Abstracts
The process of recanalization of the veins of the lower limbs after an episode of acute deep venous thrombosis is part of the natural evolution of the remodeling of the venous thrombus in patients on anticoagulation with heparin and vitamin K inhibitors. This remodeling involves the complex process of adhesion of thrombus to the wall of the vein, the inflammatory response of the vessel wall leading to organization and subsequent contraction of the thrombus, neovascularization and spontaneous lysis of areas within the thrombus. The occurrence of spontaneous arterial flow in recanalized thrombosed veins has been described as secondary to neovascularization and is characterized by the development of flow patterns characteristic of arteriovenous fistulae that can be identified by color duplex scanning. In this review, we discuss some controversial aspects of the natural history of deep vein thrombosis to provide a better understanding of its course and its impact on venous disease.
venous thrombosis; ultrasonography Doppler color; review literature as topic
O processo de recanalização das veias dos membros inferiores, após um episódio de trombose venosa profunda aguda em pacientes anticoagulados com heparina e inibidores da vitamina K, faz parte da evolução natural da remodelagem do trombo venoso. Esse complexo processo de remodelagem envolve a adesão do trombo à parede da veia, à resposta inflamatória da parede do vaso, levando à organização e subsequente contração do trombo, à neovascularização e à lise espontânea de áreas no interior do trombo. A presença de fluxo arterial espontâneo em veias com trombose recanalizada tem sido descrita como secundária à neovascularização e se caracteriza pelo desenvolvimento de fluxo com padrão de fístulas arteriovenosas, identificadas por meio de mapeamento dúplex colorido. Nesta revisão, são discutidos alguns aspectos controversos da história natural da trombose venosa profunda, para uma melhor compreensão da sua evolução e do seu impacto sobre a doença venosa.
trombose venosa; ultrassonografia Doppler em cores; literatura de revisão como assunto
INTRODUCTION
Deep vein thrombosis (DVT) of the lower extremities (LE) is a serious and potentially fatal disease in which there is acute thrombus formation in deep veins of the LE that can cause partial or total obstruction of the venous lumen. Deep vein thrombosis is currently considered a component of the nosological entity venous thromboembolism (VTE). Venous thromboembolism is a wider designation that includes both DVT and pulmonary embolism (PE).
The pathophysiologic process of thrombus formation was described by the German pathologist Rudolf Virchow (1821-1902) in 1856. The process itself is known as thrombogenesis and its chief characteristic is a loss of normal homeostasis due to an imbalance between procoagulatory factors and natural anticoagulants. These factors can act independently or interdependently, exerting varying degrees of influence on the thrombogenic process. For example, in cases of venous trauma the predominant factor in development of thrombosis is endothelial injury, whereas in spontaneous thrombosis hypercoagulability and venous stasis are the most important thrombogenic factors.
LOCATION
The most common sites in which thrombi originate are the muscular or trunk veins of
the legs, according to studies using phlebography and the labeled fibrinogen
test(11. Maffei FHA, Rollo HA. Trombose venosa profunda dos membros
inferiores: incidência, patogenia, patologia, fisiopatologia e diagnóstico. In:
Maffei FHA, Lastória S, Yoshida WB, Rollo HA, Gianini M, Moura R, editors.
Doenças Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2008. p.
1557-78.
). The thrombi can propagate proximally to the popliteal, femoral and
iliac veins, resulting in the multiple types of thrombosis that are seen in clinical
practice or autopsies(11. Maffei FHA, Rollo HA. Trombose venosa profunda dos membros
inferiores: incidência, patogenia, patologia, fisiopatologia e diagnóstico. In:
Maffei FHA, Lastória S, Yoshida WB, Rollo HA, Gianini M, Moura R, editors.
Doenças Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2008. p.
1557-78.). In the lower extremities, the deep veins most
often involved are the external iliac, the common femoral, the deep femoral, the
femoral, the popliteal, the gastrocnemius, the soleus, the posterior tibials and the
fibular(22. Caggiati A, Bergan JJ, Gloviczki P, Jantet G, Wendell-Smith CP,
Partsch H. Nomenclature of the veins of the lower limbs: an international
interdisciplinary consensus statement. J Vasc Surg. 2002;36(2):416-22.
