Postthrombotic or non-postthrombotic severe venous insufficiency: impact of removal of superficial venous reflux with or without subcutaneous fasciotomy.

BACKGROUND: Severe chronic venous insufficiency is often associated with therapy-resistant or recurrent venous leg ulcers, either as a result of deep vein thrombosis (DVT)- (postthrombotic syndrome [PTS]) or superficial venous insufficiency (SVI). Frequently present dermatoliposclerosis affects the skin as well as the subcutaneous and subfascial structures, which may impact tissue pressures and compromise skin perfusion. This study was undertaken to measure tissue pressures in PTS and SVI limbs and to evaluate the impact of removal of superficial venous reflux with or without concomitant subcutaneous fasciotomy. MATERIAL: In eight patients with recurrent, therapy-resistant venous leg ulcers, due to PTS (11 limbs, 12 ulcers) and 14 patients with severe SVI (14 limbs, 14 ulcers), subcutaneous fasciotomy was performed in addition to removal of superficial reflux. They were compared with eight patients with PTS (11 limbs, 11 ulcers) and 10 patients with SVI (13 limbs, 13 ulcers) who did not have fasciotomy in addition to removal of their superficial venous reflux. Intramuscular (i.m.) and subcutaneous (s.c.) tissue pressures and transcutaneous oxygen tension (TcPO(2)) were measured prior to, immediately after, and 3 months following the surgical intervention. Healing of ulcer (spontaneous or by skin grafting) at 3 months was also observed. RESULTS: There were no statistical differences between the groups regarding gender and age distribution or ulcer age at the time of surgery. All patients had in addition to surgery compression stockings class II (30 mm Hg). The i.m. tissue pressure was higher in patients with PTS compared with SVI patients, while s.c. tissue pressure and TcPO(2) did not differ between the groups. When fasciotomy was performed, i.m. and s.c. tissue pressures decreased and TcPO(2) increased significantly. Without fasciotomy, only s.c. tissue pressure decreased first at 3 months postoperatively. In the SVI-group, i.m tissue pressure was significantly decreased at 3 months in the group without fasciotomy. CONCLUSIONS: Patients with severe chronic venous insufficiency with therapy-resistant or recurrent ulcer disease due to deep and superficial insufficiency have higher i.m. tissue pressures than patients with only superficial venous reflux, even though both groups have higher i.m. and s.c. tissue pressures compared with normal values. Eradication of all superficial reflux lowers s.c. tissue pressure, while additional fasciotomy lowers both i.m. and s.c. tissue pressures and increases TcPO(2), which seems to promote ulcer healing.

Molecular characterization of post-thrombotic syndrome.

The post-thrombotic syndrome represents a poorly understood and significant vascular health problem. This review focuses on our current understanding of the pathogenesis of post-thrombotic syndrome. We emphasize the cellular and molecular mechanisms that are responsible for the critical components of post-thrombotic syndrome. These include the initiation of deep venous thrombosis, the pathogenesis of elevated venous pressure, and the factors responsible for nonhealing of venous stasis ulcers.

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 chronic wound exudates and MMP-2/-9 inhibitor on angiogenesis in vitro.

BACKGROUND: New evidence suggests that matrix metalloproteinases (MMPs) may facilitate angiogenesis as well as function to generate angiogenesis inhibitors. In this study, the angiogenic effect of wound exudates from patients with venous insufficiency ulcers was examined in an in vitro angiogenesis model with and without synthetic MMP-2/-9 inhibitor. METHODS: Wound exudates were obtained from 20 patients with venous insufficiency ulcers and 20 control patients with donor-site wounds after skin grafting for burns. In the angiogenesis model, suramin (20 microg/ml) was used in five wells without wound fluid as negative control, and vascular endothelial growth factor (1 microg/ml) was used in five other wells as positive control. Chronic wound fluids were analyzed without and with a synthetic MMP-2/-9 inhibitor with a concentration of 2 microM and 20 microM in the medium. The total length of tubules was calculated by map reader. Statistical analysis was performed using the Mann-Whitney test. The level of significance was considered to be p < 0.05. RESULTS: Chronic ulcer exudates inhibited angiogenesis significantly (490 +/- 130 microm) compared with acute wound fluids (1740 +/- 320 microm; p < 0.05). In wells with chronic wound exudates and high concentrations of MMP-2/-9 inhibitor, angiogenesis was stimulated significantly (870 +/- 220 microm, p < 0.05). CONCLUSIONS: In this model, reduced angiogenesis might be due to an antiangiogenic effect of MMP-2 and MMP-9. MMP-2/-9 inhibition results in a stimulation of angiogenesis and might be an approach for the treatment of patients with chronic wounds and reduced angiogenesis.

