Percutaneous mechanical thrombectomy to remove post-thrombotic obstructions and manage post-thrombotic syndrome-associated venous leg ulceration.

BACKGROUND: Up to one half of patients with a diagnosis of deep vein thrombosis will develop post-thrombotic syndrome (PTS). Patients with PTS can develop venous leg ulcers (VLUs) due to post-thrombotic obstructions (PTOs) that contribute to prolonged ambulatory venous hypertension. The current treatments for PTS, which include chronic thrombus, synechiae, trabeculations, and inflow lesions, do not target PTOs, and such obstructions can affect stenting success. The aim of the present study was to determine whether removal of chronic PTOs using percutaneous mechanical thrombectomy would promote VLU resolution and positive outcomes. METHODS: In this retrospective analysis, the characteristics and outcomes for patients with VLUs secondary to chronic PTO who were treated using the ClotTriever System (Inari Medical) between August 2021 and May 2022 were assessed. Technical success was considered the ability to cross a lesion and introduce the thrombectomy device. Clinical success was defined as a decrease of ≥1 in the severity category for the ulcer diameter using the revised venous clinical severity score (score 0, no VLU; score 1, mild VLU [size <2 cm]; score 2, moderate VLU [size 2-6 cm]; score 3, severe VLU [size >6 cm]) at the latest follow-up visit. RESULTS: A total of 11 patients with 15 VLUs on 14 limbs were identified. Their mean age was 59.7 ± 11.8 years, and four patients (36.4%) were women. The median VLU duration was 11.0 months (interquartile range [IQR], 6.0-17.0 months), and 2 patients had VLUs secondary to a deep vein thrombosis event >40 years previously. All treatments were performed in a single session, with technical success achieved in 100% of the 14 limbs. A median of five passes (IQR, four to six passes) with the ClotTriever catheter were performed per limb. Chronic PTOs were successfully extirpated, and intraprocedural intravascular ultrasound showed effective disruption of venous synechiae and trabeculations. Stents were placed in 10 limbs (71.4%). The time to VLU resolution or the latest follow-up was 12.8 ± 10.5 weeks, and clinical success was achieved for all 15 VLUs (100%), with the revised venous clinical severity score for the ulcer diameter improving from a median of 2 (IQR, 2-2) at baseline to a median score of 0 (IQR, 0-0) at last follow-up. The VLU area had decreased by 96.6% ± 8.7%. Of the 15 VLUs, 12 (80.0%) had resolved completely, and 3 had demonstrated near-complete healing. CONCLUSIONS: All patients showed complete or near-complete VLU healing within a few months after mechanical thrombectomy. Mechanical extirpation and interruption of chronic PTOs allowed for luminal gain and restoration of cephalad inflow. With additional investigation, mechanical thrombectomy with the study device could prove a vital component to the treatment of VLUs secondary to PTOs.

Meta-analysis of lytic catheter-based intervention for acute proximal deep vein thrombosis in the reduction of post-thrombotic syndrome.