PMid:12170230. http://dx.doi.org/10.1067/mva.2002.125847
12170230...
), (33. Caggiati A, Bergan JJ, Gloviczki P, Eklof B, Allegra C, Partsch
H. Nomenclature of the veins of the lower limb: extensions, refinements, and
clinical application. J Vasc Surg. 2005;41(4):719 24. PMid:15874941.
http://dx.doi.org/10.1016/j.jvs.2005.01.018
http://dx.doi.org/10.1016/j.jvs.2005.01....
). Both the great and small
saphenous veins can also be affected by thrombosis, but since these veins are part
of the superficial system this condition is known as superficial vein thrombosis
(SVT)(44. Lastoria S, Sobreira M L. Tromboflebite superficial. In: Maffei
F, Lastória S, Yoshida W, Rollo H, Gianini M, Moura R, editors. Doenças
Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2008. p.
1547-56.). However, the
saphenous veins are connected to the deep vein system and cases of SVT can progress
to PE(55. Sobreira ML, Maffei FH, Yoshida WB, et al. Prevalence of deep
vein thrombosis and pulmonary embolism in superficial thrombophlebitis of the
lower limbs: prospective study of 60 cases. Int Angiol. 2009;28(5):400-8.
PMid:19935595.),
and they should not therefore be ignored when investigating the deep vein system. In
clinical practice, DVT of LE are generally subclassified as either proximal or
distal(11. Maffei FHA, Rollo HA. Trombose venosa profunda dos membros
inferiores: incidência, patogenia, patologia, fisiopatologia e diagnóstico. In:
Maffei FHA, Lastória S, Yoshida WB, Rollo HA, Gianini M, Moura R, editors.
Doenças Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2008. p.
1557-78.). They are considered proximal when they involve
the iliac, femoral or popliteal veins, with or without involvement of veins in the
legs, and are considered distal when they only affect veins of the legs. The
importance of this differential definition is that around 46% of proximal DVT cases
can progress to PE and 4% are fatal if left untreated(11. Maffei FHA, Rollo HA. Trombose venosa profunda dos membros
inferiores: incidência, patogenia, patologia, fisiopatologia e diagnóstico. In:
Maffei FHA, Lastória S, Yoshida WB, Rollo HA, Gianini M, Moura R, editors.
Doenças Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2008. p.
1557-78.). Furthermore,
according to Susan and Kahn, up to 50% can develop postthrombotic
syndrome(66. Susan R, Kahn SR. The post-thrombotic syndrome: the forgotten
morbidity of deep venous thrombosis. J Thromb Thrombolysis. 2006;21(1):41-8.
PMid:16475040. http://dx.doi.org/10.1007/s11239-006-5574-9
http://dx.doi.org/10.1007/s11239-006-557...
).
RISK FACTORS
The most common risk factors for DVT are: prolonged immobility, traumas, postoperative period, advanced age, pregnancy, postnatal period, obesity, malignant neoplasms, estrogen-based female hormones, hereditary thrombophilias (natural anticoagulant deficiency, factor V Leiden and the G20210A prothrombin mutation) and the acquired thrombophilias (hyperhomocysteinemia and the antiphospholipid antibody syndrome)(77. Tófano VAC. Avaliação clínica e ultrassonográfica tardia de pacientes com trombose venosa prounda, portadores de trombofilia. [Tese]. Botucatu: Universidade Estadual Paulista; 2008. p. 169.).
EPIDEMIOLOGY
While it can affect young healthy people, DVT is uncommon before 20 years of
age(88. Matida CK. Trombose venosa profunda dos membros inferiores em
crianças e adolecentes tratados em um único centro no Brasil: epidemiologia e
evolução. [Tese]. Botucatu: Universidade Estadual Paulista; 2008. p.
