Deep Vein Thrombosis
The presence of a thrombus in a deep vein.
The incidence of deep vein thrombosis increases with age.
Etiology
Immobilization, prolonged sitting (as may occur during long drives or air travel), or even a relatively sedentary existence can lead to venous stasis and predisposes to thrombosis, because the emptying of veins in the extremities depends entirely on skeletal muscles that pump blood and on one-way venous valves that inhibit retrograde flow. Because incompetent venous valves lead to deep vein thrombosis, which damages the valves, deep vein thrombosis tends to recur. Thrombosis also damages the intima of the vein; such damage may lead to decreased local production of antithrombotic factors (eg, antithrombin III, prostacyclin).
Any condition that increases the Hct increases blood viscosity and results in a higher incidence of clotting. Dehydration, pulmonary disorders, smoking, and polycythemia are common causes of a high Hct in the elderly. The two most common known hypercoagulable states are hyperhomocysteinemia and protein C resistance, which is genetically determined and is present in about 15% of the population. One form of protein C resistance is due to the Leiden gene. In homozygotes, venous thrombosis begins early in life; in heterozygotes, it usually begins after age 30 and may first occur in old age or during immobilization.
Deep vein thrombosis occurs in 20 to 25% of patients > 40 after routine surgery and in almost 50% after hip surgery when no prophylaxis is given.
Symptoms and Signs
Deep vein thrombosis usually occurs in the leg, regardless of cause. The hallmark symptom is rapid onset of unilateral leg swelling with dependent edema. Generally, patients first note swelling when they awaken. In ambulatory patients, swelling is maximal at the ankle and lower leg, usually developing over 1 or 2 days. Pain may be present but is usually not severe. Physical examination often reveals pitting edema and a mild to moderate increase in skin temperature over the calf or thigh.
A gap always occurs between the level of thrombosis and the location of edema. With popliteal and lower femoral vein thrombosis, edema occurs only in the lower leg and ankle. With thrombosis in the midfemoral vein area, most or all of the leg is swollen. With upper femoral and external iliac vein thrombosis, the thigh is also swollen. Tenderness, if present, occurs in the calf with femoropopliteal venous thrombosis and in the medial thigh with iliofemoral venous thrombosis.
Calf vein thrombosis may produce no symptoms or mild tenderness and mild edema. There are four to six deep calf veins. Occlusion of one or two of them is likely to impair venous drainage, because all of them drain into the popliteal vein. Calf vein thrombosis without swelling is common only among sedentary or bedridden patients.
Complications of deep vein thrombosis include venous thromboembolism, particularly pulmonary embolism (which can lead to death within 30 minutes of onset). Unrecognized and untreated deep vein thrombosis can cause long-term morbidity from chronic venous stasis (postphlebitic syndrome) and predispose patients to recurrent venous thromboembolism. Large proximal thrombi may cause chronic severe leg swelling.
Phlegmasia cerulea dolens, a serious form of iliofemoral venous thrombosis, is characterized by massive thigh and calf edema and a cold, mottled foot. Pedal pulses are usually absent, and the leg is very tender. The risk of massive pulmonary embolism is high, even for patients receiving anticoagulation therapy. Foot gangrene also occurs but less often.
Diagnosis
The sudden onset of lower leg swelling in a gravitational distribution without trauma or a precipitating factor suggests deep vein thrombosis. However, laboratory confirmation is needed.
If swelling is absent, comparative measurements of the legs at several levels (just above the ankles is the most important) can usually be used to exclude deep vein thrombosis in ambulatory patients. However, in sedentary or bedridden patients who do not have swelling, calf vein thrombosis can be diagnosed only through laboratory evaluation.
Real-time color Doppler ultrasonography is the procedure of choice for diagnosing deep vein thrombosis above the knee. In symptomatic patients, venous ultrasonography has a sensitivity of 95%, a specificity of 96%, a positive predictive value of 97%, and a negative predictive value of 98%. Ultrasonography can detect clots in the popliteal or femoral vein but can miss clots in the calf veins.
Impedance plethysmography can indirectly detect venous thrombi by recording changes in venous volume when a thigh tourniquet is applied and removed. Plethysmography is reliable only for occlusions above the knee and those of recent onset. The sensitivity and specificity of impedance plethysmography are probably about 75% for thrombi above the knee.
Radiocontrast venography, although rarely needed, is the gold standard for confirmation of deep vein thrombosis. Venography should be considered if clinical suspicion is low but the ultrasonogram is abnormal or if the suspicion is high but the ultrasonogram is normal. In about 25% of these cases, the results of venography and ultrasonography differ. Adverse effects from venography, including allergic reactions and thrombophlebitis, occur in 2% of patients. Venography may be impossible to perform in patients with significant edema. It is contraindicated in patients with significant renal failure (creatinine level > 3 mg/dL [> 265 µmol/L]) and should be used cautiously in those with mild azotemia. Maintaining good hydration--before and 6 to 8 hours after the test--is important.
Radionuclide venography can be performed in patients with severe azotemia or an allergy to contrast material. False-negative results are common, but positive results are generally accurate.
