The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults: a systematic review.

BACKGROUND: Post-thrombotic syndrome is a chronic, potentially debilitating complication of deep vein thrombosis (DVT) of the lower extremity. Comparatively little is known about post-thrombotic syndrome after upper extremity DVT (UEDVT). OBJECTIVE: To perform a systematic review of clinical studies that have examined the incidence, clinical features, risk factors and management of post-thrombotic syndrome after UEDVT. METHODS: Using combinations of keywords venous thrombosis, postphlebitic syndrome, thrombophlebitis, arm swelling, post-thrombotic syndrome, UEDVT, Paget-Schroetter syndrome, thoracic outlet syndrome, axillary vein, subclavian vein, and central venous catheter, the MEDLINE database was searched for English language articles published between January 1967 and December 2004. Retrieval and review of articles were restricted to clinical studies in humans that described long-term outcomes after objectively confirmed UEDVT. RESULTS: Seven studies were reviewed. The frequency of PTS after UEDVT ranges from 7-46% (weighted mean 15%). Residual thrombosis and axillosubclavian vein thrombosis appear to be associated with an increased risk of PTS, whereas catheter-associated UEDVT may be associated with a decreased risk. There is currently no validated, standardized scale to assess upper extremity PTS, and little consensus regarding the optimal management of this condition. Quality of life is impaired in patients with upper extremity PTS, especially after DVT of the dominant arm. CONCLUSIONS: PTS is a frequent complication of UEDVT, yet little is known regarding risk factors and optimal management. A standardized means of diagnosis would help to establish better management protocols. The impact of upper extremity PTS on quality of life should be further quantified.

The post-thrombotic syndrome: incidence and prognostic value of non-invasive venous examinations in a six-year follow-up study.

The ability to predict severity of the post-thrombotic syndrome (PTS) early after acute deep-vein thrombosis (DVT) is limited. The aim of our study was to examine the incidence of PTS prospectively and to evaluate the predictive value of non-invasive venous examinations shortly after DVT for the development of PTS. In 93 patients with DVT thrombosis score (TS), reflux, venous outflow resistance (VOR) and calf muscle pump dysfunction (CMP) were examined prospectively. After one, two and six years patients were evaluated for PTS using the clinical scale of the CEAP-classification (PTS present > or = 3 on a scale from 0 to 6). Area under the curves (AUC) were used to evaluate the predictive value of the non-invasive examinations at one and three months after diagnosis of DVT for future PTS. The cumulative incidence of PTS increased from 49% (32/65) after one year to 55% (36/65) and 56% (27/48) after two and six years, whereas the incidence of patients with PTS class 4 progressed from 20% after two years to 33% after six years. The prognostic value to predict PTS was highest for the combination of TS, VOR and reflux measured three months after diagnosis and showed an AUC of 0.77 (0.65-0.90) for PTS after one year. In conclusion, the incidence of PTS after DVT did not increase significantly after one year, whereas during longer follow-up the severity of PTS rose in patients with PTS. Moreover, measurement of TS, VOR and reflux three months after DVT could predict, with reasonable accuracy, the risk of PTS after one year of follow-up.

Effect of physical activity after recent deep venous thrombosis: a cohort study.

PURPOSE: To determine whether increased physical activity 1 month after deep vein thrombosis (DVT) led to worsening of venous symptoms and signs within the subsequent 3 months. METHODS: By a multicenter prospective cohort study of patients with acute DVT, we used validated questionnaires at baseline, 1 month, and 4 months post-DVT for each exposure, using the Godin Questionnaire to measure physical activity, the VEINES-QOL to measure disease severity, and the postthrombotic syndrome (PTS) scale to measure symptoms and signs usually attributed to sequelae of DVT. RESULTS: Of 301 patients followed for 4 months, 25% were inactive and 25% were only mildly active before their DVT. In univariate analysis, physical activity at 1 month was not associated with a change in PTS score between 1 month and 4 months (P=0.42). After adjusting for the potential confounders of age, sex, pre-DVT physical activity, and disease severity at 1 month, the results suggested that higher physical activity levels at 1 month may be protective against worsening of the PTS score over the subsequent 3 months. Compared with those who were inactive at 1 month, the adjusted OR was 0.93 (95%CI: 0.47, 1.87) for mildly to moderately active persons, and 0.52 (95%CI: 0.24, 1.15) for highly active persons. Among patients who were active pre-DVT (N=220), 55.5% had returned to their previous levels of physical activity or greater within 4 months. CONCLUSIONS: For most persons, exercise at 1 month post-DVT does not appear to worsen venous symptoms and signs over the subsequent 3 months, and more than 50% resume their usual level of activity within 4 months.