91.)
and incidence increases with age. In one review article, Fowkes et al. report the
following annual incidence rates: 2-3 per 10,000 (ages 30-49), 5 per 10,000 (ages
50-59), 10 per 10,000 (ages 60 to 69) and 20 per 10,000 (ages 70 to 79
years)(99. Fowkes FJ, Price JF, Fowkes FG. Incidence of diagnosed deep vein
thrombosis in the general population: systematic review. Eur J Vasc Endovasc
Surg. 2003; 25(1):1-5. http://dx.doi.org/10.1053/ejvs.2002.1778). Similarly,
Naess et al.(1010. Naess IA, Christiansen SC, Romundstad P, Cannegieter SC,
Rosendaal FR, Hammerstrom J. Incidence and mortality of venous thrombosis: a
population-based study. J Thromb Haemost. 2007;5(4):692-9. PMid:17367492.
http://dx.doi.org/10.1111/j.1538-7836.2007.02450.x
http://dx.doi.org/10.1111/j.1538-7836.20...
) observed three
times greater incidence among 70-year-olds compared with people aged 20-44. In terms
of sex distribution, DVT incidence among females was 1.58 per 1,000 per year,
against 1.28 per 1,000 per year for males(1010. Naess IA, Christiansen SC, Romundstad P, Cannegieter SC,
Rosendaal FR, Hammerstrom J. Incidence and mortality of venous thrombosis: a
population-based study. J Thromb Haemost. 2007;5(4):692-9. PMid:17367492.
http://dx.doi.org/10.1111/j.1538-7836.2007.02450.x
http://dx.doi.org/10.1111/j.1538-7836.20...
). In the United State s, annual mortality
from PE has been estimated at 50,000 people and there are 300,000 to 600,000
hospital admissions for DVT and PE every year(11. Maffei FHA, Rollo HA. Trombose venosa profunda dos membros
inferiores: incidência, patogenia, patologia, fisiopatologia e diagnóstico. In:
Maffei FHA, Lastória S, Yoshida WB, Rollo HA, Gianini M, Moura R, editors.
Doenças Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2008. p.
1557-78.). A population study of 94,194 people
over the age of 20 from the Norwegian town of Nord-Trøndelag found that mortality
from DVT within 30 days of the initial event was 6.4%, that 12-month mortality was
21.6%, and that 30-day mortality for patients with PE was twice that for patients
who only had DVT(1010. Naess IA, Christiansen SC, Romundstad P, Cannegieter SC,
Rosendaal FR, Hammerstrom J. Incidence and mortality of venous thrombosis: a
population-based study. J Thromb Haemost. 2007;5(4):692-9. PMid:17367492.
http://dx.doi.org/10.1111/j.1538-7836.2007.02450.x
http://dx.doi.org/10.1111/j.1538-7836.20...
). On the basis of an analysis of hospital
admission data, it has been estimated that the rate of DVT diagnosed clinically and
confirmed by duplex mapping or phlebography in Brazil is six cases per 10,000
inhabitants per year(11. Maffei FHA, Rollo HA. Trombose venosa profunda dos membros
inferiores: incidência, patogenia, patologia, fisiopatologia e diagnóstico. In:
Maffei FHA, Lastória S, Yoshida WB, Rollo HA, Gianini M, Moura R, editors.
Doenças Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2008. p.
1557-78.). This estimate is very close to the figure
reported by Fowkes et al., who observed an incidence of DVT in the general
population of five cases per 10,000 inhabitants per year(99. Fowkes FJ, Price JF, Fowkes FG. Incidence of diagnosed deep vein
thrombosis in the general population: systematic review. Eur J Vasc Endovasc
Surg. 2003; 25(1):1-5. http://dx.doi.org/10.1053/ejvs.2002.1778). Several authors of
previous studies have also reported incidence rates that were similar or that varied
slightly. Hasson et al.(1111. Hasson PO, Welin L, Tibblin G, Eriksson H. Deep vein thrombosis
and pulmonary embolism in the general population. The study of men born in 1913.
Arch Int Med. 1997;157:1665-70.
http://dx.doi.org/10.1001/archinte.1997.00440360079008)
reported an adjusted incidence of 5.8 cases of DVT per 10,000 inhabitants per year.