Origin and natural history of deep vein thrombosis of the legs.

Deep vein thrombosis (DVT) is a disorder frequently affecting the deep veins of the lower limbs; its onset is induced by known risk factors. The main complications of DVT are pulmonary embolism and postthrombotic syndrome (PST). Clinical pulmonary embolism occurs in a high proportion of cases of untreated proximal DVT and is associated with a mortality rate of 11-23% if not treated. PST, however, is a cause of increased morbidity and disability. The natural history of DVT is a dynamic process, with both thrombolysis and thrombus extension occurring after an episode of DVT. With the introduction of duplex scanning, several clinical studies have investigated and tried to clarify the natural history of DVT, the rate of recanalization of the thrombus, and the presence of reflux and its relation to lysis of the thrombus. These and other debated issues associated with PST are reviewed here. Knowledge of the evolution of these processes could result in better understanding of PST and be applied for improvement of medical and surgical management of venous thrombosis and its complications.

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.

[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.

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 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.

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.

Postthrombotic syndrome after isolated calf deep venous thrombosis: the role of popliteal reflux.

OBJECTIVE: The purpose of this study was to evaluate the long-term clinical and hemodynamic outcomes after isolated first-time calf deep venous thrombosis (cDVT). METHODS: This retrospective clinical study was set in an academic referral center. From 1990 to 1994, 617 patients were seen with acute DVT. This number included 82 patients with phlebographically confirmed cDVT. Of those patients, 50 attended the clinical assessment 6 to 10 years (mean, 8.4 years) after the acute event. All patients with cDVT underwent treatment with anticoagulant therapy (96% heparin and warfarin, 4% only warfarin). The duration of the heparin treatment was 4.0 to 8.0 days (mean, 6.4 days), and warfarin was given for 2.0 to 7.5 months (mean, 3.4 months). Compression stockings were used regularly (mean, 9.2 months; range, 0.25 to 64 months) in 30% of the patients after acute cDVT. The initial ipsilateral phlebograms were reevaluated to confirm the diagnosis of cDVT without popliteal involvement. The clinical assessment included evaluation of both legs according to CEAP clinical classification C0-6. Bilateral color-flow duplex scan imaging was performed to assess reflux in deep popliteal segments. Photoplethysmographic measurement of venous refilling time was conducted in both legs to observe deep reflux. RESULTS: The mean age was 57 years (range, 30 to 76 years) at the time of the clinical assessment. Cause of acute cDVT was idiopathy in 52%, coagulopathy in 2%, trauma in 10%, immobilization in 22%, and postoperative in 14% of the cases. During the follow-up period, seven recurrent DVTs (14%) were seen. In the clinical assessment, 17 legs (34%) with previous cDVT had skin changes (CEAP C4-6). No active ulcers were found. Contralaterally, the frequency of C4-6 was 10% (n = 5; P <.05). After exclusion of recurrent DVTs, the distribution of the clinical classification still remained the same. Deep popliteal reflux was detected in 20 legs (40%) with previous cDVT. Contralaterally, popliteal reflux was seen in nine cases (18%; P <.05). Plethysmography showed deep reflux in 16 legs (33%) with cDVT and in nine cases (18%) contralaterally (P >.05). A significant association was found between deep popliteal reflux and skin changes (P <.05). CONCLUSION: In the long-term follow-up, cDVT may lead to significant postthrombotic disease. Reflux in the primarily uninvolved popliteal vein is frequent and may be associated with more severe disease.

The development of postthrombotic syndrome in relationship to venous reflux and calf muscle pump dysfunction at 2 years after the onset of deep venous thrombosis.

