Acute Lower Extremity Deep Venous Thrombosis

Haraldur Bjarnason

Early clot lysis may prevent or significantly decrease the incidence and severity of postthrombotic syndrome after acute lower extremity deep vein thrombosis (DVT). Several smaller studies comparing systemic thrombolytic therapy for acute DVT with anticoagulation showed that significant or complete clot lyses can be achieved by giving systemic thrombolysis, but with an unacceptably high rate of bleeding complications.1,2 Catheter-directed thrombolysis for DVT has proven to be a safe and effective method to remove acute iliofemoral DVT.^3,4 Mechanical thrombectomy has emerged as an alternative or adjunct to pharmacologic thrombolysis.⁵

Population-based studies indicate that the annual incidence of DVT is between 122 and 160 per 100,000.⁶ It is thought that approximately 10% of patients with lower extremity DVT will have iliac vein involvement; these patients have an especially high risk of developing severe postthrombotic syndrome, and this may vary significantly. A recently published article from a large tertiary care facility found that 24% of patients diagnosed with DVT did have involvement of the iliac veins.⁷ The long-term sequelae of lower extremity DVT are very significant, as has been documented by many authors. Up to two thirds of patients with acute DVT treated according to accepted algorithms will develop postthrombotic syndrome. Patients with iliac vein thrombosis have a much worse prognosis.^8–10

Indications

There are no well-established indications for thrombolytic therapy for iliofemoral DVT. The challenge lies in the lack of conclusive randomized studies that document the safety and efficacy of thrombolysis compared to conventional anticoagulation. The decision to offer thrombolytic treatment to a patient with DVT has to be weighed carefully, considering the anticipated clinical outcome of the procedure and potential risks. The decision therefore becomes individualized, taking into account age and comorbid factors such as cancer or bleeding diatheses. Based on several small and large case studies, it is believed that certain indications can be supported on an individual basis.3,4,11 The Society of Interventional Radiology (SIR) and the Cardiovascular and Interventional Radiology Society of Europe published quality improvement guidelines in 2006 that suggest certain indications. These are listed in Table e101-1.

12,13

TABLE e101-1

Indications for Catheter-Directed Venous Thrombolysis

Indications	Purpose	Bleeding Risk*	Life Expectancy
Acute iliofemoral deep venous thrombosis	Prevent postthrombotic syndrome	Low	Long
Acute femoropopliteal deep venous thrombosis	Prevent postthrombotic syndrome	Low	Long
Subacute and chronic iliofemoral deep venous thrombosis	Prevent postthrombotic syndrome	Low	Long
Phlegmasia cerulea dolens	Limb salvage	Low-moderate	Any
Acute or subacute inferior vena cava thrombosis	Preserve organs, symptom relief	Low-moderate	Any

^*Bleeding risk for thrombolysis.

Modified from Vedantham S, Thorpe PE, Cardella JF, et al. Quality improvement guidelines for the treatment of lower extremity deep vein thrombosis with use of endovascular thrombus removal. J Vasc Interv Radiol 2006;17:435–48.

The largest groups of patients currently considered for thrombolytic therapy are patients with acute iliofemoral DVT. These patients are at high risk of developing postthrombotic syndrome and recurrent DVT and are frequently very symptomatic at first presentation. The potential of changing the long-term outcomes for these patients is therefore quite significant. Catheter-directed thrombolysis may be an acceptable alternative treatment and possibly superior to conventional anticoagulation in patients with a long life expectancy and a low risk for bleeding.¹⁴

A larger group of patients in whom the indications are less studied are patients with acute femoropopliteal DVT. Earlier studies using systemic thrombolysis for femoropopliteal thrombosis did indicate that there was a potential benefit from thrombolysis.1,2 It has to be borne in mind that many patients with femoropopliteal DVT will become free of symptoms if treated conventionally with anticoagulation and compression garments. Based on this, the threshold for catheter-directed thrombolysis should be higher for femoropopliteal DVT than for iliofemoral DVT. Catheter-directed thrombolysis should be reserved for patients with severe symptoms from femoropopliteal DVT and those who experience progression of thrombosis on anticoagulation.¹⁴

A limited number of practitioners use thrombolytic therapy in conjunction with iliac vein recanalization in patients with chronic iliac vein thrombosis or subacute thrombosis. This practice is discouraged and probably has very limited benefits in this group of patients.2,14