White et al.(1212. White RH, Zhou H, Romano PS. Incidence of idiopathic deep venous
thrombosis and secundary thromboembolism among ethnic groups in California. Ann
Int Med. 1998;128:737-40.
http://dx.doi.org/10.7326/0003-4819-128-9-199805010-00006
http://dx.doi.org/10.7326/0003-4819-128-...
), conducted a
large-scale population study including around 18,000 DVT cases and calculated an
incidence of 4.9 cases per 10,000 inhabitants per year. In another study, conducted
in 1992 in the Swedish city Malmö, Nordström et al.(1313. Nordström M, Lindblad B, Bergqvist D, Kjellström T. A
prospective study of the incidence of deep vein thrombosis within a defined
urban population. J Int Med. 1992;232:155-260.
http://dx.doi.org/10.1111/j.1365-2796.1992.tb00565.x) observed an incidence of 9.5 DVT cases per 10,000
inhabitants. Oger(1414. Oger E for the EPI-GETBO Study Group. Incidence of venous
thromboembolism: A community-based in Western France. Thromb Haemost.
2000;83:657-60. PMid:10823257.) observed incidence of 8.7 cases of DVT for
every 10,000 inhabitants per year.
DIAGNOSIS
Patients with DVT may not exhibit specific and/or pathognomonic signs and symptoms of
the disease. Clinical presentation is highly variable and may be restricted to
simple localized discomfort in the affected limb, and this can also be the case with
the much-feared PE. While pain, edema and muscle rigidity have been identified in up
to 86.7% of patients with DVT, these signs and symptoms can also present in other
conditions, such as: lymphangitis , cellulites, ruptured Baker's cyst, congestive
heart failure, nephrotic syndrome, traumas, muscle hematomas, myositis and muscle
tears(11. Maffei FHA, Rollo HA. Trombose venosa profunda dos membros
inferiores: incidência, patogenia, patologia, fisiopatologia e diagnóstico. In:
Maffei FHA, Lastória S, Yoshida WB, Rollo HA, Gianini M, Moura R, editors.
Doenças Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2008. p.
1557-78.). In view of this, a clinical diagnosis alone is not
sufficient to confirm diagnosis in suspected cases of DVT(1515. Hull R, Hirsh J, Sackett DL, et al. Clinical validity of a
negative venogram in patients with clinically suspected venous thrombosis.
Circulation. 1981;64(3):622-5. PMid:7261292.
http://dx.doi.org/10.1161/01.CIR.64.3.622
http://dx.doi.org/10.1161/01.CIR.64.3.62...
), (161. Maffei FHA, Rollo HA. Trombose venosa profunda dos membros
inferiores: incidência, patogenia, patologia, fisiopatologia e diagnóstico. In:
Maffei FHA, Lastória S, Yoshida WB, Rollo HA, Gianini M, Moura R, editors.
Doenças Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2008. p.
1557-78.).
Patients who go undiagnosed and are therefore treated inadequately can suffer
chronic venous insufficiency (CVI) and even death caused by PE. Therefore, when
faced with a clinical suspicion of DVT and a need to assess the status of a
thrombosed vein in order to treat its complications, specific examinations or
supplementary diagnostic methods capable of directly or indirectly demonstrating the
presence and extent of the thrombus must be used. Clinical prediction models such as
those proposed by Wells et al.(1717. Wells PS, Anderson DR, Rodger M, et al. Evaluation of D dimer in
the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003;349:1227-35.
PMid:14507948. http://dx.doi.org/10.1056/NEJMoa023153
http://dx.doi.org/10.1056/NEJMoa023153...
), in combination with laboratory D-dimer testing and imaging exams
with color duplex mapping (CDM), have made it easier to reliably diagnose
DVT(1818. Goodacre S, Sutton AJ, Sampson FC. Meta-analysis: The value of
clinical assessment in the diagnosis of deep venous thrombosis. Ann Intern Med.
2005;143(2):129-39. PMid:16027455.
http://dx.doi.org/10.7326/0003-4819-143-2-200507190-00012
http://dx.doi.org/10.7326/0003-4819-143-...