Relationship between deep venous thrombosis and the postthrombotic syndrome.

The postthrombotic syndrome (PTS) is a frequent complication of deep venous thrombosis (DVT). Clinically, PTS is characterized by chronic, persistent pain, swelling, and other signs in the affected limb. Rarely, ulcers may develop. Because of its prevalence, severity, and chronicity, PTS is burdensome and costly. Preventing DVT with the use of effective thromboprophylaxis in high-risk patients and settings and minimizing the risk of ipsilateral DVT recurrence are likely to reduce the risk of development of PTS. Daily use of compression stockings after DVT might reduce the incidence and severity of PTS, but consistent and convincing data about their effectiveness are not available. Future research should focus on standardizing diagnostic criteria for PTS, identifying patients at high risk for PTS, and rigorously evaluating the role of thrombolysis in preventing PTS and of compression stockings in preventing and treating PTS. In addition, novel therapies should be sought and evaluated.

The post-thrombotic syndrome in young women: retrospective evaluation of prognostic factors.

Post-thrombotic syndrome (PTS) in young women may cause impairment in the quality of life of otherwise healthy people. We aimed to evaluate the prevalence of PTS and its risk factors in young women. We evaluated 51 women with at least one previous episode of symptomatic, objectively documented deep vein thrombosis (DVT) before the age of 40. Each patient asked for symptoms had a physical examination, a color-coded Doppler ultrasonography of the superficial and deep venous system and an extensive laboratory evaluation for the congenital and acquired coagulation abnormalities predisposing to thrombosis. The median follow-up was 47 months. PTS was absent in 37%, mild in 55%, moderate in 4% and severe in 4% of patients. No correlation was found between PTS and the presence of coagulation abnormalities, triggering factors, recurrences, use of elastic stockings for one year after DVT, degree of recanalization, presence of superficial reflux. Patients with a body mass index (BMI) >22 had an adjusted ratio of 4.7 (98 CI: 1.0-23.3) of developing the PTS. Though severe and moderate PTS are rare, mild PTS is present in the majority of young women after DVT. A BMI >22 is associated to the risk of developing PTS. Attempt to control weight in women after DVT should be considered and studied to prevent PTS.

Acute effects of exercise in patients with previous deep venous thrombosis: impact of the postthrombotic syndrome.

BACKGROUND: The postthrombotic syndrome (PTS) occurs frequently after deep venous thrombosis (DVT) and is believed to worsen with upright posture and physical activity. However, the effects of exercise in patients with previous DVT have not been studied. STUDY OBJECTIVES: To determine whether previous DVT and PTS limit the ability to exercise, and whether exercise increases the severity of venous symptoms and signs. DESIGN AND SETTING: A repeated-measures cohort study that was conducted at a university-affiliated teaching hospital, 1999-2000. PARTICIPANTS: Subjects with a first episode of unilateral DVT at least 1 year earlier were recruited from the Thrombosis Clinic (total, 41 subjects; with PTS, 19 subjects). INTERVENTION: Treadmill exercise session. MEASUREMENTS AND RESULTS: Venous symptoms, calf muscle fatigability, flexibility, and leg volume before and after treadmill exercise were measured and compared. Exercise did not worsen venous symptoms, despite a higher gain in affected leg volume in subjects with PTS vs subjects without PTS (mean difference: affected leg, 53 mL; unaffected leg, -15 mL; p = 0.018). Calf flexibility significantly improved after exercise in subjects with PTS (gastrocnemius: affected-unaffected, PTS vs no PTS + 4.5 degrees, p = 0.0029; soleus: affected-unaffected, PTS vs no PTS + 5.7 degrees, p = 0.0011). CONCLUSIONS: Exercise did not acutely exacerbate symptoms and, in subjects with PTS, resulted in improved flexibility in the affected leg. Our findings suggest that treadmill or similar exercise is unlikely to make symptoms of PTS worse, and may improve flexibility. Further study is indicated to determine whether a regular exercise-training program might have a role in the management of patients with PTS, since, to date, the treatment options for this condition are limited.

Thrombolytic therapy for acute deep vein thrombosis and the venous registry.

