Deep venous thrombosis and postthrombotic syndrome: invasive management.

Invasive management of postthrombotic syndrome encompasses the two ends of the deep vein thrombosis spectrum, patients with acute iliofemoral deep vein thrombosis and those with chronic postthrombotic iliofemoral venous obstruction. Of all patients with acute deep vein thrombosis, those with involvement of the iliofemoral segments have the most severe chronic postthrombotic morbidity. Catheter-based techniques now permit percutaneous treatment to eliminate thrombus, restore patency, potentially maintain valvular function, and improve quality of life. Randomized trial data support an initial treatment strategy of thrombus removal. Failure to eliminate acute thrombus from the iliofemoral system leads to chronic postthrombotic obstruction of venous outflow. Debilitating chronic postthrombotic symptoms of the long-standing obstruction of venous outflow can be reduced by restoring unobstructed venous drainage from the profunda femoris vein to the vena cava.

Prevention and treatment of venous thromboembolism--International Consensus Statement.

The aim of this document is to provide a clear and concise account of the evidence regarding efficacy or harm for various methods available to prevent and manage venous thromboembolism (VTE).

Quantity of residual thrombus after successful catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with recurrence.

OBJECTIVES: Iliofemoral deep venous thrombosis (IFDVT) is an independent risk factor for recurrent DVT. It has been observed that recurrent DVT correlates with residual thrombus. This study evaluates whether risk of recurrence is related to the amount of residual thrombus following catheter-directed thrombolysis (CDT) for IFDVT. METHODS: Patients who underwent CDT for IFDVT had their degree of lysis quantified by a reader blind to the patients' long-term clinical outcome. Patients were classified into two groups, ≥50% and <50% residual thrombus. Recurrence was defined as a symptomatic presentation with image verification of new or additional thrombus. RESULTS: A total of 75 patients underwent CDT for IFDVT. Median follow-up was 35.9 months. Sixty-eight patients (91%) had no evidence of recurrence and seven (9%) developed recurrence. Of the patients who had ≥50% (mean 80%) residual thrombus, 50% (4/8) experienced recurrence, but in those with <50% (mean 35%) residual thrombus, only 5% (3/67) had recurrent DVT (P = 0.0014). CONCLUSION: The burden of residual thrombus at completion of CDT correlates with the risk of DVT recurrence. Patients having CDT for IFDVT had a lower risk of recurrence than expected. Successful clearing of acute clot in IFDVT patients significantly reduces the recurrence risk compared to patients with a large residual thrombus burden.

Safety of catheter-delivered plasmin in patients with acute lower extremity arterial or bypass graft occlusion: phase I results.

BACKGROUND: Current treatment of acute peripheral artery or bypass graft occlusion utilizes catheter-directed thrombolysis of a plasminogen activator (PA). Plasmin is a direct-acting thrombolytic with a striking safety advantage over PA in preclinical models. OBJECTIVES: To report the first use of purified plasmin for acute lower extremity arterial or bypass graft thrombosis in a phase I dose-escalation study of a catheter-delivered agent. METHODS: Eighty-three patients with non-embolic occlusion of infrainguinal native arteries or bypass grafts were enrolled (safety population) into seven sequential dose cohorts to receive 25-175 mg of plasmin by intrathrombus infusion over 5 h. Arteriograms were performed at baseline, 2 h, and 5 h, and subjects were monitored for 30 days for clinical outcomes and laboratory parameters of systemic fibrinolysis. RESULTS: Major bleeding occurred in four patients (4.8%), and minor bleeding alone in 13 (15.7%), with no trend towards more bleeding at higher dosages of plasmin. There was a trend towards lower plasma concentrations of fibrinogen, α(2) -antiplasmin and α(2) -macroglobulin with increasing doses of plasmin, but the nadir fibrinogen concentration was > 350 mg dL(-1) at the highest plasmin dose. Individual nadir values were above 200 mg dL(-1) in 82 of 83 subjects, and were not different in patients with or without bleeding. Thrombolysis (≥ 50%) occurred in 79% of subjects receiving 125-175 mg of plasmin, as compared with 50% who received 25-100 mg. CONCLUSIONS: Catheter-delivered plasmin can be safely administered to patients with acute lower extremity arterial occlusion at dosages of 25-175 mg.

The future of deep venous thrombosis and post-thrombotic syndrome in 2020.