OBJECTIVE: Post-thrombotic syndrome (PTS) is a common complication of deep vein thrombosis (DVT) that can result in significant morbidity for the patient with detrimental impact on their quality of life. Evidence supporting lytic catheter-based interventions (LCBI) undertaken for early thrombus reduction in acute proximal DVT for the prevention of PTS is conflicting. Despite this, rates of LCBIs are increasing. To summaries the existing evidence and pool treatment effects, a meta-analysis of randomized controlled trials assessing the efficacy of LCBIs in proximal acute DVT for the prevention of PTS was undertaken. METHODS: This meta-analysis was undertaken aligning with PRISMA guidelines following a protocol pre-registered on PROSPERO. Online searches of Medline and Embase databases, as well as the gray literature, were performed up to December 2022. Included articles were randomized controlled trials that studied the use of LCBIs with additional anticoagulation vs anticoagulation alone and had determined follow-up periods. Outcomes of interest were PTS development, moderate to severe PTS, major bleeding episodes, and quality-of-life measures. Subgroup analyses were performed for DVTs involving the iliac vein and/r common femoral vein. Meta-analysis was performed using a fixed effects model. Quality assessment was performed using the Cochrane Risk of Bias and GRADE assessment tools. RESULTS: Three trials were included in the final meta-analysis, the Post-thrombotic Syndrome after Catheter-directed Thrombolysis for Deep Vein Thrombosis (CaVenT), Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT), and Ultrasound-accelerated Catheter-directed Thrombolysis Versus Anticoagulation for the Prevention of Post-thrombotic Syndrome (CAVA) trials, comprising 987 patients. Patients undergoing LCBIs had a reduced risk of PTS (relative risk [RR], 0.84; 95% confidence interval [CI], 0.74-0.95; P = .006) and a lower risk of developing moderate to severe PTS (RR, 0.75; 95% CI, 0.58-0.97; P = .03). LBCIs increased the risk of having a major bleed (RR, 2.03; 95% CI, 1.08-3.82; P = .03). In the iliofemoral DVT subgroup analysis, there was a trend toward decreasing the risk of developing PTS and moderate to severe PTS (P = .12 and P = .05, respectively). There was no significant difference in quality-of-life score (as measured by the Venous Insufficiency Epidemiological and Economic Study - Quality of Life/Symptoms) between the two groups (P = .51). CONCLUSIONS: Pooling of current best evidence suggests that LCBIs in acute proximal DVT decreases the rate of PTS and moderate to severe PTS with a number needed to treat of 12 and 18, respectively. However, this is complicated by a significantly higher rate of major bleeding with a number needed to treat of 37. This evidence supports the use of LCBIs in selected patients, including those who are at low risk of major bleeding.

Developing and optimizing a machine learning predictive model for post-thrombotic syndrome in a longitudinal cohort of patients with proximal deep venous thrombosis.

BACKGROUND: Post-thrombotic syndrome (PTS) is the most common chronic complication of deep venous thrombosis (DVT). Risk measurement and stratification of PTS are crucial for patients with DVT. This study aimed to develop predictive models of PTS using machine learning for patients with proximal DVT. METHODS: Herein, hospital inpatients from a DVT registry electronic health record database were randomly divided into a derivation and a validation set, and four predictive models were constructed using logistic regression, simple decision tree, eXtreme Gradient Boosting (XGBoost), and random forest (RF) algorithms. The presence of PTS was defined according to the Villalta scale. The areas under the receiver operating characteristic curves, decision-curve analysis, and calibration curves were applied to evaluate the performance of these models. The Shapley Additive exPlanations analysis was performed to explain the predictive models. RESULTS: Among the 300 patients, 126 developed a PTS at 6 months after DVT. The RF model exhibited the best performance among the four models, with an area under the receiver operating characteristic curves of 0.891. The RF model demonstrated that Villalta score at admission, age, body mass index, and pain on calf compression were significant predictors for PTS, with accurate prediction at the individual level. The Shapley Additive exPlanations analysis suggested a nonlinear correlation between age and PTS, with two peak ages of onset at 50 and 70 years. CONCLUSIONS: The current predictive model identified significant predictors and accurately predicted PTS for patients with proximal DVT. Moreover, the model demonstrated a nonlinear correlation between age and PTS, which might be valuable in risk measurement and stratification of PTS in patients with proximal DVT.

Double-barrel iliocaval reconstruction using closed-cell dedicated venous stents.

