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PubMed1982

Leg ulcer. Conservative management or surgical treatment?

In a specific indigent socioeconomic setting, the nonsurgical management of 65 patients with chronic leg ulcers resulted in 59 cures. There were 42 patients (67%) with postphlebitic syndrome. Twenty-two patients (33%) had varicose veins (eight had postoperative vein stripping), 14 (22%) had deep-vein thrombosis, and 11 (15%) had associated neurological problems. Fifty-six patients (86%) were treated with pressure dressings that were changed once a week in an outpatient clinic, seven patients wore skintight plaster casts for variable periods of time, and two patients had split thickness skin grafts plus lumbar sympathectomies. In more than two thirds of the patients, the ulcers healed. In another 17 patients (26%), a satisfactory response to treatment was observed. In only six patients did therapy fail. Failures were attributed to the multiple medical and surgical problems of the patients or their lack of cooperation. Nonsurgical treatment of venous stasis ulcer is inexpensive and effective.

Adult↗

PubMed1998

Review of pharmacodynamics, pharmacokinetics, and therapeutic properties of sulodexide.

Due to various side effects of heparin, such as heparin-induced thrombocytopenia type I or type II, alternative anticoagulants are in clinical development to optimize the anticoagulant regimes in patients requiring low or high anticoagulation dosages. Sulodexide is a highly purified preparation containing a fast-moving heparin fraction as well as dermatansulfate. The pharmacological effects of sulodexide differ substantially from unfractionated heparin and are mainly characterized by a prolonged half-life and reduced effect on global coagulation and bleeding parameters. The lipolytic activity of sulodexide is increased in comparison to unfractionated heparin. Clinical studies demonstrate the safety and efficacy of sulodexide. Specially, oral administration leads to fibrinolytic activities in contrast to oral administration of other glycosaminoglycans. Thus, sulodexide releases tissue plasminogen activator and decreases fibrinogen levels as well as HDL and total cholesterol levels and blood viscosity. Clinical efficacy is demonstrated in peripheral arterial disease, cardiovascular events, in postphlebitic syndrome and on albuminuria in nephropathy.

Animals↗

PubMedDate not supplied

Catheter-directed thrombolysis for thromboembolic disease during pregnancy: a viable option.

Anticoagulation with intravenous heparin has been the standard treatment for the management of gestational thromboembolic complications. Catheter-directed thrombolysis is an encouraging approach for the treatment of thromboembolic disease and has not been previously reported during pregnancy. One gravid woman with pulmonary embolism, critically ill, and hemodynamically compromised, and two gravid women with iliofemoral venous thrombosis, who failed to respond to standard treatment with intravenous heparin, were treated with catheter-directed urokinase. All three patients experienced rapid resolution of symptoms and successful pregnancy outcomes. In our three patients, catheter-directed thrombolysis for thromboembolic disease during pregnancy allowed rapid resolution of hemodynamic abnormalities and/or resolution of thrombus. Catheter-directed thrombolysis offered a reasonably safe alternative to prolonged medical management in these young, otherwise healthy, patients. Long-term, it may prevent the postphlebitic syndrome.

Adult↗

PubMed1992

Pharmacodynamics, clinical indications, and adverse effects of heparin.

Heparins are a heterogenous group of naturally occurring glycosaminoglycans characterized by anticoagulant activity and a wide range of molecular weights (low molecular weight or fractionated heparins evolving within the past two decades). Cofactors for endogenous inhibitors of coagulation (antithrombin III and heparin cofactor II), heparin administration results in a hypocoagulable state. Various platelet activities, including inhibition of activity induced by platelet-derived growth factors on vascular smooth muscle, also have been noted. Divorced of anticoagulant nature, novel applications may include a role in atherosclerosis prevention, acceleration of collateral coronary as well as peripheral circulation (i.e., angiogenesis), and continued (chronic) post-myocardial infarction therapy. Established indications include treatment of various thrombotic diseases, unstable angina, and thrombosis chemoprophylaxis in medical/surgical patients. The antithrombotic potential of the heparins is used also in thrombosis management related to extracorporeal circulatory assistance or dialysis devices. Heparin's therapeutic potential in the postphlebitic syndrome as well as in acute treatment of myocardial infarction (primarily and adjunctively with various thrombolytic agents) continues to undergo evaluation; however, early data review shows favorable trends for its inclusion in situations that favor thrombus generation (e.g., anterior myocardial infarction). Although associated with thrombocytopenia or hypertransaminasemia, the heparins are relatively well tolerated. In a small subset of patients, a severe thrombocytopenia may ensue, which generally resolves on medication withdrawal. As this class of glycosaminoglycans becomes better characterized, new indications may emerge for both native and the newer fractionated heparins.

