Last updated date: 12-Jun-2023
Originally Written in English
The production of a blood clot in the context of venous inflammation or damage is referred to as thrombophilia. Many intrinsic diseases, through a range of hypercoagulopathy syndromes, can predispose people to thrombophlebitis.
A thrombophlebitic response can also be triggered by traumatic situations. Furthermore, persistent substantial reflux into a vein that has been treated with a sclerosing agent might result in phlebitis. More typically, phlebitis develops if perforator veins in the sclerotherapy area are not identified and treated.
Superficial thrombophlebitis is an inflammatory condition of the superficial veins that is often associated with venous thrombosis. It often affects the lower limbs, notably the great saphenous vein (60-80% to 80%) or the small/short saphenous vein (10 percent to 20 percent ). It can, however, arise at different places (10% to 20%) and may occur bilaterally (5 % to 10 %)
Historically, this rather frequent process was thought to be harmless and self-limiting. Recently, superficial thrombophlebitis, also known as superficial venous thrombosis (SVT), has been linked to various venous thromboembolic illnesses, most notably deep venous thrombosis (DVT) and pulmonary embolism (PE).
As a result, it entails more than just a clinical diagnosis and supporting therapy. Affected individuals are at a higher risk of recurrent venous thromboembolic episodes. The words superficial thrombophlebitis and superficial venous thrombosis will be used interchangeably in this article.
The real prevalence of superficial thrombophlebitis remains unknown. In France, one community-based research revealed that the incidence of SVT was 0.64 percent, while another community-based study discovered that the incidence was half that of DVT and equivalent to PE. According to other research, its frequency in the general population is two to six times that of DVT and PE.
SVT is widely encountered in the outpatient population; typically, women, who made up 50% to 70% of the afflicted patients in one research; 60 years of age; a body mass index greater than 25 kg/m2; and those with varicose veins.
People with a history of SVT have a four to sixfold increased lifetime risk of DVT or PE. While the three-month mortality rate in individuals with DVT or PE is over 5%, it is less than 1% in those with SVT. One possible explanation for the reduced mortality in SVT patients is that they are younger and have less related comorbidities.
During a condition of hypercoagulability, the thrombus may migrate into deep veins at the saphenofemoral junction, the saphenopopliteal junction, or from a perforating vein, resulting in the connection of SVT with DVT or PE.
SVT risk may be increased by a hypercoagulable condition, extended immobility, or arterial wall damage. Superficial thrombophlebitis represents for 5.4 percent of the adjusted population risk for DVT or PE. In certain inheritable thrombophilias, SVT has been the presenting symptom.
Several studies have found that it occurs in 11% to 15% of individuals with protein C or S deficiency and around 40% of patients with factor V Leiden mutation. However, according to another research, these findings were not statistically significant.
In pregnancy, the risk of SVT is similar to that of DVT, and it occurs more frequently in the postpartum period. SVT risk factors include advanced age, exogenous estrogens, autoimmune or infectious disorders, obesity, recent trauma or surgery, current malignancy, a history of venous thromboembolic disease, and respiratory or heart failure. Previous incidences raise the likelihood of future occurrences. Varicose veins are thought to be the most important clinically recognizable predisposing factor for SVT, as they are present in 75% to 88 percent of patients.
A number of primary and secondary hypercoagulable conditions can be evaluated by taking a thorough patient history and reviewing systems. Only three hereditary hypercoagulable factors had been identified prior to 1993: antithrombin III, protein C, and protein S. Currently, 60-70 percent of thrombosis patients may be diagnosed as having an inherited thrombophilia.
Experts classify inherited hypercoagulable conditions into five broad categories:
- qualitative or quantitative defects of coagulation factor inhibitors,
- increased level or function of coagulation factors,
- defects of the fibrinolytic system, and
- altered platelet function.