OBJECTIVE: Double-barrel iliocaval reconstruction is performed by deploying two stents simultaneously in a side-by-side, or "double-barrel," configuration in the inferior vena cava (IVC) with extension into the bilateral common iliac veins. The aim of this study was to examine the outcomes of double-barrel reconstruction using closed-cell dedicated venous stents for the treatment of iliocaval deep venous thrombosis and iliac vein compression syndrome. METHODS: All endovascular procedural reports comprising vascular surgery and interventional radiology operators from a single urban academic hospital between May 1, 2019, and April 30, 2021, were retrospectively searched. A cohort of 22 consecutive patients who underwent double-barrel iliocaval stenting with closed-cell dedicated venous stents for chronic or acute-on-chronic iliocaval venous disease without prior endovascular iliocaval repair was identified. Baseline characteristics, procedural data, and patient outcomes were determined via a manual review of preprocedure clinical notes, diagnostic imaging studies, procedure notes and images, and follow-up clinical notes. RESULTS: The median (range) age was 59 (27-81) years, and the cohort consisted of 59.1% female. The most common presenting symptoms of venous disease were lower extremity swelling (90.9%) and pain (50.0%). CEAP clinical classification was C3 in 86.4% of patients, whereas the remainder had C4 disease. Most patients (72.7%) had post-thrombotic syndrome, 22.7% had a nonthrombotic iliac vein lesion, and one patient (4.5%) had the congenital absence of the infrarenal IVC. A total of 40.9% of patients had a pre-existing IVC filter at the time of treatment. Six of the 22 patients underwent concurrent pharmacomechanical thrombectomy during the index iliocaval reconstruction and stenting procedure. The number of stents placed ranged from 2 to 5. With a mean follow-up period of 7.1 months, ranging from 12 days to 16.7 months, the freedom from reintervention rate was 90.9%. Twenty of 22 patients achieved subjective improvement or resolution of symptoms. The major adverse event rate was 9.1%, as two patients had access site complications requiring intervention. CONCLUSIONS: Double-barrel iliocaval reconstruction with closed-cell dedicated venous stents for the treatment of post-thrombotic syndrome or iliac vein compression syndrome is technically feasible and clinically effective with a low reintervention rate.

Risk factors and classification of reintervention following deep venous stenting for acute iliofemoral deep vein thrombosis.

BACKGROUND: Acute iliofemoral deep vein thrombosis (DVT) is associated with the development of post-thrombotic syndrome (PTS). Thrombolysis and deep venous stenting can restore vessel outflow and can reduce the incidence of PTS. However, for a proportion of patients, subsequent stenosis or reocclusion will necessitate further intervention. In the present study, we aimed to identify the risk factors, examine the outcomes (reintervention success and PTS), and develop a classification system for reintervention. METHODS: A retrospective single-center cohort study of patients who had undergone successful lysis for iliofemoral DVT from 2013 to 2017. The patients' records and imaging studies were examined for demographics, risk factors, extent of thrombus and vessel clearance, stenting, flow, reintervention, anticoagulation compliance, Villalta score, and secondary patency. From our findings, a system of classification for patients for whom procedures have failed was developed, constituting technical, hematologic, flow related, or multiple factors. RESULTS: Of 143 limbs (133 patients), 48 (33.6%) had required reintervention, of which 25 had presented with reocclusion (17.4%). The median time to reintervention was 45 days. The need for reintervention was associated with inferior vena cava thrombus (risk ratio [RR], 2.16; P < .01), stenting across the inguinal ligament (RR, 2.08; P < .01), and anticoagulation noncompliance (RR, 7.09; P < .01). Successful reintervention was achieved in 31 limbs (64.6%): 23 of 23 (100%) treated before occlusion vs 8 of 25 (36.4%) treated after occlusion (RR, 32.31; P < .01). A greater incidence of any PTS was observed for patients requiring reintervention (median Villalta score, 3 [interquartile range, 1-5]; vs 1 [interquartile range, 1-4]; RR, 2.28; P = .029). Cases without complete vessel occlusion (reintervention and control) had a lower rate of any PTS (14.0% vs 42.9%; RR, 3.06; P < .01) and moderate to severe PTS (3.0% vs 14.3%; RR, 4.76; P = .046) Technical issues were observed in 54.2% of reintervention cases and 6.3% of cases not requiring reintervention (P < .01). Hematologic issues were identified in 33.3% of reintervention cases and 1.1% of cases not requiring reintervention (P < .01). Flow-related issues were observed in 43.8% of the reintervention cases and no cases not requiring reintervention (P < .01). Of the reintervention cases, 27.1% were multifactorial and were associated with a lower rate of vessel salvage; however, this did not translate into a significant difference in secondary patency on survival analysis (RR, 1.70; P = .429). CONCLUSIONS: A large proportion of patients required reintervention because of potentially preventable factors. Anticoagulation compliance, thrombus burden, and poor flow are important risk factors to consider in patient selection. Reintervention increased the risk of PTS and was more often successful when achieved before vessel occlusion.

