72 VENOUS DISEASE
Thomas A. Whitehill M.D., Mark Nehler M.D.

1. Where does deep venous thrombosis (DVT) originate?

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More than 95% of DVTs develop in the deep veins of the lower extremities; the majority originate in the valve sinuses of the calf veins.

2. What is the usual source of a pulmonary embolus?

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Calf vein thrombosis may propagate proximally into the deep venous system to involve the popliteal, femoral, or iliac veins (or a combination of veins). These proximal DVTs are the culprits in > 90% of pulmonary emboli.

3. What is Virchow’s triad?

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(1) Hypercoagulability, (2) disruption of an intact venous intimal lining, and (3) stasis of venous blood flow. In most patients with DVT, at least two of these three components are operative.

4. What are the major hypercoagulable syndromes (thrombophilia)?

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Factor V Leiden mutation, antithrombin III deficiency, protein C deficiency, protein S deficiency, dysfibrinogenemia, lupus anticoagulant, antiphospholipid syndrome, prothrombin 20210A mutation, and abnormalities of fibrinolysis are the major examples. The most common is the factor V Leiden mutation (i.e., activated protein C resistance).

5. What causes venous intimal injury?

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Venous intimal changes may be secondary to vein wall trauma, infection, inflammation, indwelling catheters, or surgery. Venodilation during anesthesia and surgery may produce microscopic intimal tears as well as stasis. The injured venous intima initiates the release of thromboplastic substances that can activate the coagulation cascade.

6. What causes stasis of venous blood flow?

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Venostasis is common in surgical patients; it occurs during anesthesia, after certain types of trauma, and with perioperative immobility.

7. What are the usual clinical risk factors for DVT?

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Risk factors include malignancy (especially pancreatic, genitourinary, stomach, lung, colon, and breast cancer), age older than 40 years, female gender, obesity, history of venous thrombosis or pulmonary embolism, major surgical procedures, pregnancy, limited mobility, hypercoagulable state, and trauma.

8. What signs and symptoms suggest DVT? How can DVT be accurately diagnosed?

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The signs and symptoms are calf or thigh pain, tenderness, increased skin temperature, swelling, or superficial venous dilatation. None of these signs is specific for DVT. Even the well-known Homan’s sign (i.e., calf pain with dorsiflexion of the foot) is unreliable; its accuracy is only 50%. Doppler ultrasound examination (duplex scanning) detects DVT proximal to the calf veins with > 95% accuracy; unfortunately, it is not as sensitive in detecting calf vein DVT. Ascending venography is still the reference standard.

9. Is there any value to D-dimer testing?

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Measurement of D-dimer cross-linked fibrin degradation products (FDPs), formed by the action of plasmin on cross-linked fibrin, has been proposed as an alternative to initial noninvasive testing. A sensitivity of 96.8% and a specificity of 35.2% have been reported for the enzyme-linked immunosorbent assay (ELISA) test, making it theoretically possible to limit noninvasive testing to those with positive D-dimer testing. Unfortunately, the ELISA test is time consuming and impractical as a screening test. More rapid (1 hour) ELISA assays are now available. Prospective evaluation of the safety of withholding anticoagulation therapy in patients who are D-dimer negative has been limited. False-positive results are a problem in patients with malignancy, infection, or recent surgery.

10. What methods of perioperative DVT prophylaxis should be used? In which surgical patients?

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Perioperative DVT prophylaxis is strongly recommended in all high-risk patients who are older than age 40 years and undergoing major general or orthopedic procedures. In general surgical patients, well-applied prophylactic measures decrease the relative risk of DVT by 67%. The best prophylaxis for DVT includes pre- and postoperative walking. Intermittent pneumatic compression stockings and some form of heparin therapy (low-dose unfractionated heparin [LDUH] or low molecular weight heparin [LMWH]) are recommended as the patient’s risk profile increases.
KEY POINTS: VENOUS DISEASE

1. More than 95% of deep vein thromboses (DVTs) develop in the deep veins of the lower extremities; the majority originate in the valve sinuses of the calf veins.
2. Virchow’s triad consists of hypercoagulability, disruption of an intact venous intimal lining, and stasis of venous blood flow.
3. The best prophylaxis for DVT includes pre- and postoperative walking.

11. How does heparin work?

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Heparin binds to antithrombin III (ATIII), rendering it more active. Low-dose heparin (5000 U administered subcutaneously every 8-12 hours until the patient is fully ambulatory) activates ATIII, inhibits platelet aggregation, and decreases the availability of thrombin.

12. What is LMWH?

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LMWH is a fragment of heparin produced by chemical breakdown. It exerts its anticoagulation effect by binding with ATIII and inhibiting several coagulation enzymes, principally factor Xa. It has a longer half-life than standard preparation heparin and can be administered once daily. LMWH gives a more predictable anticoagulant response at high doses and thus can be administered without monitoring (it is not necessary to follow the partial thromboplastin time).

