Superficial thrombophlebitis and low-molecular-weight heparins

The current status of superficial thrombophlebitis, including incidence, diagnosis, and management, are reviewed. Treatment options are assessed in the light of data from the main studies reported in the literature. These include compression, ambulation, and nonsteroidal antiinflammatory agents and surgical management with high saphenous ligation (with or without saphenous vein stripping) with or without anticoagulants, ranging from aspirin, unfractionated heparin, warfarin, and low-molecular-weight heparin (LMWH). The advantage of the surgical approach is that by ligation with or without stripping of the superficial veins the underlying pathesis (i.e., varicose veins) is also eradicated. In the presence of deep venous thrombosis (DVT), surgery could be combined with anticoagulants. The extensive current literature for DVT treatment shows that the LMWHs are at least as effective and safe as the unfractionated heparins. On this basis, one could reasonably recommend LMWH for the treatment of superficial thrombophlebitis with involvement of the deep veins. Pentasaccharide, a drug that has been recently explored for the prophylaxis and treatment of DVT could be another option. However, there are as yet no data for recommended dosages or duration of treatment for the latter two options.     

Superficial vein thrombophlebitis--serious concern or much ado about little?

Superficial vein thrombophlebitis (SVTP) appears in two distinct forms: varicose vein thrombophlebitis (TP) represents the principal cause. It is characterized by a large thrombus in a varicose vein and a modest inflammatory process localized in the vessel surrounding but not in its wall. Rarely, SVTP affects a non-varicose vein. Abundant intima proliferation and media fibrosis with non-important thrombosis are the hallmark of this form which may be associated with a systemic disease. Although SVTP is perceived as trivial and benign coexistence of (mostly distal) deep venous thrombosis (DVT), propagation to popliteal or femoral DVT, and even pulmonary embolism (PE) have been reported. Data for prevalence vary greatly: 6-53% for coexistence, 2.6-15% for propagation, and 0-33% for (asymptomatic) PE. Risk factors for these complications are those known for DVT. SVTP is diagnosed in a clinical setting but ultrasonography is useful to check for concomitant DVT. Anticoagulant treatment is mandatory if DVT is present and thrombectomy should be considered in cases of thrombus propagation into the deep veins. Historical therapy of uncomplicated SVTP consists of compression with bandages or stockings and local or systemic anti-inflammatory agents. Low-molecular-weight heparin (LMWH) has been given in high-prophylactic doses and found equally effective when compared with anti-inflammatory agents and full-therapeutic dose LMWH. Prophylactic saphenous vein ligation alone was found less effective than conservative therapy. Ligation combined with stripping proved the potential of eliminating at once all problems associated with SVTP but was associated with a complication rate of 10% or higher. Careful patient selection and saphenous vein thrombectomy prior to stripping may be the clue for better results.     

Comparison of low-molecular-weight heparin, administered primarily at home, with unfractionated heparin, administered in hospital, and subcutaneous heparin, administered at home for deep-vein thrombosis.

In this study, 294 patients with acute proximal DVT (deep venous thrombosis) were randomly assigned to receive intravenous standard heparin in the hospital (98 patients) or low-molecular-weight heparin (LMWH) (nadroparin 0.1 mL [equivalent to 100 AXa IU] per kg of body weight subcutaneously twice daily) administered primarily at home (outpatients) or alternatively in hospital (97 patients) or subcutaneous calcium heparin (SCHep) (99 patients, 0.5 mL bid) administered directly at home. The study design allowed outpatients taking LMWH heparin to go home immediately and hospitalized patients taking LMWH to be discharged early. Patients treated with standard heparin or LMWH received the oral anticoagulant starting on the second day, and heparin was discontinued when the therapeutic range (INR 2-3) had been reached. Anticoagulant treatment was maintained for 3 months. Patients treated with SCHep were injected twice daily for 3 months without oral anticoagulants. Patients were evaluated for inclusion and follow-up with color duplex scanning. Venography was not used. In case of suspected pulmonary embolism (PE) a ventilatory-perfusional lung scan was performed. Endpoints of the study were recurrent or extension of DVT, bleeding, the number of days spent in hospital, and costs of treatments. Of the 325 patients included, 294 completed the study. Dropouts totaled 31 (10.5%); six of the 325 included patients (1.8%) died from the related, neoplastic illness. Recurrence or extension of DVT was observed in 6.1% of patients in the LMWH group, in 6.2% in the standard heparin group, and in 7.1% in the SCHep group. Most recurrences (11/17) were in the first month in all groups. Bleedings were all minor, mostly during hospital stay. Hospital stay in patients treated with LMWH was 1.2+/-1.4 days in comparison with 5.4+/-1.2 in those treated with standard heparin. There was no hospital stay in the SCHep group. Average treatment costs in 3 months in the standard heparin group (US $2,760) were considered to be 100%; in comparison costs in the LMWH group was 28% of the standard heparin and 8% in the SCHep group. This study indicated that LMWH and SCHep can be used safely and effectively to treat patients with proximal DVT at home at a lower cost.     