Interim outcomes of mechanical thrombectomy for deep vein thrombosis from the All-Comer CLOUT Registry.

OBJECTIVES: The multicenter, prospective, single arm CLOUT registry assesses the safety and effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) for the treatment of acute and nonacute lower extremity deep vein thrombosis (DVT) in all-comer patients. Reported here are the outcomes of the first 250 patients. METHODS: All-comer patients with lower extremity DVT were enrolled, including those with bilateral DVT, those with previously failed DVT treatment, and regardless of symptom duration. The primary effectiveness end point is complete or near-complete (≥75%) thrombus removal determined by independent core laboratory-adjudicated Marder scores. Safety outcomes include serious adverse events through 30 days and clinical outcomes include post-thrombotic syndrome severity, symptoms, pain, and quality of life through 6 months. RESULTS: The median age was 62 years and 40% of patients had contraindications to thrombolytics. A range of thrombus chronicity (33% acute, 35% subacute, 32% chronic) was observed. No patients received thrombolytics and 99.6% were treated in a single session. The median thrombectomy time was 28 minutes. The primary effectiveness end point was achieved in 86% of limbs. Through 30 days, one device-related serious adverse event occurred. At 6 months, 24% of patients had post-thrombotic syndrome. Significant and sustained improvements were observed in all clinical outcomes, including the Revised Venous Clinical Severity Score, the numeric pain rating scale, and the EuroQol Group 5-Dimension Self-Report Questionnaire. CONCLUSIONS: The 6-month outcomes from the all-comer CLOUT registry with a range of thrombus chronicities demonstrate favorable effectiveness, safety, and sustained clinical improvements.

Hybrid operative thrombectomy is noninferior to percutaneous techniques for the treatment of acute iliofemoral deep venous thrombosis.

OBJECTIVE: Hybrid operative thrombectomy (HOT) is a novel technique for the treatment of acute iliofemoral deep venous thrombosis (IFDVT) and is an alternative to percutaneous techniques (PTs) that use thrombolytics. In this study, we compare perioperative and intermediate outcomes of HOT vs PT as interventions for early thrombus removal. METHODS: From July 2008 to May 2015, there were 71 consecutive patients who were treated with either PT (n = 31) or HOT (n = 40) for acute or subacute single-limb IFDVT. HOT consisted of surgical thrombectomy with balloon angioplasty with or without stenting by a single incision and fluoroscopically guided retrograde valve manipulation to extract the thrombus. PT included catheter-directed thrombolysis with or without pharmacomechanical thrombectomy using the Trellis-8 system (Bacchus Vascular, Santa Clara, Calif). Patients who presented with bilateral DVT (n = 4), inferior vena cava involvement (n = 8), or venous gangrene (n = 1) were excluded. Perioperative outcomes, quality measures, and thrombus resolution were compared between the two treatment groups. Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification, Villalta score, and venous duplex ultrasound at intermediate follow-up were also analyzed. RESULTS: The left limb was the most common site of the IFDVT overall. Technical success (≥50% resolution) was 100% for both groups, and >80% resolution was achieved in all patients treated with HOT. There were eight major bleeding events in the PT group compared with three in the HOT group (P = .04). PT patients had a significantly longer length of stay (13 vs 10 days; P = .028) compared with HOT. At 2-year duplex ultrasound examination, there was no difference between HOT and PT in mean reflux times at the femoral-popliteal segment. At 2 years, 85% and 87% of the patients (HOT vs PT, respectively) had not developed post-thrombotic syndrome, and there was no difference between the groups for mean Villalta score (2.1 ± 1.9 vs 2.3 ± 2; P = .79). CONCLUSIONS: PT and HOT have demonstrated good outcomes in the perioperative and intermediate periods. HOT is noninferior to PT as a technique for early thrombus removal and has the advantages that thrombus resolution is established in one operation and length of stay is significantly decreased. HOT avoids thrombolytic therapy, which may reduce major bleeding events.