Hemorrhage↗

PubMed1988

Deep vein thrombosis and pulmonary embolism: clinical presentation and pathophysiologic consequences.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are both characterized by unreliable clinical diagnosis and significant long-term sequelae. In patients with DVT, popliteal valvular insufficiency is associated with increased risk for postphlebitic syndrome. Current data show thrombolytic therapy to be more effective than anticoagulation for DVT, accomplishing significant or complete clearing of the deep venous system in nearly half of all patients treated. Results of investigation show lytic therapy to also be more effective than heparin in treatment of PE, both in terms of acute resolution and long-term function.

Fibrinolytic Agents↗

PubMed1988

Fibrinolytic therapy for deep vein thrombosis and pulmonary embolism.

The troublesome sequelae of pulmonary embolism (PE) and deep vein thrombosis (DVT) justify an aggressive therapeutic approach. Results of anticoagulation in patients with DVT have shown that a significant percentage of patients have no clot resolution and may progress to develop the postphlebitic syndrome. Lytic therapy has been more effective, with patients showing improvement within 24 h of treatment. This approach has also been found to compare favorably with anticoagulation in the treatment of PE. Preliminary research also suggests a potential role for recombinant human tissue-type plasminogen activator to resolve PE.

Fibrinolytic Agents↗

PubMed1999

Percutaneous ilio-caval thrombectomy with the Amplatz device: preliminary results.

The Amplatz Thrombectomy Device (ATD) is a percutaneous, rotational thrombectomy catheter, capable of recirculating and homogenizing the thrombus in order to obtain mechanical clot dissolution. The authors present their experience with mechanical thrombectomy with the ATD in eight cases of ilio-caval thrombosis. Under temporary caval filter protection, the ATD was introduced through the right transjugular approach (in one patient this was used in combination with the right femoral approach) and activated for a time ranging from 90 to 180 s. Complete clearing of thrombotic material in the treated venous segments was achieved in six cases (75 %), partial success was obtained in one case (12.5 %) and failure occurred in one patient (12.5 %). One patient developed a recurrence of venous iliac thrombosis 1 week after the procedure and postphlebitic syndrome 6 months after the first episode of deep venous thrombosis, and one patient died from acute myocardial infarction, unrelated to thrombectomy session, after 3 days. A negative clinical and radiological follow-up at 3, 6, 12 and 24 months was obtained in the remaining six patients. If a fresh free-floating ilio-caval clot must be removed immediately, the ATD can be effective under temporary filter protection.

Adult↗

PubMed2004

Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. A cost-utility analysis.

