Fig. 20.1
Decision process of thromboprophylaxis in hospitalized patients. 1. At admission, each hospitalized patient must have an assessment of his/her risks of VTE and bleeding according to the clinical settings and patient’s history. Several risk assessment scores exist and can help the practitioner. 2. Each patient must be informed of the risks of VTE and bleeding and must be offered a prophylactic treatment according to the recommendation for his or her clinical settings and his or her preferences. 3. For all patients, VTE prophylaxis starts with a good hydration state (unless otherwise indicated for concurrent clinical settings) and early and frequent ambulation. 4. In patients assessed to be at increased risk of VTE, mechanical VTE prophylaxis is a noninvasive and simple thera Fig. 20.1 (continued) peutic option and the only option when the risk of bleeding is high. Anti-embolism graduated compression stockings should be offered unless contraindicated (severe peripheral arterial disease, stroke, skin lesions, etc.). Intermittent pneumatic compression is an alternative to stockings and is recommended in many surgical settings. 5. Pharmacological VTE prophylaxis comprises several drugs such as low-molecular-weight heparin, low-dose unfractionated heparin, and direct oral anticoagulants. The choice is guided by clinical settings, patient’s comorbidities, and preferences. 6. In all patients, tolerance of the prophylactic treatment must be monitored, with the help of monitoring of therapeutic serum levels for some regimens. Indication for VTE prophylaxis and correct dosage should be reevaluated every day during the hospital stay. 7. At discharge, the indication for starting or continuing VTE prophylaxis should be reevaluated. If needed, the patient must leave the hospital with a detailed prescription for VTE prophylaxis, including the length of treatment and the modality of surveillance. Comprehensive information should be given to the patient and his or her helpers, in particular to his or her family practitioner in order to improve compliance and detect complications
Table 20.1
Venous thromboembolism (VTE) risk assessment
Risk factors for VTE among hospitalized patients |
|---|
Constitutive variables |
• Age > 60 yearsa |
• Known thrombophilias |
• Personal history or first-degree relative with a history of VTE |
• Obesity (body mass index [BMI] over 30 kg/m2) |
• Varicose veins with phlebitis |
Transient or modifiable variables |
• One or more significant medical comorbidities (e.g., heart disease; metabolic, endocrine, or respiratory pathologies; acute infectious diseases; inflammatory conditions) |
• The use of hormone replacement therapy or estrogen-containing contraceptive |
• Critical care admission |
• Dehydration |
Table 20.2
Bleeding risk assessment
Risk factors for bleeding among hospitalized patients |
|---|
Constitutive variables |
• Untreated inherited bleeding disorders (such as hemophilia and von Willebrand’s disease) |
Transient or modifiable variables |
• Active bleeding |
• Acquired bleeding disorders (such as acute liver failure) |
• The use of anticoagulants known to increase the risk of bleeding |
• Acute stroke |
• Thrombocytopenia (platelets less than 75 × 109/l) |
• Uncontrolled systolic hypertension (230/120 mmHg or higher) |
• Lumbar puncture/epidural/spinal anesthesia within the previous 4 h or expected within the next 12 h |
Patients are at increased risk of VTE if they are expected to have their mobility highly reduced for ≥3 days or relatively reduced compared to their basal state, in addition to one or more of the risk factors listed in Table 20.1. In addition, surgical patients and patients with major trauma are considered at increased risk of VTE if they were admitted with an inflammatory or intra-abdominal condition or had undergone or will undergo a surgical procedure >90 min (>60 min for pelvic or lower-limb surgery).
Several risk assessment models have been developed to score the risks of VTE and bleeding, although their routine use can be cumbersome. The Padua prediction score has been evaluated in hospitalized medical patients [5]. Among a total of 11 items, the major risk factors are active cancer, previous VTE, reduced mobility, and known thrombophilic conditions (each item scores 3 points). A cumulative score ≥4 defines high risk of VTE [5].
For general surgery patients, the Rogers score evaluates 15 items, including the type of surgical procedure and some biological parameters [6]. A score above 10 correlates with a moderate risk in the vocabulary of the American College of Chest Physicians (ACCP) guidelines [1]. The Caprini score is relatively easy to use and has been adapted by the ACCP guidelines, after validation in a large retrospective study of general, vascular, and urological surgery patients [7, 8]. It also helps assess patients undergoing gynecological surgery.
For orthopedic surgery, the ACCP guidelines state that the surgery-specific risk of DVT outweighs the contribution of the patient-specific factors. Therefore, there is no validated risk assessment model, and recommendations on DVT prevention are mainly based on the type of surgery. Likewise, there is not any specific score giving a threshold for the use of anticoagulants [3].
VTE prevention starts with good hydration of the patient and encouragement to ambulate as early and as often as possible. The risk/benefit ratio and the method of thromboprophylaxis should be reassessed every 24 h for all hospitalized patients.
Mechanical Versus Pharmacological Prophylaxis
In all clinical conditions, these two modalities should be complementary rather than antagonistic.
Mechanical prophylaxis, based on graduated compression stockings (GCS) or intermittent pneumatic compression (IPC) , is offered as a primary prophylaxis in all patients with increased VTE risk, in particular surgical and trauma patients [4].
In patients with stroke, GCS should not be used because of an increased incidence of skin injury [9]. In other situations, GCS are an efficacious first-line measure for hospitalized patients with increased risk of VTE, as an alternative to anticoagulants when the risk of bleeding is high, or in combination with anticoagulants in patients with high risk of VTE.
