Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism.

BACKGROUND: The standard initial treatment of hemodynamically stable patients with pulmonary embolism is intravenous unfractionated heparin, requiring laboratory monitoring and hospitalization. METHODS: We conducted a randomized, open-label trial involving 2213 patients with acute symptomatic pulmonary embolism to compare the efficacy and safety of the synthetic antithrombotic agent fondaparinux with those of unfractionated heparin and to document noninferiority in terms of efficacy. Patients received either fondaparinux (5.0, 7.5, or 10.0 mg in patients weighing less than 50, 50 to 100, or more than 100 kg, respectively) subcutaneously once daily or a continuous intravenous infusion of unfractionated heparin (ratio of the activated partial-thromboplastin time to a control value, 1.5 to 2.5), both given for at least five days and until the use of vitamin K antagonists resulted in an international normalized ratio above 2.0. The primary efficacy outcome was the three-month incidence of the composite end point of symptomatic, recurrent pulmonary embolism (nonfatal or fatal) and new or recurrent deep-vein thrombosis. RESULTS: Forty-two of the 1103 patients randomly assigned to receive fondaparinux (3.8 percent) had recurrent thromboembolic events, as compared with 56 of the 1110 patients randomly assigned to receive unfractionated heparin (5.0 percent), for an absolute difference of -1.2 percent in favor of fondaparinux (95 percent confidence interval, -3.0 to 0.5). Major bleeding occurred in 1.3 percent of the patients treated with fondaparinux and 1.1 percent of those treated with unfractionated heparin. Mortality rates at three months were similar in the two groups. Of the patients in the fondaparinux group, 14.5 percent received the drug in part on an outpatient basis. CONCLUSIONS: Once-daily, subcutaneous administration of fondaparinux without monitoring is at least as effective and is as safe as adjusted-dose, intravenous administration of unfractionated heparin in the initial treatment of hemodynamically stable patients with pulmonary embolism.

Effect of obesity on outcomes after fondaparinux, enoxaparin, or heparin treatment for acute venous thromboembolism in the Matisse trials.

BACKGROUND: Selecting initial anticoagulant dose by patient weight for acute pulmonary embolism and deep vein thrombosis has clinical credibility; however, uncertainty remains regarding how to dose obese patients with newer anticoagulants because outcome data are sparse. OBJECTIVES: To use the Matisse trials' comparison of sc fondaparinux once daily with control heparin therapies (intravenous unfractionated heparin for pulmonary embolism, sc enoxaparin 1 mg/kg b.i.d. for deep vein thrombosis) for initial treatment in order to compare primary outcomes (venous thromboembolism recurrence and major bleeding) in obese patients. PATIENTS AND METHODS: Primary outcomes were compared in subsets composed of patients weighing < or = and > 100 kg and with body mass index (BMI) < 30 and > or = 30 kg/m(2). Medians and ranges for weight and BMI were compared for patients suffering either recurrence or major bleeding. RESULTS: Twenty-two thousand and one patients received fondaparinux and 2217 received enoxaparin or unfractionated heparin. Four hundred and ninety-six patients (11%) weighed > 100 kg and 1216 (28%) had a BMI > or = 30. Treatment groups had similar characteristics. The upper limit in subject weight for recurrence was 166 kg (BMI 58), and for major bleeding 120 kg (BMI 39). The incidences of recurrence and major bleeding were similar for each patient subset of weight and BMI for both fondaparinux and heparin treatment groups. Among patients with a primary outcome, median weights and BMIs were also similar. CONCLUSIONS: The current recommended doses of fondaparinux and heparins for the treatment of venous thromboembolism appear to provide similar protection against recurrence and major bleeding to one another and to obese and non-obese patients.

New agents in medical oncology and the risk of venous thromboembolism.

