Inferior Vena Caval Thrombosis

Back

Background

Thrombosis of the inferior vena cava (IVC) is an underrecognized entity with a variety of clinical presentations. The general concepts of deep venous thrombosis (DVT) and thrombophlebitis are discussed in detail in Deep Venous Thrombosis. However, the implications and complexity of IVC thrombosis (IVCT) merit specific attention.[1, 2]

From a global standpoint, IVCT represents a subset of DVT. Virchow recognized and described the factors predisposing a patient to venous thrombosis. The triad of stasis, vessel injury, and hypercoagulability formulated by Virchow remain the foundation for our understanding of the pathophysiology of DVT in general and for IVCT in particular (see the image below).



View Image

Virchow triad/venous thromboembolism (VTE) risk factors.

As appreciation of the impact of these factors on the patient has improved, therapy has become more directed.

The clinical presentation of IVCT varies, depending on extent and location of the thrombus. Because of the variability in signs and symptoms, using a classification system to describe the clinical features may aid in the diagnosis of this condition.

Thrombophilic screening and evaluation of the clotting and fibrinolytic systems may aid in the diagnosis of IVCT. Contrast venography remains the criterion standard as the optimal diagnostic study for this condition.

Medical management of vena caval thrombosis focuses on anticoagulation and thrombolytic therapy. Surgical management of this condition consists of caval interruption, thrombectomy, or endovascular interventions.

Patient education

For patient education information, see the Circulatory Problems Center, as well as Deep Vein Thrombosis (Blood Clot in the Leg, DVT).

Anatomy

Understanding the anatomy of the IVC and its tributaries is essential to understanding the variability in the clinical presentations of patients with IVCT (see the image below).



View Image

Veins of abdomen and thorax. Unless stated otherwise, lithograph plate is from Gray's Anatomy (online edition of the 20th US edition of Gray's Anatomy....

The IVC is formed by the confluence of the left and right common iliac veins. Numerous paired segmental lumbar veins drain into the IVC throughout its length. The right gonadal vein empties directly into the cava, whereas the left gonadal vein generally empties into the left renal vein. The azygous system has connections with the IVC or the renal veins at the level of the renal veins.

The next major veins encountered are the renal veins, followed by the hepatic veins. No valves are within the IVC. The cava enters the thoracic cavity through the tendinous portion of the diaphragm and terminates at its junction with the right atrium.

Several congenital anomalies of venous anatomy can involve the IVC, and their presence can increase the likelihood of IVCT. The symptomatology related to IVCT follows directly from the anatomic location of the thrombus and the degree of the lumen occupied by the thrombus.

Pathophysiology

Congenitally normal inferior vena cava

Thrombosis of the IVC in the absence of congenital abnormalities is rare; when it does occur, it is usually the result of a predisposing hypercoagulable state along with an acquired pathology in the IVC or one of its adjacent structures.[3, 4, 5, 6, 7] Iatrogenic thrombotic occlusion of IVC filters is increasing, particularly in the United States. As a consequence of the high number of IVC filter placements and the low retrieval rates (10-34%),[8, 9, 10] late filter thrombosis has been reported in as many as 33% of patients.[4, 5, 11, 12]

Congenital abnormalities of inferior vena cava

Congenital abnormalities of the IVC are rare (incidence, ~1%); however, IVCT thrombosis is more common among patients with such anomalies (range, 60-80%).[13, 14, 15] In patients with congenital cardiac defects, the incidence ranges from 2% to 3%.[16] Congenital IVC anomalies have three main anatomic configurations, as follows.[17, 6, 18] :

Because of well-developed collaterals, patients with congenital IVC anomalies rarely experience symptoms. The anatomic variants listed above are often noted as incidental findings on abdominal imaging.[14] Symptoms (eg, acute or chronic proximal DVT or evidence of chronic venous insufficiency) observed in patients are usually attributable to the involvement of the venous collaterals (frequently the deep pelvic veins or common iliac veins).

Etiology

To a large degree, the etiology of IVCT mirrors that of DVT in general. However, specific situations relate to the IVC only, but the wide variety of these situations all relate in one or more ways to Virchow's classic description.

Tumors

Numerous malignancies have been associated with IVCT.[19] Perhaps the most familiar is renal cell carcinoma (RCC). The intravascular tumor extends from the renal vein and can propagate as far as the heart. It can partially or completely occlude the IVC. Not all intravascular irregularities of the kidney represent tumor thrombus. In one case report, a patient who underwent radical nephrectomy for presumed RCC was subsequently found to have only renal vein thrombosis.[20] Other genitourinary tumors that reportedly cause IVCT are seminomas and teratomas.

Numerous other less common tumors reportedly involve the IVC. Intuitively, it is reasonable that any structure anatomically related to the IVC can generate either direct compression or vascular invasion. Retroperitoneal leiomyosarcoma,[21] adrenal cortical carcinoma,[22] and renal angiomyolipoma[23] have all presented in association with IVCT. Even hepatic hemangioma has caused IVCT from extrinsic compression.[24] Additionally, malignancy itself is a risk factor for DVT and thus represents a risk factor for the extension of DVT into the IVC.

Compression

Extrinsic compression may also result from nontumoral sources and increase the likelihood of IVCT. The distortion of the normal caval anatomy generates both venous stasis and turbulent flow. This situation facilitates the formation of a thrombus. An activity as innocuous as bicycle riding has reportedly caused IVCT.[25] The spectrum of medical diagnoses that can cause compression of the IVC is determined by those structures anatomically adjacent to the IVC.

