Definitions and Pathophysiology
The ability to form a clot after injury prevents life-threatening bleeding. Clotting at improper sites (thrombosis) or clots that migrate (emboli) can block vessels and lead to life-threatening tissue damage and organ failure. Fatal pulmonary embolism (PE) can occur after minor orthopaedic procedures such as arthroscopy and after ankle fractures. For high-end athletes, the only sign of PE may be a reduction in aerobic performance. Most clots cause so few symptoms that they are not recognized clinically. This dichotomy in clinical severity, as well as the expense and complications of thromboembolic prophylaxis, leads to the controversy that surrounds venous thromboembolic disease prophylaxis.
A thrombus is the pathologic production of clotting products inside blood vessels. The term embolus describes a moving clot and was coined by Rudolph Virchow. In his honor, the three primary influences on thrombosis formation were later called “Virchow’s triad.” Endothelial damage exposes collagen, which triggers the extrinsic clotting cascade and the three main roles of platelets: to stick (adhesion), to release thrombotic chemicals (secretion), and to combine other platelets into a group (aggregation) ( Fig. 17-1 ). Stasis allows the bonds of clotting proteins and platelets to form. Stasis results from immobility (as a result of postoperative pain, a cast, limb paralysis, or a stroke), increased blood viscosity (as a result of cancer, estrogens, or polycythemia), decreased inflow (resulting from tourniquets and vascular disease), and increased venous pressure (caused by venous scarring from postthrombotic syndrome, varicose veins, or heart failure). Hypercoagulability results from activation of the catalytic system of plasma proteins known as the coagulation cascade, whose main product—thrombin—converts soluble fibrinogen to insoluble fibrin. The biologic goal of this web of interdependent enzyme-mediated reactions is to limit bleeding at sites of damage by rapidly stabilizing the initial platelet plug with insoluble fibrin.
The predisposition to venous thromboembolism (VTE), called thrombophilia, is caused by inherited (primary) and acquired (secondary) factors. Primary hypercoagulability is usually a result of genetic mutations causing an abnormal quantity or quality of clotting proteins. Screening for prothrombotic defects has not been shown to be effective in selecting a strategy for thromboembolic prophylaxis. Secondary acquired clinical factors are found in nearly every orthopaedic patient and have a significant role in their perioperative thrombosis. Risk factors for VTE include cancer, pregnancy, use of oral contraceptives, lupus antiphospholipid antibodies, obesity, smoking, and a host of medical conditions. VTE incidence rises exponentially with age, with substantial increases seen in persons older than 40 years.
Once formed, a thrombus can dissolve by the fibrinolytic system ( dissolution ), remain stationary in a vein and incorporate into the vein wall (termed organization and recanalization ), continue to grow ( propagation ) and/or break free to travel downstream to lodge in the pulmonary vessels ( embolization ). Ninety percent form in the veins of the lower extremity. Distal clots (below the popliteal space) that occur in the smaller veins of the calf pose little clinical threat, because most dissolve spontaneously. Larger diameter veins in the proximal thigh are associated with thrombus that rarely completely lyse and increase the risk of embolism. Fifty percent of patients with known proximal clots have asymptomatic PE according to a ventilation/perfusion (V/Q) scan. Seventy percent of patients with a PE proven by a V/Q scan have proximal VTE. When a thrombus embolizes to the lung, the size of the clot becomes a critical issue.
Diagnosis and Clinical Manifestations: Imaging and Laboratory Findings
The physical examination for venous thrombosis is notoriously unreliable, and clinical diagnosis relies most heavily on the history of primary and secondary risk factors. Although VTE can cause leg pain, tenderness, swelling, or a palpable cord, most cases are asymptomatic. The “classic” physical examination tests include Homan’s sign (calf pain with foot dorsiflexion when the knee is flexed) and Moses sign (pain with calf compression against the tibia). Objective evidence is found in fewer than 50% of patients with these classic signs of VTE. Only 50% of patients with venographically proven VTE have the classic clinical signs. Most orthopaedic patients with PE are asymptomatic. Large occlusions cause a greater increase in pulmonary arterial resistance, which can lead to right heart failure and hypoxemia. If less than 60% of the pulmonary circulation is obstructed, a healthy patient may remain asymptomatic. In symptomatic patients diagnosed with pulmonary angiograms, the most common symptoms are chest pain (often pleuritic) and sudden onset of shortness of breath (dyspnea). Examination findings encountered in more than 50% of patients are tachypnea (>20 breaths per minute) and crackles. Massive “saddle emboli” block all cardiopulmonary function and cause immediate death.