Over the past several years the medical approach to cancer patients has made important steps forward both in the field of novel, selective, antiproliferative agents and more effective supportive therapies. A greater understanding of the molecular pathways regulating cell proliferation and metastasis has led to the identification of a range of targets specifically inhibited by these new drugs. The clinical development of these compounds (the so called "targeted therapies") has shown distinctive adverse effects with respect to standard chemotherapeutic agents but the potential increasing risk of venous thromboembolism remains unvaried. In fact, the incidence of this potentially life-threatening complication in patients receiving standard chemotherapy ranges from about 11% to 20% and even more depending on the type of drug administered and on the possible association with other anti-neoplastic and supportive therapies. In this paper we reviewed all the available evidences concerning the increasing risk of venous thromboembolism in cancer patients during treatment with new agents currently used in medical oncology together with data concerning the clinical value of a concomitant prophylactic anticoagulation. At present, additional information concerning safety in terms of thromboembolic risk of novel biological and molecular therapies should be collected from specifically designed original basic science studies and clinical trials in order to optimize their use in current oncology practice.

Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement.

BACKGROUND: With the best prophylactics now available, venous thromboembolism after total knee replacement remains substantial (25% to 27%). Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of factor VIIa/tissue factor complex that has the potential to reduce this risk. The present study was performed to determine an efficacious and safe dose of rNAPc2 for prevention of venous thromboembolism after elective, unilateral total knee replacement. METHODS AND RESULTS: This open-label, sequential dose-ranging study was conducted in 11 centers in Canada, Europe, and the United States. Five regimens were tested. Injections were administered subcutaneously on the day of surgery (day 1) and days 3, 5, and optionally, day 7. Primary efficacy outcome was a composite of overall deep vein thrombosis based on mandatory unilateral venography (day 7+/-2) and confirmed symptomatic venous thromboembolism recorded

A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial.

BACKGROUND: Dabigatran etexilate is an oral direct thrombin inhibitor undergoing evaluation for the prevention of venous thromboembolism (VTE) following orthopedic surgery. METHODS: In a multicenter, parallel-group, double-blind study, 1973 patients undergoing total hip or knee replacement were randomized to 6-10 days of oral dabigatran etexilate (50, 150 mg twice daily, 300 mg once daily, 225 mg twice daily), starting 1-4 h after surgery, or subcutaneous enoxaparin (40 mg once daily) starting 12 h prior to surgery. The primary efficacy outcome was the incidence of VTE (detected by bilateral venography or symptomatic events) during treatment. RESULTS: Of the 1949 treated patients, 1464 (75%) patients were evaluable for the efficacy analysis. VTE occurred in 28.5%, 17.4%, 16.6%, 13.1% and 24% of patients assigned to dabigatran etexilate 50, 150 mg twice daily, 300 mg once daily, 225 mg twice daily and enoxaparin, respectively. A significant dose-dependent decrease in VTE occurred with increasing doses of dabigatran etexilate (P < 0.0001). Compared with enoxaparin, VTE was significantly lower in patients receiving 150 mg twice daily [odds ratio (OR) 0.65, P = 0.04], 300 mg once daily (OR 0.61, P = 0.02) and 225 mg twice daily (OR 0.47, P = 0.0007). Compared with enoxaparin, major bleeding was significantly lower with 50 mg twice daily (0.3% vs. 2.0%, P = 0.047) but elevated with higher doses, nearly reaching statistical significance with the 300 mg once-daily dose (4.7%, P = 0.051). CONCLUSIONS: Oral administration of dabigatran etexilate, commenced early in the postoperative period, was effective and safe across a range of doses. Further optimization of the efficacy/safety balance will be addressed in future studies.

Deep-vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography.