[Treatment of postoperative thrombosis]. / Therapie der postoperativen Thrombose.

For the treatment of deep vein thrombosis (DVT), rapid diagnosis and prompt therapy are crucial to minimize the risk of fatal pulmonary embolism and long-term complications, including the postthrombotic syndrome and recurrent thromboembolism. The treatment of acute DVT remains controversial. In this review, treatment options in relation to exposing and predisposing risk factors are discussed. Evidence-based data and recommendations from official guidelines are presented.

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.

Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months.

BACKGROUND: The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear. AIM: To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis. METHODS: In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry. RESULTS: Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes. CONCLUSION: The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.

Neovalve construction in postthrombotic syndrome.

OBJECTIVE: The purpose of this study was to evaluate a new neovalve construction technique in postthrombotic syndrome. The surgical procedure is described, and preliminary results of the first case series are given. METHODS: From December 2000 to June 2004, neovalve construction in 18 limbs was performed on 16 patients (8 male and 8 female; median age, 55.5 years; range, 34-79 years) to treat severe chronic venous insufficiency in cases of postthrombotic syndrome. Surgical treatment was recommended in cases of nonhealing or recurrent ulcers (CEAP classification class C6). Preoperative duplex scanning, ascending/descending venography, and air plethysmography were routinely performed. Valvular cusps were created by dissecting the thickened venous wall to obtain material with which to fashion a new monocuspid or bicuspid valve. Mean follow-up was 22 months (range, 1-42 months). Postoperative duplex scanning and air plethysmography were performed in all patients. Descending venography was performed after surgery in 15 limbs. RESULTS: In 16 lower extremities (89%), the ulcer healed within 4 to 25 weeks (median, 12 weeks), and no recurrences occurred. Neovalve competence was confirmed in 17 cases (95%). Postoperative duplex scan and air plethysmography showed a significant improvement in hemodynamic parameters (P < .001), especially in younger patients with good muscle pump function. In 17 limbs (95%), the treated segments remained primarily patent at median follow-up of 22 months. Early thrombosis below the neovalve site occurred in two patients (12%). No perioperative pulmonary embolism was observed. A late occlusion occurred in one patient (6%), 8 months after surgery. Minor postoperative complications occurred in three patients (17%). CONCLUSIONS: Neovalve construction seems to be effective in restoring femoral competence in postthrombotic reflux. Although these preliminary results are encouraging, long-term follow-up and a larger series are required to validate the technique.

The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease.

BACKGROUND: The post-thrombotic syndrome (PTS) is a frequent complication of deep vein thrombosis (DVT). Patients with recurrent ipsilateral DVT have an increased risk of PTS; other risk factors are unknown. OBJECTIVES: To establish risk factors of PTS and its impact on venous thrombotic disease. PATIENTS: We prospectively followed 406 patients after a first symptomatic DVT for a median of 60 months. Patients with recurrent DVT, a natural inhibitor deficiency, the lupus anticoagulant, cancer, long-term anticoagulation, an observation time < 18 months and DVT-recurrence prior PTS-assessment were excluded. Study outcomes were occurrence of PTS and recurrent symptomatic DVT. RESULTS: PTS was assessed after 44 +/- 23 months (mean +/- SD) using a clinical classification score. PTS developed in 176 of 406 patients (43.3%). Severe PTS was rare (1.4%). Proximal DVT was the strongest risk factor of PTS [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3-3.7]. Male gender (OR 1.6, 95% CI 1.0-2.8) and elevated D-dimer levels (OR 1.9, 95% CI 1.0-3.9) were weaker risk factors. Factor V Leiden, factor II G20210A or high factor VIII did not confer an increased risk of PTS. At 4 years, the cumulative probability of recurrence was 7.4% (95% CI 3.2-11.7) among patients with PTS when compared with 1.6% (95% CI 0-3.5; P < 0.02) among patients without PTS. The risk of recurrence was 2.6-fold (95% CI 1.2-5.9) increased when PTS was present. CONCLUSIONS: Proximal DVT, male gender, and high D-dimer levels are independently associated with the development of PTS in patients with a first DVT. Patients with PTS have an increased risk of recurrent venous thromboembolism.

