The diagnosis of DVT and/or PE can often be made, or at least strongly suggested, based on the results of the historical review and clinical examination, and combinations of diagnostic criteria have been shown to be more or less suggestive of DVT (Table 2.2) [14, 16]. Clinically, DVT of the lower extremities is commonly associated with pain localized to, and swelling in the extremity distal to, the site of the thrombus. The involved extremity can also be warm, with cutaneous erythema, and regional varicosities may be evident. Homan’s sign, which is pain in the calf upon dorsiflexion of the ankle, is commonly thought to be evidence of calf DVT; however, this has been shown to be an unreliable assessment for calf DVT [17]. Multiple thrombosed deep and collateral veins in an extremity can result in a severely edematous, inflamed extremity known as phlegmasia cerulea dolens, which can be limb threatening due to ischemia, and may be associated with prothrombotic disorders such as heparin-induced thrombocytopenia (HIT), myeloproliferative disease, factor V Leiden mutation, polycythemia vera, and paroxysmal nocturnal hemoglobinuria (PNH). As for PE, signs and symptoms include chest pain; tachypnea and dyspnea, along with a sense of impending doom; tachycardia ; hyperpyrexia; cough; hemoptysis; syncope; and, frequently, evidence of an associated DVT. Unfortunately, DVT can be clinically silent until the clinical signs of PE become evident.

Contrast, magnetic resonance, and computerized axial tomographic venography can also be used to identify DVT in the lower extremity. The routine use of contrast venography has dwindled over the past 20–30 years, due to the potentially hazardous nature of invasive contrast media (nephrotoxicity), limitations related to inadequate deep vein filling with the contrast dye, and the steady improvement and availability of noninvasive magnetic resonance venography (MRV) and computerized axial tomographic venography (CATV).

Prevention of VTE is a worthwhile and potentially lifesaving endeavor. The basic elements of VTE prophylaxis include patient education, mechanical methods that promote venous blood flow in the extremities, chemoprophylactic measures that inhibit thrombus formation, and variations in anesthesia and fluid management. Nurses [26] and surgeons, as well as house and office staff, can play an important role in teaching patients the basic physiology and warning signs of VTE, both DVT and PE, and this can go a long way in regard to compliance with prophylactic measures and even early diagnosis should a complication develop. As a rule, combined prophylactic modalities decrease significantly the incidence of VTE, in particular DVT [27]. Of course, lower extremity movement, in particular ambulation with active contraction and relaxation of the crural musculature and resultant knee and ankle motion, is an important deterrent to VTE. In fact, most VTE prophylaxis protocols in otherwise healthy individuals are discontinued once regular knee and ankle motions are resumed following foot and ankle surgery. When lower extremity range of motion cannot be implemented, such as when complete bed rest is a required element of treatment or when the extremity is immobilized, then graduated compression stockings (GCS) , and intermittent pneumatic compression (IPC) devices on one or both extremities can be employed (Fig. 2.3). A 2010 review of the literature pertaining to the use of GCS revealed that their use reduced the incidence of DVT from 26% to 13% (p < 0.0001) in comparison to patients treated without GCS [28]. IPC devices applied to any extremity can also provide beneficial fibrinolytic activity, as evidenced by elevated blood-borne fibrinolytic activity in assays procured from sites distant to the location of the IPC device [29, 30], and this could be particularly useful to foot and ankle surgical patients when both lower extremities have to be in the surgical field [31]. In general, when foot and/or ankle surgery is undertaken on one lower extremity, an IPC device is typically applied to the contralateral lower extremity during the operative procedure and throughout the course of hospitalization.

In regard to anesthesia and its potential adverse influence on venous stasis and the development of VTE, it is generally considered favorable to avoid cessation of the calf muscle pump influence on venous return from the lower extremities, and, therefore, avoidance of skeletal muscle paralysis and general anesthesia, when possible, is likely to decrease the risk of DVT [32–35]. In fact, the American Association of Plastic Surgeons has recommended that when possible, the use of non-general anesthesia, such as monitored anesthesia care, local anesthesia with sedation, or neuraxial anesthesia instead of general anesthesia, should be used in order to diminish the risk of VTE [31].