Abdominal aortic aneurysms (AAAs) can compress the IVC and cause thrombosis. Although this clinical situation is uncommon, the implications for surgical repair of the aneurysm are significant. The surgeon must be prepared for enlarged venous collaterals and the possibility of unusual tissue-plane configurations. One reported case described incorporation of the IVC into the aneurysm[26] ; the wall of the IVC was actually part of the wall of the aneurysm. Knowing that AAA is a risk factor for IVCT should heighten clinical suspicion in appropriate cases.

Hepatic abscesses, either from amebae or echinococci, can also generate thrombosis of the IVC from compression. Because of the propensity of these processes to evolve over time, patients may present without symptoms suggestive of IVC occlusion. They may only demonstrate evidence of the primary process or of collateral venous hypertrophy. The initial presenting symptom may even be pulmonary embolization.

Other retroperitoneal organ systems that have been shown to cause IVCT include the pancreas and the kidneys. Polycystic disease of the right kidney has reportedly been clinically associated with thrombosis of the IVC.[27] Pancreatic pseudocysts have been observed to cause thrombosis of the IVC.[28] Acute pancreatitis has also been found to generate thrombosis of the IVC.[29, 30]

The pathophysiology of the evolution of the thrombosis may reflect either the local impact of inflammation of the pancreatic head or the impact of a hypercoagulable state on the IVC. Although IVCT in the setting of pancreatitis is uncommon, this clinical entity may account for an unexplained deterioration in the status of a patient with acute pancreatitis.

Hematoma/trauma

Other aspects of compression can be attributed to the presence of a hematoma adjacent to the cava or the iliac systems. Psoas hematomas and other hematomas of the retroperitoneum have been identified as causing IVCT. In one case, the hematoma was the result of a common iliac artery injury. Because the venous system was not involved, the presumed mechanism of compression of the cava by clot seems credible.

Unique among causes, trauma combines the limbs of the Virchow triad. Stasis, vessel injury, and hypercoagulability may all exist in the same clinical situation. Direct trauma to the IVC may be the result of either penetrating or blunt trauma.[31, 32, 33] In the absence of venous laceration, blunt endothelial damage has been postulated to cause IVCT. Other mechanisms observed secondary to trauma include extension of hepatic venous thrombosis and thrombus formation after perihepatic packing.

Dysfunctional coagulation system

By necessity and function, the balance between the coagulation system and the fibrinolytic system is delicate and dynamic. Disorders that disrupt this balance can cause a situation in which IVC thrombus formation may occur.

The nephrotic syndrome is a classic example. Patients with this syndrome have urinary protein losses. Both renal vein thrombosis and IVCT have been described. The exact mechanism of the hypercoagulability of patients with the nephrotic syndrome has not been fully delineated. However, these patients have massive urinary protein loss, and diminished levels of antithrombin III have been observed.

Iatrogenic

Patients with a recent history of medical care may present with iatrogenic IVCT. The expansion of endovascular technology has led to increased recognition of iatrogenic IVCT.[34] Interventions that reportedly have identifiable rates of IVCT include the following:

Awareness of the association of these procedures with IVCT allows clinicians to make educated decisions. Recognizing the association allows an accurate risk-benefit assessment for a given procedure. Additionally, recognizing these factors may aid in determining a prompt diagnosis in patients who have postprocedural clinical changes.

Congenital absence of inferior vena cava

Anomalies of the IVC have been described more frequently (0.6-2%) in those with other cardiovascular defects[35] and less so in otherwise healthy individuals. Various abnormalities of the IVC have been described, including complete absence, partial absence, or presence of bilateral IVC.[36]

Absent IVC is an extremely rare anomaly that is associated with idiopathic DVT, particularly in the young. Controversy exists as to whether an absent IVC has a true embryonic etiology or whether it is the result of perinatal IVC thrombosis causing regression and disappearance of the once present IVC.[37]

A case report has described an absent IVC and left renal hypoplasia and a right hypertrophic kidney.[38] A more commonly recognized association is right renal aplasia, as suggested in a review by Gayer et al, in which all nine patients with complete absence of the IVC had an absent or very small right kidney.[39]

The association of an absent or hypoplastic kidney is related (or may contribute to an absent IVC) to perinatal renal vein thrombosis.[40] Veen et al proposed naming this condition KILT (kidney and IVC abnormalities with leg thromboses) syndrome (when associated with DVT).[38]

It is estimated that DVT occurs at a rate of 1 case per 1000 patient-years[41] ; in as many as 80% of patients who are affected, a risk factor can be identified. Ruggeri et al presented four cases of absent IVC over a 5-year period that presented with idiopathic DVT in patients younger than 30 years,[42] representing an estimated 5% of cases of idiopathic DVT in young people.

Chee et al similarly noted that as many as 5% of 20- to 40-year-old patients presenting with DVT had an IVC anomaly (four in total, of which three had a complete absence of IVC).[13] This was much higher than the expected 0.5%.

Other associated conditions

Numerous other clinical situations have been associated with IVCT. They may meet some classification criteria to be listed in one or more of the categories mentioned above; however, they are noted here for clarity and can include (1) developmental anomalies of the IVC, (2) retroperitoneal fibrosis, (3) pregnancy, and (4) oral contraceptives.

Although not all-inclusive, the foregoing information provides a review of many of the known clinical situations in which IVCT may be evident. Knowledge of the potential for thrombosis of the IVC increases physicians' level of clinical awareness in patients who present with the identified primary processes.

