Migratory thrombophlebitis is an inflammatory lesion of the venous wall of the superficial or deep bed with a recurrent course. Pathology is characterized by the appearance of one or more thrombotic foci in the form of nodules or dense strands along the vein with signs of inflammation (hyperemia, swelling, soreness), which disappear without a trace, migrating to other areas. Venous lesion is diagnosed according to clinical examination, laboratory and instrumental methods (ultrasound, MR and radiopaque phlebography). Treatment involves anticoagulant therapy, elastic compression, manual techniques, some aspects of surgical correction.
I82.1 Migratory thrombophlebitis
Recurrent thrombophlebitis is a frequent companion of oncological and autoimmune pathologies. They are detected in 42% of people with pancreatic adenocarcinoma, 12% of women with breast cancer. It is known that the presence of a malignant process increases the risk of developing thrombotic conditions by 6.5 times. Migratory phlebitis occurs in 38-65.4% of cases of obliterating thrombangiitis, in 24% of persons suffering from Behcet syndrome. Pathology can be registered at any age, including children. Gender characteristics are determined by the primary process: if with systemic vasculitis or idiopathic thrombophlebitis, venous lesion usually occurs in men, then Mondor’s disease is typical for women.
Recurrent thrombophlebitis has a polyetiological nature. Usually, the disease is secondary in nature, developing against the background of other pathological conditions that trigger permanent hypercoagulation with endothelial damage. In practical phlebology , the role of the following etiofactors is recognized:
- Malignant neoplasms. About half of the cases of migratory thrombophlebitis are associated with oncological processes and are considered as paraneoplasia (Trousseau syndrome). Pathology is often associated with adenocarcinoma of the tail and body of the pancreas, but also occurs in breast, stomach, lung and other cancers.
- Systemic diseases. Thrombotic disorders are often mediated by autoimmune pathology – systemic vasculitis (Behcet syndrome), obliterating thrombangiitis (Burger’s disease), lupus erythematosus. Recurrent phlebitis occurs in inflammatory bowel disease (ulcerative colitis, Crohn’s disease).
- Injuries and operations. Migrating inflammation of the thoracoepigastric veins often occurs after mechanical damage to the chest wall (including permanent injury of a professional nature). Significant factors of Mondor’s disease are surgical interventions on the mammary gland – biopsy, resection, cosmetic mammoplasty.
- Thrombophilia. The association of migrating thrombosis with congenital coagulation defects (deficiency of proteins C and S, Hageman factor deficiency) was noted. The risk of pathology increases in the presence of antiphospholipid and anticardiolipin antibodies, which is due to the increased procoagulant ability of serum.
- Taking medications. The relationship of pathology with chemo- and hormone therapy of malignant tumors, taking antiangiogenic drugs, co-trimoxazole has been proved. The negative effect of medications is mediated by vascular toxicity and the triggering of thrombosis.
Among other reasons, some researchers note the influence of infectious diseases (syphilis, tuberculosis), diaphragmatic hernia. Risk factors include prolonged bed rest, smoking, and a history of deep thrombosis. In some cases, it is not possible to establish the nature of recurrent phlebitis, which allows us to speak of an independent nosological unit (idiopathic form), the occurrence of which is associated with allergic reactions.
Trousseau syndrome develops according to the mechanisms of the Virchow triad – with the participation of hypercoagulation, stasis, endothelial damage. Cytokines (tumor necrosis factor, interleukin-1b), direct invasion, cytotoxic agents, radiotherapy have a destructive effect on the venous wall. Malignant cells have procoagulant properties – they enhance the production of thrombogenic substances (tissue factor, cysteine protease, fibrinolysis inhibitors), inhibit the anticoagulant ability of blood cells (macrophages, platelets, monocytes) and endotheliocytes.
High thrombotic potential is characteristic of lung, pancreatic, and ovarian cancers. Malignant neoplasms are characterized by the constant generation of fibrin, which is a protective barrier against immune factors and trophic material supporting tumor progression. Many tumors are characterized by stagnation of blood due to external compression, insertion into the vessel wall with its deformation, and other factors (prolonged immobilization, concomitant diseases).
The pathogenesis of migratory thrombophlebitis in Burger’s disease remains unknown. The role of hypercoagulation is assumed to be less significant than for paraneoplasias. Phlebopathology in patients with Behcet syndrome is caused by immunopathological inflammation with endothelial dysfunction. The development of Mondor’s disease is most often explained by pressure on the surface vessels, followed by stasis or direct mechanical damage. In other cases, we are talking about repetitive movements with contraction and relaxation of the pectoral muscles, which leads to stretching and dilation of the thoracic veins.