Naturally occurring, physiologic anticoagulants such as antithrombin III and activated protein C prevent widespread thrombosis and localize clot formation to sites of vascular injury. The clotting cascade is also balanced by plasmin-mediated fibrinolysis, resulting in the formation of d-dimers and other fibrin degradation products. When the body’s intrinsic anticoagulation system requires bolstering to prevent or treat VTE complicating surgery or medical care, a wide range of therapeutic agents are available (Table 2.3), including unfractionated heparin (UFH), which is typically administered subcutaneously (SC) or via intravenous (IV) infusion; low-molecular-weight (fractionated) heparins (LMWHs), which are administered via subcutaneous injection or IV infusion and include agents such as enoxaparin, dalteparin, and tinzaparin; vitamin K antagonists like warfarin, which can be administered orally or via IV infusion; factor Xa inhibitors, which are administered via subcutaneous injection or IV infusion and include agents such as fondaparinux, rivaroxaban, apixaban, and edoxaban; direct thrombin inhibitors like dabigatran, which can be administered orally; and combined factor Xa and thrombin inhibitors like danaparoid, which can be administered via subcutaneous injection or IV infusion. The decision to choose one anticoagulant over another varies by indication and patient-specific factors, and surgeons are always encouraged to use their clinical judgment in order to tailor evidence-based guidelines for VTE prophylaxis or treatment to the particular needs of their individual patients. Useful guidelines for VTE prophylaxis and treatment are available, and readers are encouraged to review these [31, 36–38]. Surgeons are also encouraged to read the clinical pharmacology information contained in the package insert specific to each of these medications in order to review the details related to their proper use for VTE prophylaxis, treatment, and reversal (which is beyond the scope of this text). Surgeons are also encouraged to recruit the medical expertise of other experienced clinicians in the management of acute DVT and/or PE, since the care of such patients can be complicated and requires a wide range of expertise and intervention. Although the primary adverse effect of anticoagulant pharmacological agents is hemorrhage, parenteral administration and patient and surgeon nonadherence to treatment and guidelines are important limitations of their use [39].

Prophylaxis is generally continued until the risk factors are such that VTE is not likely, and this is typically at a time when lower extremity immobilization is discontinued and surgeons need to individualize the duration of prophylaxis based on the needs of each individual patient. The duration of treatment for confirmed DVT and/or PT depends to a large degree on the risk of recurrence. Patients at a high risk for recurrence include those with idiopathic DVT or PE, malignancy, antiphospholipid syndrome, an inferior vena cava filter, obesity, the elderly, and males. As always, the risk of prolonged anticoagulation is hemorrhage.

Anticoagulants that are commonly used for VTE prophylaxis include unfractionated heparin, fractionated heparins such as dalteparin and enoxaparin, the factor Xa inhibitor fondaparinux, and the heparinoid danaparoid, which is particularly useful in patients with a history of heparin-induced thrombocytopenia (HIT). Aspirin can also play a role in prophylaxis [40], although it is not considered to be a sole method of prophylaxis. Warfarin can also be used and is often initiated after surgery using a bridging protocol that also employs heparin or another anticoagulant.

The main goals of treatment for DVT include prevention of PE, postphlebitic syndrome, and recurrent thrombosis. Once VTE is suspected, anticoagulation should be started immediately unless there is a contraindication. In their review of the treatment of VTE, Wells et al. [4] divided therapies into acute (first 5–10 days), long-term (from the end of acute to 3–6 months), and extended (beyond 3–6 months) phases. And, despite the potentially lethal and acutely morbid nature of DVT and PE, they found that low-molecular-weight heparin (LMWH) along with vitamin K antagonists or the use of two oral agents without LMWH, along with ambulation and other physical measures, allows for outpatient management of most cases of DVT and some cases of PE, in the acute phase. Unless there is a specific contraindication, anticoagulation should be initiated as soon as VTE is diagnosed. Beyond the use of LMWH and/or oral therapies combined with physical measures, the use of thrombectomy is reserved for severe VTE threatening limb loss or stroke, and retrievable inferior vena cava (IVC) filters are indicated when anticoagulation is contraindicated. Typically, adequate treatment of DVT and PE entails 3 months of use of anticoagulants, such as single or combinations of LMWH, vitamin K antagonists, or direct factor Xa or factor IIa inhibitors, after which additional therapy used over the long-term and extended phases of VTE is based on the risk of recurrence, cause of the initial thrombus, and the risk of a serious bleeding event over time.

Although prevention of the development of VTE is generally considered a worthwhile aspect of foot and ankle surgery, hemorrhage, particularly bleeding related to methods of anticoagulation and clot prevention, can be problematic and lead to wound as well as systemic complications. Patients with a platelet count <100,000/mm³; those with active or a history of heparin-induced thrombocytopenia; those taking aspirin, clopidogrel, or nonsteroidal anti-inflammatory drugs; and those with renal or hepatic disease may not be satisfactory candidates for VTE chemoprophylaxis. In such patients, non-pharmacologic methods of prophylaxis, including GCS and ICDs, early active motion with activation of the calf muscle venous pump, and avoidance of general anesthesia if possible are likely to be the mainstays of VTE prophylaxis.