Epidemiology

The exact number of patients who have IVCT remains elusive because of the clinical variability in presentation. By compiling information from several epidemiologic studies that investigated DVT prevalence, the following US estimates can be generated:

These numbers are estimates generated from various population-based studies. Various groups within the general population have a greater propensity for IVCT (see Etiology).

Prognosis

The outcome of patients with IVCT is often determined by the underlying condition that initially caused the thrombosis. However, some general statements can be made. The impact and outcome of IVCT are as variable as the clinical presentation. In one study, only one third of patients had a correct diagnosis before venography. Adult patients with ligation of their vena cava reportedly have either no symptoms or mild edema after ligation.[43]

A report on children who had IVCT unrelated to catheterization revealed that 50% had persistent IVCT. Symptoms of chronic limb pain and chronic abdominal pain were observed. Another series of pediatric patients with IVCT secondary to central venous access identified no sequelae unless concurrent superior vena cava thrombosis was present.

Finally, the outcome of patients who have IVCT relates to the embolic risk associated with DVT overall. If the cava is occluded, pulmonary embolization does not present a significant risk. However, if a caval lumen remains, embolization may occur.

History

Patients with inferior vena caval (IVC) thrombosis (IVCT) may present with a spectrum of signs and symptoms. Patients may be asymptomatic, or they may present only after complications occur.

This variability is a significant part of the challenge of diagnosis. Using a classification system may help the clinician make the correct diagnosis. Thus, patients may present with symptoms that are predominantly thrombotic in origin or predominantly embolic in nature. Additionally, the thrombotic findings are dependent on the degree of occlusion of the IVC and on the location between the iliac confluence and the right atrium.

Patients who have IVCT may present only after having pulmonary embolism (PE). The lack of uniform symptoms and the significant number of asymptomatic patients contribute to this feature of IVCT. In one retrospective review of all patients who had cavography to document IVC thrombus, 20% had angiographically proven PE with no symptoms of deep vein thrombosis (DVT). Thus, PE may be the first sign of IVCT.

In patients with complete absence of the IVC, symptoms associated with severe venous hypertension (eg, bilateral lower-extremity edema, varicose veins, nonhealing venous ulcers, caput medusae, or other manifestations of collateral venous system hypertension/dilatation) may be varied in their manifestation and, in some cases, may not be apparent until later in life.

Physical Examination

The classic presentation of IVCT includes bilateral lower-extremity edema with dilated, visible superficial abdominal veins. Intuitively, this constellation makes sense, though it is not universally found. In one study, almost 60% of patients did not have bilateral leg edema. In addition, if the thrombus is confined to the cava and does not involve the iliac or femoral system, the collateral pathways form along the posterior abdominal wall. This scenario may have significant impact on surgical procedures involving this anatomic region.

Occlusive thrombus of the IVC at the juxtarenal level can affect renal function by altering renal perfusion.

It is hypothesized that blood return with an absent IVC is inadequate, despite adequate collaterals, resulting in chronic venous hypertension in the lower extremities and causing venous stasis that precipitates thrombosis.

Budd-Chiari syndrome

Budd-Chiari syndrome merits specific attention, though a discussion of the entire syndrome is beyond the scope of this article. The essentials of this condition as they relate to IVCT are important. Patients typically have significant ascites, portal hypertension, hepatomegaly, collateral vein enlargement, and hepatic fibrosis. The pathophysiology of this syndrome centers on either IVC or hepatic venous thrombosis. If it is at the hepatic venous level, two or three of the major hepatic veins must be occluded before the syndrome can develop. Both hypercoagulable states and membranous venous webs have been postulated as the etiologic agents of Budd-Chiari syndrome.

Approach Considerations

No specific laboratory test includes or excludes the diagnosis of inferior vena cava (IVC) thrombosis (IVCT), though evaluation of the clotting and fibrinolytic systems and assessment of the thrombin antagonists may be helpful.

The ideal imaging modality to help diagnose an IVC anomaly must have high diagnostic accuracy and also be safe and reproducible. It is difficult to establish a diagnosis of any IVC anomaly by means of ultrasonography (US). However, various clues are recognized on radiologic imaging that could help diagnose an absent IVC or anomaly.

One of the more common and helpful clues is well-developed and possibly dilated intrathoracic hemiazygos or azygos continuations. These collateral circulations, as well as other retroperitoneal venous pathways, are usually well developed before symptoms present.[44] However, plain radiography should not be used as a primary diagnostic tool.

The most reliable noninvasive methods for establishing a diagnosis of IVC anomalies are computed tomography (CT) with intravenous (IV) contrast and magnetic resonance imaging (MRI). CT, unlike US, is a good imaging modality for the retroperitoneal space.[45] Another accurate, albeit more invasive, imaging modality is venography, which is particularly useful if any surgery is planned.

Although other modalities may have a more primary role, IVCT may still be diagnosed intraoperatively in patients who were treated with laparotomy for their primary problem.

IVCT remains a challenging process to diagnose and treat. Opinions differ among critical care physicians, surgeons, radiologists, and other physicians regarding the optimal diagnostic study for this condition.Technologic advances in US, endovascular US (EVUS), CT, and MRI, as well as endovascular procedures, have increased the detection rates of vena cava anomalies and venous thrombosis.[46]  Bilateral lower-limb venous duplex US coupled with MRI is an optimal noninvasive approach in most patients.[47]  However, the current general consensus is that contrast venography remains the criterion standard.

Go to Deep Venous Thrombosis for more complete information on this topic.