Pathomorphological changes in the venous wall in recurrent thrombophlebitis of the superficial bed are characterized mainly by polymorphonuclear inflammatory infiltrates. Lymphocytes and histiocytes are gradually added to granulocytes, sometimes giant cells are found. Initially, the thrombus that closes the lumen of the vessel later undergoes recanalization and fibrosis with preservation of hemodynamics.
A separate classification for migratory thrombophlebitis has not been developed. The defeat of the venous network can be systematized taking into account the localization of the pathological process, highlighting several forms:
- Superficial. It is the most typical for migratory phlebitis. Vessels of the lower extremities or trunk (thoracoabdominal, epigastric, lateral thoracic) are usually involved.
- Deep. Among deep phlebitis, the lesion of the ileofemoral segment is common. Phlebothrombosis of the femoral area and lower legs are less common.
- Atypical. Signs of a tumor-associated thrombotic process can be found in the hepatic, splenic, and ovarian veins. Atypical forms also include subclavian, jugular, cerebral localization.
Venous changes can be single or multiple, occurring in several segments at once. According to the clinical classification, the disease goes through an acute stage and takes a chronic course with alternating phases of relapses and remissions.
The onset of the disease is sudden, with the appearance of slightly painful nodes of various sizes, usually located along the superficial veins of the thigh and lower leg. At the same time or a little later, inflammatory changes are added: the skin over the affected areas turns red, swells, thickens, becomes sensitive on palpation. In the acute stage, there are pains that spread to the entire limb and interfere with walking. General well-being is usually not disturbed, sometimes persistent fever is noted. The multiple process is characterized by increased fatigue and weakness.
Symptoms of superficial thrombophlebitis persist from several days to 3-4 weeks, are not accompanied by a violation of hemodynamics and pass without a trace. In the future, the disease becomes recurrent: each time the thrombotic process covers all new zones, migrating from one place to another. Sometimes several foci of different localization are detected at once, including on the upper extremities. Often, within the general anatomical zone, only a compacted vein is felt in some areas, and in others the picture is complemented by pronounced inflammation.
Migratory phlebitis in the structure of Behcet’s disease is manifested by small red nodules on the medial surface of the lower leg, along the large superficial vein. New elements arise as the old ones heal, which is accompanied by hyperpigmentation. With obliterating thrombangiitis, signs of venous lesion are combined with arterial ischemia: pallor, decreased skin temperature, paresthesia, intermittent lameness. Some patients are characterized by the development of a painless dense string, others pay attention to areas of edematous migrating erythema.
Mondor’s disease debuts with the sudden appearance of a soft, sometimes painful subcutaneous cord running from the breast into the axillary area or towards the abdomen. The skin over the thrombosed vessel is hyperemic, infiltrated, local pain and burning are noted. When the inflammation subsides, the organization and recanalization of the thrombus, the subcutaneous tissue becomes dense and fibrous, it contours well when raising the arm with the removal of the gland. Skin tension is accompanied by the formation of radiant wrinkles, retractions. Symptoms persist for several weeks.
There are no violations of venous blood flow in superficial migratory thrombophlebitis, which is associated with the reverse development and recanalization of stenosis. However, Trousseau syndrome with deep segment lesions is associated with a high risk of pulmonary embolization, which is typical for 4-20% of cancer patients. Other complications of the paraneoplastic process include chronic DIC syndrome, non-infectious thrombotic endocarditis (7.7–13% in lung cancer), arterial thrombosis (2-5% of cases).
The diagnostic program consists of two directions – identifying the thrombotic process itself and determining its root cause. In addition to physical examination, a complex of laboratory imaging methods helps to determine the nature of the venous system lesion with recurrent symptoms:
- Blood test. From laboratory studies, a detailed clinical blood test and a coagulogram are required. If deep venous thrombosis is suspected, fibrin degradation products (D-dimer, RFMC) are examined. To detect thrombophilia, individual coagulation factors (proteins C, S, antithrombin III), specific antibodies (antiphospholipid, anticardiolipin, antinuclear) are determined.
- Ultrasonography of veins. According to the results of the ultrasound, the thrombosed areas are visible as tubular resistant structures with a compacted wall, anechoic or hypoechoic contents, a decrease in the flow signal or its recovery after recanalization of stenosis. The technique determines the localization of clots, the extent of the lesion, the condition of the surrounding tissues.