Review: Fondaparinux reduces VTE and recurrence in superficial thrombophlebitis of the leg

QUESTION What are the efficacy and safety of treatments for superficial thrombophlebitis (ST) of the leg? REVIEW SCOPE Included studies compared topical, medical, and surgical treatments for ST of the leg with placebo, another treatment, or no treatment in patients diagnosed on the basis of signs and symptoms, clinical examination, and ultrasonography of the lower limbs. Exclusion criteria included concomitant deep venous thrombosis (DVT) identified on ultrasonography. Outcomes included objectively confirmed symptomatic pulmonary embolism (PE) or DVT, extension or recurrence of ST, and treatment side effects. Symptoms were not reported consistently and are not reported in this abstract. REVIEW METHODS Cochrane Peripheral Vascular Diseases Group Specialised Register, which includes search results from MEDLINE, EMBASE/Excerpta Medica, CINAHL, and AMED databases and hand-searches of journals (to Nov 2011); Cochrane Central Register of Controlled Trials (2011, Issue 4); conference proceedings; and reference lists were searched for randomized controlled trials (RCTs). Experts were contacted. 26 RCTs (n =?5521, mean age range 39 to 63 y, 43% to 79% women) met inclusion criteria and evaluated ≥?1 treatment type: 11 evaluated low-molecular-weight heparin (LMWH) (n =?1651); 8 oral, intramuscular, or IV treatments (n =?1139); 7 topical agents (n =?296); 5 nonsteroidal antiinflammatory drugs (NSAIDs) (n =?710); 3 surgery (n =?705); and 1 fondaparinux (n =?3002). 3 RCTs had adequate allocation concealment, 14 used a double-blind design, and 7 did intention-to-treat analyses. MAIN RESULTS The main results for fondaparinux and LMWH are in the Table. Limited data were reported for other treatment comparisons. CONCLUSIONS In patients with superficial thrombophlebitis of the leg, prophylactic doses of fondaparinux reduce venous thromboembolism and extension or recurrence of disease without evidence of increasing major bleeding. Insufficient high-quality evidence exists to evaluate the effect of low-molecular-weight heparin or other treatments on patient-important outcomes.Treatments for superficial thrombophlebitis (ST) of the leg*TreatmentsNumber of trials (n)OutcomesSelected findingsFondaparinux vs placebo1 (3002)Symptomatic DVT or PE0.20% vs 1.3%; RRR 85%, 95% CI 50 to 96ST extension0.27% vs 3.4%; RRR 92%, CI 78 to 97ST recurrence0.33% vs 1.6%; RRR 79%, CI 46 to 92Major bleeding0.07% vs 0.07%; RRR 1%, CI -1486 to 94LMWH?11 (1651)VTENo difference in 10 RCTs; NR in 1 RCT.ST extension or recurrence1 RCT, n =?328. Prophylactic LMWH 12% vs placebo 29%; RRR 60%, CI 28 to 78. Therapeutic LMWH 12% vs placebo 29%; RRR 58%, CI 25 to 77.1 RCT, n =?225. Prophylactic LMWH + ECS 1.3% vs ECS alone 17%; RRR 92%, CI 41 to 99. Prophylactic UFH + ECS 2.8% vs ECS alone 17%; RRR 83%, CI 28 to 96No difference in 5 RCTs; NR in 4 RCTs.Major bleeding0 events reported in 6 RCTs; NR in 5 RCTs.*DVT = deep venous thrombosis; ECS = elastic compression stocking; LMWH = low-molecular-weight heparin; NR = not reported; PE = pulmonary embolism; RCT = randomized controlled trial; UFH = unfractionated heparin; VTE = venous thromboembolism; other abbreviations defined in Glossary.?Comparisons included placebo, ECSs, nonsteroidal antiinflammatory drugs, defibrotide, venoruton, topical heparin spray gel, surgery, or different heparin doses.     