This manuscript addresses six major issues involving deep venous thrombosis (DVT) and post-thrombotic syndrome. Prevention will likely see modest advances in pharmacological therapy, mainly by extending prophylaxis in high-risk patients. More notable advances will be observed in mechanical means of prophylaxis, focusing on sustained application of devices that can move larger volumes of blood. Silent, large-vein thrombi continue to place patients at risk for fatal pulmonary embolism. Improved imaging techniques will permit us to identify these patients over the next eight years. In many of those patients, vena caval interruption will be required. Elimination of high-risk filters and the production of improved filters placed through low-profile systems with antithrombotic agents bound to their surface will improve the short- and long-term results for inferior vena cava filters. The long-term management of DVT will focus on establishing appropriate duration for the individual patient and will see the evolution towards direct Xa and IIa inhibitors. Patients with extensive DVT will more commonly receive treatment strategies designed to eliminate thrombus and restore patency. This will substantially reduce post-thrombotic morbidity and reduce recurrence. Post-thrombotic syndrome will see greater attention towards treating the intraluminal fibrosis, thereby eliminating post-thrombotic venous obstruction. Unfortunately, neovalves will still be searching for the appropriate application.

Treatment of acute iliofemoral deep venous thrombosis: a strategy of thrombus removal.

Patients with acute iliofemoral deep vein thrombosis (DVT) suffer the most severe postthrombotic sequelae. The majority of physicians treat all patients with acute DVT with anticoagulation alone, despite evidence that postthrombotic chronic venous insufficiency, leg ulceration, and venous claudication are common in patients treated only with anticoagulation. The body of evidence to date in patients with iliofemoral DVT suggests that a strategy of thrombus removal offers these patients the best long-term outcome. Unfortunately, currently published guidelines use outdated experiences to recommend against the use of techniques designed to remove thrombus, ignoring recent clinical studies showing significant benefit in patients who have thrombus eliminated. Contemporary venous thrombectomy, intrathrombus catheter-directed thrombolysis, and pharmacomechanical thrombolysis are all options that can be offered to successfully remove venous thrombus with increasing safety. The authors review evidence supporting the rationale for thrombus removal and discuss the most effective approaches for treating patients with acute iliofemoral DVT.

Peripheral arterial disease detection, awareness, and treatment in primary care.

CONTEXT: Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis that is common and is associated with an increased risk of death and ischemic events, yet may be underdiagnosed in primary care practice. OBJECTIVE: To assess the feasibility of detecting PAD in primary care clinics, patient and physician awareness of PAD, and intensity of risk factor treatment and use of antiplatelet therapies in primary care clinics. DESIGN AND SETTING: The PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) program, a multicenter, cross-sectional study conducted at 27 sites in 25 cities and 350 primary care practices throughout the United States in June-October 1999. PATIENTS: A total of 6979 patients aged 70 years or older or aged 50 through 69 years with history of cigarette smoking or diabetes were evaluated by history and by measurement of the ankle-brachial index (ABI). PAD was considered present if the ABI was 0.90 or less, if it was documented in the medical record, or if there was a history of limb revascularization. Cardiovascular disease (CVD) was defined as a history of atherosclerotic coronary, cerebral, or abdominal aortic aneurysmal disease. MAIN OUTCOME MEASURES: Frequency of detection of PAD; physician and patient awareness of PAD diagnosis; treatment intensity in PAD patients compared with treatment of other forms of CVD and with patients without clinical evidence of atherosclerosis. RESULTS: PAD was detected in 1865 patients (29%); 825 of these (44%) had PAD only, without evidence of CVD. Overall, 13% had PAD only, 16% had PAD and CVD, 24% had CVD only, and 47% had neither PAD nor CVD (the reference group). There were 457 patients (55%) with newly diagnosed PAD only and 366 (35%) with PAD and CVD who were newly diagnosed during the survey. Eighty-three percent of patients with prior PAD were aware of their diagnosis, but only 49% of physicians were aware of this diagnosis. Among patients with PAD, classic claudication was distinctly uncommon (11%). Patients with PAD had similar atherosclerosis risk factor profiles compared with those who had CVD. Smoking behavior was more frequently treated in patients with new (53%) and prior PAD (51%) only than in those with CVD only (35%; P <.001). Hypertension was treated less frequently in new (84%) and prior PAD (88%) only vs CVD only (95%; P <.001) and hyperlipidemia was treated less frequently in new (44%) and prior PAD (56%) only vs CVD only (73%, P<.001). Antiplatelet medications were prescribed less often in patients with new (33%) and prior PAD (54%) only vs CVD only (71%, P<.001). Treatment intensity for diabetes and use of hormone replacement therapy in women were similar across all groups. CONCLUSIONS: Prevalence of PAD in primary care practices is high, yet physician awareness of the PAD diagnosis is relatively low. A simple ABI measurement identified a large number of patients with previously unrecognized PAD. Atherosclerosis risk factors were very prevalent in PAD patients, but these patients received less intensive treatment for lipid disorders and hypertension and were prescribed antiplatelet therapy less frequently than were patients with CVD. These results demonstrate that underdiagnosis of PAD in primary care practice may be a barrier to effective secondary prevention of the high ischemic cardiovascular risk associated with PAD.