Risk factors (eg, dehydration, estrogen use, heart failure, hip fracture, hypercoagulable states, immobilization or decreased physical activity, malignancy, obesity, polycythemia, thrombocytosis, trauma, venous damage) should be sought unless the cause is clear. All patients with iliofemoral venous thrombosis should have an abdominal diagnostic study (ultrasonography is usually adequate) to rule out extrinsic compression by a tumor or clot in the inferior vena cava. Right iliofemoral venous thrombosis is of particular concern if there is no local problem in the right lower extremity; an abdominal tumor causing compression must be suspected, because the inferior vena cava is located on the right. Thrombosis of the left common iliac vein, which is normally compressed by the right iliac artery, is more likely to be due to conditions other than compression by a tumor.
If a mechanical obstruction is not a risk factor, tests to detect hypercoagulable states are indicated, especially for patients with recurrent and migratory deep vein thrombosis.
Differential diagnosis: The effects of trauma can resemble those of deep vein thrombosis. Traumatic edema should be suspected if edema initially develops during or shortly after walking. Forcefully dorsiflexing the foot during a sudden downward movement can rupture the plantar tendon or injure the gastrocnemius muscle. The resultant swelling tends to be asymmetric and confined; it occurs above the ankle, is very tender, and is often associated with visible ecchymosis.
A popliteal cyst that extends into the calf can cause upper leg swelling and later compress the popliteal vein. Therefore, palpation of the popliteal fossa is important. A popliteal cyst should be suspected if the edema initially develops during physical activity. Ultrasonography can easily confirm or exclude this possibility.
Phlegmasia cerulea dolens may be mistaken for arterial embolism, but misdiagnosis can be avoided by remembering that acute arterial occlusion does not cause edema. Phlegmasia cerulea dolens often indicates occult malignancy.
Prophylaxis
Choice of prophylactic measures depends on the surgical situation. (see Table 70-3)
Low-dose heparin is the prophylactic measure most widely used before surgery. The usual dose is 5000 U sc q 8 to 12 h--a dose that rarely results in significant bleeding. Heparin is contraindicated in patients undergoing ophthalmologic or neurosurgical procedures. Aspirin and dextran are not recommended for deep vein thrombosis prophylaxis.
Intermittent pneumatic compression (oscillating) boots applied to the calves are a safer prophylactic measure. A pump rhythmically inflates the boot to 30 to 40 mm Hg, then deflates it, thus keeping the peripheral veins drained. Results are comparable to those of low-dose heparin but without the risk of bleeding. Galvanic stimulation of calf muscles, begun intraoperatively and continued until the patient is ambulatory, is also effective.
Even when other prophylactic measures are taken, patients should be mobilized as quickly as possible and encouraged to move their legs frequently while in bed.
The risk of venous thromboembolism is greatest early in the postoperative period. After orthopedic procedures, prophylaxis should be continued for 10 to 14 days, or longer if the patient has had postoperative complications that delay rehabilitative efforts and ambulation. After general surgery, prophylaxis is indicated; patients with an underlying malignancy or prior venous thromboembolism should be treated longer. In general, prophylaxis should be continued until full ambulation is resumed.
Orthopedic procedures: Deep vein thrombosis is common among the elderly because they commonly undergo high-risk orthopedic procedures, particularly semi-elective or urgent procedures (eg, after a traumatic fracture). If the procedure involves the extremities, the value of low-dose heparin is limited; full-dose heparin or warfarin is effective, but each has a significant risk of bleeding. Hirudin prevents deep vein thrombosis in patients undergoing orthopedic procedures and is useful when heparin-induced thrombocytopenia occurs.
After elective total hip replacement, the incidence of proximal deep vein thrombosis (without prophylaxis after surgery) approaches 25%, and the incidence of fatal pulmonary embolism is 3 to 4%. Prophylaxis reduces the occurrence of venous thromboembolism by 30 to 50%. The most effective regimens include low-molecular-weight heparin (30 mg sc q 12 h) and oral anticoagulants (warfarin dose adjusted to keep the international normalized ratio [INR] between 2.0 and 2.5).
After elective total knee replacement, the incidence of deep vein thrombosis is nearly 60%. Low-molecular-weight heparin and intermittent pneumatic compression boots reduce the incidence of proximal deep vein thrombosis to 5 to 10%. Low-dose subcutaneous heparin is ineffective.
After hip fracture surgery, the incidence of venous thromboembolism (without prophylaxis) is about 50%. A low-intensity oral anticoagulant or low-molecular-weight heparin is the treatment of choice and should be instituted preoperatively if possible. Intermittent pneumatic compression boots may help.
Medical disorders: Prophylaxis for deep vein thrombosis has not been studied extensively in hospitalized patients with medical disorders.
Among patients who have had an acute myocardial infarction and who are not given low-dose heparin, the overall incidence of venous thromboembolism is about 20%; the elderly and patients with complicated infarctions are at greatest risk. Low-dose heparin, low-molecular-weight heparin, or intermittent pneumatic compression boots are recommended as prophylaxis.
