people were found to have coagulation activation after air travel [62]. A study by Schreijer et al. showed that 17 % of healthy subjects had increased thrombin-antithrombin complexes after an 8-h flight, but not after an 8-h movie marathon [62]. The remaining subjects in this study showed no activation of coagulation.
10.4.2 Procedure-Specific Factors
Orthopedic surgery in and of itself is an independent risk factor for DVT as it causes damage to muscle and bone, which triggers the release of coagulation factors and activation of platelets at the surgical site, which in turn activate local clotting processes [8, 40]. In addition, surgical stress and pain can provoke catecholamine release intravascularly, which also increase blood coagulability [8, 40].
The use of a tourniquet has been shown to increase blood coagulability during surgery, which may be related to tissue ischemia or pain [15, 40]. Hirota et al. evaluated tourniquet use and the amount of pulmonary emboli detected in the right atrium after tourniquet release in a couple different studies [32, 33]. They discovered that an increase in pulmonary emboli after tourniquet release is dependent on the duration of tourniquet inflation. In clinical studies, simply the use of a tourniquet during knee arthroscopy or ACL reconstruction is not associated with an increased incidence of DVT [46, 61, 63]. However, tourniquet time has conflicting evidence. Several studies did not find any correlation between tourniquet time and incidence of DVT postoperatively [12, 67, 77]. However, other studies demonstrated an increased incidence of DVT with longer tourniquet times >60 or 120 min [13, 15, 37, 46].
Most literature did not find an association between surgical duration and incidence of DVT [13, 46, 61, 67, 77]. It has been suggested that the type of anesthesia, either general or epidural/spinal, may have an effect on the incidence of DVT. However, two studies that evaluated regional/epidural anesthesia versus general anesthesia found no difference in risk of DVT [13, 61].
10.5 Mechanical and Pharmacological Thromboprophylaxis
The decision-making process involved in choosing the right form of thromboprophylaxis for a specific patient starts with proper risk assessment [8]. The American College of Chest Physicians (ACCP) divides patients into low, moderate, high, and very high risk based on the expected incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) in the absence of prophylaxis (Table 10.2) [58]. Based on this risk stratification, they recommend different types of prophylaxis. This can include mechanical prophylaxis such as sequential compression devices and compression stockings, or pharmacological prophylaxis. Some of the more commonly used ones are discussed below.
Table 10.2
ACCP VTE risk classification system
Low risk | Moderate risk | High risk | Very high risk | |
|---|---|---|---|---|
Uncomplicated minor surgery in patients <40 years without risk factors | Uncomplicated surgery in patients 40–60 years without risk factors | Major surgery in patients >60 years with additional risk factors | Major surgery in patients >40 years with prior VTE, malignancy, hypercoagulable state, elective major orthopedic surgery or hip fracture, polytrauma, spinal cord injury | |
Major surgery in patients <40 years without risk factors | ||||
Minor surgery in patients with risk factors | ||||
Distal leg DVT | 2 | 10–20 | 20–40 | 40–80 |
Proximal leg DVT | 0.4 | 2–4 | 4–8 | 10–20 |
Clinical PE | 0.2 | 1–2 | 2–4 | 4–10 |
Fatal PE | 0.002 | 0.1–0.4 | 0.4–1 | 1–5 |
Successful preventing strategies | No specific measures | Low-dose unfractionated heparin Q12h, low-molecular-weight heparin, fondaparinux, SCD, compression stockings | Low-dose unfractionated heparin Q8h, low-molecular-weight heparin, fondaparinux, SCD | Low-molecular-weight heparin, oral anticoagulants, SCD |
10.5.1 Sequential Compression Devices (SCD)
Pneumatic/sequential compression devices are frequently used during and immediately after orthopedic surgery. SCDs utilize sleeves with separated areas or pockets of inflation, which works to squeeze on the limb in a “milking action” (Fig. 10.6). The most distal areas will initially inflate, and subsequent pockets will follow in the same manner. The pneumatic compression is thought to prevent venous stasis and encourage blood flow in the extremity while the patient is not actively moving the operative as well as the non-operative limb [50]. However, its use is mostly limited to the hospital setting.
Fig. 10.6
A patient undergoing left knee arthroscopy. The right leg is placed in a sequential compression device to prevent DVT
10.5.2 Compression Stockings
Elastic compression stockings can be used in the immediate postsurgical period while the patient is recovering at home (Fig. 10.7). They reduce the diameter of distended veins and cause an increase in venous blood flow velocity and valve effectiveness. Compression stockings have been shown to help decrease venous pressure and prevent venous stasis [53]. Knee or thigh high compression stockings can therefore help prevent the formation of blood clots in the lower legs. Thromboembolism-deterrent (TED) hose are a type of gradient compression stocking. Gradient compression stockings provide the highest level of compression at the ankle which gradually lessens toward the top of the stocking. They have been shown to be effective in supporting the venous and lymphatic drainage of the leg, especially when combined with activations of the calf muscles [3]. Mechanical prophylaxis has a strong support for its use from the ACCP [21, 22].