Superficial thrombophlebitis in non varicose veins of the lower limbs. A prospective analysis in 42 patients

Recent publications allow better understanding of superficial thrombophlebitis (ST) of the lower limb veins. However ST occurring in non varicose veins (NVV) and those occurring in varicose veins (VV) are seldom distinguished in literature. AIMS OF THE STUDY: 1) To estimate the potential gravity of ST occurring in NVV by putting a figure on the frequency of associated deep venous thrombosis (DVT) and symptomatic pulmonary embolism (PE); 2) to identify some risk factors (thrombophilia, systemic disease, thromboembolic events); 3) to assess the different types of thromboembolic recurrent events after superficial thrombophlebitis (TRST) and identify the risk factors for recurrence. MATERIAL AND METHOD: Forty-two cases of ST occurring in NVV were included consecutively and prospectively in this series; TRST possible risk factors were evaluated. Patients were assessed at 1 month and followed up to 3 years. Isolated ST was treated with low-molecular-weight heparin at prophylactic dosage from 15 to 21 days and with elastic compression. RESULTS: 1) A DVT was combined in 12 cases (28.6%) located in the calf (n=9) or in the femoro-politeal axis (n=3). One symptomatic PE occurred confirmed by ventilation-perfusion lung scan; 2) The risk factor investigations identified a neoplasm in 2 patients (4.8%), a non neoplasic systemic disease in 4 (9.5%) and a thrombophilia in 20 patients. The most frequent thrombophilia was the heterozygous mutation of coagulation factor V (Leiden); 3) All patients were assessed at 1 month with a clinical examination and Duplex Scanning. We did not identify either new DTV, PE or extension of the previous DVT; 4) 17 TRST were identified in 13 patients. Three patients had 2 recurrences; one patient presented a TRST located at 2 different sites. In total 8 new ST and 9 DVT were identified. DISCUSSION: The analysis of the literature shows that early complications or combinations (DVT and PE) occur with the same prevalence in NVV and VV groups. A risk factor was identified in 62% of patients in this series (thrombophilia was the most common) and TRST were statistically more frequent in this series than in groups of ST occurring in VV we had previously analyzed. A post-thrombotic syndrome and a DVT associated with the ST were identified as statistically significant risk factors for recurrence. CONCLUSION: ST occurring in NVV, although representing 5 to 10% of all ST, is seldom reported in the literature. Like ST occurring in VV, they have a potential gravity (associated DVT and PE). However these two diseases should be distinguished. A risk factor is more often identified and TRST are more frequent in the group of ST occurring in NVV. We advise active management of these thromboses including screening for a risk factor, the implementation of measures for preventing venous thrombosis recurrence and patient follow-up.     

Liposomal heparin spray: a new formula in adjunctive treatment of superficial venous thrombosis

The objective of this study was to assess the efficacy and safety of liposomal heparin spray-a new formula of topical heparin delivery. This was a randomized, multicenter, controlled open clinical trial with 2 parallel groups. Forty-six outpatients with clinical signs of superficial venous thrombosis (SVT) were treated with either topical liposomal heparin spraygel (LHSG) (Lipohep Forte Spraygel, 4 puffs of 458 IU tid (n = 22) or with low-molecular-weight heparin (LMWH) (Clexane 40 mg once a day (n = 24), administered subcutaneously (sc). Main outcome measures were efficacy parameters (improvement of local symptoms-pain control and planimetric evaluation of erythema size, duplex Doppler assessment of thrombus regression) and safety parameters (documentation of adverse events, with particular reference to deep vein thrombosis [DVT] by duplex sonography, and patients' and investigators' assessment of drug tolerance). Patients' and investigators' subjective assessment of efficacy of treatment and change in basic biochemical parameters were defined as secondary outcome measures. Statistical analysis was performed with use of Wilcoxon test, Mann-Whitney U-test and Chi-square test. Regression of SVT-related symptoms, including pain, erythema, and thrombus presence, was shown as comparable in LHSG and LMWH groups. These results were corroborated by efficacy assessment by investigators and patients. Three cases of deep venous thrombosis in heparin spraygel and 1 in heparin sc group were reported. No significant adverse reactions were observed in the spraygel group, but 1 serious allergic reaction was observed in the LMWH group. Tolerance of new formula heparin was assessed as good. Heparin spraygel-a new topical mode of heparin application, seems a promising method of heparin delivery. This initial study has demonstrated comparable efficacy and safety of LHSG and LMWH in local treatment of SVT. These findings should be confirmed by further extensive study that will reach appropriate statistical power to support such conclusion, for despite heparin treatment, significant risk of DVT was demonstrated in both groups.     

