notes by dr Claudio Italiano
Surface thrombophlebitis (ST) are often mistakenly considered, in their various clinical expressions, a minor form of phlebopathy, easy to diagnose and with a benign course.
At the side you can see a patient with
superficial thrombophlebitis, reddened
area in the popliteal region, expression of the underlying saphenous phlebopathy.
In reality, they deserve the right attention for a number of reasons:
a) increasing prevalence in the population (incidence, probably underestimated,
of 1 case per thousand subjecST / year),
b) association with even serious systemic diseases
c) potential evolution in the sense of pulmonary embolism
d) source of diagnostic error, with consequent administration of therapies.
The attention shown by the international scientific literature for ST. it is
demonstrated in fact by the publication in January 2007 of a systematic review
in the Cochrane database of systematic review and, even more recently, of two
paragraphs in the eighth edition of the American College of Chest Physicians
guidelines on the antithrombotic therapy of venous thromboembolic disease,
published on Chest in June 2008. As we will see below, from these publications
it is possible to derive useful indications for the management and therapy of
this disease, albeit with some limitations related to the relative scarcity and
heterogeneity of the studies that the Authors have identified and to review.
ST from the etiopathogenetic point, such as deep vein thrombosis (DVT), depend
on:
• Venous varices
• Surgical interventions
• Neoplasms
• Autoimmune diseases
• Hereditary thrombophilia
• Pregnancy, puerperium,
• Previous venous thromboembolic episodes.
A substantial difference with DVT is however the much closer association of ST
with varicose disease of the lower limbs, reported in about 70% of cases, and
the lower comorbidity, as shown by the much better prognosis: even three-month
mortality 0.1-1% for ST and 5% for DVT.
A complete etiological and pathogenetic classification of ST is as follows:
Cannulation / venous infusion
Dialysis arteriovenous fistula
Traumas / microtraumas of the limbs
- From prevalent venous stasis:
- varices
- From prevalence hypercoagulability:
- Hereditary coagulopathies: mutation of Factor V of Leiden, mutation of Factor
II, excessive levels of Factor VIII, Factor IX or Factor XI, C / S protein
deficiency, antithrombin deficiency, hyperhomocysteinemia, fibrinolysis
deficiency, etc. Solid neoplasms: pancreas, lung, prostate, stomach, endometrium,
breast, colon Hematologic malignancies: polycythemia, thrombocythemia, myelitis
and lymphoproliferative syndromes Widespread diseases of connective Vasculitis:
Buerger, Takayasu, Behcet, Wegener, Inflammatory bowel disease: Chron's disease,
ulcerative rectocolitis > Chronic nephropathy and dialysis Drugs:
estro-progestin, tamoxifen, pyoderma, skin abscess, infected syringe.
ST usually occur acutely, with intense pain at a subcutaneous vein of the limbs
or trunk, followed rapidly by localized erythema-edema and hardening of the
affected vein, which becomes palpable in the form of a cord sometimes found on
the skin. Generally, even in the forms with a marked inflammatory and painful
component, the fever is absent, with the exception of the now rare forms of
infectious thrombophlebitis, for which the custom still widely used at the
outpatient level to systematically administer antibiotics in the treatment of ST
is completely wrong. From the prognostic and therapeutic point of view, it is
important to make a first distinction between the iatrogenic and spontaneous
forms of ST, between the forms arising on healthy vein and those affecting a
venous varice, between the forms with important infectious and inflammatory
components. The diagnosis requires careful medical history to investigate
possible predisposing and triggering factors and a careful objective examination
in search of typical inspection and palpatory findings.
It is often possible to exclude with the clinic only some conditions that can
simulate an ST:
a) acute infectious lymphangitis, characterized by the presence of a cutaneous
lesion usually at the level of the foot, entrance door of the responsible germs,
of an undetected erythematous lymphatic stria and by a palpable satellite
lymphadenopathy;
b) the acute dermo-hypodermitis of the lower limbs, such as erysipelas, which
sometimes complicates the chronic dermo-hypodermitis from venous stasis or
chronic lymphatic stasis of the lower limbs. This disease is characterized by
the appearance of high fever with rapid onset, pain and functional impotence of
a limb, the lack of palpatory finding of the hardened subcutaneous venous cord
corresponding to the superficial thrombosed vein, the extension to spot or sock
of the subcutaneous inflammation, clear separation of the inflamed skin from the
healthy skin with a level usually located below the knee ("stair sign") and the
good response to therapy with antibiotics effective against Gram-positive germs
(amoxicillin / clavulanic acid or cephalosporins of fourth generation);
c) the vasculitic nodules palpable in the lower limbs sometimes present
during panarteritis nodosa or tuberculosis (hardened erythema of Bazin). In
addition to the biopsy examination for the histological characterization of
these morbid forms of uncertain identification, an aid of fundamental importance
for the differential diagnosis is constituted by the method ecocolordoppler
which, in expert hands and using high frequency probes (17 MHz), allows a
accurate differential diagnosis between thrombophlebitis and other nodular
lesions of the subcutaneous tissue. Among all the forms of ST, infusion
thrombophlebitis, varicoflebites and so-called "thrombophlebitis revealers"
deserve a more in-depth treatment. Infusion thrombophlebitis represent an
emerging disease in patients with central venous catheters, as increasingly the
cannula needle is inserted into the basilic vein at the arm rather than the
subclavian vein to reduce the immediate risks of the procedure; this morbid form
is mainly managed by the hospital doctor, as it is believed that it can occur in
25-35% of hospitalized patients with central venous catheter. Thrombophlebitis
originates at the insertion of the catheter and usually remains confined to the
superficial circle, but sometimes it can extend to the deep circle through the
confluence of the basilic vein in the axillary vein or it can affect the deep
circle without character of contiguity. Bacterial contamination of the catheter
from the insertion site is possible with the appearance of sepsychic pictures
and endocarditic localizations.