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.

[The potential of conservative therapy and surgical treatment of microcirculatory distress in chronic venous insufficiency of the lower extremities in a stage of trophic disorders]. / Vozmozhnosti konservativnoi terapii i khirurgicheskogo lecheniia narushenii mikrotsirkuliatsii pri khronicheskoi venoznoi nedostatochnosti nizhnikh konechnostei stadii troficheskikh rasstroistv.

The present work describes the results of an all-round examination and treatment of 120 patients suffering from different forms of chronic venous insufficiency (CVI) of the lower extremities with trophic disorders of soft tissues. Of these, varicosis was present in 91 (75.8%) patients and postthrombotic disease - in 29 (24.2%), patients. Hemomicrocireulation was examined by laser Doppler flow-metry. Assessment was made of the functional activity of neutrophilic granulocytes of the microcirculatory bed. The data were obtained indicating the decrease of skin perfusion and activation of neutrophils in the hemomicrocirculatory bed of the involved extremity at venous outflow decompensation. Of the 120 persons, conservative treatment was provided to 23 patients, in 45 patients, the conservative measures represented a stage in the preoperative preparation. Ninety-seven patients were operated on. The studies of hemomicrocirculation carried out at different times after treatment have demonstrated that conservative treatment produces a beneficial effect on hemomicrocirculatory disorders in the lower extremities of patients with CVI. However, the effects of conservative therapy are unstable and not long-lasting. Surgical correction of the venous outflow in patients with decompensated forms of CVI of the lower extremities leads to a stable improvement of the functional parameters of microcirculation.

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.

Post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) is a potentially disabling complication occurring in up to 67% of adult patients following deep venous thrombosis (DVT). PTS has recently been recognised in children. We present three cases of symptomatic PTS in children, which occurred following the use of central venous lines (CVLs). In two cases, no symptoms of acute thrombosis were noted. The cases highlight the clinical presentation of this syndrome. A review of the literature revealed two reports describing PTS occurring in children following DVT with an estimated incidence of 7-12%. It is concluded that PTS is an important complication of DVT in children. The clinical findings of pain, swelling, and brawny induration are similar to adult patients. The effect on growing limbs is not known. Paediatricians should be aware of the potential of PTS in all children who are at risk of DVT, including patients with malignancy, congenital heart disease, and children who have had previous CVLs, even in the absence of documented acute DVT.

Long term complications of inferior vena cava thrombosis.

AIM: To evaluate the long term outcome after paediatric inferior vena cava (IVC) thrombosis. METHODS: A combined retrospective and prospective study on infants and children with IVC thrombosis treated at Aachen and Maastricht University Hospitals between 1980 and 1999. RESULTS: Forty patients were enrolled, including four with preceding cardiac catheterisation, 18 with central venous saphenous lines, and an additional eight with umbilical venous catheters. Six patients died within three months of diagnosis; one patient was lost to follow up. Twelve of the remaining 33 patients had suffered from limited IVC thrombosis; during follow up (for up to nine years) none showed persisting caval obstruction (successful thrombolysis, n = 2; spontaneous recanalisation, n = 10). The remaining 21 patients presented with extensive IVC thrombosis. During follow up (for up to 18 years) complete restitution was found in only four cases (one thrombolysis, two surgery, one spontaneous recanalisation). Persisting iliac and/or caval venous obstruction occurred in 17 patients, including six with thrombolysis. Varicose veins were found in 12, and post-thrombotic syndrome in seven of these cases. According to Kaplan-Meier analysis, 30% of patients with persisting venous disease will develop post-thrombotic syndrome within 10 years of the thrombotic event. CONCLUSIONS: Infants and children with extensive IVC thrombosis are at high risk for persisting venous disease and serious long term complications. Prospective trials are urgently needed to establish effective treatment strategies and to improve long term prognosis. Central venous catheters, contributing to IVC thrombosis in the majority of cases reported here, should be inserted only if essential.