Diagnostik venöser Erkrankungen

Venous disease of the lower extremities comprises several common conditions such as varicose veins, superficial thrombophlebitis, deep venous thrombosis and chronic venous insufficiency. The high prevalence and increasing incidence with age of these disorders impose relevant diagnostic and therapeutic concerns. Varicose veins and superficial thrombophlebitis are easily diagnosed clinically and additional diagnostic means, i. e., duplex scan, is needed for documentation or planning of surgery. Deep venous thrombosis cannot be confirmed clinically and further imaging based on clinical probability is usually required for correct diagnosis. Color-coded duplex and compression sonography have emerged as the means of choice in skilled hands. Phlebography still remains the gold standard based on its investigator-independent characteristics. However, it is becoming more and more a research tool. CT scan and magnetic resonance imaging are too expensive for broad application, but may be helpful in cases of uncertainty such as iliac vein thrombosis. CT scans, magnetic resonance imaging and sonography reveal additional information compared to phlebography about surrounding tissue and may help in establishing a differential diagnosis. Limitations of CT scan and phlebography are radiation exposure and contrast media application. Chronic venous insufficiency is basically established by medical history and clinical findings. Functional and imaging tests such as plethysmography, color-coded duplex sonography and phlebography are essential for confirming the diagnosis, evaluating a surgical intervention or defining the cause of chronic venous insufficiency.     

Management of superficial vein thrombosis and thrombophlebitis: status and expert opinion document

Superficial vein thrombosis is characterized by clotting of superficial veins (ie, following direct trauma) with minimal inflammatory components. Superficial thrombophlebitis is a minimally thrombotic process of superficial veins associated with inflammatory changes and/or infection. Treatments generally include analgesics, elastic compression, anti-inflammatory agents, exercise and ambulation, and, in some cases, local or systemic anticoagulants. It is better to avoid bed rest and reduced mobility. Topical analgesia with nonsteroidal, anti-inflammatory creams applied locally to the superficial vein thrombosis/superficial thrombophlebitis area controls symptoms. Hirudoid cream (heparinoid) shortens the duration of signs/symptoms. Locally acting anticoagulants/antithrombotics (Viatromb, Lipohep, spray Na-heparin) have positive effects on pain and on the reduction in thrombus size. Intravenous catheters should be changed every 24 to 48 hours (depending on venous flow and clinical parameters) to prevent superficial vein thrombosis/superficial thrombophlebitis and removed in case of events. Low molecular weight heparin prophylaxis and nitroglycerin patches distal to peripheral lines may reduce the incidence of superficial vein thrombosis/superficial thrombophlebitis in patients with vein catheters. In case of superficial vein thrombosis/superficial thrombophlebitis, vein lines should be removed. In neoplastic diseases and hematological disorders, anticoagulants may be necessary. Exercise reduces pain and the possibility of deep vein thrombosis. Only in cases in which pain is very severe is bed rest necessary. Deep vein thrombosis prophylaxis should be established in patients with reduced mobility. Antibiotics usually do not have a place in superficial vein thrombosis/superficial thrombophlebitis unless there are documented infections. Prevention of superficial vein thrombosis should be considered on the basis of patient's history and clinical evaluation.     

The home treatment of deep vein thrombosis with low molecular weight heparin, forced mobilisation and compression.