), (1919. Bernardi E, Prandoni P, Lensing AW, et al. D-dimer testing as an
adjunct to ultrasonography in patients with clinically suspected deep vein
thrombosis: prospective cohort study. The Multicentre Italian D-dimer Ultrasound
Study Investigators Group. BMJ. 1998;317(7165):1037-40. PMid:9774286
PMCid:PMC28685. http://dx.doi.org/10.1136/bmj.317.7165.1037
http://dx.doi.org/10.1136/bmj.317.7165.1...
).
TREATMENT
Current recommendations on treating DVT are the same as for VTE and are based on anticoagulant therapy, as described in the 9th edition of the American College of Chest Physicians Evidence Based Clinical Practice Guideline (ACCP)(201. Maffei FHA, Rollo HA. Trombose venosa profunda dos membros inferiores: incidência, patogenia, patologia, fisiopatologia e diagnóstico. In: Maffei FHA, Lastória S, Yoshida WB, Rollo HA, Gianini M, Moura R, editors. Doenças Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2008. p. 1557-78.). Initial treatment consists of parenteral administration for 5 to 7 days of unfractionated heparin (UFH), or subcutaneous administration of low molecular weight heparin (LMWH) and oral vitamin K antagonists (VKA), adjusting the dose to achieve a prothrombin time as close as possible to the international standard for thromboplastin, which is expressed in INR (international normalized ratio) and should remain between 2 and 3. In addition to conventional anticoagulant therapy, the ACCP has recommended that all patients with acute symptomatic DVT should wear graduated elastic compression stockings, because of their potential to cut the rate of postthrombotic syndrome (PTS) by half(2020. Guyatt GH, Akl EA, Crowther M, Gutterman DD, therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141 (2)(Suppl): 7S-47S.). In addition to anticoagulant treatments, some ongoing studies have suggested that pharmacological removal of acute thrombi using fibrinolytic therapies can preserve vein valve function(2121. Watson LI, Armon MP. Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev. 2004;(4):CD002783. PMid:15495034.). The ATTRACT study has been designed to show whether the new treatment prevents the serious later complications of DVT by conducting a prospective assessment of 692 patients with symptomatic proximal thrombosis of the iliac, common femoral and femoral veins(2222. Vedantham S. The Attract Study (Acute Venous Thrombosis: Thrombus removal with adjunctive catheter-directed thrombolysis). St. Louis: Washington University, School of Medicine; 2010.).
CLINICAL COURSE
One feature of the natural history of DVT that remains controversial is its
progression. After a DVT episode, there is an acute inflammatory response in the
vein wall and in the thrombus itself, leading to a dynamic process in which the
thrombus regresses due to recanalization. Recanalization is defined as the return of
blood flow to a venous segment that had previously been occluded. Recanalization is
a complex process that initially involves adhesion of the thrombus to the vein wall
and an inflammatory response in the vessel wall, leading to organization and
subsequent contraction of the thrombus, and to neovascularization and spontaneous
lysis of areas inside the thrombus(2323. Van Ramshorst B, Van Bemmelen PS, Hoeneveld H, Faber JA,
Eikelboom BC. Thrombus regression in deep venous thrombosis.Quantification of
spontaneous thrombolysis with duplex scanning. Circulation. 1992;86 (2):414-9.
PMid:1638710. http://dx.doi.org/10.1161/01.CIR.86.2.414
http://dx.doi.org/10.1161/01.CIR.86.2.41...
). However, recanalization is not the only
phenomenon observed during the natural course of DVT and propagation of the thrombus
has been identified in 20 to 40% of patients monitored using CDM, despite adequate
anticoagulation(2424. Krupski WC, Bass A, Dilley RB, Bernstein EF, Otis SM.
Propagation of deep venous thrombosis identified by duplex ultrasonography. J
Vasc Surg. 1990;12(4):467-74. PMid:2214041.). It is therefore very important to understand
these pathophysiologic mechanisms because delayed regression or propagation of the
thrombus may be related with development and exacerbation of the signs and symptoms
of CVI.