The nonspecific nature of the signs and symptoms of VTE demand a high clinical suspicion in patients at high risk. No ideal objective test exists for thromboembolic disease, but contrast venography, duplex compression ultrasound, spiral computed tomography (CT) venography, CT pulmonary angiography, V/Q scans, and d -dimer levels are useful. Contrast venography demonstrating an intraluminal defect is the most predictable test for the diagnosis of distal thrombosis (below the popliteal fossa) and can also demonstrate iliac thrombosis ( Fig. 17-2 , upper panel ). Duplex ultrasound is the most practical diagnostic tool for most patients because it is inexpensive, noninvasive, and easily repeatable at the patient’s bedside. The inability to visualize compressibility of a vein with real-time B-mode Doppler ultrasound is more than 95% sensitive and specific for detecting proximal deep vein thrombosis (DVT). When DVT is suspected, urgent outpatient screening with duplex ultrasound serves as the best first-line test in a stable patient ( Fig. 17-2 , lower panel ). All guidelines agree that routine screening with duplex ultrasound at discharge from the hospital is not recommended. In cases with nearby wounds, burns, or the presence of a plaster cast or when DVT of pelvic and inferior vena cava vessels are suspected, CT and magnetic resonance venography demonstrate good sensitivity and specificity.
When chest pain, dyspnea, or cardiovascular collapse raises the clinical suspicion of PE, the workup includes a chest radiograph, electrocardiogram (ECG), and determination of an arterial blood gas value. The plain film of the chest usually has subtle and nonspecific findings. The most common ECG findings in persons with a PE are nonspecific: sinus tachycardia, T-wave inversion, and ST abnormalities. Arterial blood gas analysis frequently demonstrates no hypoxemia but shows hypocapnia (a low carbon dioxide level) from hyperventilation. d -dimer levels often are not helpful in the orthopaedic setting because the trauma from fracture and surgery can cause prolonged elevations with or without thromboembolic disease. A negative d -dimer excludes DVT or PE in patients with low probability of thromboembolic disease. The first-line study to confirm a diagnosis of acute PE is multidetector spiral (helical) CT pulmonary angiography. A PE is confirmed when spiral CT shows an intravascular filling defect in a pulmonary artery that occludes all or part of a vessel ( Fig. 17-3 , left panel ). Sensitivities and specificities greater than 95% have raised concerns about overdiagnosis of clinically unimportant PEs and have made V/Q scintigraphy scans a second-line diagnostic study. Although a negative perfusion scan excludes significant PE, V/Q scans are best reserved for patients with contraindications to radiographic dye ( Fig. 17-3 , right panel ). The growing use of spiral CT angiography has been linked with an increase in both the diagnosis of PEs and bleeding complications but not with a decrease of overall mortality.
Thromboembolic Prophylaxis and Treatment Options
The need for prophylaxis should be based on the risks of developing venous thrombosis and PE balanced by the cost and dangers of prophylaxis. The location, extent, and duration of surgery can influence the size, location, and frequency of thrombosis. Sports medicine generally involves less invasive procedures on younger and healthier patients who are often motivated to return to function at an accelerated pace. Despite a population with low thromboembolic risk, fatal PEs can occur and can command considerable attention.