Randomized clinical trials have defined anticoagulation with unfractionated or low molecular weight heparin followed by warfarin as standard therapy for acute deep venous thrombosis (DVT). Such treatment is highly effective in preventing recurrent venous thromboembolism, but provides imperfect protection against development of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, catheter-directed thrombolytic therapy potentially affords an improved long-term outcome in selected patients with DVT. A national venous registry, compiling data from 63 participating centers, was established to collect data regarding the technical details of the procedure and early outcome. Data from the registry have established the optimal technical approach and patient population. An antegrade catheter-directed approach using urokinase in patients with acute iliofemoral DVT of less than 10 days duration and no prior history of DVT may achieve complete lysis in 65% of patients. Analysis of the clinical outcome is pending, but early results suggest improved valve function and fewer symptoms at 1 year in patients with complete thrombolysis. These promising data should serve as the basis for future randomized trials of catheter-directed thrombolysis for the treatment of acute DVT.

Pathogenesis and pathophysiology of the post-thrombotic syndrome: clinical implications.

Anticoagulant therapy can successfully prevent pulmonary embolism and rethrombosis in most cases, but cannot affect either early morbidity or the late post-thrombotic sequelae. In carefully selected cases, early clot removal by thrombolysis or thrombectomy may be justified by improved outcome because of the significant role early and late outflow obstruction plays in determining the ultimate severity of post-thrombotic sequelae. Nevertheless, it is recognized that anticoagulant therapy will continue to be used in the majority of patients because of serious intercurrent disease, sedentary lifestyle, limited extent of thrombosis, lack of tissue loss and, unfortunately, delay in referral for treatment.

Importance of valvular incompetence after acute deep venous thrombosis.

The color Doppler scanner was used to analyze acute deep venous thrombosis in 14 patients. A thrombus was found in the superficial femoral vein in 4 patients and in the superficial femoral and popliteal veins in 6 patients; a popliteal occlusion was found in 4 patients. All 14 patients were treated with intravenous heparin followed by at least 3 months of warfarin therapy. Patients were re-examined between 24 and 48 months. Six patients were symptomatic; 8 were asymptomatic. Five patients had occluding thrombus in the distal popliteal vein; major competent collateral channels developed from the proximal superficial femoral vein, and they remained asymptomatic. Three patients whose superficial femoral veins recanalized without valvular incompetence were asymptomatic. Valvular incompetence was observed in all of the symptomatic patients. Patients with persistent popliteal occlusion and collateral channels have fewer symptoms than patients with valvular incompetence in the superficial femoral and popliteal veins.

Long term results of vein valve transplants placed in the popliteal vein for intractable post-phlebitic venous ulcers and pre-ulcer skin changes.

Most patients with chronic venous ulceration or severe pre-ulcer damaged skin have incompetent popliteal valves and a high ambulant venous pressure (AVP). Competency can be restored by a vein valve transplant taken from the arm and placed in the popliteal fossa, with subjective and objective improvement. In this study 23 patients with post-phlebitic syndromes received 25 vein valve grafts as part of management. Seventeen patients had large recurrent ulcers after unsuccessful venous surgery: 6 patients had extensive pre-ulcer skin damage. Fifteen of 17 patients healed their ulcers, and all 6 patients with skin damage showed rapid improvement with relief of symptoms. Falls in the AVP, ranging from 10 to 40 mmHg occurred in 19 patients. All vein valve transplants were patent, after 18 months, but 5 grafted valves have evidence of venous reflux. These results suggest a functioning valve replacement in the popliteal fossa may lower the AVP sufficiently to heal intractable venous ulcers or severely damaged skin. Vein valve transplants function well long term, and the falls in the AVP are usually maintained. The popliteal fossa may be the ideal site since a component popliteal valve has been shown to limit adverse post-phlebitic changes.

Microcirculation in high perfusion microangiopathy.

Using laser-Doppler flowmetry in association with other noninvasive microcirculatory techniques such as transcutaneous PO2 and PCO2 and capillary filtration measurements it is possible to define two major types of microangiopathy. Low perfusion microangiopathy (LPM) is observed in peripheral vascular disease, essential hypertension, Raynaud's disease etc. High perfusion microangiopathy (HPM) is observed in venous hypertensive microangiopathy and diabetic microangiopathy. In both these conditions there is an increased skin flux, decreased venoarteriolar response and increased capillary filtration leading to edema formation. In HPM elastic compression and drugs acting on capillary filtration effectively reduce skin flux and the increased capillary leakage and edema formation.

Haemodynamics of the postphlebitic syndrome.