Laboratory Studies

Assessing the clotting and fibrinolytic systems may be helpful. Confounding factors include variations caused by heparin and warfarin therapy, and dynamic factors involved with acute thrombosis may also alter measured parameters because of the active consumption of factor by the thrombus.

Gayer et al recommended that all patients with an IVC anomaly be screened for a thrombophilic disorder.[14]  In their series, seven of nine patients with an IVC anomaly and deep vein thrombosis (DVT) had a positive thrombophilic screen. Thus, protein C, protein S, antithrombin III, and anticardiolipin studies may all be helpful, but many of these assessments can only be made after the fact.

However, there have been three case reports in the English-language medical literature of thromboembolism due to an IVC anomaly (absence of the infrarenal portion of the IVC, infrarenal IVC hypoplasia), in which the thrombophilic screen was negative in all cases.[48, 49, 50]  It was hypothesized that multiple emboli from DVT in the common and superficial femoral veins migrated through the well-developed hemiazygos or azygos system to the pulmonary circulation.

Contrast Venography

This imaging modality is the criterion standard for diagnosis of DVT. Two access sites may be required to document the extent of a thrombus in situations of IVC occlusion by clot. However, the caudal extent of the clot may be overestimated because of preferential flow into collaterals.

Advantages of contrast venography include the following:

Disadvantages of this technique include the following:

Duplex Ultrasonography

Advantages of duplex US include the following:

Disadvantages of this imaging modality include the following:

Go to Bedside Ultrasonography for more complete information on this topic.

Computed Tomography

CT scans are often obtained as part of the diagnostic evaluation for the primary process (eg, malignancy). The use of IV contrast materials is typically required. Pseudothrombosis, particularly of the infrarenal IVC, is generally thought to result from the variable amounts of contrast in the cava above and below the renal veins. It may also result from collapse of the IVC at the diaphragm when patients are supine.

The very limited data from the literature suggest that, in cases of an absent IVC in young people (in some data, patients younger than 30 years; in other data, patients aged 20-40 years), an abdominal CT scan should be performed (see the images below). False-positive study results sometimes occur.



View Image

Photo showing dilated superficial abdominal veins (upper quadrant), with bruising and thrombosed large abdominal veins (lower quadrant).



View Image

Abdominal CT scan shows absent inferior vena cava with thrombosis of very prominent collateral veins in the abdominal wall, corresponding to right sid....

Magnetic Resonance Imaging

MRI allows examination in multiple planes and estimation of the thrombus age. Reconstructive imaging technology can generate images similar to those seen with venography.

Advantages of MRI include the following:

Disadvantages of this imaging modality include the following:

Approach Considerations

Once the diagnosis has been confirmed, the clinician must choose an appropriate treatment regimen for inferior vena cava (IVC) thrombosis (IVCT) on the basis of the underlying pathophysiology. Both surgical and medical options are available. Medical professionals are encouraged to investigate the most recent research to keep apprised of the latest information relating to the various risks and benefits of treatment modalities.

In the broadest sense, surgical therapy of IVCT encompasses caval interruption and thrombectomy. Currently, both of these modalities are being used less frequently.

There is very little evidence available on the surgical correction or the treatment of a complete absence of the IVC. A case report, in which there was a complete absence of the IVC but patent iliac veins and nonhealing pretibial ulceration, described successful treatment with a prosthetic graft from the iliac vein to the intrathoracic azygos vein.[40] Authors of another case report concluded, on the basis of their review of the available literature, that surgical options in this patient population are limited.[51]

Go to Deep Venous Thrombosis for more complete information on this topic.

The goals of therapy center on managing the primary impact of deep vein thrombosis (DVT) and the impact of embolization. Medical management can include anticoagulation therapy and thrombolytic agents (see Medication).

Anticoagulants and Thrombolytic Agents

Heparin or warfarin may be used to prevent the propagation of thrombi. One group reported no embolic events with this therapy, even with so-called free-floating IVCT. However, propagation may still occur. Therapy is usually converted to oral anticoagulation with warfarin, but the time course of warfarin therapy is somewhat empiric.

Most thrombolytic agents have been reported in the treatment of IVCT. The relative merits of thrombolytic therapy must be weighed against the risks of hemorrhagic complications.

Urokinase, tissue-type plasminogen activator (tPA), and streptokinase have all been used. Typically, delivery is catheter-directed, with or without a pulse spray. Patients require concurrent heparin therapy; however, tPA protocols do not use concurrent heparin because of the risk of bleeding complications.

Up to a 25% risk of pulmonary embolism (PE) during therapy has been reported. Some reports advocate using filters above the thrombolysis site[52] ; some do not. This therapy may play the greatest role as part of combination therapy with endovascular interventions.

Caval Interruption

When using ligation for caval interruption, the proper level must be chosen. Ligation effects a permanent, complete occlusion of the IVC, but the risk of recurrent PE is not zero.

Filters are relatively noninvasive, allow central flow, and may be placed at several different anatomic levels as indicated by the clinical situation. However, thrombosis may occur at the insertion site or at the site of the filter itself. There are numerous proprietary configurations of filters available, and the technology is constantly changing; therefore, data from older studies may not extrapolate to current devices.

Go to Inferior Vena Cava Filters for more complete information on this topic.

Thrombectomy and Endovascular Intervention

Thrombectomy is often carried out for therapy of phlegmasia, but rethrombosis rates are significant and thrombectomy often does not completely remove the thrombus. The procedure is typically performed in conjunction with a distal arteriovenous fistula to maintain high flow, and it may be required for cases of septic thrombus. The operative mortality is reportedly 2%; the morbidity is 30%.

