VENOUS REVIEW - The Official Journal of Center for Vein Restoration
Vol. 5, Issue 1

Relation Between Superficial Vein Reflux and Deep Vein Disease: Clinical Impact of Modern Treatment

by Nicos Labropoulos, PhD, DIC, RVT, Professor of Surgery and Radiology, Stony Brook Universtiy Medical Center. and Antonios P. Gasparis, MD, Associate Professor of Surgery, Director, Stony Brook Vein Center

Chronic venous disease (CVD) is the most prevalent form of vascular disease, affecting about a third of adult Americans. Most patients present with varicose veins but swelling and skin damage are common as well. The signs and symptoms of CVD are result of venous hypertension that develops from reflux, obstruction or a combination of both. In patients with CVD, around 70-80% will have superficial reflux with or without perforator vein incompetence and 10% isolated deep reflux. Combined superficial and deep vein disease has been reported to occur in about 10-20%. Congenital CVD and chronic venous obstruction are rare (Figure 1). While treatment of the isolated superficial venous system in patients with CVD is expected and has been shown to have good outcomes, the role, efficacy and complications of superficial intervention in patients with combined disease has been controversial. In patients with mixed pathology, deep venous obstruction occurs in a small number of limbs, which is either primary or secondary. The majority though, will have underlying reflux which will be segmental and is likely to occur due to volume overload from the recirculating reflux blood in the superficial veins. However, axial vein reflux, which is most often a result of previous thrombosis, also is seen, as about two thirds of patients with proximal vein thrombosis will develop reflux at one year. Patients with a previous episode of thrombosis may have vein segments without or with partial recanalization leading to obstruction or to a combination of reflux and obstruction.

Segmental deep-vein reflux due to superficial vein incompetence is most often seen at the saphenofemoral (SFJ) and saphenopopliteal junctions (SPJ). It also can be due to reflux in the gastrocnemius veins (almost always the medial) and perforator veins (Figure 2). The reflux in the perforator veins is not isolated but it occurs only in the presence of reflux in superficial veins that are connected with the affected perforators. Longstanding reflux in the superficial and perforator veins may lead to reflux development in the deep veins that are connected with the affected perforators. This is the same phenomenon as in the case of SFJ, SPJ and gastrocnemial veins. Deep vein reflux which is induced by the superficial vein incompetence is easily eliminated in >95% of patients after treating the superficial veins. This has been demonstrated in different studies and it does concur with our experience as well. It has to be noted that many patients may have deep vein reflux due to previous thrombosis. In such occasions the deep vein reflux may improve in some cases after elimination of the superficial reflux, but it does not disappear. The latter is more prevalent in the presence of axial reflux, such as when there is reflux in continuity from the common femoral vein to popliteal or more distal (Figure 3).

Traditional advice has been against saphenous ablation in the presence of deep venous obstruction. This was felt because of the thought that secondary saphenous varices result from deep venous obstruction and function as collaterals. Therefore, it was feared that obstructive disease may be made functionally more severe by removing the saphenous vein that may be functioning as important collateral. When testing venous outflow function in patients with previous deep vein thrombosis, Labropoulos et al. demonstrated that only 9.6% of limbs had their venous outflow reduced by occlusion of the superficial veins. The deep collaterals seem to be more important than the superficial venous system in bypassing the obstruction. Raju et al.,when comparing patients with and without deep obstruction who underwent saphenectomy, found similar outcomes in the two groups with no clinical deterioration in those with obstruction. In addition, the risk of DVT following saphenous ablation does not seem to be increased in patients with previous thrombotic events as shown by Puggioni et al. Therefore, the saphenous vein plays an insignificant role as a collateral pathway in patients with deep venous obstruction and can be safely treated to correct underlying hemodynamic pathology.