The higher risks of arthroplasty and larger case volumes of hip and knee replacements have provided a fertile opportunity to study thromboembolic problems. Even in patients undergoing arthroplasty, the incidence of fatal PE is so low it is impractical to measure, and no study has had sufficient power to demonstrate a significant decrease. In place of symptomatic or fatal PE, the most common end points have been both asymptomatic and symptomatic distal and proximal DVT (“total DVT”). Total DVT is a high-frequency surrogate outcome that is practical to objectively measure but may not be clinically relevant. Experts question whether adequate data are available to say whether DVT causes PE. The majority (79%) of studies of thromboprophylaxis after total joint arthroplasty were sponsored by industry, and evidence of potential bias exists. However, these studies include some of the highest level of evidence available in orthopaedic surgery and are used by panels that create clinical practice guidelines and review comparative effectiveness. Most studies are powered to show efficacy in reducing total DVT. It takes a much smaller study group to statistically demonstrate a decrease in a high frequency but less clinically relevant event such as total DVT (which occurs in ~30% to 50% of patients undergoing arthroplasty) than to detect an increase of a clinically relevant, low frequency event such as bleeding (which occurs in 1% to 5% of patients undergoing arthroplasty). Large prospective randomized trials frequently exclude patients who have increased bleeding risks, but these patients suffer equally from arthritis and are often candidates for arthroplasty. Bleeding is a predictable complication of surgery and the most common complication of the use of anticoagulants. Higher rates of bleeding are seen when more effective prophylactic drugs are used and when drugs with more rapid onset of action are used closer to the time of surgery. Potent anticoagulation is not associated with a reduced mortality or the proportion of deaths related to PE. Thromboembolic prophylaxis after arthroplasty is used as a “quality measure” in the Surgical Care Improvement Project guidelines that financially incentivize hospitals in the United States to use DVT prophylaxis. Observational studies show that compliance with Surgical Care Improvement Project thromboprophylaxis measures are related to higher infection rates (odds ratio 1.5), which may be due to increased bleeding.
Clinical practice guidelines, comparative effectiveness research, and consensus opinions can serve as a convenient starting point for surgeons and hospitals to make daily care decisions based on current evidence. The orthopaedic community has resisted a single standard regimen in favor of individualized judgments based on a patient’s clinical information. Understanding the recommendations in guidelines creates opportunities for improved patient care ( Fig. 17-4 ). Mechanical methods of prophylaxis have low bleeding risks and include aggressive range of motion and early weight-bearing activity and use of graduated compression stockings (GCS), venous foot pumps, and intermittent pneumatic compression hose. Use of mechanical devices is encouraged in patients at high risk for bleeding and as adjuncts for other prophylactic techniques. When allowed by bleeding risks, chemoprophylaxis is supported for persons undergoing all major orthopaedic surgeries, including pelvic fractures, multiple trauma, hip fractures, and joint replacement of the hip and knee. For selected higher risk sports procedures and athletes with multiple risk factors, chemoprophylaxis may help minimize VTE complications. Common medicines used in the prophylaxis and treatment of VTE are listed in Table 17-2 with their mechanisms of action.
|Drug||Mechanism of Action||Complications||Notes||Reversal|
|Aspirin||Irreversibly blocks platelet COX-1 production of TXA 2||Bleeding and GI issues |
|Least effective chemical agent||None|
|Heparin||Binds AT to inactivate Xa and II (thrombin) and IXa, XIa, XIIa||Bleeding |
HIT and osteoporosis
|Must monitor aPTT or anti-Xa activity||Protamine 1 mg IV per 100 units UFH|
|LMWH||Bind AT to inactivate Xa and IIa (thrombin)||Bleeding |
|Monitor anti-Xa activity if BMI >50 or CrCl <30||Protamine 1 mg IV per 1 mg LMWH|
|Fondaparinux||Binds AT to selectively inactivate only Xa||Bleeding||Avoid in thin patients (<50 kg), elderly patients (>75 y), CRI: CrCl <30||No antidote (?) Recombinant VIIa|
|Blocks γ-carboxylation of Factors II, VII, IX, and X||Bleeding |
Fetal Warfarin syndrome
|Oral good for long-term therapy |
Multiple reactions: diet, drugs, disease
|Vitamin K1 (phytonadione) |
FFP 8-10 mL/kg
|Dabagitran||Direct thrombin inhibitor||Bleeding||Oral||No antidote|
|Rivaroxaban||Direct Factor Xa inhibitor||Bleeding||Oral |
Avoid if the patient is taking antifungal or antiviral drugs