BACKGROUND: Among patients undergoing elective total hip or knee replacement, prolonged prophylaxis with low-molecular-weight heparin significantly reduces the risk of symptomatic venous thromboembolism. Whether implementing routine prolonged prophylaxis is cost-effective remains uncertain. METHODS: We performed an economic modeling study to compare the costs and health outcomes of standard (12 days) with prolonged (42 days) enoxaparin prophylaxis against venous thromboembolism after elective total hip and knee replacement. The primary economic perspective was that of a societal healthcare payer, taking Belgium as a case country. We used cost-utility analysis, a form of cost effectiveness analysis in which costs are reported in monetary terms (euros) and health outcomes are converted into quality-adjusted life years (QALYs) gained, thereby incorporating a measure of quality of life (utility) into the health outcomes. Costs for diagnosis and treatment of proximal and distal deep vein thrombosis, pulmonary embolism, postphlebitic syndrome, and major bleeding were obtained from a Delphi panel (orthopaedic surgeons) and the official reimbursement rates (Federal Ministry of Health). QALYs for these health outcomes were based on utility scores as reported in the literature. The main outcome measure was the incremental cost-utility ratio, reported as the incremental cost per quality-adjusted life year gained (euros/QALY). The incremental cost-utility ratio refers to the amount of money needed to produce one additional QALY. We also performed sensitivity analyses on clinical and economic parameters to identify important model uncertainties. RESULTS: In the base-case analysis, incremental costs of prolonged prophylaxis amounted to 58 euros and 114 euros per patient, with an additional gain in QALY of 0.0083 and 0.0018 after total hip and knee replacement, respectively. Thus, a strategy of prolonged enoxaparin prophylaxis was associated with a cost-utility ratio of 6,964 euros/QALY and 64,907 euros/QALY after total hip and knee replacement, respectively. This tenfold difference in incremental cost-utility ratios between hip and knee replacement might have important practical implications. According to recent European guidelines, an intervention costing less than 20,000 euros per QALY is said to exhibit strong evidence for adoption, whereas one costing 20,000-100,000 euros exhibits moderate evidence for adoption. By current European guidelines, the cost of 6,964 euros and 64,907 euros per QALY gained would give strong evidence for adoption of prolonged enoxaparin prophylaxis among total hip replacement patients, but moderate evidence for adoption among total knee replacement patients. Sensitivity analyses using 20% changes from the base-case analysis showed this outcome to be robust. CONCLUSIONS: Our findings indicate that, among patients undergoing elective total hip or knee replacement, prolonged enoxaparin prophylaxis leads to increased health benefits at increased cost. Given the additional costs that healthcare decision makers in Europe are usually prepared to pay for a gain in utility, prolonged prophylaxis with enoxaparin is cost-effective after elective total hip replacement, and our data provide strong evidence for adoption of prolonged enoxaparin prophylaxis after elective total hip replacement.

Anticoagulants↗

PubMed1999

Thrombolytic therapy: the treatment of choice for iliac vein thrombosis in the presence of kidney transplant.

A 49-year-old kidney transplant recipient was admitted with the diagnosis of acute iliofemoral deep venous thrombosis (DVT) extending into the external iliac vein in close proximity to the renal vein anastomosis. Thrombolytic therapy with urokinase was used and complete lysis of the thrombus was achieved within 36 hr. We feel that this method of therapy, rather than standard anticoagulation, represents the treatment of choice for acute DVT in the presence of a renal graft. Using this method we were able to salvage the kidney and avoid the complications of postphlebitic syndrome and pulmonary embolus.

Humans↗

PubMed2001

Venous Thrombosis of the Upper Extremities.

The goals of treating patients with upper-extremity deep vein thrombosis (UEDVT) are to relieve acute symptoms of venous occlusion, prevent pulmonary embolism, reduce the likelihood of recurrent thrombosis, and avoid the development of postphlebitic syndrome. Although the details of management differ, depending on the underlying cause and precipitating factors, anticoagulant therapy should be the first-line treatment of choice in all cases. For patients with primary or idiopathic UEDVT (Paget-von Schroetter syndrome), aggressive measures including catheter-directed thrombolysis, vascular procedures (eg, balloon angioplasty, stenting, filter), and surgical maneuvers (eg, first rib resection) have been advocated by some surgeons, but none of these high-risk interventions has been evaluated properly in prospective controlled trials. In contrast, for patients with catheter-associated central venous thrombosis (CACVT), or other secondary cases of UEDVT, many clinicians simply withdraw the catheter and avoid anticoagulant therapy. Because well-designed clinical trials are lacking, recommendations about the management of UEDVT are derived from descriptive studies and case series. Until further research identifies the natural history and optimum management of UEDVT, it seems reasonable to base treatment on anticoagulant regimens with proven effectiveness in lower-extremity deep vein thrombosis (LEDVT). The use of additional intervention(s) should be reserved for carefully selected patients.

Journal Article↗

PubMed1978

The posterior stocking seam approach to radical subfascial clipping of perforating veins.

The posterior stocking seam approach to radical subfascial ligation of perforating veins has been advocated for the patient with postphlebitic syndrome presenting with severe stasis dermatitis, leg edema, and recurrent ulceration. Our indications for this procedure have been extended to include signs and symptoms of advanced venous insufficiency which persist after multiple operative procedures for recurrent varicose veins in the absence of deep venous thrombosis. In this series of twenty-five operations there was one instance of recurrent stasis ulceration after the procedure, and reversal of the pigmentation of stasis dermatitis was dramatic in the majority of cases. All limbs have completely healed, and there has been no significant swelling. The long-term results of this surgical procedure have been excellent, and short-term complications have been minimal.