Endovascular interventions

Endovascular techniques are particularly helpful to treat patients with IVCT that has arisen from iatrogenic causes (see Etiology). The numerous clinical scenarios that lend themselves to this approach can include (1) long-term venous access, (2) hemodialysis access, and (3) surgery on the IVC, including hepatic transplantation.

Several interventional modalities are available to treat IVCT. The optimal result can often be obtained by using a combination of the following options:

The number and type of expandable stents are changing as product development continues. The various stents have limitations both in vessel diameter and length of available stent. Consulting with vascular surgeons, radiologists, and available literature to identify the locally available devices is encouraged and recommended.

Medication Summary

The goals of pharmacotherapy for inferior vena caval thrombosis (IVCT) and deep vein thrombosis (DVT) are to reduce morbidity, to prevent the postthrombotic syndrome (PTS), and to prevent pulmonary embolism (PE), all with minimal adverse effects and cost. The main agent classes include anticoagulants and thrombolytics.

Heparin

Clinical Context:  Heparin augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. It does not actively lyse but is able to inhibit further thrombogenesis. Heparin prevents reaccumulation of a clot after a spontaneous fibrinolysis.

Dalteparin (Fragmin)

Clinical Context:  Dalteparin is a low molecular weight heparin that enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases the inhibition of factor Xa.

Enoxaparin (Lovenox)

Clinical Context:  Enoxaparin is a low molecular weight heparin that is produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). It binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin). It does not actively lyse but is able to inhibit further thrombogenesis. It prevents reaccumulation of clots after spontaneous fibrinolysis.

Tinzaparin (Innohep)

Clinical Context:  Tinzaparin is a low molecular weight heparin that enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases the inhibition of factor Xa.

Class Summary

Heparin or warfarin may be used to prevent the propagation of thrombi. Therapy is usually converted to oral anticoagulation with warfarin, but the time course of warfarin therapy is somewhat empiric.

Warfarin (Coumadin, Jantoven)

Clinical Context:  Warfarin interferes with hepatic synthesis of vitamin K–dependent coagulation factors. It is used for prophylaxis and treatment of venous thrombosis, PE, and thromboembolic disorders. Warfarin may be used to prevent the propagation of thrombi.

Class Summary

Coumarins are a class of oral anticoagulant drugs that act as antagonists to vitamin K. The mechanism of action is to interfere with the interaction between vitamin K and coagulation factors II, VII, IX, and X. Vitamin K acts as a cofactor at these levels. Coumarins produce their anticoagulant effect by inhibiting the carboxylation necessary for biologic activity.

Urokinase

Clinical Context:  Urokinase is a direct plasminogen activator isolated from human fetal kidney cells grown in culture. It acts on endogenous fibrinolytic system and converts plasminogen to enzyme plasmin. Plasmin degrades fibrin clots, fibrinogen, and other plasma proteins. Urokinase is nonantigenic but more expensive than streptokinase, which limits its use. When used for purely local fibrinolysis, it is administered as local infusion directly into area of thrombus and with no bolus. The dose must be adjusted to achieve clot lysis or patency of the affected vessel.

Streptokinase (Streptase)

Clinical Context:  Streptokinase acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. An increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 hours takes place with intravenous (IV) infusion of streptokinase.

Alteplase (Activase, Cathflo Activase)

Clinical Context:  Alteplase is a tPA used in the management of acute myocardial infarction, acute ischemic stroke, and PE. Safety and efficacy with concomitant administration of heparin or aspirin during the first 24 hours after symptom onset have not been investigated.

Class Summary

Most thrombolytic agents have been reported in the treatment of IVCT. The relative merits of thrombolytic therapy must be weighed against the risks of hemorrhagic complications.

Thrombolytic agents are used to dissolve a pathologic intraluminal thrombus or embolus that has not been dissolved by the endogenous fibrinolytic system. They are also used for the prevention of recurrent thrombus formation and rapid restoration of hemodynamic disturbances. Urokinase, tissue-type plasminogen activator (tPA), and streptokinase have all been used. Typically, delivery is catheter directed with or without a pulse spray. Patients require concurrent heparin therapy; however, tPA protocols do not use concurrent heparin because of the risk of bleeding complications. This therapy may play the greatest role as part of combination therapy with endovascular interventions.