Intermittent claudication: magnitude of the problem, patient evaluation, and therapeutic strategies.

Intermittent claudication (IC), the symptom of exercise-induced muscle ischemia of peripheral arterial disease (PAD), afflicts and limits the activities of a significant number of patients. Incidence and prevalence of IC depends on the population studied and the diagnostic instruments used. In large studies, prevalence has ranged from 3% to 10%, with a sharp increase in those aged > or =70 years. Over the next 20 years, the total number of patients affected is expected to increase significantly due to anticipated demographic changes. Analysis of the natural history of IC demonstrates that the risk of cardiovascular morbidity and mortality far exceeds that of severe limb ischemia or limb loss. In fact, only 2% to 4% of all patients with IC will require a major amputation in their lifetime. However, life expectancy is approximately 10 years less than that of an age-matched cohort. By now, PAD is well recognized as a marker of systemic atherosclerosis. The cornerstone of patient evaluation is a history and physical examination, including a detailed atherosclerotic risk-factor assessment. In the differential diagnosis of IC, clinicians should consider etiologies such as arthritis, spinal stenosis, radiculopathy, venous claudication, or inflammatory processes. In >80% of all patients, it is possible to locate the responsible arterial segment by combining the location and severity of pain with a pulse examination. Noninvasive diagnostic studies help determine the level of disease, may unmask a hemodynamically significant stenosis, and are useful in follow-up. Arteriography is reserved for patients in whom the decision for revascularization has been made. Knowing the anatomic detail of a lesion allows the clinician to determine whether and what type of intervention is feasible. Standard therapy for all patients should be directed at both peripheral and systemic atherosclerosis, beginning with risk-factor modification in the form of smoking cessation, optimal diabetes control, and lipid normalization. The benefits of supervised exercise rehabilitation include significantly increased walking distance and enhanced quality of life. Platelet inhibition has been shown to reduce the risk of ischemic stroke, myocardial infarction, and vascular death and should be prescribed for all but those in whom it is medically contraindicated. Symptom-specific pharmacotherapy with a broad range of medications has yielded disappointing results in the past. However, recent studies have demonstrated that patients receiving the novel agent cilostazol experienced increases in walking distance and improvements in quality of life.

Endovascular and surgical revascularization for patients with intermittent claudication.

Intermittent claudication (IC), the most common symptom of peripheral arterial disease (PAD), most often results from flow-reducing lesions in the arteries of the lower extremity that cause exercise-induced muscle ischemia. Intermittent claudication has a significant impact on quality of life and calls attention to PAD, which is secondary to systemic atherosclerosis and a major marker for cardiovascular morbidity and mortality. Most IC patients improve with a regimen that includes aggressive risk-factor modification, exercise, platelet inhibition, and pharmacotherapy to improve walking distance. Selected patients may require endovascular or surgical intervention if it can be offered with low risk. Endovascular procedures, most often percutaneous balloon angioplasty with or without stenting, are recommended for short-segment stenotic lesions in the aortoiliac and infrainguinal arterial segments. Combined platelet inhibition and endoluminal radiation are under study and may be useful to improve long-term outcome with these procedures. Percutaneous hemostatic puncture closure devices can also be used to reduce bleeding complications and allow more aggressive and immediate antithrombotic therapy, further improving results. Operative revascularization is recommended for patients with long-segment and multisegment disease, especially if obstruction is present. Aortofemoral reconstruction is associated with a low operative mortality and an 80% to 85% 5-year patency rate. Iliac reconstruction is recommended for isolated unilateral iliac arterial disease. Infrainguinal arterial reconstruction is associated with a 60% to 80% 5-year patency rate, with better outcomes noted for autogenous conduits than for prosthetic devices. Mechanical modification and pharmacotherapy with platelet inhibitors and anticoagulants improve long-term patency.

Intraoperative lytic therapy: agents and methods of administration.