BACKGROUND: The aim of this prospective study was to analyse a group of patients with DVT (deep vein thrombosis) treated at home with LMWH (low-molecular weight heparin), compression and intensive mobilisation and to evaluate its feasibility, efficacy and safety from possible risks of pulmonary embolism. METHODS: From March 1997 to September 1999, 96 consecutive patients with diagnosed DVT were enrolled in a prospective study and treated at home with enoxaparin (Clexane Rh ne-Poulenc) administered subcutaneously at doses depending on body weight (1 mg/kg) b.i.d. for a minimum of seven days. Oral anticoagulants were started two days before discontinuing LMWH and given later for three months according to the haemocoagulation parameters. All patients wore elastic second degree compression stockings during the whole period of treatment and for 12 months there after. They were encouraged to walk 1-3 km daily. The sites of thrombosis were ilio-femoral vein--38 patients (40%), femoral or popliteal vein--32 patients (33%), crural veins--26 patients (27%). According to our surgical criteria two years ago 17 patients would have been operated on and trombectomy performed. The diagnosis was made by compression ultrasonography using a colour duplex scanner (Acuscan 125), by contrast phlebography, and platelet scintigraphy (Tromboscint test). Perfusion-ventilation scintigraphy of the lungs was performed only if there were clinical signs or even a suspicion of pulmonary embolism and on all patients with iliofemoral thrombosis. Perfusion gamagraphy of lungs was carried out on 51 patients where thrombosis was localised in proximal veins. RESULTS: In 27 patients there were signs of non-fatal pulmonary embolism (53%), but only seven patients (26%) suffered mild non-specific clinical signs; 20 patients with diagnosed pulmonary embolism (74%) were symptom-free. Out of 96 patients, three admitted to hospital (3%), 67 (70%) injected LMVH themselves and felt comfortable. Eight to 12 weeks after this treatment control sonography and phlebography were carried out in 70 patients to assess the localisation and progress of the thrombosis. In 51% (36 patients) partial and 31% (22 patients) total recanalisation was found. Five out of 96 complained of minor bleeding (5%). No thrombocytopenia was noticed. The first five days on home treatment were crucial. All patients were able to walk and live at home without difficulty. None of our patients with proximal deep vein thrombosis used a vena cava filter. CONCLUSIONS: Home treatment of DVT is possible and is effective, safe and less costly on average and per patient 40% in costs was saved compared with those of a hospital stay in spite of the greater expense of LMWH. The patients who received LMWH spent a mean of 1.2 days in the hospital, as compared with 12.7 days for the standard-heparin group.     

Deep vein thrombosis and pulmonary embolism: prevention, diagnosis, and treatment.

Pulmonary embolism (PE) is a significant cause of mortality in the elderly. More than 90% of pulmonary emboli originate from a thrombus in the deep veins of the legs. Proper diagnosis and treatment of deep vein thrombosis (DVT) are thus essential to prevent PE. Diagnosis of new or recurrent DVT is based on the results of one or more tests, including impedance plethysmography (IPG) or duplex venous scan; venography can often be avoided, based on results of initial testing. For suspected PE, perfusion lung scanning is the initial test of choice, followed by IPG/duplex or venography. Pulmonary angiography is indicated for patients with decreased cardiorespiratory reserve. Decisions governing prophylaxis of DVT are based on individual relative risk; prophylactic therapies include intermittent compression, low-dose heparin, and oral anticoagulants. Management of thromboembolism requires IV and oral anticoagulant therapy.     

Home treatment of deep venous thrombosis with low molecular weight heparin: Long-term incidence of recurrent venous thromboembolism

Outpatient treatment of deep venous thrombosis (DVT) with low molecular weight heparin (LMWH) seems as safe and effective as inpatient treatment with unfractionated heparin (UFH). However, most of the randomized trials comparing a LMWH with UFH described clinical outcomes within 3-6 months. The long-term incidence of recurrent VTE after treatment of DVT with LMWH remains to be established. The primary objective of this retrospective study was to document the long-term incidence of recurrent venous thromboembolism (VTE) in patients with DVT treated with a LMWH, nadroparin in an outpatient basis. The patients were evaluated 46 months after inclusion in two cohorts comparing home treatment with nadroparin (n = 130) with in-hospital treatment with intravenous UFH (n = 149). More than 60% of the patients in the nadroparin group could be treated at home, either entirely or after a short stay in hospital. The age-adjusted thrombosis-free survival was not statistically significant between nadroparin and UFH-treated patients (P = 0.084). There was a nonsignificant trend favoring nadroparin as compared with UFH. The hazard ratio (HR) for recurrent VTE in the nadroparin group with respect to the UFH group was 0.44 (95% confidence interval, 0.17-1.12). No significant differences were observed in overall mortality or major hemorrhage between the two treatment groups. Our study suggests that home treatment of DVT with LMWH is at least as effective and safe as in-hospital UFH after a long-term follow-up period.     

Superficial venous thrombosis of the lower extremities co-existing with deep venous thrombosis. A phlebographic study on 57 cases

The incidence of deep venous thrombosis (DVT) coexistent in patients suffering from superficial venous thrombosis (SVT) has not been well documented. In a series of 57 consecutive patients with SVT of the lower extremities treated in our Department in the last five years without any obvious clinical signs of co-existing DVT, an ascending phlebographic study was performed. Co-existent DVT was disclosed in 19.6% of the patients. There was no correlation between the location or the length of thrombus and the co-existence of DVT. Patients in whom SVT developed in existing varicose veins were younger in age and the incidence of co-existence of DVT was lower. Our findings show that SVT does not always have a benign course. The disclosure of a high incidence of co-existing DVT in our series suggests the necessity of the examination of the deep venous system in all the cases of SVT by using ultrasonic technics, triplex and preferably of the ascending phlebography. The disclosure of DVT in those cases makes the application of anticoagulant treatment mandatory.     