Fig. 10.7
A postsurgical patient wearing bilateral knee high compression stockings to prevent DVT
10.5.3 Aspirin
Aspirin is a salicylate drug which has antiplatelet effect by inhibiting the production of thromboxane. Aspirin is therefore often used to help prevent heart attacks, strokes, and blood clot formation in people at high risk [43]. Its side effects include gastrointestinal bleeding, tinnitus, Reye’s syndrome, hives, swelling, and hyperkalemia. It is contraindicated in patients with peptic ulcers, diabetes, gastritis, or a history of gastrointestinal bleeding. Although commonly used as a form of thromboprophylaxis by orthopedic surgeons, the ACCP recommends against the use of aspirin alone for DVT prophylaxis in its most recent guideline due to lack of high-level evidence to support this [27].
10.5.4 Low-Dose Unfractionated Heparin
Heparin is one of the most commonly used pharmacologic DVT prophylaxes, both in orthopedic surgery and in medicine as a whole. It is recommended by the ACCP for patients with moderate, high, and very high risk [27]. Heparin works by binding to the enzyme inhibitor antithrombin III. It then inactivates thrombin and other proteases involved in blood clotting such as factor Xa [10]. Unfractionated heparin is heparin that has not been fractionated to sequester the fraction of molecules with low molecular weight. It is available for intravenous (IV) as well and subcutaneous (SQ) administration. The most common side effects include bleeding, allergic reaction, injection site reaction, increase in liver enzymes, and heparin-induced thrombocytopenia (HIT) [57]. The incidence is up to 5 % of patients treated with unfractionated heparin [57].
10.5.5 Low-Molecular-Weight Heparin
Low-molecular-weight heparin (LMWH) has undergone fractionation with the goal of making its pharmacodynamics more predictable. An example of a commonly used one is enoxaparin (trade name Lovenox, Sanofi, Bridgewater, NJ, USA) (Fig. 10.8). LMWH only consists of the short chains of polysaccharide. It can be dosed less frequently than unfractionated heparin, once or twice a day versus two to three times daily. Other potential benefits of LMWH are a smaller risk of bleeding, osteoporosis, and HIT (1 % versus 5 %). However, an advantage of unfractionated heparin is that it is reversible with protamine sulfate, while the effect of this on LMWH is limited. The use of LMWH does need to be monitored in elderly patients and those with decreased renal function as it is renally cleared.
Fig. 10.8
A postsurgical patient receiving a subcutaneous administration of Lovenox in the abdominal region for DVT prophylaxis
10.5.6 Fondaparinux
Fondaparinux is an anticoagulant medication chemically related to LMWH. The most common brand name is Arixtra (GlaxoSmithKline, Coraopolis, PA, USA). It is a synthetic pentasaccharide factor Xa inhibitor. In contrast to heparin, fondaparinux does not inhibit thrombin. The risk of HIT is substantially lower than with the use of both unfractionated and LMWH. However, its renal excretion precludes its use in patients with decreased renal function.
10.5.7 Oral Anticoagulants
There are several forms of oral anticoagulation. The most commonly used ones in orthopedic surgery belong to the coumarin family. Coumarins are plant-derived vitamin K antagonists. Warfarin is the most common generic with Coumadin (Bristol-Myers Squibb, New York, NY, USA) as the corresponding brand name. It takes at least 48–72 h for the anticoagulant effect to develop. The effectiveness is monitored by determination of the international normalized ratio (INR) in the patient’s blood. For DVT prophylaxis the recommended INR is 2.5. It can be reversed using either vitamin K and/ or the administration of fresh frozen plasma.
Another category is the direct factor Xa inhibitors. The most commonly used example is rivaroxaban (brand name: Xarelto, Janssen Pharmaceuticals, Titusville, NJ, USA). The benefit of this class of medications is that they do not require regular blood monitoring of the INR. However, they are less frequently used because they have only recently become clinically available and have less awareness than some of the other medications listed. Further it is not possible to reverse their effect. Recently there have been several class action law suits regarding specific oral Xa inhibitors secondary to increased bleeding risk. However, medical literature about this is conflicting. A recent small retrospective pilot study showed that after joint replacement surgery, postoperative bleeding occurred in 6.8 % of the patients using rivaroxaban versus in 3.2 % of the patients on enoxaparin (p < 0.0001) [76]. In contrary, a Cochrane review on the effectiveness of oral direct thrombin inhibitors and oral factor Xa inhibitors showed a similar rate of DVT and PE as compared to other forms of pharmacological anticoagulation and a decreased incidence of bleeding [56].
The last category is direct thrombin inhibitors [14]. Again, these are not very commonly used in orthopedic surgery for the same reason as the factor Xa inhibitors: they do not have a method of monitoring and cannot be quickly reversed. Some examples include argatroban (no brand name, GlaxoSmithKline, Coraopolis, PA, USA) and dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA).
Most of the oral thromboprophylaxes have been approved for use in hip and knee replacement surgery; however, their use in prophylaxis following ACL reconstruction or knee arthroscopy has not been studied.
One of the biggest considerations with oral anticoagulation is their interaction with certain foods and nutritional supplements. The blood thinning effect can be increased with the use of beer, celery, cranberries, fish oil, garlic, ginger, ginkgo, ginseng, green tea, licorice, niacin, onion, papaya, pomegranate, red clover, soybean, St. John’s wort, turmeric, wheatgrass, willow bark, danshen, and feverfew [75]. Foods and supplements that encourage clotting are alfalfa, avocado, cat’s claw, coenzyme Q10, and dark leafy greens such as spinach [75]. Grapefruit interferes with some anticoagulant drugs, increasing the amount of time it takes for them to be metabolized out of the body [75].
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