Intraoperative intraarterial thrombolysis is a valuable adjunct for the removal of residual arterial thrombi after mechanical thromboembolectomy. Early reports by some investigators indicated high rates of bleeding complications, most likely caused by inappropriately high doses of plasminogen activators infused over long periods of time, which led to systemic lytic effects. Animal models and controlled human experiments subsequently have shown the potential efficacy and safety of intraarterial thrombolysis. Since urokinase (UK) has been withdrawn from the market, recombinant tissue-type plasminogen activator (rt-PA) has become the plasminogen activator of choice. Reteplase and other plasminogen activators may be beneficial (and safe); however, data on intraoperative use currently are not available. The most common methods of delivery into the distal arterial tree are bolus infusion with inflow occlusion, drip infusion after restoration of arterial inflow, and the isolated limb perfusion technique. The number of distal vessels involved, the amount of residual thrombus, and severity of ischemia guide the dose of plasminogen activator, volume of perfusate, and the technique and duration of infusion.

Catheter-directed thrombolysis for iliofemoral deep venous thrombosis improves health-related quality of life.

PURPOSE: Treatment designed to eliminate thrombus in patients with iliofemoral deep venous thrombosis (DVT) is theoretically attractive; however, its benefits, compared with those of anticoagulation, have not been definitively demonstrated. Although not previously analyzed, an effective measure of treatment success is likely to be the assessment of health-related quality of life (HRQOL). This study evaluated whether catheter-directed thrombolysis for iliofemoral DVT is associated with improved HRQOL, compared with standard anticoagulation, and whether HRQOL outcome in the thrombolysis group is related to lytic success. METHODS: An 80-item self-administered HRQOL questionnaire was developed. It contained the Health Utilities Index, Short Form-12, and disease-targeted scales, including health distress, stigma, health interference, physical functioning, and symptoms (eg, leg swelling, pain, ulcers). The HRQOL questionnaire was confirmed to be reliable and valid by means of psychometric testing. Questionnaires were administered to 98 retrospectively identified patients who had had iliofemoral DVT treated at least 6 months earlier. Sixty-eight patients who were identified through a DVT registry were treated with catheter-directed thrombolysis with urokinase (UK), and 30 patients who were identified by means of a medical record review were treated with anticoagulation alone. The treatment decision was made by the attending physician, and all patients were candidates for both thrombolysis and anticoagulation. RESULTS: Most patients were women (61%), white (95%), married (65%), and had a mean interval since initial DVT of 16 months. The group treated with UK was younger (53 +/- 17 years) than the group treated with heparin (61 +/- 6 years; P =.039). After treatment, patients treated with UK reported better overall physical functioning (P =.046), less stigma (P =.033), less health distress (P =.022), and fewer post-thrombotic symptoms (P =. 006), compared with the patients treated with anticoagulation alone. Within the UK group, phlebographically successful lysis correlated with improved HRQOL (P =.038). Patients classified as lytic failures had similar outcomes to patients treated with heparin. CONCLUSION: Patients with iliofemoral DVT treated with catheter-directed thrombolysis have better functioning and well-being, compared with patients treated with anticoagulation alone. Successful lysis was directly correlated with improved HRQOL, with patients who were classified as lytic failures having similar outcomes to patients treated with heparin. These data support the need for a future randomized trial, which should include an HRQOL measure as part of the outcome analysis.

Venous severity scoring: An adjunct to venous outcome assessment.

Some measure of disease severity is needed to properly compare the outcomes of the various approaches to the treatment of chronic venous insufficiency. Comparing the outcomes of two or more different treatments in a clinical trial, or the same treatment in two or more reports from the literature cannot be done with confidence unless the relative severity of the venous disease in each treatment group is known. The CEAP (Clinical-Etiology-Anatomic-Pathophysiologic) system is an excellent classification scheme, but it cannot serve the purpose of venous severity scoring because many of its components are relatively static and others use detailed alphabetical designations. A disease severity scoring scheme needs to be quantifiable, with gradable elements that can change in response to treatment. However, an American Venous Forum committee on venous outcomes assessment has developed a venous severity scoring system based on the best usable elements of the CEAP system. Two scores are proposed. The first is a Venous Clinical Severity Score: nine clinical characteristics of chronic venous disease are graded from 0 to 3 (absent, mild, moderate, severe) with specific criteria to avoid overlap or arbitrary scoring. Zero to three points are added for differences in background conservative therapy (compression and elevation) to produce a 30 point-maximum flat scale. The second is a Venous Segmental Disease Score, which combines the Anatomic and Pathophysiologic components of CEAP. Major venous segments are graded according to presence of reflux and/or obstruction. It is entirely based on venous imaging, primarily duplex scan but also phlebographic findings. This scoring scheme weights 11 venous segments for their relative importance when involved with reflux and/or obstruction, with a maximum score of 10. A third score is simply a modification of the existing CEAP disability score that eliminates reference to work and an 8-hour working day, substituting instead the patient's prior normal activities. These new scoring schemes are intended to complement the current CEAP system.