POSTTHROMBOTIC SYNDROME
Postthrombotic syndrome (PTS) is a common cause of CVI and has significant
socioeconomic consequences for both patients and for health services. The total
additional cost of treating PTS, over 15 years, was approximately US $3,000 in the
United States. Additionally, PTS was responsible for 74 to 81% of all DVT treatment
costs(2525. Ashrani AA, Heit JA. Incidence and cost burden of
post-thrombotic syndrome. J Thromb Thrombolysis. 2009;
28(4):465-76.). A study that analyzed data from patients with
diagnoses of PE or DVT estimated that on average health services in the United
States spent US$7,000 per patient/year on PTS(2525. Ashrani AA, Heit JA. Incidence and cost burden of
post-thrombotic syndrome. J Thromb Thrombolysis. 2009;
28(4):465-76.). In Brazil, Ramacciotti et al.
calculated that average annual cost was US$ 400 for moderate cases and US$ 1,200 for
more serious PTS cases(2626. Ramacciotti E, Gomes M, De Aguiar ET, et al. A cost analysis of
the treatment of patients with post-thrombotic syndrome in Brazil. Thromb Res.
2006; 118(6):699-704. PMid:16417913.
http://dx.doi.org/10.1016/j.thromres.2005.12.005
http://dx.doi.org/10.1016/j.thromres.200...
). According to Susan and Kahn, around 20 to 50%
of patients with idiopathic DVT will develop PTS(66. Susan R, Kahn SR. The post-thrombotic syndrome: the forgotten
morbidity of deep venous thrombosis. J Thromb Thrombolysis. 2006;21(1):41-8.
PMid:16475040. http://dx.doi.org/10.1007/s11239-006-5574-9
http://dx.doi.org/10.1007/s11239-006-557...
).
POSTTHROMBOTIC SYNDROME AND VENOUS RECANALIZATION
The pathophysiology of PTS is not entirely understood. However, it is probable that
the presence of the thrombus releases inflammatory mediators which, together with
the process of recanalization that takes place after a DVT episode, damage venous
valves, leading to valve incompetence. Valve incompetence, persistent obstruction of
veins by residual thrombus, or both, cause chronic venous hypertension, which leads
to edema, to tissue hypoxia and even to ulcerations of the skin. Many different
authors have proposed definitions of PTS based on combinations of clinical symptoms
and signs, evidence of venous obstructions, elevated venous pressure or valve
reflux, identified on the basis of ultrasound and/or plethysmograph findings. While
a diagnosis of PTS cannot be made in the absence of these clinical signs, the
majority of symptomatic patients exhibit valve incompetence, although many people
with incompetence do not manifest PTS clinically(66. Susan R, Kahn SR. The post-thrombotic syndrome: the forgotten
morbidity of deep venous thrombosis. J Thromb Thrombolysis. 2006;21(1):41-8.
PMid:16475040. http://dx.doi.org/10.1007/s11239-006-5574-9
http://dx.doi.org/10.1007/s11239-006-557...
), (2727. Kahn SR, Ginsberg JS. Relationship between deep venous
thrombosis and the postthrombotic syndrome. Arch Intern Med. 2004;164(1):17-26.
PMid:14718318. http://dx.doi.org/10.1001/archinte.164.1.17).
Therefore, delayed recanalization after a thrombotic episode appears to be an
important predictor of PTS development. However, the time and rates that are
favorable to restoration of the lumen of different thrombosed venous segments have
yet to be well-defined. Sevitt(2828. Sevitt S. The vascularisation of deep-vein thrombi and their
fibrous residue: a post mortem angio-graphic study. J Pathol. 1973;111(1):1-11.
PMid:4757506. http://dx.doi.org/10.1002/path.1711110102
http://dx.doi.org/10.1002/path.171111010...
),
(2929. Sevitt S. The mechanisms of canalisation in deep vein
thrombosis. J Pathol. 1973;110(2):153-65. PMid:4125876.
http://dx.doi.org/10.1002/path.1711100207
http://dx.doi.org/10.1002/path.171110020...
) have suggested that
recanalization is part of the process of fibrocellular organization of the thrombus.