What is inferior vena caval thrombosis (IVCT)?What is the anatomy relevant to inferior vena caval thrombosis (IVCT)?What causes inferior vena caval thrombosis (IVCT)?What is the role of compression in the pathogenesis of inferior vena caval thrombosis (IVCT)?What is the role of hematomas in the pathogenesis of inferior vena caval thrombosis (IVCT)?What is the role of nephrotic syndrome in the pathogenesis of inferior vena caval thrombosis (IVCT)?What are the iatrogenic causes of inferior vena caval thrombosis (IVCT)?Which anomalies the of inferior vena caval are associated with inferior vena caval thrombosis (IVCT)?Which conditions are associated with inferior vena caval thrombosis?What is the prevalence of inferior vena cava thrombosis (IVCT)?What is the prognosis of inferior vena cava thrombosis (IVCT)?What are the signs and symptoms of inferior vena cava thrombosis (IVCT)?Which physical findings are characteristic of inferior vena cava thrombosis (IVCT)?What are the signs and symptoms of Budd-Chiari syndrome in patients with inferior vena caval thrombosis?Which conditions should be included in the differential diagnoses of inferior vena cava thrombosis (IVCT)?How is inferior vena caval thrombosis diagnosed?What is the role of lab testing in the workup of inferior vena cava thrombosis (IVCT)?What is the role of contrast venography in the workup of inferior vena cava thrombosis (IVCT)?What is the role of duplex ultrasonography in the workup of inferior vena cava thrombosis (IVCT)?What is the role of CT scanning in the workup of inferior vena cava thrombosis (IVCT)?What is the role of MRI in the workup of inferior vena cava thrombosis (IVCT)?How is inferior vena cava thrombosis (IVCT) treated?What is the role of anticoagulants and thrombolytic agents in the treatment of inferior vena cava thrombosis (IVCT)?What is the role of caval interruption in the treatment of inferior vena cava thrombosis (IVCT)?What is the role of thrombectomy in the treatment of inferior vena cava thrombosis (IVCT)?What is the role of endovascular intervention in the treatment of inferior vena cava thrombosis (IVCT)?What combination of several interventional modalities are available to treat inferior vena caval thrombosis (IVCT)?What is the role of medications in the treatment of inferior vena cava thrombosis (IVCT)?Which medications in the drug class Thrombolytics are used in the treatment of Inferior Vena Caval Thrombosis?Which medications in the drug class Vitamin K Antagonists are used in the treatment of Inferior Vena Caval Thrombosis?Which medications in the drug class Anticoagulants are used in the treatment of Inferior Vena Caval Thrombosis?

Author

Luis G Fernandez, MD, FACS, FASAS, FCCP, FCCM, FICS, KHS, KCOEG, Professor of Surgery, Department of Surgery, University of Texas Health Science Center; Adjunct Clinical Professor of Medicine and Nursing, University of Texas; Adjunct Clinical Assistant Professor, Department of Medical Education Health Science Center, Adjunct Clinical Assistant Professor, Department of Physician Assistant Studies, School of Health Professions, University of North Texas; Medical Director, Trauma Wound Care, UT Health; Member, ACS National Committee on Trauma; Vice Chairman, State Guard Association of the United States (SGAUS) Medical Academy; Commander Emeritus, Texas Commandery, MOFW; Brigadier General (Ret/HR), Past Commanding General, TXSG Medical Brigade/Medical Rangers

Disclosure: Received honoraria from KCI for speaking and teaching; Partner received honoraria from PACIRA for speaking and teaching. for: Received honoraria from PACIRA for speaking and teaching: Researcher / Speaker for Steadmed.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

John Geibel, MD, MSc, DSc, AGAF, Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, Professor, Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow; Fellow of the Royal Society of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Douglas M Geehan, MD Associate Professor, Department of Surgery, University of Missouri-Kansas City School of Medicine

Disclosure: Nothing to disclose.

Michael A Grosso, MD Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital

Michael A Grosso, MD is a member of the following medical societies: American College of Surgeons, Society of Thoracic Surgeons, and Society of University Surgeons

Disclosure: Nothing to disclose.