OBJECTIVE: Postthrombotic syndrome (PTS) develops in 40% to 60% of patients with deep venous thrombosis. Factors that are important in the development of PTS include venous reflux, deep vein obstruction, and calf muscle pump dysfunction (CMD). METHODS: Reflux and CMD in relationship to the severity of PTS were evaluated in a 2-year follow-up study of patients with acute deep venous thrombosis. Duplex scanning was used to measure reflux. The supine venous pump function test (SVPT) measures CMD with strain-gauge plethysmography. The base-line examination was performed within 1 to 5 days after diagnosis. The next examinations were scheduled at 3, 6, 12, and 24 months. RESULTS: The study included 86 legs, and the 2-year follow-up period was completed for 70 legs. Significantly more reflux was found in previously thrombosed vein segments, with an odds ratio of 1.8 after 3 months, of 2.1 after 6 months, of 2.5 after 12 months, and of 3.2 after 24 months. Multiple regression results showed that the most important risk factor for early clinical signs of PTS was superficial reflux in months 3, 6, and 12 (P < or =.02). Deep reflux did not have a synergistic relationship with superficial reflux in correlation with the clinical signs of PTS. The SVPT was not able to predict the development of PTS. CONCLUSION: More reflux develops in previously thrombosed vein segments. As early as after the third month, patients with superficial reflux have an increased risk of development of the first clinical signs of PTS. Within 2 years, the SVPT shows no relationship with clinical signs of PTS.

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.

Improved hemodynamic effectiveness and associated clinical correlations of a new intermittent pneumatic compression system in patients with chronic venous insufficiency.

PURPOSE: A new intermittent pneumatic compression device (SCD Response System) has recently been shown in healthy volunteers to have the ability to detect the postcompression refilling of the calf veins and to respond by initiating the subsequent cycle when these veins are full. This has proven to be more effective in expelling blood proximally than the conventional intermittent pneumatic compression device (SCD Sequel System). The aim of this study was to test the influence of venous disease on the postcompression refill time detected by means of the SCD Response and the effectiveness of the new system in expelling blood in patients who have venous reflux caused by post-thrombotic syndrome or varicose veins. METHODS: This open, controlled trial was conducted in an academic vascular unit with 10 patients who had post-thrombotic syndrome and 10 patients who had varicose veins. The new SCD Response System was tested against the existing SCD Sequel System in both legs in the supine, semirecumbent, and sitting positions. The refilling time sensed by means of the device was correlated with the venous filling index by using air plethysmography. The total volume of blood expelled per hour during compression was compared with that expelled by the SCD Sequel System in the same volunteers and in the same positions. RESULTS: An inverse association was found between the mean postcompression refilling time in the sitting position and the venous filling index of the apparently healthy or less severely affected leg (r = -0.52, P =.019), the refill time being significantly shorter in patients with advanced venous disease. The SCD Response System increased the volume expelled per hour in the post-thrombotic leg, when compared with the SCD Sequel System, by 109.9% (P =.005) in the supine position, by 85.1% (P =.009) in the semirecumbent position, and by 40.2% (P =.005) in the sitting position. The corresponding results in the more severely affected leg in patients with varicose veins were 71.9% (P =.005) in the supine position, 77.9% (P =.005) in the semirecumbent position, and 55.7% (P =.013) in the sitting position. Similar improved results were also found in the contralateral leg in both groups. CONCLUSIONS: The deflation settings of the new SCD Response System are able to be adjusted selectively, correlating with the physiological severity of chronic venous insufficiency. By achieving more frequent compression cycles, the new system is more effective than the current one in expelling blood proximally, confirming our earlier findings in healthy volunteers. Further studies testing a possible improved efficacy in preventing deep venous thrombosis in this high-risk group are justified.

The post-thrombotic syndrome.

One of every three patients with deep-vein thrombosis of the lower extremities will develop, within 5 years, post-thrombotic sequelae that vary from minor signs to severe manifestations such as chronic pain, intractable edema, and leg ulceration. The post-thrombotic syndrome (PTS) develops as a result of the combination of venous hypertension due to persistent outflow obstruction or valvular incompetence and abnormal microvasculature or lymphatic function. Among factors potentially related to the development of PTS, recurrent ipsilateral thrombosis plays a major role. Whether the extent and the location of the initial thrombosis are associated with the development of PTS is still controversial. The diagnosis of PTS can be accepted on clinical grounds for patients with a history of venous thrombosis. The combination of a standardized clinical evaluation with the results of compression ultrasonography and Doppler ultrasonography helps diagnose or exclude a previous proximal-vein thrombosis. Prevention of recurrent thrombosis and use of compression elastic stockings are the cornerstones of PTS prevention. The management of this condition is demanding and often frustrating. Although several surgical procedures have been tested, conservative treatment is largely preferable, as more than 50% of patients either remain stable or improve during long-term follow-up, if carefully supervised and instructed to wear proper elastic stockings. Clinical presentation helps predict the prognosis, being the outcome of patients who refer with initially severe manifestations more favorable than that of patients whose symptoms progressively deteriorate over time.