Surgical management of ascending saphenous thrombophlebitis.

BACKGROUND: Acute saphenous vein ascending thrombophlebitis is recognised to be a dangerous condition due to the reported high incidence of deep vein thrombus involvement and possibly fatal pulmonary embolism. We assessed the accuracy of duplex scanning in determining the extent of thrombosis as well as the effectiveness of surgical treatment. METHODS: We retrospectively reviewed 146 patients referred to our Vascular Laboratory for acute superficial thrombophlebitis from 1987 to 1997. Duplex scanning identified 85 cases of superficial thrombophlebitis involving at least a segment of the saphenous vein localised below the knee (58.2%); 37 of thrombophlebitis extending into both the superficial and deep venous systems (25.3%), and 24 of saphenous thrombosis extending to within 5 cm of the saphenofemoral junction (16.4%). The latter group underwent saphenofemoral disconnection. We compared the preoperative duplex with the surgical reports and evaluated the surgical results. RESULTS: We did not observe any complication. Return to work and normal activity occurred within 3-5 days. When varicose vein thrombectomy was performed concurrently, the patients had better postoperative pain control. CONCLUSIONS: Duplex scanning showed 100% accuracy both in determining the presence of thrombosis and its extent. Saphenofemoral disconnection for thrombosis involving the saphenofemoral junction is a safe procedure and can be performed on an outpatient basis.     

Matrix metalloproteinases in the vein wall.

AIM: Matrix metalloproteinases contribute to extracellular matrix remodelling that can influence mechanical properties of the vein wall and predispose to varicose veins development. The aim of the study was to assess the following matrix metalloproteinases in the wall of varicose veins: tissue collagenase I (MMP-1), gelatinase A (MMP-2), gelatinase B (MMP-9) and stromelysin 1 (MMP-3). METHODS: Normal, varicose and varicose veins complicated by thrombophlebitis were collected during the surgical treatment of 26 patients. In harvested tissues the presence of gelatinases was detected with zymography, contents of MMP-1, MMP-2, MMP-3 and MMP-9 were evaluated with ELISA, activity of MMP-1 was assessed with HPLC and activity of MMP-2 with ELISA. RESULTS: Zymography demonstrated particularly high contents of both gelatinases in the wall of varicose veins complicated by thrombophlebitis. The contents of MMP-1, MMP-2 and MMP-9 were significantly increased only in the wall of varicose veins complicated by thrombophlebitis, whereas the increased content of MMP-3 was also found in the wall of varicose veins. A significantly higher activity of MMP-1 was shown only in the wall of varicose veins complicated by thrombophlebitis, whereas an active form of MMP-2 was increased in the wall of varicose, as well as varicose veins complicated by thrombophlebitis, when compared with normal ones. CONCLUSION: The wall of varicose veins, particularly those complicated by thrombophlebitis shows extensive alterations in the content and activity of matrix metalloproteinases, that may result in extracellular matrix remodelling, influence mechanical properties of the vein wall and predispose to further progression of the disease.     

No difference in risk for thrombocytopenia during treatment of pulmonary embolism and deep venous thrombosis with either low-molecular-weight heparin or unfractionated heparin: a metaanalysis

BACKGROUND: Low-molecular-weight heparin (LMWH) is a popular alternative to unfractionated heparin (UH) for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), in part based on the perception of a lower risk for heparin-induced thrombocytopenia (HIT). To investigate the evidence supporting this perception, we performed a metaanalysis to compare the incidence of thrombocytopenia between LMWH and UH during PE and/or DVT treatment. METHODS: Randomized trials comparing LMWH with UH for PE and/or DVT treatment were searched for in the MEDLINE database, bibliographies, and by correspondence with published investigators. Two reviewers independently selected high-quality studies and extracted data regarding heparin-associated thrombocytopenia (HAT), HIT confirmed by laboratory testing, and heparin-induced thrombocytopenia with thrombosis (HITT). Outcome rates between LMWH and UH were compared using a binomial, generalized linear mixed model with a logit link and Gaussian random effects for study. RESULTS: Thirteen studies involving 5,275 patients met inclusion criteria. There were no statistically significant differences in HAT rates between the two treatments (LMWH, 1.2%; UH, 1.5%; p = 0.246). The incidence of documented HIT and HITT was too low to make an adequate comparison between groups. CONCLUSIONS: Our review disclosed no statistically significant difference in HAT between LMWH and UH and insufficient evidence to conclude that HIT and HITT rates were different between them. There was no evidence from randomized comparative trials to support the contention that patients receiving treatment for PE or DVT with UH are more prone to these complications than those receiving LMWH.     