They consider that this process involves contraction of the thrombus, multiple tears
between the thrombus and the tunica intima, localized fibrinolysis and fragmentation
of the thrombus after cellular invasion by newly formed vessels(2828. Sevitt S. The vascularisation of deep-vein thrombi and their
fibrous residue: a post mortem angio-graphic study. J Pathol. 1973;111(1):1-11.
PMid:4757506. http://dx.doi.org/10.1002/path.1711110102
http://dx.doi.org/10.1002/path.171111010...
), (2929. Sevitt S. The mechanisms of canalisation in deep vein
thrombosis. J Pathol. 1973;110(2):153-65. PMid:4125876.
http://dx.doi.org/10.1002/path.1711100207
http://dx.doi.org/10.1002/path.171110020...
).
RECANALIZATION AND NEOANGIOGENESIS
Wakefield et al. reported the results of on an experimental study that suggested that
neoangiogenesis occurs during the process of organization of a thrombus, resulting
in recanalization of occluded vessels(3030. Wakefield TW, Linn MJ, Henke PK, et al. Neovascularization
during venous thrombosis organization: a preliminary study. J Vasc Surg.
1999;30(5):885-92.
http://dx.doi.org/10.1016/S0741-5214(99)70013-3
http://dx.doi.org/10.1016/S0741-5214(99)...
). Along the same lines, other authors have
claimed that recanalization is part of the physiological process of thrombus
remodeling. Labropoulos et al. studied the remodeling process in veins of the calf
and found that length, lysis patterns and the location of thrombi are all factors
that affect this process(3131. Labropoulos N, Kang SS, Mansour MA, Giannoukas AD, Moutzouros V,
Baker WH. Early thrombus remodelling of isolated calf deep vein thrombosis. Eur
J Vasc Endovasc Surg. 2002;23(4):344-8. PMid:11991697.
http://dx.doi.org/10.1053/ejvs.2002.1608
http://dx.doi.org/10.1053/ejvs.2002.1608...
). Furthermore, Labropoulos et al., and Barros
et al. have observed flow patterns that fit the profile of arteriovenous fistulae
(AVF) in the thrombus interior as part of neovascularization after acute DVT
episodes(3232. Labropoulos N, Bhatti AF, Amaral S, et al. Neovascularization in
acute venous thrombosis. J Vasc Surg. 2005;42(3):515-8. PMid:16171599.
http://dx.doi.org/10.1016/j.jvs.2005.05.036
http://dx.doi.org/10.1016/j.jvs.2005.05....
), (3333. Barros F, Pontes S, Silva W, Prezzote B, Sandri J. Identificação
pelo eco-doppler de fístula arteriovenosa na trombose venosa profunda. J Vasc
Bras. 2006;5(3):224-8.
http://dx.doi.org/10.1590/S1677-54492006000300012
http://dx.doi.org/10.1590/S1677-54492006...
). The spontaneous arterial flow
that can be identified by color duplex mapping of thrombosed veins during the first
weeks after an acute event appears to be secondary to the inflammation and
neovascularization that occur after formation and remodeling of a
thrombus(3232. Labropoulos N, Bhatti AF, Amaral S, et al. Neovascularization in
acute venous thrombosis. J Vasc Surg. 2005;42(3):515-8. PMid:16171599.
http://dx.doi.org/10.1016/j.jvs.2005.05.036
http://dx.doi.org/10.1016/j.jvs.2005.05....
). Pulsating flow in the interior and adjacent
to a thrombus can be identified by the observation of aliasing (which appears as a
mixture of colors) and is characterized by a spectral curve with high end-diastolic
velocity and low resistance index (RI), which is a typical AVF presentation, as
illustrated below in Figures 1 and 2.
Color duplex mapping (cross-section) of the acutely thrombosed left common femoral vein. The vein exhibited pulsating flow, increased end-diastolic velocity, low resistance index and absence of normal physiological flow. These flow characteristics are consistent with an AVF.
Color duplex mapping (cross-section) of the acutely thrombosed right external iliac vein. The vein exhibited pulsating flow, increased end-diastolic velocity, low resistance index and absence of normal physiological flow. These flow characteristics are consistent with an AVF.