BACKGROUND: The incidence of postsurgical venous thromboembolism is thought to be low in Asian ethnic populations. OBJECTIVE: We studied the incidence of deep-vein thrombosis (DVT) in Asian patients undergoing major orthopedic surgery of the lower limbs. PATIENTS/METHODS: We performed a prospective epidemiological study in 19 centers across Asia (China, Indonesia, South Korea, Malaysia, Philippines, Taiwan, and Thailand) in patients undergoing elective total hip replacement (THR), total knee replacement (TKR) or hip fracture surgery (HFS) without pharmacological thromboprophylaxis. The primary endpoint was the rate of DVT of the lower limbs documented objectively with bilateral ascending venography performed 6-10 days after surgery using a standardized technique and evaluated by a central adjudication committee unaware of local interpretation. RESULTS: Overall, of 837 Asian patients screened for this survey, 407 (48.6%, aged 20-99 years) undergoing THR (n = 175), TKR (n = 136) or HFS (n = 96) were recruited in 19 centers. DVT was diagnosed in 121 of 295 evaluable patients [41.0%, (95% confidence interval (CI): 35.4-46.7)]. Proximal DVT was found in 30 patients [10.2% (7.0-14.2)]. Total DVT and proximal DVT rates were highest in TKR patients (58.1% and 17.1%, respectively), followed by HFS patients (42.0% and 7.2%, respectively), then THR patients (25.6% and 5.8%, respectively). DVT was more frequent in female patients aged at least 65 years. Pulmonary embolism was clinically suspected in 10 of 407 patients (2.5%) and objectively confirmed in two (0.5%). CONCLUSIONS: The rate of venographic thrombosis in the absence of thromboprophylaxis after major joint surgery in Asian patients is similar to that previously reported in patients in Western countries.

Does the type of hormone replacement therapy influence the risk of deep vein thrombosis? A prospective case-control study.

BACKGROUND: Although hormone replacement therapy (HRT) is associated with an increased risk of deep vein thrombosis (DVT), it is not clear if the risk differs in users of combined estrogen-progestin HRT and estrogen-only HRT. METHODS: We prospectively studied postmenopausal women with suspected DVT in whom HRT use status was ascertained and who subsequently had objective diagnostic testing to confirm or exclude DVT. Cases were patients with idiopathic DVT, in whom there were no DVT risk factors, and controls were patients without DVT, in whom there were also no DVT risk factors. The risk of DVT was determined in users of estrogen-progestin HRT and estrogen-only HRT by comparing the prevalence of current HRT use in cases with idiopathic DVT and controls without DVT (reference group). Multivariable regression analysis was done to adjust for factors that might confound an association between HRT use and the risk of DVT. RESULTS: One thousand one hundred and sixty-eight postmenopausal women with suspected DVT were assessed, from whom 95 cases of idiopathic DVT and 610 controls without DVT and no DVT risk factors were identified. Estrogen-only HRT was associated with an increased risk for DVT that was not statistically significant [odds ratio (OR) = 1.22; 95% confidence interval (CI) 0.57, 2.61]. Estrogen-progestin HRT was associated with a greater than 2-fold increased risk for DVT (OR = 2.70; 95% CI 1.44, 5.07). CONCLUSION: The risk of developing DVT may be higher in users of combined estrogen-progestin HRT than in users of estrogen-only HRT.

Congenital antithrombin III deficiency. Incidence and clinical features.

Antithrombin III (ATIII) deficiency is inherited as an autosomal dominant trait. Three types of ATIII deficiency are recognized clinically. The prevalence of ATIII deficiency is uncertain; it has been estimated to occur in between one in 2,000 and one in 20,000 subjects. ATIII deficiency is found in between 4 and 6 percent of young patients with venous thrombosis, similar to but slightly lower than the prevalence of protein C and protein S deficiency in young subjects with thrombosis. The chances of finding a deficiency is increased if there is a history of familial or recurrent venous thrombosis. Cross-sectional reports in the literature are that between 30 and 80 percent of carriers have thrombosis. Thrombosis is uncommon in the first decade, but the risk rises sharply between the ages of 15 and 30. The major clinical manifestations of ATIII deficiency are young age at onset, idiopathic thrombosis, family history, and recurrent venous thromboembolism. Pregnancy and surgery are predisposing factors. Approaches to prophylaxis and treatment are discussed.

Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis.