The following are the particular hereditary thrombophilias. The majority of these hereditary disorders have recognized gene mutations, some of which are utilized to diagnose the condition. Protein C deficiency alone is connected with more than 160 genetic abnormalities that cause illness. The following are the qualitative/quantitative flaws of coagulation factor inhibitors:
- Antithrombin deficiency
- Protein C deficiency
- Protein S deficiency
- Heparin cofactor II deficiency
- Tissue factor pathway inhibitor deficiency
- Thrombomodulin deficiency
Increased levels/function of coagulation factors are as follows:
- Activated protein C resistance and factor V Leiden
- Prothrombin gene mutation (G20210A)
- Dysfibrinogenemia and hyperfibrinogenemia
Defects of the fibrinolytic system are as follows:
- Tissue plasminogen activator
- Thrombin-activatable fibrinolysis inhibitor
- Factor XIII
- Lipoprotein (a)
Altered platelet function conditions are as follows:
- Platelet glycoprotein GPIb-IX
The frequency of an inherited thrombotic syndrome in the general population is currently estimated to be one in every 2500-5000 people; among individuals with a history of thrombosis, the prevalence rises to 4%. A history of deep venous thrombosis (DVT) raises the chance of new postoperative venous thrombosis from 26% to 68%, and a history of both DVT and pulmonary embolism (PE) predicts a near 100% thrombosis incidence.
This article does not go into further information about hypercoagulable conditions. The most frequent conditions are covered in further detail below. The reader is directed to a number of review papers on hypercoagulable conditions for more information.
The most frequent genetic risk factor for venous thrombosis is resistance to activated protein C (APC). The majority of instances are caused by a point mutation in the factor V gene, which prevents APC from cleaving and disrupting active factor V, promoting continuing clot growth. This mutation is heterozygous in around 3-8 percent of white individuals, yielding a 5-fold greater lifetime risk of venous thrombosis relative to the general population.
Inherited factor deficiency
Although endothelial damage is thought to be required for symptomatic thrombosis, venous thrombosis may be caused by a deficit in one of numerous anticoagulant factors. Antithrombin III, protein C, and protein S deficiencies are found in roughly 5% of apparently healthy patients under the age of 45 who are referred for venous thrombosis examination.
Antithrombin (antithrombin III) deficiency affects one in every 2000-5000 persons and is the most prothrombotic of the hereditary thrombophilias. Acquired antithrombin deficiency can arise as a result of liver illness or oral contraceptive usage. Antithrombin binds to coagulation factors, limiting biologic action and thrombosis.
Other major anticoagulant components include protein C and protein S, two vitamin K–dependent proteins. Protein S functions as a cofactor in the action of APC on factors Va and VIIIa. The frequency of heterozygous protein C deficiency in the United States is estimated to be one instance in every 60-300 healthy persons.
More than 95% of the patients are asymptomatic. A substantial shortage in any protein, on the other hand, might predispose an individual to DVT. In fact, 75% of people with homozygosity for protein S deficiency develop venous thrombosis before the age of 35.
Although factor shortage can result in venous thrombosis, a genetic change in factor V that leads to APC resistance is at least ten times more prevalent than other variations. This genetic change is observed in around one-third of DVT patients who are referred for examination. Precipitating variables for thrombosis, such as pregnancy and oral contraceptive usage, are present in 60% of these individuals. APC resistance is described under Hypercoagulable conditions at the beginning of the Pathophysiology section.
Defects in the fibrinolytic system, especially plasminogen, affect up to 10% of the healthy population. The risk of thrombosis is low when the abnormalities occur alone. Abnormal plasminogen levels may potentially predispose an individual to thrombosis in specific conditions.
Antiphospholipid antibodies can lead to venous and arterial thrombosis, as well as recurrent spontaneous miscarriage. They might appear as a primary thrombophilic condition or as a secondary manifestation of autoimmune illnesses. Lupus-like anticoagulants are seen in 16-33 percent of lupus erythematosus patients, as well as many people with other autoimmune illnesses. Thrombosis can develop in 30-50% of people who have circulating lupus-like anticoagulants.
Symptoms of thrombophlebitis
Patients with superficial thrombophlebitis generally have a reddish, heated, inflammatory, sensitive region above a superficial venous track. There is frequently a perceptible chord. There may be some surrounding edema or accompanying pruritis.
Significant limb swelling is more typically linked with DVT and should be attributed to SVT only after DVT has been ruled out. Patients may have a history of prior trauma, such as intravenous cannulation or irritant infusion, as well as recent sclerotherapy for varicose veins.