Anche in questi casi si dimostra prezioso l'ecocolordoppler, in grado di evidenziare
la presenza anche di minimi depositi trombotici pericatetere, evento che richiede
monitoraggio e profilassi antitrombotica , e l'eventuale coesistenza di TVP. Le
varicoflebiti interessano nella maggior parte dei casi la vena grande safena (60-80%),
con frequenza minore la vena piccola safena (10-20%) e le varici reticolari extrasafeniche
(10-20%); nel 5-10% dei casi, la malattia interessa entrambi gli arti inferiori.
Leg STs usually have a shorter course and a better prognosis; the thigh
localizations deserve more attention, especially if the clinical evolution is of
a type involving the sapheno-femoral confluence and the deep circle in an
unexpected way from the clinical point of view. Another possibility of
involvement by contiguity of the deep circle is the so-called shirt button
varicoflebite (superficial circle => perforating => deep circle). Indeed, in the
most recent cases, the involvement of the deep veins starting from a superficial
phlebitis both with the character of contiguity and as the association of
separate morbid forms, is reported in variable percentages from 8.6% to 44% of
the cases examined with ultrasound survey. If superficial thrombophlebitis
affects the thigh, more than 30% of pulmonary scintigraphy with a high
probability of pulmonary embolism has been reported. The revealing
thrombophlebitis are characterized from the clinical point of view by the
appearance of an erythematous and painful cutaneous lesion in a non-varicose
superficial vein stroke, often atypical (anterior region of the thorax, dorsal
vein of the penis: "Mondor's phlebitis"). The lesion typically has a relapsing
and migrating clinical course over a period of weeks to months from one healthy
venous segment to another. In this clinical context, it may be necessary to
invest resources in diagnostic tests aimed at excluding the presence of the most
frequently associated systemic diseases (neoplasms, autoimmune diseases,
inherited thrombophilias), even if it is not currently possible to indicate a
validated diagnostic procedure. The close clinical monitoring of these patients
in search of symptoms / signs of systemic disease and the possible recourse to
specialist advice are desirable.
Regarding treatment options, STs have been much less studied than DVT by randomized controlled trials of adequate potency, so no grade A recommendations are available. In the latest "Antithrombotic therapy far venous thromboembolic disease: american college of chest physicians evidence-based Clinical practice guidelines (8th Edition) "have been evaluated several interventional trials with topical therapies based on anti-inflammatories or heparinoids, systemic therapies with non-steroidal anti-infammers (Fans), calcium heparin and various low-weight heparins molecular, surgical therapies with ligation of the great saphenous vein or saphenectomy with non-definitive conclusions. T
he objectives
of trials for the ST study should ideally be constituted by the lack of
extension to the deep venous circulation or by recurrence in the follow-up
period (usually limited to 3-6 months), even though in many studies it was not
even objectivised the eventual extension of the thrombosis to the deep circle.
For this reason, experts in the field recommend, in case of infusion
thrombophlebitis, the use of topical or generalized Fans until resolution of
symptoms or for 2 weeks (grade 2B), while they express themselves to the
disadvantage of anticoagulant therapy (degree 1C), an attitude that can be
shared only if the certainty of the lack of involvement of the deep circle is
available. The therapeutic recommendations are different in case of spontaneous
superficial thrombophlebitis, in which a therapy with unfractionated heparin or
with a low molecular weight heparin (Ebpm) with a prophylactic dose (nadroparin
2.850 IU anti Xa / 0.3mi or enoxaparin 40 mg is recommended) or die at fixed
doses) or intermediate (nadroparin 92,7 IU anti Xa / kg / day or enoxaparin 1 mg
/ kg / day once again) for at least 4 weeks (grade 2 B), offering the use of
Ebpm for 5 days and the overlap of an oral anticoagulant with an Inr target of
2.5 (2.0-3.0), to be continued for 4 weeks (grade 2 C), without associating
non-steroidal anti-inflammatories (grade 2B) and without resorting to surgical
interventions (grade 1B).
The recommendation to administer non-therapeutic doses
of Ebpm derives from the results of the important trial conducted by The Vesalio
Investigators Group, in which the substantial equivalence of a prophylactic dose
of nadroparin administered for 1 month was demonstrated (0.3 ml: 2.850 / day)
compared to the adjusted therapeutic dose on body weight in 164 patients with ST
of the great saphenous vein in preventing local recurrences and thromboembolic
complications in the 3-month observation period. A substantially similar
conclusion, based on the review of 24 studies on 2,469 patients, is based on the
review "Treatment for superficial thrombophlebitis of the leg" published in the
Cochrane register in 2007. The authors report a substantial equivalence between
Ebpm and Fans in reducing approximately 70% relapse or extension to the deep
circulation, while topical treatments are attributed to an improvement in local
symptoms, but without documentation on the extension of the thrombotic process.
However, an improvement in the symptomatology is associated with treatment with Ebpm nadroparin calcium compared to naproxen, as observed in the study by Titon et al. Moreover, due to the poor methodological quality of most of the clinical trials available so far, it is widely carrying out further studies adequately designed and conducted to clarify the diagnostic procedure and the optimal treatment of TSs. In the meantime, in consideration of the increasing availability and reliability of the ecocolordoppler, it seems appropriate to recommend the use of this method in most cases, to avoid potentially serious diagnostic and therapeutic errors, administering in all cases where Ebpm therapy is necessary. at the doses and for the time recommended in the recent guidelines.
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