Adult↗

PubMed1980

Long-term follow-up of partial caval occlusion by clip.

A series of 55 patients with partial caval occlusion by a smooth clip is presented with a follow-up period of 5 to 12 years. The clip provided continuing protection from fatal emboli, Persistent new postoperative leg swelling was present in 18 percent of patients but was generally well controlled with elastic stockings. In two patients with previous thromboembolism a postphlebitic syndrome proved troublesome. The quality of life led by patients was high and was enhanced by their knowledge of permanent protection against lethal embolism.

Clothing↗

PubMed1984

Late sequelae of deep venous thrombosis. Diagnostic and therapeutic considerations.

The efficacy of heparin, sodium warfarin, and elastic stockings in preventing the late leg sequelae of deep venous thrombosis was evaluated by reexamining 15 patients with previous acute deep venous thrombosis so treated. All 5 patients with iliocommon femoral disease and only 5 of 10 patients with distal disease had evidence of postphlebitic syndrome. Venous Doppler and strain gauge plethysmography confirmed these clinical findings. The most striking and consistent laboratory abnormalities were in the patients with proximal disease. Treatment of acute deep venous thrombosis by traditional means does not prevent the clinical and laboratory late leg sequelae. In light of these findings, serious investigation of new therapeutic modalities is strongly suggested.

Clothing↗

PubMed1984

Pulmonary embolism secondary to venous thrombosis of the arm.

Pulmonary embolism is described as an infrequent complication of axillary and subclavian vein thrombosis. We have reported our recent clinical experience with 14 patients admitted to the Harbor-UCLA Medical Center who had a clinical diagnosis of axillary and subclavian vein thrombosis documented by phlebography of the thrombosed arm. The causes of thrombosis were effort (three patients), trauma (three patients), drug abuse (four patients), underlying neoplastic disease (three patients), and congenital venous malformation (one patient). Pulmonary emboli were diagnosed by arteriogram, ventilation perfusion scans, and arterial blood gas abnormalities in five patients with respiratory symptoms for an incidence of 35.7 percent. Immediate anticoagulation with heparin, then switching to warfarin sulfate after 5 days, was the standard therapy in all patients. Follow-up examinations between 3 and 24 months demonstrated mild postphlebitic syndrome consisting of pain and minimal swelling in two patients. We conclude that pulmonary emboli may be a more frequent complication of axillary and subclavian vein thrombosis than has generally been recognized.

Adolescent↗

PubMed1992

Lower limb paralysis: its effect on the recanalization of deep-vein thrombosis.

Fifty patients with lower limb deep-vein thrombosis (DVT) confirmed by venography were studied prospectively to determine the time required for recanalization. The patients were anticoagulated with heparin and warfarin for at least three months; impedance plethysmography, Doppler, and duplex scans were repeated at scheduled intervals. The 24 patients who were paralyzed took longer for recanalization than did the 26 nonparalyzed patients; this difference was statistically significant between the paraplegic-quadriplegic and nonparalyzed groups (54 vs 33 days; t = 2.12, p = .04). Patients with motor complete paraplegia or quadriplegia took longest for recanalization (57 days). Although most variables were not statistically significant on comparison, a somewhat longer recanalization time was seen in men and in those with DVTs located more proximally. Because of delay in recanalization, patients with lower limb paralysis may have persistent swelling due to venous insufficiency and may be at greater risk for development of the postphlebitic syndrome.

Adult↗

PubMedDate not supplied

Fibrinolytic therapy for venous thrombosis.

In the treatment of DVT fibrinolytic therapy offers the possibility of rapid clot dissolution resulting in symptomatic relief of the acute episode as well as preservation of venous valve function and prevention of long-term disability from chronic venous insufficiency. A review of published studies comparing fibrinolytic therapy with SK to anticoagulation alone indicates that substantial venographic improvement occurs in 45% of SK treated patients compared with only 5% receiving only anticoagulation. Substantial data indicate a high incidence of venous valvular dysfunction and eventual development of chronic venous insufficiency in patients with extensive leg DVT treated with anticoagulants alone. The available data on the long-term benefits of thrombolytic therapy in preventing chronic venous insufficiency suggest that fibrinolytic therapy reduces long-term morbidity. Because best results are obtained by treatment soon after the onset of symptoms, it follows that the postphlebitic syndrome can be best avoided by prompt thrombolytic therapy of patients with acute DVT. Bleeding complications are more frequent after thrombolytic therapy than anticoagulant therapy, but most are related to invasive vascular procedures and can be minimized by proper patient selection and management. Available studies of rt-PA in treatment of DVT indicate that infusion durations of 24 hours or more may be required; further studies will be needed to evaluate the response to rt-PA compared with those of SK or UK. Thrombosis of the axillary/subclavian veins of the upper extremity, occurring spontaneously or in association with indwelling venous catheters, also respond well to regional or systemic fibrinolytic therapy, which may reduce the likelihood of developing chronic arm symptoms related to venous insufficiency.