- MR-venography. The complexity of ultrasound imaging of deep areas above the inguinal fold or in obese people determines the diagnostic value of MR phlebography. It is able to analyze low-speed blood flows without the need for contrast and radiation exposure. It defines pelvic veins and collaterals well, helps to assess embolism risk of thrombosis.
- Radiopaque phlebography. Allows you to accurately assess the patency of the deep venous bed by the presence of filling defects, a symptom of “amputation” of branches. Provides information about the localization of stenosis, the condition of the valve apparatus, collaterals. But traditional phlebography has a number of disadvantages – invasiveness, radiation load on the patient, the risk of catheter-associated thrombosis.
The pathology has to be differentiated with nodular erythema, lymphangitis, vasculitis. It is also necessary to exclude cellulite, panniculitis. Histological analysis of biopsy material in thrombophlebitis shows occlusive thrombi, inflammatory infiltrate in the wall. Immunohistochemical staining of membrane proteins (CD31, D240) allows to distinguish small veins from lymphatic vessels.
In many cases, recurrent thrombophlebitis indicates an asymptomatic course of a malignant neoplasm, which requires constant oncological alertness from phlebologists. Along with a detailed medical history and physical examination, chest CT, abdomen, pelvis, endoscopy of the stomach, intestines, mammography can successfully diagnose the primary tumor.
Treatment of phlebitis included in the structure of paraneoplastic syndrome is aimed at reducing the risk of complications, improving the quality of life of patients. In case of venous lesion, it is recommended to provide the affected limb with rest and an elevated position, avoiding prolonged bed rest. Significant directions of conservative correction are:
- Pharmacotherapy. The basis for the treatment of phlebothrombosis is pathogenetically based anticoagulant therapy. The advantage is given to low molecular weight heparins – both at the initial stage and in the long term. In the absence of oncology, warfarin and fondaparinux may be an alternative, although they have lower efficacy. NSAIDs and semi-alcoholic compresses are used for symptomatic correction.
- Compression therapy. Elastic bandaging and medical knitwear are indicated for lesions of superficial vessels. They allow you to speed up blood flow, preventing an increase in the size of clots. But for deep migrating thrombosis, this method is considered ineffective, since it does not prevent the development of complications.
- Manual therapy. Manual therapy, including myofascial releasing, soft tissue mobilization, lymphatic drainage massage, is recommended as a safe and effective correction of axillary network syndrome (a type of Mondor’s disease). Methods of physical influence are complemented by therapeutic gymnastics with exercises aimed at stretching tissues, improving the range of movements in the limb.
- Antitumor treatment. The most important aspect of the treatment of Trousseau syndrome is specific antitumor therapy, which is carried out with the help of chemotherapy drugs, hormones, immune and targeted drugs. Radiotherapy of malignant tumors is another way to eliminate the cause of paraneoplastic migratory thrombophlebitis.
In severe cases, the issue of performing a phlebectomy or thrombectomy is considered. But with the remaining risk factors, surgical tactics do not give the expected effect, since the pathological process migrates, affecting new vessels. In cases of recurrent floating thrombosis of the deep veins of the lower extremities, implantation of a cava filter may be recommended for the prevention of pulmonary embolism. The diagnosed tumor, depending on the stage of development, is subject to radical removal or palliative correction.
A promising direction of pharmacotherapy for migratory thrombophlebitis of paraneoplastic genesis, which constitute an alternative to traditional drugs, may be new oral anticoagulants: selective factor Xa inhibitors (rivaroxaban, apixaban), direct thrombin inhibitors (dabigatran). According to clinical trials, rivaroxaban shows similar efficacy to low-molecular-weight heparins, providing a lower risk of massive bleeding, better adherence to therapy.
Prognosis and prevention
With adequate therapeutic correction, recurrent migratory thrombophlebitis is successfully stopped, which provides a stable clinical improvement. But without eliminating the causal factor, it is not possible to completely cure the pathology. Of particular concern are malignant tumors, which, with aggressive course and metastasis, are accompanied by an extremely unfavorable prognosis. Therefore, oncological alertness of the doctor and the patient, early detection of neoplasms and their complex treatment becomes important. Secondary prevention of recurrent thrombophlebitis involves taking anticoagulants.
- Superficial migratory thrombophlebitis: a clinical and histologic review of 8 cases/ Laguna C, Alegre V, Pérez A.// Actas Dermosifiliogr. – 2008 – Jun; 99(5).
- Thrombophlebitis migrans as a footprint of Buerger’s disease: a prospective-descriptive study in north-east of Iran/ Fazeli B, Modaghegh H, Ravrai H, Kazemzadeh// Clin Rheumatol. – 2008 – Jan; 27(1).