References

  1. Anderson FA Jr, Wheeler HB, Goldberg RJ, Hosmer DW, Patwardhan NA, Jovanovic B, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med. 1991 May. 151 (5):933-8. [View Abstract]
  2. White RH. The epidemiology of venous thromboembolism. Circulation. 2003. 107(23 Suppl 1):I4–8.
  3. McAree BJ, O'Donnell ME, Fitzmaurice GJ, Reid JA, Spence RA, Lee B. Inferior vena cava thrombosis: a review of current practice. Vasc Med. 2013 Feb. 18 (1):32-43. [View Abstract]
  4. Alkhouli M, Shafi I, Bashir R. Inferior vena cava filter thrombosis and suprarenal caval stenosis: a double whammy. JACC Cardiovasc Interv. 2015 Feb. 8 (2):e23-e25. [View Abstract]
  5. Alkhouli M, Morad M, Narins CR, Raza F, Bashir R. Inferior Vena Cava Thrombosis. JACC Cardiovasc Interv. 2016 Apr 11. 9 (7):629-43. [View Abstract]
  6. Kaufman LB, Yeh BM, Breiman RS, Joe BN, Qayyum A, Coakley FV. Inferior vena cava filling defects on CT and MRI. AJR Am J Roentgenol. 2005 Sep. 185 (3):717-26. [View Abstract]
  7. Marcy PY, Magné N, Frenay M, Bruneton JN. Renal failure secondary to thrombotic complications of suprarenal inferior vena cava filter in cancer patients. Cardiovasc Intervent Radiol. 2001 Jul-Aug. 24 (4):257-9. [View Abstract]
  8. Alkhouli M, Bashir R. Inferior vena cava filters in the United States: less is more. Int J Cardiol. 2014 Dec 20. 177 (3):742-3. [View Abstract]
  9. Angel LF, Tapson V, Galgon RE, Restrepo MI, Kaufman J. Systematic review of the use of retrievable inferior vena cava filters. J Vasc Interv Radiol. 2011 Nov. 22 (11):1522-1530.e3. [View Abstract]
  10. Dabbagh O, Nagam N, Chitima-Matsiga R, Bearelly S, Bearelly D. Retrievable inferior vena cava filters are not getting retrieved: where is the gap?. Thromb Res. 2010 Dec. 126 (6):493-7. [View Abstract]
  11. Ahmad I, Yeddula K, Wicky S, Kalva SP. Clinical sequelae of thrombus in an inferior vena cava filter. Cardiovasc Intervent Radiol. 2010 Apr. 33 (2):285-9. [View Abstract]
  12. Fox MA, Kahn SR. Postthrombotic syndrome in relation to vena cava filter placement: a systematic review. J Vasc Interv Radiol. 2008 Jul. 19 (7):981-985. [View Abstract]
  13. Chee YL, Culligan DJ, Watson HG. Inferior vena cava malformation as a risk factor for deep venous thrombosis in the young. Br J Haematol. 2001 Sep. 114(4):878-80. [View Abstract]
  14. Gayer G, Luboshitz J, Hertz M, Zissin R, Thaler M, Lubetsky A, et al. Congenital anomalies of the inferior vena cava revealed on CT in patients with deep vein thrombosis. AJR Am J Roentgenol. 2003 Mar. 180(3):729-32. [View Abstract]
  15. Sitwala PS, Ladia VM, Brahmbhatt PB, Jain V, Bajaj K. Inferior vena cava anomaly: a risk for deep vein thrombosis. N Am J Med Sci. 2014 Nov. 6 (11):601-3. [View Abstract]
  16. Chuang VP, Mena CE, Hoskins PA. Congenital anomalies of the inferior vena cava. Review of embryogenesis and presentation of a simplified classification. Br J Radiol. 1974 Apr. 47 (556):206-13. [View Abstract]
  17. Spentzouris G, Zandian A, Cesmebasi A, Kinsella CR, Muhleman M, Mirzayan N, et al. The clinical anatomy of the inferior vena cava: a review of common congenital anomalies and considerations for clinicians. Clin Anat. 2014 Nov. 27 (8):1234-43. [View Abstract]
  18. Truty MJ, Bower TC. Congenital anomalies of the inferior vena cava and left renal vein: implications during open abdominal aortic aneurysm reconstruction. Ann Vasc Surg. 2007 Mar. 21 (2):186-97. [View Abstract]
  19. Kraft C, Schuettfort G, Weil Y, Tirneci V, Kasper A, Haberichter B, et al. Thrombosis of the inferior vena cava and malignant disease. Thromb Res. 2014 Sep. 134(3):668-73. [View Abstract]
  20. Takayama H, Kinouchi T, Meguro N, Maeda O, Saiki S, Kuroda M, et al. Renal vein thrombosis misdiagnosed as a renal cell carcinoma with a tumor thrombus in the inferior vena cava. Int J Urol. 1998 Jan. 5(1):94-5. [View Abstract]
  21. Hartman DS, Hayes WS, Choyke PL, Tibbetts GP. From the archives of the AFIP. Leiomyosarcoma of the retroperitoneum and inferior vena cava: radiologic-pathologic correlation. Radiographics. 1992 Nov. 12(6):1203-20. [View Abstract]
  22. Figueroa AJ, Stein JP, Lieskovsky G, Skinner DG. Adrenal cortical carcinoma associated with venous tumour thrombus extension. Br J Urol. 1997 Sep. 80(3):397-400. [View Abstract]
  23. Gotoh A, Gohji K, Fujisawa M, Okada H, Arakawa S, Hanioka K, et al. Renal angiomyolipoma associated with inferior vena caval tumour thrombus. Br J Urol. 1998 May. 81(5):773-4. [View Abstract]
  24. Paolillo V, Sicuro M, Nejrotti A, Rizzetto M, Casaccia M. Pulmonary embolism due to compression of the inferior vena cava by a hepatic hemangioma. Tex Heart Inst J. 1993. 20(1):66-8. [View Abstract]
  25. Simpson AH, Kilby JO. Inferior vena cava thrombosis following a cycle ride. J R Soc Med. 1988 Dec. 81(12):738-9. [View Abstract]
  26. Flynn P, Zammit-Maempel I. Case report: computed tomography demonstration of inferior vena caval thrombosis and incorporation into an abdominal aortic aneurysm. Clin Radiol. 1998 Apr. 53(4):306-7. [View Abstract]
  27. O'Sullivan DA, Torres VE, Heit JA, Liggett S, King BF. Compression of the inferior vena cava by right renal cysts: an unusual cause of IVC and/or iliofemoral thrombosis with pulmonary embolism in autosomal dominant polycystic kidney disease. Clin Nephrol. 1998 May. 49(5):332-4. [View Abstract]
  28. Peillon C, Manouvrier JL, Testart J. Inferior vena cava thrombosis secondary to chronic pancreatitis with pseudocyst. Am J Gastroenterol. 1991 Dec. 86(12):1854-6. [View Abstract]