External banding valvuloplasty of the superficial femoral vein in the treatment of recurrent varicose veins.

OBJECTIVES: The aim of this study is to evaluate the efficacy of reconstructive surgery of primary deep venous insufficiency in preventing recurrent varicose veins. DESIGN: Retrospective analysis of patients affected by recurrent varicose veins submitted to external banding valvuloplasty of the superficial femoral vein. SETTING: A division of vascular surgery in a hospital/scientific institute. MATERIALS: Nineteen limbs (19 patients) with recurrent varicose veins, severe chronic venous insufficiency and 3rd or 4th grade reflux in the superficial femoral vein and competence of the profunda femoris vein were selected for surgical reconstructive treatment after a complete diagnostic study by continuous wave Doppler duplex scanning and descending phlebography. INTERVENTIONS: External banding valvuloplasty of the superficial femoral vein was performed in all cases: A Dacron sleeve was used in nine patients and Venocuff in 10. RESULTS: In one case a deep venous thrombosis of the calf occurred in the first postoperative period; in three cases the correction of the deep reflux was incomplete and a recurrence of the varices was observed. After a mean follow-up of 50 months, abolition of reflux and relief of symptomatology were obtained in 15 cases (78%). CONCLUSIONS: Primary deep venous insufficiency, unknown at the time of the initial operation, may be the cause of recurrent varicose veins. External banding valvuloplasty of the superficial femoral vein may abolish the reflux and correct venous hypertension, preventing recurrences.     

Effectiveness and safety of ultrasound-guided foam sclerotherapy for recurrent varicose veins: immediate results.

PURPOSE: To evaluate the effectiveness and safety of ultrasound-guided foam sclerotherapy in treating recurrent varicose veins. METHODS: Between July 2003 and January 2005, 38 outpatients (25 women; median age 59 years, interquartile range 53.5-66.0) with recurrent varicose veins in 45 legs were treated. Ultrasound was used to identify sites of reflux. The Tessari method was used to produce foam using 3% sodium tetradecyl sulphate; up to 6 mL of foam was injected per session under ultrasound control. Results are shown as median (interquartile range). RESULTS: A single sclerotherapy session was adequate in 26 (58%) legs. In 87% of all legs, complete elimination of both varicose veins and all reflux points was achieved. A positive association between the amount of injected foam and CEAP class (r=0.45, p=0.002) and venous clinical severity score (r=0.37, p=0.012) was found. There was a trend for more sclerotherapy sessions [median 2 (1-2)] in legs with incomplete saphenofemoral junction/ great saphenous vein (GSV) ligation or accessory GSV (n=16) to achieve varicose vein ablation versus legs with other primary sites of reflux [median 1 (1-2), p=0.12]. There were no instances of deep vein thrombosis or systemic complications; superficial thrombophlebitis occurred in 6 (8.2%) of the 73 injection sessions. Legs with proximal reflux due to previous incomplete ligation or fed by an incompetent pelvic vein experienced superficial thrombophlebitis more frequently (4/12, 33%) than legs without proximal reflux [1/33 (3%); OR 16, 95% CI 1.6-164, p=0.014]. CONCLUSION: In most patients, ultrasound-guided foam sclerotherapy is a safe treatment for recurrent varicose veins, with an excellent immediate result. However, the presence of proximal reflux may decrease the immediate results and predispose to superficial thrombophlebitis.     