The venous function has been assessed after deep vein thrombosis (DVT) by Doppler, strain gauge plethysmography (55 patients) and exercise plethysmography (10 patients) for a mean period of 63 weeks. Venous volume and venous outflow remain significantly lower throughout the study, whatever the site of thrombosis and the initial therapy (Heparin, local or general Urokinase). There are no significant correlations between clinical and functional parameters except for patients with proximal obstruction and popliteal valvular incompetence. Exercise plethysmography evaluates the importance of the calf pump in the postphlebitic syndrome. Static plethysmographic measurements prove to be unreliable for the long term prognosis whereas associated dynamic tests should be a better way to assess the haemodynamic changes after DVT and to control the efficiency of the prevention of the post-phlebitic syndrome.

Heat conductivity and skin temperature at the treatment of ischemic heart disease with curantyl and isoptin.

Forty one patients with ischaemic heart disease (IHD) of the age 60 +/- 12.3 years were hospitalized and treated two weeks with Curantyl (Dipyridamol) which was applied per os in a dose of 75 mg 3 times, and after another two weeks 34 of them wass applied Isoptin (Verapamil) in a dose of 40 mg 3 times daily. The heat conductivity (J.m-1, sec-1.degree C.10(-2), HC) and skin temperature (degree C, ST) were examined at the isothermic level 2 cm above the inner ankle by the apparatus Fluvograph 2 of Hartmann and Braun A. G. (BRD). The HC after Isoptin application above the left and right ankle was in 34 patients increased significantly (p less than 0.001). In patients with IHD after Curantyl application the HC and ST was significantly decreased above the left and right ankle in 9 (21.9%) and in 12 (30.0%), respectively. Curantyl could deteriorate HC and so to worsen legs ulceration healing and to point ap ischemia in patients with associated chronic postphlebitic syndrome with ulcera crurium.

Influence of healing on the disturbed blood flow regulation in venous ulcers.

Cutaneous blood flow regulation is disturbed in severe chronic venous insufficiency (CVI). The feedback system between the transmural pressure in the postcapillary venules and the precapillary resistance regulating arterioles has gone awry. The upregulated control system causes "luxus"-hyperperfusion. In this study laser Doppler fluxmetry was performed in 6 patients' florid venous ulcers (U) and later in the former ulcer area after healing (H) and in the inner ankle area of 12 healthy volunteers (C). Laser Doppler flux (LDF) changes were measured with the leg elevated and lowered as well as after arterial and during venous occlusion. The results proved a diminished (p < 0.01) flux increase with the leg elevated (U: LDF = -9%, H: LDF = 3.1%, C: LDF = 80%) and after arterial occlusion (U: LDF = 1.3%, H: LDF = 0%; C: 189.6%) in severe CVI both in florid ulcers and after healing. The ability to reduce flux when transmural pressures were increased remained. Leg lowering reduced flux by 46.4% in ulcers and by 36.8% after healing. This postural response to high transmural pressures, however, seemed weakened compared to controls, where LDF decreased by 65.8%. Our findings suggest that the postural feedback system remains disturbed and upregulated even after a venous ulcer has healed.

Skin flow and swelling in post-phlebitic limbs.

It has been demonstrated that skin blood flow of postphlebitic limbs is increased. Also the venoarteriolar response (VAR), i.e. precapillary vasoconstriction present in normal limbs on standing up, is reduced in limbs with venous insufficiency, resulting in capillary hypertension. The supine skin resting flow (SF) and the skin flow on standing (SF) have been measured with laser-Doppler in 30 normal lower limbs and 70 postphlebitic limbs with ambulatory venous pressure greater than 65 mmHg; also, the rate of ankle swelling (RAS) has been measured with strain-gauge plethysmography. The VAR was derived from VAR = 100* (RF-SF)/RF. The reduction of VAR and the increase in SF, which has been demonstrated in the postphlebitic limbs, correlated well with the rate of ankle swelling (RAS). The measurements of SF, VAR and RAS evaluate objectively the degree of impairment of the microcirculation because of severe venous disease. They offer the possibility to study the natural history and the effect of treatment of venous hypertensive microangiopathy.

The reproducibility of the ratio of volume flow in the common femoral vein and artery for quantification of the severity of venous insufficiency.