PURPOSE: To obtain reliable estimates of the relative efficacy and safety of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) in the treatment of patients with venous thromboembolism. METHODS: A literature search of randomized trials evaluating LMWH and UFH for the period from 1980 to 1994 was conducted to obtain data for a meta-analysis. Studies were classified as level 1 if they were double-blind or if there was blinded assessment of outcome measures, and level 2 if they did not provide assurance of blinded outcome assessment. RESULTS: In level 1 studies, the relative risk (RR) of recurrent venous thromboembolism during the first 15 days and over the entire period of anticoagulant therapy was 0.24 (95% confidence intervals [CI] 0.06 to 0.80, P = 0.02) and 0.39 (95% CI 0.30 to 0.80, P = 0.006), respectively, in favor of LMWH treatment. The RR for major bleeding was 0.42 (95% CI 0.2 to 0.9, P = 0.01), in favor of LMWH. In level 2 studies, no significant differences in the rates of recurrent venous thromboembolism or major bleeding were observed. Pooling level 1 and level 2 studies, the RR for overall mortality and mortality in cancer patients was 0.51 (95% CI 0.2 to 0.9, P = 0.01), and 0.33 (95% CI 0.1 to 0.8, P = 0.01), respectively in favor of LMWH. CONCLUSIONS: LMWH are likely to be more effective than UFH in preventing recurrent venous thromboembolism, to produce less major bleeding, and to be associated with a lower mortality rate, particularly in the subgroup of patients with cancer.

Defect of platelet aggregation and adhesion induced by autoantibodies against platelet glycoprotein IIIa.

A young patient developed chronic idiopathic thrombocytopenic purpura. Prednisone therapy normalized platelet number, but bleeding symptoms did not disappear. Platelet function was severely impaired, since platelet aggregation, ATP release and adhesion to collagen and subendothelial matrix were significantly reduced. Plasma and purified immunoglobulins of the patient reproduced the functional defects in normal platelets. Immunoblotting revealed that patient's plasma contained an antibody reacting with a component of platelets with the same electrophoretic mobility of glycoproteins IIIa of normal platelets. Moreover, patient's plasma inhibited the binding of an anti-GPIIb/IIIa monoclonal antibody to platelet surface. Additional immunosuppressive therapy with prednisone and azathioprine normalized platelet function and induced the disappearance of bleeding symptoms.

Protection of low density lipoprotein oxidation at chemical and cellular level by the antioxidant drug dipyridamole.

1. The oxidative modification of low density lipoprotein (LDL) is thought to be an important factor in the initiation and development of atherosclerosis. Natural and synthetic antioxidants have been shown to protect LDL from oxidation and to inhibit atherosclerosis development in animals. Synthetic antioxidants are currently being tested, by they are not necessarily safe for human use. 2. We have previously reported that dipyridamole, currently used in clinical practice, is a potent scavenger of free radicals. Thus, we tested whether dipyridamole could affect LDL oxidation at chemical and cellular level. 3. Chemically induced LDL oxidation was made by Cu(II), Cu(II) plus hydrogen peroxide or peroxyl radicals generated by thermolysis of 2,2'-azo-bis(2-amidino propane). Dipyridamole, (1-10 microM), inhibited LDL oxidation as monitored by diene formation, evolution of hydroperoxides and thiobarbituric acid reactive substances, apoprotein modification and by the fluorescence of cis-parinaric acid. 4. The physiological relevance of the antioxidant activity was validated by experiments at the cellular level where dipyridamole inhibited endothelial cell-mediated LDL oxidation, their degradation by monocytes, and cytotoxicity. 5. In comparison with ascorbic acid, alpha-tocopherol and probucol, dipyridamole was the more efficient antioxidant with the following order of activity: dipyridamole > probucol > ascorbic acid > alpha-tocopherol. The present study shows that dipyridamole inhibits oxidation of LDL at pharmacologically relevant concentrations. The inhibition of LDL oxidation is unequivocally confirmed by use of three different methods of chemical oxidation, by several methods of oxidation monitoring, and the pharmacological relevance is demonstrated by the superiority of dipyridamole over the naturally occurring antioxidants, ascorbic acid and alpha-tocopherol and the synthetic antioxidant probucol.

Digital clubbing associated with pulmonary artery sarcoma.

A case of digital clubbing in a patient with pulmonary artery sarcoma and severe pulmonary hypertension is presented. The differential diagnosis of clubbing and clinical features of pulmonary artery sarcoma are reviewed with emphasis on the possible association of clubbing with pulmonary artery sarcoma.

The effect of ticlopidine on human endothelial cells in culture.