Unfractionated heparin (UFH) occurs naturally and is contained in mast cell granules and released via degranulation in response to numerous stimuli, including hypersensitivity and tissue injury, in particular blood vessel disruption. Fractionated heparins (enoxaparin, dalteparin, tinzaparin), which are derived from depolymerization of long-chain polysaccharide heparin, are categorized as low molecular weight and useful as anticoagulants if their molecular weights average ≤ 8000 Daltons. The clotting cascade (Fig. 2.1), via sequential protease activity, amplifies conversion of soluble fibrinogen to insoluble strands of fibrin that combine with platelets to form a thrombus. Antithrombin is a serine protease inhibitor that disrupts the clotting cascade and, as such, serves as the key plasma inhibitor of coagulation. Heparins bind to antithrombin and inhibit factor Xa (activated factor X), thereby impeding the clotting cascade. Interestingly, LMWHs can only bind to and inhibit antithrombin, whereas heparin can bind to antithrombin and inhibit both antithrombin and thrombin. UFH also binds other plasma proteins, whereas LMWH is limited in its binding activity, and as such LMWH is associated with a more consistent dose-response and fewer non-hemorrhagic adverse effects. Heparins can be neutralized by protamine if problematic hemorrhage develops. Moreover, immune-mediated heparin-induced thrombocytopenia (HIT)) can develop in response to administration of heparin, and this can lead to devastating thrombosis. The incidence of HIT in patients that have been heparinized for more than 7 days is approximately 1% [41], and the 30-day incidence of mortality associated with HIT is 16.6% [42].

A number of factor Xa inhibitors can be used for VTE prophylaxis and/or treatment, including fondaparinux, rivaroxaban, apixaban, and edoxaban. Although specific indications may be more broadly defined than just prophylaxis or treatment of DVT and/or PE, all of these agents can potentially be used in the realm of foot and ankle surgery. Fondaparinux is indicated for VTE prevention in patients undergoing hip fracture surgery, hip replacement surgery, knee replacement surgery, and abdominal surgery and for the treatment of acute DVT and/or PE when administered in conjunction with warfarin. Rivaroxaban is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the treatment of DVT and PE, for the reduction in the risk of recurrence of DVT and of PE, and for the prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery. Apixaban is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the prophylaxis of DVT, which may lead to PE, in patients who have undergone hip or knee replacement surgery, for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy. Edoxaban is indicated to reduce the risk of stroke and systemic embolism (SE) in patients with nonvalvular atrial fibrillation and for the treatment of DVT and PE following 5–10 days of initial therapy with a parenteral anticoagulant. The direct thrombin inhibitor dabigatran is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the treatment of DVT and PE in patients who have been treated with a parenteral anticoagulant for 5–10 days, to reduce the risk of recurrence of DVT and PE in patients who have been previously treated, and for the prophylaxis of DVT and PE in patients who have undergone hip replacement surgery. The combined factor Xa-thrombin inhibitor danaparoid, a heparinoid, is indicated for the treatment of patients with an acute episode of heparin-induced thrombocytopenia (HIT) and for prophylaxis in patients with a history of HIT.

One risk stratification scheme that has been found to be useful in the management of a wide range of patients is the Padua Prediction Score, which was developed based on a prospective cohort study that involved 1180 consecutive hospitalized patients who were followed for 90 days following their admission [66]. The Padua Prediction Score was based on the summation of risk factor scores, and a score ≥4 was considered to indicate a high risk for venous thromboembolism (VTE), whereas a score <4 was considered to indicate a low risk for VTE (Table 2.4). Of the patients, 469 (39.7%) were labeled as being at a high risk for thrombosis, and VTE developed in 4 (2.2%) of 186 who received thromboprophylaxis and 31 (11%) of 283 who did not (HR of VTE = 0.13; 95% CI, 0.04–0.40). Furthermore, VTE developed in 2 (0.3%) of 711 low-risk patients (HR of VTE in high-risk patients without prophylaxis as compared with low-risk patients, 32.0; 95% CI, 4.1–251.0), and bleeding occurred in 3 (1.6%) of 186 high-risk patients who had thromboprophylaxis . The authors concluded that their risk assessment model (the Padua Prediction Score) discriminated between medical patients at high and low risk of VTE and that adequate thromboprophylaxis in high-risk patients during hospitalization could result in long-standing (up to 90 days) protection against thromboembolic events with a low risk of bleeding.