BACKGROUND: The ratio of volume flow in the common femoral vein and artery denoted as venous-arterial Flowindex (VAFI) is significantly increased in venous insufficiency according the clinical grade of the disease. This study was done to investigate the reliability and reproducibility of VAFI as quantitative pattern. PATIENTS AND METHODS: In 43 patients with varicose veins C4-6 EPAS,D,PPR (PVV), 40 with postthrombotic syndrome C4-6 ESAS,D,PPR,O (PTS) and 48 healthy volunteers volume flow in the common femoral vein (VFV) and artery (VFA) were measured by duplex. Division of VFV by VFA calculated VAFI. VAFI-measurement was repeated 5 times at an interval of ten minutes in 63 subjects (23 PVV, 20 PTS, 20 healthy) and it was performed at three different days in 68 subjects (20 PVV, 20 PTS, 28 healthy). RESULTS: Mean VAFI +/- standard deviation was 1.39 +/- 0.26 in PVV, 1.42 +/- 0.26 in PTS and 0.93 +/- 0.13 in healthy veins (p < 0.001). VAFI remained stable and significantly increased (p < 0.001) in PVV and PTS compared to healthy veins during 40 minutes and also within three different days. CONCLUSION: The venous-arterial flowindex VAFI is a reproducible pattern of the hemodynamic severity in venous insufficiency.

[Post-thrombotic venous disease of the legs. Current data]. / Maladie post-thrombotique veineuse des membres inférieurs. Données actuelles.

The post-thrombotic syndrome (PTS) is the first cause of the severe chronic venous insufficiency (CVI) of which the total cost is very high. The lack of precise definitions, the long latency time between the deep vein thrombosis (DVT) and the trophic changes, the difficulties in treating the post-thrombotic ulcers, are partly responsible for the difficulties in analysing the problem of the PTS (epidemiology, pathophysiology, exploration) and consequently for the lack of interest in this disease. The recent data show that: 1) trophic venous changes are not all of PTS origin, 2) calf DVT are not to be neglected concerning the PTS risk, 3) the calf deep valvular destruction and the calf perforating veins reflux play the first part in the PTS evolution, 4) we should take into consideration the whole venous hemodynamic function of the lower limbs (macro and microcirculation) when analysing the long term clinical and hemodynamical consequences of a DVT. Today, the best treatment of a PTS is still its prevention not only by a better diagnosis and treatment of DVT but also by a long term ambulatory elastic stocking therapy with the aim of prolonging the disease-free interval.

[Efficacy of TTFCA in reducing the ratio between lymphatic and plasma protein concentration in lymphatic and postphlebitic edema]. / Efficacia di TTFCA nel ridurre il rapporto tra concentrazione linfatica e plasmatica di proteine nell'edema linfatico e postflebitico.

In subjects with lymphatic problems and postphlebitic edema there is a significant difference in the ratio between lymphatic and plasma concentration of protein (CL/CP) in the foot. Two groups of patients were studied (one group with lymphedema and the other with postphlebitic limbs) in order to assess the CL/CP ratio before and after TTCFA treatment (Centellase). The study confirmed the efficacy of treatment in achieving a significant reduction of CL/CP and distal edema.

[The microcirculatory activity of Centella asiatica in venous insufficiency. A double-blind study]. / Attività microcircolatoria della Centella asiatica nell'insufficienza venosa. Studio in doppio cieco.

In 87 patients with chronic venous hypertensive microangiopathy the efficacy of oral FTTCA (Centella asiatica) administered for 60 days was tested. The microcirculatory effects of two dosages (30 mg bid and 60 mg bid) versus placebo was assessed in a double blind study. The compound was well tolerated and no unwanted effects were observed. Microcirculatory parameters--peri-malleolar skin flux at rest (RF) and transcutaneous PO2 and PCO2--improved as did the abnormally increased RF, PCO2 decreased and PO2 increased in comparison with values measured at inclusion. These results confirm the efficacy of FTTCA in venous hypertensive microangiopathy. Furthermore the effects of FTTCA appear to be dose-related.

[Venous and lymphatic reasons for edema--the swollen leg from the angiologist's point of view]. / Phlebödem und Lymphödem--das dicke Bein aus angiologischer Sicht.

Peripheral edema develop as a consequence of imbalance in the processes of filtration, resorption and lymphatic transport in the capillary bed. Venous hypertension and impaired lymphatic function belong to the most important underlying pathomechanisms. Chronic venous insufficiency as a result of valve degeneration as well as venous obstruction in acute deep thrombosis lead to venous hypertension and to an increase of filtration pressure. As venous diseases are frequent, they are one of the most reasons for a swollen leg in clinical everyday life. Primary and secondary disturbances of the lymphatic system are another important reason for interstitial liquid retention. Although there are about 140 millions of people suffering from lymphedema worldwide, the disease is still underdiagnosed.