A thorough medical history is required to identify risk factors for venous thromboembolism. Patients over the age of 40 who appear with no additional risk factors should be evaluated for underlying cancer. Patients with migrating thrombophlebitis, a well-known paraneoplastic condition, should be investigated further for underlying malignancy.
Migratory thrombophlebitis is commonly associated with pancreatic or other visceral cancers and is known as Trousseau syndrome. It might be the presenting symptom in 5% to 15% of pancreatic cancer cases, notably in the body and tail.
Traditionally, superficial thrombophlebitis was diagnosed clinically. However, because of the rising recognition of the relationship with concurrent DVT or PE, compressive ultrasonography is advised. Physical examination does not accurately determine the amount of disease; in up to 77% of cases, it has been proven to underestimate it.
Compressive ultrasonography can detect concurrent DVT, assess the thrombus's size, and confirm the diagnosis. The Prospective Observational Superficial Thrombophlebitis (POST) research examined venous duplex screening of the afflicted lower leg and discovered that 23.5 percent of patients also had DVT.
More than half of these DVTs were not connected to the SVT; 17% affected the contralateral lower extremity, whereas just 1% had an isolated DVT in the contralateral leg.
These data support the use of ultrasonography to assess SVT on a frequent basis. The POST research also aimed to identify acoustic results that enhanced the chance of concomitant DVT. It discovered that the risk rose significantly if a perforating vein was involved, with an odds ratio of 8.1, or if an SVT was present less than 3 cm from the saphenofemoral junction, with an odds ratio of 3.3.
D-dimer testing is only marginally useful in identifying SVT. It is variable in SVT and cannot be utilized to differentiate isolated SVT from DVT.
Experts disagree on whether individuals with severe superficial thrombophlebitis without an obvious cause should be evaluated for thrombophilia, considering that hypercoagulability is related with SVT. However, there have been no definitive studies establishing a link between hypercoagulability and SVT to yet.
As previously stated, migrating thrombophlebitis should be investigated for visceral neoplasia. Patients over the age of 40 who are experiencing their first bout of thrombophlebitis should be checked for underlying malignancy. Mondor disease is defined as superficial thrombophlebitis of the superficial breast veins.
Despite several research, there is still disagreement over the best therapy for superficial thrombophlebitis.
Multiple techniques have been proposed to manage symptoms, reduce thrombus extension, and reduce the risk of PE in low-risk superficial thrombophlebitis. Low-risk thromboses are those that are not related with the existence of other thromboembolic disorders or a propensity to them. Nonsteroidal anti-inflammatory drugs, heat, and anticoagulants are all considered appropriate in these instances.
Patients who have an SVT in the lower extremity that is at least 5 cm long, SVT proximal to the knee, especially within 10 cm of the saphenofemoral junction, severe symptoms, greater saphenous vein involvement, previous SVT/venous thromboembolic disease, active malignancy, or recent surgery are at higher risk. According to a 2018 Cochrane study, these individuals should be given fondaparinux 2.5 mg subcutaneously for 45 days.
Topical and surgical therapies were discussed, however it was observed that the evidence on these treatments and their impact on venous thromboembolic illness is insufficient, thus further research is needed at this time. It advocated for more research into the usage of nonsteroidal anti-inflammatory drugs and low molecular weight heparins.
Multiple medications have been explored for treatment of individuals who develop superficial thrombophlebitis as a result of an infusion. According to a 2015 Cochrane analysis, there is no consensus advice on the safety, dose necessary, or length of therapy for topical therapies, nonsteroidal anti-inflammatory drugs, or systemic anticoagulation.
Compression stockings may be used with or without other treatments in the United Kingdom, however there is no current recommendation for or against their usage in the United States of America.
- Antibiotics are useful only with clear infection.
The ultimate focus of Trousseau syndrome treatment is to remove the underlying cancer. However, considering that several mechanisms contribute to the formation of the thrombus, heparin is the suggested therapy. Low molecular weight heparins have been utilized, however some have been shown to be less effective than heparin; hence, more research is needed.
Fondaparinux has also been studied, however it was shown to be less effective than heparin, and its value warrants additional investigation. A case study on the subject suggested starting with heparin and then moving on to oral anticoagulants, but it didn't specify which agent or dose schedule to use.