Venous thromboembolism associated with long-term use of central venous catheters in cancer patients

OBJECTIVES: Increased incidence of cancers and the development of totally implanted venous access devices that contain their own port to deliver chemotherapy will lead to a greater than before numbers of central venous catheter related thrombosis (CVCT). Medical consequences include catheter dysfunction and pulmonary embolism. Compared with lower extremity deep venous thrombosis (DVT) (3 d) and with non CVC associated thrombosis (5 d), CVCT is associated with an increased duration of hospitalisation (9 d). CVCT oftentimes leads to the need to replace such ports at an average cost of 4500 euros. CURRENT KNOWLEDGE AND KEY POINTS: Vessel injury caused by the procedure of CVC insertion is the most important risk factor for development of CVCT. This event could cause the formation of a fresh thrombus, which is reversible in the large majority of patients. The incidence of CVC-related DVT assessed by venography has been reported to vary from 30 to 60% but catheter-related DVT in adult patients is symptomatic in only 5% of cases. The majority of patients with CVC-related DVT is asymptomatic or has non-specific symptoms: arm or neck swelling or pain, distal paresthesias, headache, congestion of subcutaneous collateral veins. In the case of clinical suspicion of CVC-related DVT, compressive ultrasonography (US), especially with Doppler and color imaging, currently is first used to confirm the diagnosis. The main criteria of color-Doppler US are visualization of mural thrombi or incompressibility of the veins. Consequently, contrast venography is reserved for clinical trials and difficult diagnostic situations. There is no consensus on the optimal management of patients with CVC-related DVT. Treatment of CVC-related VTE requires a 5- to 7-day course of adjusted-dose unfractionated heparin or LMWH followed by oral anticoagulants. Long-term LMWH that has been shown to be more effective than oral anticoagulant in cancer patients with lower limb DVT could be used in these patients. The optimal duration of oral anticoagulation treatment for CVC-related DVT is unknown, but patients with active cancer should be treated for at least 6 months or indefinitely. FUTURE PROSPECTS AND PROJECTS: The efficacy and safety of pharmacologic prophylaxis for CVC related thrombosis is not established. Additional studies performed in high risk populations are needed to define if LMWH or oral anticoagulation is indicated in this clinical setting.     

Venous thrombosis from air travel: the LONFLIT3 study--prevention with aspirin vs low-molecular-weight heparin (LMWH) in high-risk subjects: a randomized trial

The LONFLIT1 and 2 studies established that in high-risk subjects after long (>10 hours) flights, the incidence of deep venous thrombosis (DVT) may be between 4% and 6%, The LONFLIT3 study aimed to evaluate methods of prevention in high-risk subjects. Of 467 subjects contacted for the study, 300 were included. These 300 subjects at high risk for DVT were randomized, after informed consent, into three groups: 1) a control group that had no prophylaxis; 2) an aspirin treatment group, in which patients were treated with 400 mg (tablets of oral, soluble aspirin; one dose daily for 3 days, starting 12 hours before the beginning of the flight); and 3) a low-molecular-weight heparin (LMWH) group, in which one dose of enoxaparine was injected between 2 and 4 hours before the flight. The dose was weight-adjusted (1,000 IU [equivalent to 0.1 mL per 10 kg of body weight). Subjects with potential problems due to prophylaxis with aspirin or LMWH or at risk of drug interactions were excluded. Of the 100 included subjects in each group, a total of 249 subjects completed the study (dropouts due to low compliance or traveling/connections problems were 17%). Age and sex distribution were comparable in the three groups as well as risk distributions. Mean age was 47 (range, 28-75; SD, 11; 65% males). Of the 82 subjects in the control group, there were 4.82% of subjects with DVT with two superficial thromboses. In total 4.8% of limbs suffered a thrombotic event. Of 84 subjects in the aspirin treatment group, there were 3.6% of patients with DVT and three superficial thrombosis. In total 3.6% of limbs had a thrombotic event. In the LMWH group (82 subjects), there were no cases of DVT. One superficial thrombosis was documented. In total only 0.6% of limbs had a thrombotic event (p<0.002 in comparison with the other two groups). DVT was asymptomatic in 60% of subjects; 85% of DVTs were observed in passengers in non-aisle seats. Mild gastrointestinal symptoms were reported in 13% of patients taking aspirin. One dose of LMWH is an important option to consider in high-risk subjects during long-haul flights.     

Mondor's disease of the penis following a long-haul flight

Mondor's disease of the penis, otherwise known as superficial thrombophlebitis (STP) or thrombosis of the dorsal vein, is an under-reported benign condition, the aetiology of which is poorly understood. It is characterized by a sudden, indurated swelling of the vein, often occurring after vigorous sexual activity. We report a case of Mondor's disease occurring 24 h following a 15-h flight. This gentleman also reported a history of STP of his left lower limb varicose veins following a similar-length flight three years previously. In the absence of any other clear predisposing factor, we propose long-haul flight as an important factor contributing to the development of dorsal vein thrombosis.