Among patients who have had an ischemic stroke that paralyzes a lower extremity, the incidence of deep vein thrombosis is about 30 to 40%. Low-dose heparin or low-molecular-weight heparin reduces the occurrence of deep vein thrombosis by at least 50%. Intermittent pneumatic compression boots are probably beneficial, but supportive data are lacking.
Treatment
The objective is to prevent pulmonary embolism and chronic venous insufficiency.
Anticoagulation therapy: The mainstay of treatment is anticoagulation therapy, beginning with heparin and continuing with warfarin. Heparin is given sc q 12 h, by IV injection q 4 to 6 h, or by continuous IV infusion for at least 4 days. For continuous IV infusion, the patient must first receive a rapid infusion (bolus) of usually 5,000 to 10,000 U. The initial infusion rate is usually about 18 U/kg/h; thereafter, the rate is adjusted according to the partial thromboplastin time, which should be kept between 1.5 and 2.0 times the normal control value. The partial thromboplastin time must be measured daily, because the infusion rate may need to be changed.
Continuous IV infusion offers the most flexibility for adjusting dose. Accurate infusion is critical; inadvertent increases in rate can lead to severe bleeding, and temporary interruptions of the infusion can lead to inadequate anticoagulation within 1 hour. When an IV infusion is restarted, a rapid infusion of 5000 U must generally be given.
Heparin (usually about 240 U/kg) sc q 12 h is as effective as continuous IV infusion. How long therapy should be given is debatable. One recommendation is 4 days for patients with femoropopliteal venous thrombosis and 5 to 7 days for those with iliofemoral venous thrombosis.
For patients receiving heparin, periodic platelet counts should be obtained, usually after 5 days of therapy. If thrombocytopenia develops (incidence is about 1%), heparin should be discontinued. Unexpected embolism, with arterial and venous thrombi, develops in a small proportion of patients with thrombocytopenia.
Low-molecular-weight heparin can be used. The drug is given in a fixed dose, does not require blood monitoring, and has a much lower incidence of heparin-induced thrombocytopenia. Low-molecular-weight heparin (injected sc q 12 h) can be used to treat outpatients with deep vein thrombosis (femoropopliteal area) if they are mentally competent and free of major cardiopulmonary disease.
Warfarin should be started 4 days before heparin is stopped, generally about a day after heparin is begun. A therapeutic level of warfarin must be reached before heparin is stopped. The elderly are more sensitive to warfarin than are younger patients, and doses are usually smaller. The prothrombin time should be kept at 1.2 to 1.5 times the normal control value (INR 2.0 to 2.5). For patients with uncomplicated venous thrombosis, at least 3 months of therapy is usually recommended, but patients at high risk of recurrent thrombosis may need extended therapy. Patients with protein C resistance and multiple episodes of venous thrombosis are given long-term warfarin therapy.
Patients > 70 (especially women) receiving warfarin therapy are at high risk of hemorrhage. Because many elderly persons with arthritic or neurologic disorders fall frequently, warfarin is generally contraindicated in patients > 80 and frail patients > 70.
Insertion of an inferior vena cava filter (umbrella): The decision to insert an umbrella depends on how likely deep vein thrombosis is to recur, whether pulmonary emboli are present, and where the venous clot is. Tibial vein thrombi, which rarely embolize, can remain untreated in patients at high risk of hemorrhage. For iliofemoral vein thrombi, which embolize often, an umbrella is strongly indicated if patients cannot be given warfarin.
Indications for umbrella insertion include hemorrhage during anticoagulation therapy, bleeding diatheses that are a contraindication to anticoagulation, phlegmasia cerulea dolens, massive pulmonary embolism, and pulmonary embolism that recurs in spite of adequate anticoagulation.
The umbrella acts as a plication device, preventing the occurrence of large pulmonary emboli. The complication rate is low, although occasionally, an umbrella loosens and migrates into another vein or into a pulmonary artery. Pulmonary embolism due to thrombi in the legs is uncommon after umbrella insertion but can occur after a few months, when emboli travel through collateral veins.
Thrombolytic (fibrinolytic) therapy: Patients with severe iliofemoral venous thrombosis and massive edema are at particularly high risk of chronic venous insufficiency and should be considered for thrombolytic therapy (eg, streptokinase, urokinase, tissue plasminogen activator).
The risk of bleeding is higher with these drugs than with anticoagulants. The older the patient, the greater the risk of bleeding. The risks of severe bleeding must be weighed against the morbidity of chronic severe leg edema. Contraindications include coagulopathy, recent gastrointestinal bleeding, recent stroke, uremia, history of cerebral hemorrhage, or surgical procedures within the preceding 7 days.
Thrombolytic therapy is unlikely to be effective if thrombi are > 3 days old. Before thrombolytic therapy is started, heparin's effect must be allowed to abate.
To be effective, streptokinase and urokinase must increase the thrombin time to at least twice the normal value; if they do not, they should be discontinued and heparin restarted.
Treatment of underlying disorders: For hyperhomocysteinemia, folic acid, vitamin B6 (pyridoxine), and/or vitamin B12 (cyanocobalamin) supplements may be used. For protein C resistance, long-term therapy with warfarin is used if episodes of venous thrombosis recur.
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