Mondor disease, which is addressed separately, is often self-limiting and benign, resolving in four to eight weeks. If it is caused by vasculitis, cancer, or a hypercoagulable condition, therapy is directed at the underlying cause.
The underlying etiology influences the prognosis of Superficial thrombophlebitis. It is typically beneficial in low-risk SVT, although there is a distinct danger of recurrent illness. With effective therapy, the overall prognosis is also excellent in patients with higher risk SVT. The prognosis for patients with SVT caused by an underlying tumor is determined by the causal mechanism.
If treated early, both SVT and DVT have a favourable prognosis. A proper treatment plan should result in a quick resolution. Following the resolution of the acute condition, the following varicose vein treatment methods should be considered: ambulatory phlebectomy, ligation and stripping, endovenous radiofrequency ablation, and endovenous laser ablation.
According to a large Italian patient registry, DVT induces edema (79.8 percent), discomfort (74.6 percent), and erythema (26.1 percent). If left untreated, it may also be linked to the development of life-threatening PE. Similarly, superficial thrombophlebitis is not something to be taken lightly. If left untreated, the inflammation and clot may extend to the deep venous system via the perforating veins. This prolongation may result in valvular injury and perhaps pulmonary embolism.
SVT to DVT progression may occur in up to 15% of individuals. Surprisingly, despite therapy, 10% of SVT recurs, extends, or progresses to DVT. SVT in the presence of an acquired thrombotic risk factor raises the likelihood of VT by a ratio of ten to one hundred. A higher chance of recurrence is related with superficial thrombophlebitis.
Coincidental DVT with SVT is said to be more prevalent in people who do not have varicose veins than in those who do (60 % vs 20 % ). As a result, people with SVT are predisposed to DVT due to other intrinsic variables.
In a study of 145 individuals, 23 percent of the afflicted limbs exhibited proximal extension into the saphenofemoral junction due to superficial thrombophlebitis (SFJ). PE was identified in 7 (33.3 percent) of 21 individuals with greater saphenous vein (GSV) thrombophlebitis above the knee. Varicose veins were seen in 17 of the 21 individuals. Only one of the seven participants in this research had clinical signs indicative with PE. In a study of 78 individuals, the incidence of DVT was 25% (32%) of those with below-knee SVT.
Thrombophlebitis is defined as thrombotic inflammation of a previously healthy superficial vein, whereas varicophlebitis is described as varicosity-related inflammation. The latter appears to be the most common cause of thrombotic venous occlusions. Unlike venous thrombosis, which is caused by thrombotic involvement of deep veins, thrombophlebitis normally cures without complications, and neither thrombophlebitis nor varicophlebitis is related with the risk of pulmonary embolism.
The clinical manifestation of thrombophlebitis is a sensitive, hardened superficial vein that may be highly painful in the presence of inflammation. The lower extremities are the most commonly implicated. Bacterial cellulitis and lymphangitis are two differential diagnoses to consider. The cause of thrombophlebitis, which is uncommon in the absence of precipitating factors, may be a mechanical lesion such as kinking of the vein or trauma to the vein wall, as well as other primary disease such as auto-immune afflictions, endangiitis obliterans, or malignancy; in particular, with localization in the area of the rump, concomitant occurrence in various regions, or extending phlebitis. Phlebitis is occasionally related with TB and syphilis.
Iatrogenically, thrombophlebitis can be produced by incorrect application of chemical compounds that cause venous wall injury, as well as by indwelling catheters or cannulas. This condition can lead to sepsis and pulmonary embolism. Varicophlebitis, on the other hand, accounts for around 90% of all occurrences of phlebitis and is a common late consequence of varicosities in the superficial venous system.
Given the prevalence of concurrent venous thromboembolic illness and the risk of progression, it is critical for members of the health care team to know that superficial thrombophlebitis is no longer regarded as a benign condition. As a result, if non-providers notice such signs, they might bring the issue to the attention of providers. To assess for concurrent venous thromboembolic illness, providers should have a low threshold for ultrasounding both the afflicted and contralateral limbs.
It is also critical for the interprofessional health care team, which includes clinicians, nurses, mid-level practitioners, and pharmacists, to recognize that migratory thrombophlebitis requires a team evaluation because it is a rare presentation of visceral malignancy and requires a coordinated team effort to treat the patient for the best outcomes.