The effect of ticlopidine at various concentrations (150, 30, 6 microM), has been studied on cultured endothelial cells derived from human umbilical cord vein. Ticlopidine affects the initial attachment of endothelial cells to artificial substrata and has an inhibitory effect on endothelial cell growth rate which correlates to the concentration of the chemical in the culture medium. These effects are related to a marked reduction of intra- and extracellular fibronectin as evidentiated by immunofluorescence. The drug seems to interfere with the formation of fibronectin filaments from intracellular granules. The reduction of fibronectin availability could affect platelet adhesion to subendothelium as well as endothelial cell repair, and subsequently influence the bleeding time. The inhibition of cell proliferation and its possible effect on the thickness of the vessel wall should be considered as additional mechanisms of action for this substance.

Can causes of false-normal D-dimer test [SimpliRED] results be identified?

BACKGROUND: To simplify the diagnostic strategy of patients suspected for venous thromboembolism, the use of D-dimer tests has been advocated. Very important for the safety of such diagnostic strategies would be the capacity to recognise false-normal D-dimer results, in order to prevent inadequately withholding anticoagulant treatment in patients who actually have the disease. Insight in the causes of false-normal D-dimer results would therefore be necessary. We hypothesised that certain patient characteristics are associated with relatively low plasma D-dimer levels and, therefore, could increase the risk of false-normal results. METHODS: Consecutive patients with an objectively confirmed venous thromboembolic event and an independently obtained false-normal SimpliRED D-dimer test result were included in the study. For each patient, two controls with objectively confirmed venous thromboembolism and an adequate abnormal D-dimer result were selected. Baseline patient characteristics, obtained by standardised questionnaires, were compared between the two groups of patients. RESULTS: In total, 686 patients had a venous thromboembolic event and 47 of these patients had a false-normal SimpliRED result. Therefore, the overall sensitivity of the SimpliRED test for venous thromboembolism was 94% (95% CI: 92-95%). Although the prevalence of certain clinical characteristics was significantly higher in patients with a false-normal D-dimer result than in the controls [odds ratios for (LMW)heparin treatment and symptoms lasting more than 10 days: 5.1 (95% CI: 1.5-18.7) and 3.2 (95% CI:1.4-7.4), respectively], the prevalence of these characteristics was also high in the control group with an adequate abnormal D-dimer. Combining two or more of these characteristics had a low prevalence and did not further improve the ability to identify those patients with a false-normal D-dimer test at presentation. CONCLUSIONS: Although these findings clearly indicate an association between certain baseline clinical characteristics and the occurrence of a false-normal SimpliRED test, the clinical utility for these characteristics is limited.

Long-term management of deep vein thrombosis.

A venous thromboembolic event may cause substantial long-term morbidity despite the best available treatment. Venous thromboembolism (VTE) recurs in approximately 30% of patients within eight years of the acute event, and a similar proportion develop post-thrombotic syndrome, imposing a notable clinical and financial burden. Conventional treatment of VTE comprises an initial 5-10 day course of intravenous unfractionated heparin (UFH), followed by oral anticoagulants for 3-6 months. Thrombolytic therapy, vena caval filters and surgical thrombectomy are reserved for patients with complications. Alternative approaches, including more intensive initial anticoagulation or extended secondary prevention, may improve long-term outcomes. Low-molecular-weight heparins (LMWHs) are at least as effective as UFH in acute therapy and are suitable for home treatment, offering the potential for cost reductions and improved patient convenience. Consequently, LMWHs are replacing UFH in initial treatment of VTE. The optimal duration of secondary VTE prophylaxis remains uncertain. Extended therapy with LMWH reduces the frequency of VTE recurrence, but routine use of prolonged therapy is not economically viable. Targeting extended therapy to patients at greatest risk of recurrence, for example, patients with identified congenital thrombophilia, would maximize cost-effectiveness. Comprehensive risk assessment models are now needed to stratify patients for primary VTE risk level, allowing appropriate targeting of prophylaxis, more intensive initial treatment or extended therapy for acute VTE.

Pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension: hemodynamic characteristics and changes.