Phlegmasia cerulea dolens, an acute fulminating form of DVT characterized by reactive arterial spasm, pronounced edema, severe cyanosis, petechiae, and purpura, carries a high risk of amputation and significant morbidity and mortality.15–17 Many patients have significant comorbid factors such that any correctible management—surgical, endovascular, or medical—carries high risk. Several case reports of catheter-directed thrombolysis for phlegmasia cerulea dolens have been published^17,18 describing good short-term clinical improvement. Catheter-directed thrombolysis is found to be justified for most patients with this condition if they do not have a high risk of bleeding. When bleeding risk is believed to be prohibitory for thrombolysis, surgical thrombectomy should be considered. This is regarded as an emergent procedure.¹⁴

Acute thrombosis of the inferior vena cava is often very symptomatic, leading to bilateral lower extremity leg and genital congestion. If the thrombosis extends above the renal and hepatic veins, renal failure and Budd-Chiari syndrome may result. Filter placement may not be possible to prevent pulmonary emboli. For these reasons, catheter-directed thrombolysis may be justified to prevent or relieve the sequelae mentioned earlier.¹⁴

Both the American College of Chest Physicians ¹⁹ and the American Heart Association²⁰ have now included catheter-directed thrombolysis as an option for treatment of selected patients with lower extremity deep vein thrombosis.

Contraindications

Contraindications to venous thrombolysis and mechanical thrombectomy are practically the same as for any other thrombolytic therapy and are listed in Table e101-2.

TABLE e101-2

Contraindications to Catheter-Directed Venous Thrombolysis

Absolute Contraindications

Active internal bleeding or disseminated intravascular coagulation

Recent cerebrovascular event, transient ischemic attack, neurosurgery, or intracranial trauma (<3 mo)

Absolute contraindication to anticoagulation

Strong Relative Contraindications

Recent cardiopulmonary resuscitation, major surgery, obstetrical delivery, organ biopsy, or major trauma (<10 days); recent eye surgery (3 mo)

Intracranial tumor, other intracranial lesions, or seizure disorder

Uncontrolled hypertension with systolic blood pressure > 180 mmHg and diastolic blood pressure >110 mmHg

Recent major gastrointestinal bleeding (<3 mo)

Serious allergic or other reactions to contrast media (not controlled by corticosteroid/antihistamine pretreatment)

Severe thrombocytopenia

Known right-to-left cardiac or pulmonary shunt or left-sided heart thrombus

Massive pulmonary emboli with hemodynamic compromise

Suspicion of infected venous thrombus

Other Relative Contraindications

Renal failure (serum creatinine > 2.0 mg/dL)

Pregnancy or lactation

Severe hepatic dysfunction

Bacterial endocarditis

Diabetic hemorrhagic retinopathy

Contraindications to thrombolysis are often unclear, such as abnormal bleeding parameters in a patient with impaired liver function or in a patient with reduced platelets. Many patients have also undergone surgery on different body parts in the recent past, and it can be difficult to estimate what is a safe time from surgery. For the optimal outcome of thrombolysis, it has to be carried out soon after symptoms first appeared or within 10 to 14 days, which adds to the limitations but still gives some leeway to correct correctable bleeding diatheses.

Equipment

The equipment needed is the same as that used for arterial thrombolysis. Additional equipment is needed for mechanical thrombectomy. The main items needed are listed in Table e101-3.