[Changes in microcirculation and their correction in patients with varicose veins and post-thrombotic syndrome]. / Izmeneniia mikrotsirkuliatsii i vozmozhnosti ikh korrektsii u liudei pri varikoznoi bolezni i s posttromboticheskim sindromom.

Variety of disturbances of microcirculation can be stipulated by vasomotorial disfunction's of blood circulation in terminal vascular bed, changes of rheologic and coagulative characteristics of blood as well as morphological changes of structure of tissue and vessels of microcirculatory bed of destructed lower limb. In case of a varicose disease without complications changes of microvessels are considered to be compensatory adaptation. Patients suffering from a complicated type of varicose disease and post-thrombotic syndrome have "failure" of compensatory adaptation reaction. It results from significant functional disturbances of microcirculation and sudden morphological changes of structure of blood and lymphatic capillaries and tissue of a destructed lower limb. Correlative dependence can be found between degree of clinical evidences and a level of structural changes of microcirculatory bed. They are mostly significant in groups of patients having complicated varicose disease and post-thrombotic syndrome. It was shown that functional and morphological states of microcirculatory bed are of prognostic importance for estimation of effectiveness of operative interferences during diseases being analysed.

Leukocyte rheology before and after chemotactic activation in some venous diseases.

OBJECTIVE: to evaluate leukocyte rheology, polymorphonuclear leukocyte (PMN) membrane fluidity and cytosolic Ca2+ concentration in subjects with post-phlebitic leg syndrome (PPS) and acute deep-venous leg thrombosis (DVT). SUBJECTS: twenty-two subjects with leg PPS and 14 subjects with leg DVT. METHODS: we evaluated the leukocyte filtration (unfractionated, mononuclear cells (MN) and PMN), the PMN membrane fluidity and the PMN cytosolic Ca2+ concentration. Subsequently, we evaluated the same PMN variables after in vitro chemotactic activation with 4-phorbol 12-myristate 13-acetate (PMA) and N -formyl-methionyl-leucyl-phenylalanine (fMLP). RESULTS: at baseline we observed a significant difference in the filtration variables of unfractionated and MN cells and in PMN cytosolic Ca2+ concentration. After activation, in normal subjects and subjects with PPS and DVT, a significant variation in PMN filtration at 5 and 15 minutes was evident. In normal subjects, no variation was present in PMN membrane fluidity or cytosolic Ca2+ concentration after activation. In subjects with PPS and DVT, we found a decrease in PMN membrane fluidity and an increase in PMN cytosolic Ca2+ concentration. After PMN activation (at 5 and 15 min) Delta% of IRFR distinguished normal subjects from subjects with PPS and DVT, while no difference was found in Delta% of membrane fluidity or cytosolic Ca2+ concentration. CONCLUSIONS: there is a functional alteration of leukocytes in these patients whose mechanisms are not yet clear.

The postthrombotic syndrome in relation to venous hemodynamics, as measured by means of duplex scanning and strain-gauge plethysmography.

PURPOSE: Venous hemodynamics were evaluated in relation to the postthrombotic syndrome (PTS) 7 to 13 years after deep venous thrombosis (DVT). METHODS: The presence of flow, reflux, and compressibility of 1394 vein segments in 82 patients was assessed by means of duplex scanning. The venous outflow resistance was measured by means of strain-gauge plethysmography. The venous hemodynamics were related to the clinical severity of the PTS, characterized by the CEAP (clinical, etiologic, anatomic, pathophysiologic) classification. RESULTS: In patients with severe clinical symptoms of PTS, the prevalence of reflux was significantly higher. There was no relationship between the severity of the PTS and the noncompressibility or the combination of reflux and noncompressibility or an increased venous resistance. By means of multiple regression analysis with the variables of age, gender, reflux, and venous resistance, age and reflux were shown to be the main contributors to the severity of PTS. Significantly more patients (64%) with severe signs of PTS had a combination of deep and superficial reflux. In each of the traceable vein segments, the mean of the CEAP classification was calculated for the vein segments with and without reflux. In the proximal superficial femoral vein (P <.001), distal superficial femoral vein (P <.05), and popliteal vein (P <.05), a significantly higher mean CEAP classification was found in the veins with reflux, whereas in the distal, long, and short saphenous veins, no such relationship was found. CONCLUSION: Most patients with severe PTS had a combination of deep and superficial reflux. Reflux in the deep proximal veins contributes significantly to the PTS.