CONCLUSIONS
In the past, studies employing serial phlebographic examinations gave the impression
that recanalization was a late reaction, occurring over periods varying from 6
months to years after the acute event(3434. Bergvall U, Hjelmstedt A. Recanalisation of deep venous
thrombosis of the lower leg and thigh. A phlebographic study of fracture cases.
Acta Chir Scand. 1968;134(3):219-28. PMid:5730893.). However, contemporary research reported
by several authors(2525. Ashrani AA, Heit JA. Incidence and cost burden of
post-thrombotic syndrome. J Thromb Thrombolysis. 2009;
28(4):465-76.), (3434. Bergvall U, Hjelmstedt A. Recanalisation of deep venous
thrombosis of the lower leg and thigh. A phlebographic study of fracture cases.
Acta Chir Scand. 1968;134(3):219-28. PMid:5730893.) who have employed CDM shows that
the recanalization of thrombi in lower extremities with DVT is not a slow process,
as was previously believed. Killewich et al. have published evidence that lysis of
the thrombus and recanalization of venous segments can be observed on CDM in the
first week after initial diagnosis(3535. Killewich LA, Macko RF, Cox K, et al. Regression of proximal
deep venous thrombosis is associated with fibrinolytic enhancement. J Vasc Surg.
1997; 26(5):861-8.
http://dx.doi.org/10.1016/S0741-5214(97)70101-0
http://dx.doi.org/10.1016/S0741-5214(97)...
). Studies using phlebography to monitor the
course of DVT have become less common because of its invasivity. Color duplex
mapping has therefore expanded the possibilities for studying the natural history of
DVT, because it makes it possible to conduct an unlimited number of sequential
scans, thereby revealing patterns of events in the natural history of DVT that are
different to what has been suggested in the past. Color duplex mapping also provides
the possibility of using methods to quantify the recanalization process, such as the
thrombotic score described by Porter et al.(3636. Porter JM, Moneta GL; International Consensus Committee on
Chronic Disease. Reporting standards in venous disease: An update. J Vasc Surg.
1995;21:635-45. http://dx.doi.org/10.1016/S0741-5214(95)70195-8
http://dx.doi.org/10.1016/S0741-5214(95)...
) and the venous compressibility test using an ultrasound
transducer described by Prandoni et al.(3737. Prandoni P, CogoA, Bernardi E, et al. A simple ultrasound
approach for detection of recurrent proximal-vein thrombosis. Circulation.
1993;88:1730-5. PMid:8403319.
http://dx.doi.org/10.1161/01.CIR.88.4.1730
http://dx.doi.org/10.1161/01.CIR.88.4.17...
). It can therefore be considered that color duplex mapping
has become the new gold standard method in phlebology.
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35Killewich LA, Macko RF, Cox K, et al. Regression of proximal deep venous thrombosis is associated with fibrinolytic enhancement. J Vasc Surg. 1997; 26(5):861-8. http://dx.doi.org/10.1016/S0741-5214(97)70101-0
» http://dx.doi.org/10.1016/S0741-5214(97)70101-0 -
36Porter JM, Moneta GL; International Consensus Committee on Chronic Disease. Reporting standards in venous disease: An update. J Vasc Surg. 1995;21:635-45. http://dx.doi.org/10.1016/S0741-5214(95)70195-8
» http://dx.doi.org/10.1016/S0741-5214(95)70195-8 -
37Prandoni P, CogoA, Bernardi E, et al. A simple ultrasound approach for detection of recurrent proximal-vein thrombosis. Circulation. 1993;88:1730-5. PMid:8403319. http://dx.doi.org/10.1161/01.CIR.88.4.1730
» http://dx.doi.org/10.1161/01.CIR.88.4.1730
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*All authors should have read and approved of the final version of the article submitted to J Vasc Bras.
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Study carried out at Hospital das Clínicas da Faculdade de Medicina de Botucatu, Botucatu, SP, Brazil
Publication Dates
-
Publication in this collection
21 Oct 2013 -
Date of issue
Oct-Dec 2013
History
-
Received
24 Apr 2012 -
Accepted
05 Aug 2013