Anticoagulants↗

PubMed2005

Are temporary inferior vena cava filters really temporary?

BACKGROUND: Despite significant risk for venous thromboembolism, severely injured trauma patients often are not candidates for prophylaxis or treatment with anticoagulation. Long-term inferior vena cava (IVC) filters are associated with increased risk of postphlebitic syndrome. Retrievable IVC filters potentially offer a better solution, but only if the filter is removed; our hypothesis is that the most of them are not. METHODS: This retrospective study queried a level I trauma registry for IVC filter insertion from September 1997 through June 2004. RESULTS: One IVC filter was placed before the availability of retrievable filters in 2001. Since 2001, 27 filters have been placed, indicating a change in practice patterns. Filters were placed for prophylaxis (n = 11) or for therapy in patients with pulmonary embolism or deep vein thrombosis (n = 17). Of 23 temporary filters, only 8 (35%) were removed. CONCLUSIONS: Surgeons must critically evaluate indications for IVC filter insertion, develop standard criteria for placement, and implement protocols to ensure timely removal of temporary IVC filters.

Adult↗

PubMed2005

Vein wall remodeling after deep vein thrombosis involves matrix metalloproteinases and late fibrosis in a mouse model.

HYPOTHESIS: Deep venous thrombosis (DVT) confers vein wall injury associated with fibrosis and extracellular matrix (ECM) turnover, likely mediated by matrix proteases. This study investigated the expression of proteases and collagen involved in early vein wall remodeling. METHODS: In the mouse, DVT was produced by ligation of the infrarenal inferior vena cava (IVC) or sham operation, and tissue was harvested at 4, 8, and 12 days. The vein wall tissue was processed for real-time reverse transcriptase-polymerase chain reaction (6 to 8 per time point), Western immunoblotting (5 per time point), and gelatin zymography (5 per time point). Analysis of variance was used for multiple comparisons, and a P < .05 was significant. RESULTS: Thrombus resolution was documented by a 38% decrease in the thrombosed IVC weight from day 4 to day 12 (P = .007). Total vein wall collagen increased over time, with a corresponding increase in procollagen I and III, and expression peaked at 12 days (24-fold and 6.1-fold, respectively, P < .02). Matrix metalloproteinase-2 (MMP-2) gene expression was 23-fold greater at 12 days after thrombus formation compared with sham or 4 days after thrombosis (P < .05). Total MMP-2 activity was also significantly elevated at 12 days compared with sham (P < .05). MMP-9 expression was 19-fold and 27-fold higher at days 4 and 8, respectively, relative to sham (P < .05), with no difference in activity. MMP-14 expression was twofold to 3.6-fold greater at day 12 compared with earlier time points and shams (P < .001), but no differences in protein levels were found. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) protein levels were not significantly different from sham over time; however, the ratio of uPA to PAI-1 was decreased through 8 days. CONCLUSIONS: Vein wall remodeling after DVT is similar to wound healing and is associated with increased procollagen gene expression and total collagen. It is also associated with increased early MMP-9 expression, followed by MMP-2 expression and activity after DVT resolution. CLINICAL RELEVANCE: Deep vein thrombosis is an often neglected problem that long term is associated with the postphlebitic syndrome of limb swelling, pain, and often ulceration. The basic mechanisms of the vein wall damage that results have not been delineated. The following study describes the vein wall matrix metalloproteinase gene and activity response induced over time in the vein wall after DVT. Additionally, the corresponding collagen upregulation and proximate plasmin system mediators are determined. With this knowledge, potential therapies to reduce vein wall injury directly might be possible.

Animals↗