OBJECTIVE: To see whether degree of pulmonary hypertension or severity of cardiac failure affect the success of pulmonary thromboendarterectomy (PTE) in chronic thromboembolic pulmonary hypertension. METHODS: From May 1996 to June 1999, 33 patients, all in New York Heart Association (NYHA) class 3 or 4 were treated with PTE. Preoperative hemodynamic values were: central venous pressure (CVP) 8+/-6 (1-23), mean pulmonary artery pressure (mPAP) 50+/-10 (30-69), cardiac output (CO) 3.3+/-0.9 (1.8-5.2), pulmonary vascular resistance (PVR) 1056+/-344 (523-1659), and right ventricle ejection fraction (RVEF) 12+/-5 (5-21). To establish whether some hemodynamic or cardiac variables correlate with surgical failure (early death or functional non-success), these patients were divided into a low risk or a high risk group for each variable: CVP (<9 or > or =9), mPAP (<50 or > or =50), CO (> or =3.5 or <3.5), PVR (> or =1100 or <1100), and RVEF (> or = 10 or <10). The duration of 3-4 NYHA class period (<24 or > or = 24 months) was also included in the study. RESULTS: Three patients (9. 1%) died in hospital, one (3.0%) underwent lung transplant shortly after PTE, and in five cases (15.2%) mPAP and PVR at the 3-month follow-up examination corresponded with our definition of functional nonsuccess (mPAP and PVR decreased by less than 40% of preoperative values). One of the five functional nonsuccess patients underwent lung transplant 3 months after the operation and another died 17 months after the operation from a non-related cause. Thus PTE was successful in 24 patients and unsuccessful in nine. None of the hemodynamic variables considered was found to be associated with the disparate outcomes. At the 3-month examination, all surviving patients were in NYHA class 1 or 2 except for three in NYHA class 3. At 2 years, hemodynamic values were: CVP 2+/-2 (0-4), mPAP 16+/-3 (12-21), CO 5.0+/-1.0 (3.4-6.5), PVR 182+/-51 (112-282), and RVEF 35+/-5 (26-40). All differences were significant with respect to baseline values (P<0.001). Preoperative mPAP and RVEF values had a strict linear correlation (R=0.45; P=0.014). CONCLUSIONS: None of the variables considered was correlated with early death or functional nonsuccess. Neither preoperative severity of pulmonary hypertension nor degree of cardiac failure influenced the outcome of the operation. PTE leads to hemodynamic recovery even in very compromised patients.

P-selectin and von Willebrand factor in bovine mesenteric lymphatics: an immunofluorescent study.

P-selectin (PADGEM, GMP-140, CD62) is an integral membrane protein specific to alpha granules of platelets and Weibel-Palade bodies of blood vascular endothelial cells. The presence in lymphatic endothelial cells of numerous Weibel-Palade bodies and their positivity to immunocytochemical reaction for von Willebrand factor have previously been characterized and described. Because von Willebrand factor and P-selectin codistribute in Weibel-Palade bodies of blood vascular endothelial cells we investigated the presence of both P-selectin and von Willebrand factor in lymphatic endothelium. Lymphatic vessels expressed positive reaction to immunocytochemical assay thereby demonstrating the presence of P-selectin in the endothelium. Distribution and intensity of the reaction were similar to those observed in bovine blood vascular endothelium.

[Clinical course and incidence of post-thrombophlebitic syndrome after profound asymptomatic deep vein thrombosis. Results of a transverse epidemiologic study]. / Decorso clinico ed incidenza della sindrome post-tromboflebitica dopo trombosi venosa profonda asintomatica. Risultani di uno studio epidemiologico trasversale.