  29. Jones AL, Ojar D, Redhead D, Proudfoot AT. Case report: Use of an IVC filter in the management of IVC thrombosis occurring as a complication of acute pancreatitis. Clin Radiol. 1998 Jun. 53(6):462-4. [View Abstract]
  30. Stringer MD, Michell M, McIrvine AJ. Inferior vena caval thrombosis complicating acute pancreatitis. Case report. Acta Chir Scand. 1988 Feb. 154(2):161-3. [View Abstract]
  31. Campbell DN, Liechty RD, Rutherford RB. Traumatic thrombosis of the inferior vena cava. J Trauma. 1981 May. 21(5):413-5. [View Abstract]
  32. Nagy KK, Duarte B. Post-traumatic inferior vena caval thrombosis: case report. J Trauma. 1990 Feb. 30(2):218-21. [View Abstract]
  33. Takeuchi M, Maruyama K, Nakamura M, Chikusa H, Yoshida T, Muneyuki M, et al. Posttraumatic inferior vena caval thrombosis: case report and review of the literature. J Trauma. 1995 Sep. 39(3):605-8. [View Abstract]
  34. Peck KE, Bonoan JT, Cunha BA. Postlaparoscopic traumatic inferior vena caval thrombosis. Heart Lung. 1998 Jul-Aug. 27(4):279-82. [View Abstract]
  35. ANDERSON RC, ADAMS P Jr, BURKE B. Anomalous inferior vena cava with azygos continuation (infrahepatic interruption of the inferior vena cava). Report of 15 new cases. J Pediatr. 1961 Sep. 59:370-83. [View Abstract]
  36. Bass JE, Redwine MD, Kramer LA, Huynh PT, Harris JH Jr. Spectrum of congenital anomalies of the inferior vena cava: cross-sectional imaging findings. Radiographics. 2000 May-Jun. 20(3):639-52. [View Abstract]
  37. Ramanathan T, Hughes TM, Richardson AJ. Perinatal inferior vena cava thrombosis and absence of the infrarenal inferior vena cava. J Vasc Surg. 2001 May. 33(5):1097-9. [View Abstract]
  38. Van Veen J, Hampton KK, Makris M. Kilt syndrome?. Br J Haematol. 2002 Sep. 118(4):1199-200. [View Abstract]
  39. Gayer G, Zissin R, Strauss S, Hertz M. IVC anomalies and right renal aplasia detected on CT: a possible link?. Abdom Imaging. 2003 May-Jun. 28(3):395-9. [View Abstract]
  40. Dougherty MJ, Calligaro KD, DeLaurentis DA. Congenitally absent inferior vena cava presenting in adulthood with venous stasis and ulceration: a surgically treated case. J Vasc Surg. 1996 Jan. 23(1):141-6. [View Abstract]
  41. White RH. The epidemiology of venous thromboembolism. Circulation. 2003 Jun 17. 107(23 Suppl 1):I4-8. [View Abstract]
  42. Ruggeri M, Tosetto A, Castaman G, Rodeghiero F. Congenital absence of the inferior vena cava: a rare risk factor for idiopathic deep-vein thrombosis. Lancet. 2001 Feb 10. 357(9254):441. [View Abstract]
  43. Perhoniemi V, Salmenkivi K, Vorne M. Venous haemodynamics in the legs after ligation of the inferior vena cava. Acta Chir Scand. 1986 Jan. 152:23-7. [View Abstract]
  44. Koc Z, Oguzkurt L. Interruption or congenital stenosis of the inferior vena cava: prevalence, imaging, and clinical findings. Eur J Radiol. 2007 May. 62(2):257-66. [View Abstract]
  45. Ueda J, Hara K, Kobayashi Y, Ohue S, Uchida H. Anomaly of the inferior vena cava observed by CT. Comput Radiol. 1983 May-Jun. 7(3):145-54. [View Abstract]
  46. Tsuji Y, Inoue T, Murakami H, Hino Y, Matsuda H, Okita Y. Deep vein thrombosis caused by congenial interruption of the inferior vena cava—A case report. Angiology. 2001. 52:721–725.
  47. Giordano P, Weber K, Davis M, Carter E. Acute thrombosis of the inferior vena cava. Am J Emerg Med. 2006. 24:640-642. [View Abstract]
  48. Cho BC, Choi HJ, Kang SM, Chang J, Lee SM, Yang DG, et al. Congenital absence of inferior vena cava as a rare cause of pulmonary thromboembolism. Yonsei Med J. 2004 Oct 31. 45(5):947-51. [View Abstract]
  49. D'Aloia A, Faggiano P, Fiorina C, Vizzardi E, Bontempi L, Grazioli L, et al. Absence of inferior vena cava as a rare cause of deep venous thrombosis complicated by liver and lung embolism. Int J Cardiol. 2003 Apr. 88(2-3):327-9. [View Abstract]
  50. Takehara N, Hasebe N, Enomoto S, Takeuchi T, Takahashi F, Ota T, et al. Multiple and recurrent systemic thrombotic events associated with congenital anomaly of inferior vena cava. J Thromb Thrombolysis. 2005 Apr. 19(2):101-3. [View Abstract]
  51. Iqbal J, Nagaraju E. Congenital absence of inferior vena cava and thrombosis: a case report. J Med Case Reports. 2008 Feb 12. 2:46. [View Abstract]
  52. Lei F, Li X, Qian A, Yu X, Rong J, Sang H, et al. [Therapy of catheter-directed thrombolysis for inferior vena cava thrombosis after filter implantation]. Zhonghua Yi Xue Za Zhi. 2014 Jul 22. 94(28):2197-200. [View Abstract]

Virchow triad/venous thromboembolism (VTE) risk factors.

Veins of abdomen and thorax. Unless stated otherwise, lithograph plate is from Gray's Anatomy (online edition of the 20th US edition of Gray's Anatomy of the Human Body, originally published in 1918).

Photo showing dilated superficial abdominal veins (upper quadrant), with bruising and thrombosed large abdominal veins (lower quadrant).

Abdominal CT scan shows absent inferior vena cava with thrombosis of very prominent collateral veins in the abdominal wall, corresponding to right side of abdomen as seen in earlier photo.

Virchow triad/venous thromboembolism (VTE) risk factors.

Photo showing dilated superficial abdominal veins (upper quadrant), with bruising and thrombosed large abdominal veins (lower quadrant).

Abdominal CT scan shows absent inferior vena cava with thrombosis of very prominent collateral veins in the abdominal wall, corresponding to right side of abdomen as seen in earlier photo.

Veins of abdomen and thorax. Unless stated otherwise, lithograph plate is from Gray's Anatomy (online edition of the 20th US edition of Gray's Anatomy of the Human Body, originally published in 1918).