Intermittent pneumatic compression (IPC) can be offered in all settings ; however, good observance and efficacy are obtained only with battery-powered portable devices and sustained explanation to the patients [10–13]. IPC is a first-choice modality whenever the risk of VTE and bleeding are both high [14]. In a meta-analysis, Ho et al. showed that compared to anticoagulants, the use of IPC provides a similar level of protection against VTE (RR 0.93; P = 0.66) with a risk of hemorrhage decreased by 58% (RR 0.41; P = 0.0002) [14]. However, dual therapy, e.g., the use of pharmacological prophylaxis in addition to IPC in patients with high risk of VTE, provides increased protection when compared to IPC alone (RR 0.54; P = 0.02). For that reason, all guidelines recommend the use of mechanical and pharmacological prophylaxis in patients who are at high risk of VTE and low risk of bleeding [15].
Pharmacological agents used for VTE prevention comprise both antiplatelet and anticoagulant drugs. Although the role of antiplatelet drugs, in particular aspirin, remains controversial in primary prevention of VTE, it is accepted by several guidelines as a sole prophylactic agent in surgical settings [16]. Low-molecular-weight heparin (LMWH) used subcutaneously, replaced by low-dose unfractionated heparin (LDUH) in cases of renal insufficiency, has played a major role as a prophylactic agent, and can still be used in all clinical contexts excluding increased bleeding risk and allergy. Fondaparinux is a synthetic analog of the antithrombin-binding pentasaccharide found in heparins, with a more specific anti-Xa activity and a longer half-life. Because of a higher risk of bleeding, fondaparinux is not recommended over LMWH in surgical patients but is allowed for use in some settings. Recently, direct oral anticoagulants such as dabigatran (antithrombin), rivaroxaban, and apixaban (anti-Xa) have been evaluated and recommended for use in prevention of DVT in several clinical settings, mainly postsurgical, in particular after orthopedic surgery. Their use is limited to patients without severe renal insufficiency and low risk of bleeding. Nevertheless, these agents are prescribed with increasing frequency as they are taken orally and do not need laboratory testing. The main drawback is the lack of approved antidote, although some candidates are under study.
All guidelines emphasize that the choice of either prophylactic method should take into account the patient preference [17]. Comprehensive explanations are required to expose the benefits and risks of each method to the patient. For example, some patients may prefer having injections of heparin rather than wearing IPC for 18 h a day, whereas others may prefer not receiving a drug that increases bleeding risk.
It is also very important to reassess the need for VTE prophylaxis every day and stop or change the modality according to new information as medical conditions change.
Nonsurgical Hospitalized Patients
Patients with Acute Medical Condition (Including Cancer)
All guidelines recommend the use of a pharmacologic prophylaxis as a first-line therapy in acutely ill patients, including cancer, who are at increased risk of VTE. One of several agents can be chosen including fondaparinux, low-molecular-weight heparin (LMWH) , or low-dose unfractionated heparin (LDUH) . The latter is specifically recommended for patients with acute or severe chronic renal insufficiency. The use of anticoagulants decreases the risk of fatal pulmonary embolism (RR 0.41; 95% CI, 0.22–0.76) and symptomatic DVT (RR 0.47; 95% CI, 0.22–1) when compared to no anticoagulants [2].
All guidelines agree that one mechanical prophylaxis, either GCS or IPC, can be used alone in acutely ill patients with increased risk of thrombosis when pharmacologic prophylaxis is contraindicated and should be substituted with anticoagulants when the bleeding risk decreases [2, 4, 18–20]. Aspirin is not recommended by any society as a sole thromboprophylactic agent in medical patients. Dual therapy (anticoagulation + mechanical prophylaxis) may improve the efficacy of VTE prevention in high-risk cancer patients [19].
The use of anticoagulants is not recommended for low-risk patients, and thromboprophylaxis should be stopped when the patient is capable of ambulation or discharged from the acute hospital stay. For example, patients who are chronically immobilized at home or institutions should not receive routine thromboprophylaxis .
Patients with Ischemic Stroke or Intracranial Hemorrhage
The ACCP guidelines recommend systematic use of thromboprophylaxis in patients with acute ischemic stroke or primary intracerebral hemorrhage with restricted mobility [21].
In acute ischemic stroke, anticoagulants and/or IPC should be started as early as possible and maintained until mobility is regained on time of discharge. Dual therapy may yield additional benefits based on studies in postoperative patients. Aspirin therapy is prescribed within 48 h but does not confer protection against VTE. LMWH is favored over LDUH.
Published after the ACCP guidelines, the CLOTS 3 trial compared IPC to no IPC in 2876 patients after stroke; the rate of DVT within 30 days was significantly lower in the treatment group (8.5%) compared to the control group (12.1%) (OR 0.65; P = 0.001) [9]. This study convinced the NICE guideline committee to recommend offering IPC to patients with ischemic stroke within 3 days of the event and until 30 days after the event. Contrary to the ACCP guidelines, NICE guidelines consider prophylactic doses of anticoagulants only in cases where the diagnosis of hemorrhagic stroke has been excluded and the risk of secondary hemorrhage is considered low. Both guidelines recommend against the use of GCS in these patients, since studies have shown increased risk of skin injury (RR 4.02; 95% CI, 2.34–6.91) [4, 21].
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