In patients with advanced CVD (C4-6) and superficial reflux, interrogation of the deep venous system for proximal obstruction, even in the absence of previous DVT, is warranted. Marston et al. found that as many as 30% of patients with chronic venous insufficiency have iliac vein obstruction on CT scan. When obstruction is in the iliac veins, consideration for its significance and intervention should be considered. The presence of such combined disease (superficial reflux and iliac vein obstruction) may warrant treatment of both levels of disease, as it is impossible to identify the pivotal diseased segment that contributes to the clinical presentation. In fact, we are presently unable to quantify segmental reflux or obstruction or describe how they interact. It is, therefore, reasonable to treat the superficial reflux and the proximal obstruction with iliac vein stenting. This can be done in a staged or combined fashion. Neglen et al. reported combined saphenous ablation and iliac vein stenting in 99 limbs with significantly improved hemodynamic parameters, improved clinical symptoms (pain and swelling) and significant improvement in all quality-of-life categories after treatment. This was achieved with good 4-year patency (>90%) and low complication rate.

Patients with mixed superficial and deep pathology and significant clinical symptoms (especially C4-6) should be offered not only treatment of their superficial system but also evaluation and therapy of any underlying iliac vein obstruction with excellent clinical outcomes. When evaluating the superficial veins in patients with deep vein obstruction it is necessary to demonstrate significant reflux in the superficial veins prior to intervening. This is very important as superficial veins can be dilated in order to compensate for the deep vein obstruction. In such patients the diameter change should not be compared with the studies on patients with primary superficial vein reflux. Therefore, superficial veins with large diameter should not be removed unless there is significant reflux that may contribute to the patients' signs and symptoms. Patients with deep vein obstruction are evaluated in the supine position. However, when these patients are tested for reflux, this must be done in the standing position. This is paramount as reflux should be evaluated in the standing position in all patients. We overemphasized this for the patients with venous obstruction as many centers still examine reflux in the supine position in such patients.

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Thrombophilia: Patients Who Clot Too Much
Part 2: Acquired Thrombophilia

by Robert C. Kiser, DO, MSPH

In the last article (Venous Review, Vol. 4, No. 4), we discussed congenital thrombophilias. However, thrombophilia can develop at any time in one's life. Generally this is due to development of autoantibodies against specific factors. This requires both a genetic component (the capacity to manufacture certain autoantibodies in response to specific environmental stressors) and an environmental component (the exposure to a substrate or antigen that prompts the manufacture of the autoantibody). The following is by no means an exhaustive list, but merely the more commonly encountered of the acquired thrombophilias.

Pregnancy and Hormone Treatment

Pregnancy is a state that predisposes to increased coagulation. Risk factors include left leg symptoms, symptoms of swelling, and swelling causing a greater than 1cm difference in calf circumference. Anatomically, the left lower-extremity venous system is mechanically predisposed to compression at the left common iliac vein by the right common iliac artery, which may or may not explain the left-sided predisposition found in one study.1 Likewise, treatment with estrogen-containing medicines such as oral contraceptive pills increases clotting. The survival advantage for a woman clotting more than usual during and after child birth is the reduction in bleeding during and immediately after child birth.

Anti-phospholipid Antibody Syndrome

Graham Hughes first described Anti-phospholipid antibody syndrome (APLAS) in the British Medical Journal in 1983. The syndrome occurs with the development of antibodies such as lupus anticoagulant and anticardiolipin antibody as well as antibodies to b2-glycoprotein.

People with APLAS may develop venous or arterial thrombosis, and hence are at increased risk of DVT and PE as well as myocardial infarction (MI) and stroke. Additionally, APLAS is associated with an increased risk of miscarriage, especially in the first 12 weeks of pregnancy and in pre-eclampsia. Although the risk of APLAS is increased in those with systemic lupus erythematosus (SLE), most people with APLAS, even those who have the so-called lupus anticoagulant, do not have systemic lupus. APLAS requires two positive tests, at least six weeks apart (some authors say 12 weeks).2 Tests for APLAS should include:

• Anticardiolipin antibodies (IgG, IgM, and IgA)
• Lupus anticoagulant - a panel of blood clotting tests that may include the dilute Russell Viper venom time (dRVVT), lupus aPTT, mixing studies, and hex-phase phospholipid test or platelet neutralization procedure
• Antibodies to b2-glycoprotein I (IgG, IgM, IgA)

Myeloproliferative Disorders

Myeloproliferative disorders, which can lead to thrombocytosis, are also at increased risk of clotting. Paroxysmal nocturnal haemoglobinuria is a rare disorder that is associated with increased thrombosis.3

Inflammatory Bowel Disease

Other diseases are also associated with increased risk of clotting. Inflammatory bowel diseases (ulcerative colitis and Crohn's Disease) are correlated with an increased risk of venous thromboembolism (VTE).4 The precise mechanism of IBD associated thrombophilia has not been elucidated.5

Cancer

It has long been recognized that cancer is associated with an increased risk of VTE, especially lung, kidney, brain, gastrointestinal, female reproductive system, and leukemia and lymphoma.6 Treatments for cancer, including surgery and chemotherapy, also increase the risk of thrombosis.7

Transient Protein C & S Deficiency

Because protein C & S are vitamin K dependent factors, vitamin K antagonists (such as warfarin) create a transient factor C & S deficiency during the first few days of exposure to warfarin. It is for this reason that a second method of anticoagulation (most commonly heparin) should be prescribed for at least the first five days of warfarin treatment, even if the INR is therapeutic before the fifth day. Failure to do so increases the risk of thromboembolic adverse events such as warfarin induced skin necrosis, arterial and venous thrombosis and embolism.3

Heparin-induced Thrombosis

Up to 3% of patients given unfractionated heparin, and up to 1% of patients given low molecular-weight heparin (LMWH) will develop heparin-induced thrombosis or HIT. Untreated, the mortality rate is 20% with an additional 10% requiring amputations. Currently there is no reliable, widely available method of predicting who will develop HIT, excepting those patients who have previously developed HIT. Those who have developed HIT in the past should not be rechallenged with heparin or heparinoids. The syndrome tends to develop after approximately 5-10 days of heparinoid exposure and is characterized by the onset or worsening of thromboembolic events despite anticoagulation. Treatment requires not only withdrawing the heparin but also immediately starting a direct fibrin inhibitor such as Argatroban or leiperidine. Consultation with a hematologist is important and useful.8

Assessing for Increased Risk

Thrombophilia is a complex syndrome, with diverse etiologies that can be either congenital or acquired. It is also possible for a person to have both congenital and acquired thrombophilias. Regardless of the cause, people with known thrombophilia should be assessed for increased risk when they are undergoing or likely to be exposed to circumstances that may further increase their risk of clotting, this included pregnancy, prolonged immobility, surgery, cancer, chemotherapy, trauma, certain medical diagnoses, and hormone replacement therapy. When any of these factors provoke a thrombotic response in someone without a known thrombophilia, consideration should be given to a thorough work-up for a preexisting thrombophilia, including taking a personal and family history and laboratory tests when appropriate.

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Labropoulos N, Patel PJ, Tiongson JE, Pryor L, Leon LR Jr., Tassiopoulos AK. Patterns of venous reflux and obstruction in patients with skin damage due to chronic venous disease. Vasc Endovascular Surg 2007;41:33-40.

Labropoulos N, Waggoner T, Sammis W, Samali S, Pappas PJ. The effect of venous thrombus location and extent on the development of post-thrombotic signs and symptoms. J Vasc Surg 2008;48:407-12.

Gasparis AP, Labropoulos N, Tassiopoulos AK, Phillips B, Pagan J, Lo C, Ricotta J. Midterm Follow-up After Pharmacomechanical Thrombolysis for Lower Extremity Deep Venous Thrombosis. Vasc Endovascular Surg 2009;43:61-8.

Labropoulos N, Gasparis A, Pefanis D, Leon LR, Tassiopoulos AK. Secondary chronic venous disease progresses faster than primary. J Vasc Surg 2009;49:704-10.

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