Having a good fluoroscopy unit with image-capturing capability for documentation is a necessity. The fluoroscopic unit is used to obtain the necessary venogram and guide placement of the infusion catheters and mechanical thrombectomy. A C-arm fixed to either the floor or ceiling is preferable, and the larger the receptor, the better (40 cm diameter). Mobile fluoroscopic units can be used but should have image-capturing capability. Ultrasound to guide venous access is required, especially when the popliteal vein or posterior tibial vein is used for access. Puncturing the artery inadvertently can have serious consequences when the thrombolytic therapy subsequently starts. For the venous access it is advisable to use a micro-puncture access set. A 20-gauge needle with a 0.018-inch guidewire and 4F coaxial dilator that accepts a 0.035-inch guidewire is available from many vendors. There are many guidewires available, but the basic system is a 0.035-inch guidewire system. A multipurpose guidewire such as the Bentson (Cook Medical, Bloomington, Ind.) can be used, but a glide-coated guidewire such as the Glidewire (Terumo Medical Corp., Somerset, N.J.) may be needed to negotiate the thrombotic veins. To facilitate navigation through the clot, a 5F angiographic catheter, preferably with glide coating, should be used to help direct the guidewire as it is passed through the clotted vein. Contrast medium can be intermittently injected through it to obtain venography as it is advanced. An introducer sheath should be used that is 1F size larger than the infusion catheter so heparin solution can be infused through the side port around the infusion catheter going through it, either for low-dose anticoagulation or to keep the sheath from forming thrombus. There are many brands available, and a 10-cm-long introducer is sufficient. If mechanical thrombectomy is used, a larger introducer is needed, which is then left in place during the following infusion. Selection of an infusion catheter is based on the length of the clot to be treated. There are many different brands offered, but most are available with a 5-, 10-, 20-, 30-, 40-, and 50-cm-long infusion segment and come in 5F diameters, although some are also available in a 4F diameter. Construction of individual catheters differs, but the most important property is equal distribution of the drug throughout the length of the infusion segment.

The large number of mechanical thrombectomy devices available may be an indicator of their shortcomings thus far. They can be divided into so-called wall contact devices and non–wall contact devices (Table e101-4). Many of the devices have undergone preclinical and clinical evaluation for DVT and have been found to be effective, with very little trauma to the valvular elements, which is one of the main concerns. Concomitant pulmonary emboli have been one of the concerns with mechanical thrombectomy, and placement of an inferior vena caval filter has been recommended with some devices.²¹

Technique

Anatomy and Approaches

Anatomic Considerations

The anatomy of the lower extremity, iliac veins, and inferior vena cava is familiar to all interventionists, but the nomenclature of some of the lower extremity veins has recently changed.²² For example, the superficial femoral vein is now called the femoral vein.²³ The following is a short practical review with correlation to the approach for venous thrombolysis. It is important to recognize that the anatomy of the lower leg veins varies.

The three leg veins are paired and travel parallel to the main leg arteries and bear the same names: the posterior tibial vein, anterior tibial vein, and fibular or peroneal vein. The posterior tibial vein pair traverses behind the medial malleoli with the posterior tibial artery. The anatomy here is important because access can be gained into the posterior tibial vein at this level. This access can be used for placement of infusion catheters through which thrombolytic agents can be infused into thrombosed popliteal vein. The deep leg veins communicate with the superficial veins via perforating veins. The perforating veins have been used for placement of infusion catheters into thrombosed deep veins.²⁴ The leg veins will then merge and form the popliteal vein. The anatomy in the popliteal fossa is quite variable.²⁵ The vein is often partially or entirely duplicated.

The small saphenous vein (formerly the short saphenous vein) is formed from the dorsal venous arch and travels subcutaneously between the two heads of the gastrocnemius muscle. It then penetrates the fascia to enter the popliteal fossa and joins the popliteal or femoral vein, most commonly above or at the level of the femoral condyles. The small saphenous vein is very useful as an access vein for thrombolysis if the thrombus extends no farther distal than the mid- to distal femoral vein. One has to be aware of variation in the connection of the small saphenous vein, which may join the deep system above the popliteal vein, which will affect the use of this access if thrombus extends caudal to the junction. The sural nerve is just lateral to the vein, and precaution has to be taken not to harm it during puncture.

The femoral vein is quite consistent even though it can be duplicated (21.2%) or even have multiple channels (13.8%).²⁶ Usually only one infusion catheter is placed, so in the case of a split femoral vein, one has to select one channel to infuse into. The femoral vein will then merge with the profunda femoris vein, forming the common femoral vein. One major branch drains into it, the great saphenous vein (formerly the greater saphenous vein). The transition to the external iliac vein is at the inguinal ligament and the deep circumflex iliac vein, which is a tributary and anatomic landmark. As the internal iliac vein joins the external iliac vein, the common iliac vein is formed. The right and left common iliac veins will subsequently form the inferior vena cava, which will ascend to the right and anterior of the spine to the right atrium. A variant that is commonly seen with iliac vein thrombosis is compression of the left common iliac vein by the right common iliac artery crossing it anteriorly. Commonly, a stenosis is present at this point in the left common iliac vein, and the vein is often septate or webbed, which causes partial or complete obstruction with variable collateral formation. It has been estimated that between 14% and 30% of these patients have May-Thurner syndrome.²⁷