UNLABELLED: Currently, there are not reliable data on the incidence and prevalence of post-phlebitic syndrome (PTS) after an episode of asymptomatic postoperative deep vein thrombosis (DVT). In order to evaluate the epidemiology and the clinical course of PTS in patients who were submitted to hip and knee replacement, we performed a cross sectional study in orthopedic patients with previous asymptomatic postoperative DVT. For reducing potential biases, we used currently accepted and objectively documented criteria to define the clinical manifestations and severity of PTS. RESULTS: 98 of 217 (45.1%) patients, who underwent orthopedic surgery in the previous 2-4 years, have been included in the study. 46 of them (46.9%) had postoperative asymptomatic DVT, confirmed by venograph 23.9% satisfied criteria to be classified as having PTS. When compared with the control group (PTS 3.8%), the difference in the incidence of PTS was statistically significant (p = 0.03). The comparison of the distribution of proximal and distal thrombi in patients with PTS showed that proximal venous involvement constitutes and independent risk factor for developing PST (RR 4). We conclude that: a) about 24% of patients with previous asymptomatic postoperative DVT developed the SPT in the following 2-4 years, b) in asymptomatic DVTs, the localization of thrombi in the proximal venous segment is the most important independent risk factor for the PTS. Therefore, these results can influence the use and the choice of an adequate antithrombotic prophylaxis for reducing the incidence of postoperative proximal DVT.

[Venous thromboembolism: epidemiology and risk factors]. / Tromboembolismo venoso. Epidemiologia e fattori di rischio.

The prevalence of DVT in the general community has been estimated from large descriptive studies of symptomatic patients; the annual incidence of proximal DVT has been reported to be 48 cases for 100,000. When associated to known risk factors, the incidence of DVT is strongly elevated; postoperative DVT occurs, for instance, in 5% to 40% of patients undergoing surgical procedures. Estimated of the incidence and prevalence of PE are less reliable than for DVT because the ante-morten diagnosis of PE is difficult and the post-mortem diagnosis highly selective. An analysis conducted on 11,000 autopsies showed that 316 of these had macroscopic pulmonary emboli; nevertheless, 11% of cases only had the diagnosis before death, while 32% of the patients were diagnosed as died of myocardial infarction, 15% of cerebrovascular disease and 14% of pneumonia. Update results, indicate that mortality due to PE is the first cause of death in hospitalized patients. Venous thromboembolism is a common disease often misdiagnosed because of low accuracy of clinical diagnosis; correct approaches for prophylaxis, therapy and to diagnosis are necessary to manage high-risk patients for DVT and/or PE and to reduce costs and social impact.

D-dimer testing as an adjunct to ultrasonography in patients with clinically suspected deep vein thrombosis: prospective cohort study. The Multicentre Italian D-dimer Ultrasound Study Investigators Group.

OBJECTIVE: To investigate the efficacy of using a rapid plasma D-dimer test as an adjunct to compression ultrasound for diagnosing clinically suspected deep vein thrombosis. DESIGN: D-dimer concentrations were determined in all patients with a normal ultrasonogram at presentation. Repeat ultrasonography was performed 1 week later only in patients with abnormal D-dimer test results. MAIN OUTCOME AND MEASURES: Patients with normal ultrasonograms were not treated with anticoagulants and were followed for 3 months for thromboembolic complications. SETTING: University research and affiliated centres. SUBJECTS: 946 patients with clinically suspected deep vein thrombosis. RESULTS: Ultrasonograms were abnormal at presentation in 260 (27.5%) patients. Of the remaining 686 patients tested for D-dimer, 88 (12.8%) had abnormal concentrations. During follow up venous thromboembolic complications occurred in one of the 598 patients who were not treated with anticoagulants and who had an initial normal ultrasonogram and D-dimer concentration, whereas thromboembolic complications occurred in two of the 83 untreated patients who had abnormal D-dimer concentrations but a normal repeat ultrasonogram. The cumulative incidence of venous thromboembolic complications during follow up was 0.4% (95% confidence interval 0% to 0.9%). The rapid plasma D-dimer test used as an adjunct to compression ultrasonography resulted in a reduction in the mean number of repeat ultrasound examinations and additional hospital visits from 0.7 to 0.1 per patient. CONCLUSIONS: Testing for D-dimer as an adjunct to a normal baseline ultrasound examination decreased the number of subsequent ultrasound examinations considerably without any increased risk of venous thromboembolic complications in patients not receiving anticoagulants. The use of ultrasound and testing for D-dimer enabled treatment decisions to be made at the time of presentation in most patients.