13. Should the placement of an inferior vena cava (IVC) filter ever be considered?

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In patients with a documented, recurrent pulmonary embolism while taking adequate anticoagulation therapy or with an absolute contraindication to anticoagulation, an IVC filter can be placed to prevent embolization or propagation of clot to the lungs. A significant rate of recurrent DVT has been associated with IVC filters.

14. What are the characteristics of chronic venous insufficiency and postphlebitic syndrome?

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The primary characteristic is venous valvular incompetence with distal ambulatory venous hypertension. After DVT, involved venous segments eventually recanalize to some degree. However, their delicate valves remain scarred or trapped by residual organized thrombus. The loss of valvular function disables the venomotor pump. The vein walls become thicker and less compliant, increasing resistance to proximal blood flow. These factors result in distal venous hypertension. Protein-rich fluids, fibrin, and red blood cells are extravasated and deposited through large pores in the distended microcirculation during periods of venous hypertension. This process leads to inflammation, scarring, fibrosis of the subcutaneous tissues, and discoloration by hemosiderin deposition (”brawny” edema). The resultant inflammatory reaction, scarring, and interstitial edema create a further barrier to capillary flow and diffusion of oxygen; adequate nutrition to the skin is inhibited. These changes may lead to tissue atrophy and ulceration (i.e., venous stasis ulcer).

15. Do all patients with DVT develop postphlebitic syndrome?

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No. Recent epidemiologic studies suggest that the incidence of venous ulceration is about 5%. As many as one in five post-DVT patients have absolutely no symptoms and maintain normal noninvasive vascular test data. The median time for the appearance of a first venous stasis ulcer is 2.5 years. Of interest, 50% of patients with venous ulcers have no history of DVT (probably because of previous asymptomatic calf vein DVT).

16. How are patients with postphlebitic syndrome treated?

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With proper patient education and compliance, postphlebitic stasis sequelae can be controlled by nonoperative means in well over 90% of patients, particularly if no residual venous outflow obstruction complicates valvular incompetence. Nonoperative treatment consists of graded elastic compression stockings (or Unna boots) to retard swelling and periodic leg elevation during the day. Patients must be taught to elevate their legs above the heart (”toes above your nose”) at regular intervals (e.g., 10-15 minutes every 2 hours). Compliance is critical.

17. Distinguish between phlegmasia alba dolens and phlegmasia cerulea dolens.

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Iliofemoral venous thrombosis is characterized by unilateral pain and edema of an entire lower extremity, discoloration, and groin tenderness. A total of 75% of the cases of iliofemoral venous thrombosis occur on the left side, presumably because of compression of the left common iliac vein by the overlying right common iliac artery (May-Thurner syndrome). In phlegmasia alba dolens (literally, painful white swelling), the leg becomes pale and white. Arterial pulses remain normal. Progressive thrombosis may occur with propagation proximally or distally and into neighboring tributaries. The entire leg becomes both edematous and mottled or cyanotic. This stage is called phlegmasia cerulea dolens (literally, painful purple swelling). When venous outflow is seriously impeded, arterial inflow may be reduced secondarily by as much as 30%. Limb loss is a serious concern; aggressive management (i.e., venous thrombectomy, catheter-directed lytic therapy, or both) is necessary.

18. What is venous claudication?

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When venous recanalization fails to occur after iliofemoral venous thrombosis, venous collaterals develop to bypass the obstruction to venous outflow. These collaterals usually suffice while the patient is at rest. However, leg exercise induces increased arterial inflow, which may exceed the capacity of the venous collateral bed and result in progressive venous hypertension. The pressure buildup in the venous system results in calf pain commonly described as tight, heavy, or bursting (venous claudication). Relief is obtained with rest and elevation but is not as prompt as with arterial claudication.

19. How can one distinguish primary varicose veins from secondary varicose veins?

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Primary varicose veins result from uncomplicated saphenofemoral venous valvular incompetence and have a greater saphenous distribution, positive tourniquet test result, no stasis sequelae (dermatitis or ulceration), and no morning ankle edema (lymphedema).
Secondary varicose veins are most commonly a consequence of deep and perforator venous incompetence secondary to postphlebitic syndrome.

20. Why do people develop primary varicose veins?

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The most common cause is congenital absence of venous valves proximal to the saphenofemoral junction. There are normally no valves in the vena cava or common iliac veins and only an occasional valve in the external iliac veins. Thus, the sentinel valve in the common femoral vein just above the saphenofemoral junction is of critical importance. However, anatomic studies reveal that this valve is absent on one or the other side in 30% of patients.

21. How, when, and in whom should varicose veins be treated?

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Varicose veins that cause discomfort or serious cosmetic embarrassment require treatment. Better results are obtained with early treatment before continuous retrograde pressure and flow down the superficial system and into communicating perforating veins (whenever the patient is standing) cause secondary, irreversible perforator incompetence. High saphenous vein ligation at an early stage can arrest progression of this gravitational process. The distal varicosities can be managed by selective surgical stripping, sclerotherapy, or both.

References
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