Long-term recurrence of venous thromboembolism after short-term treatment of symptomatic isolated distal deep vein thrombosis: A cohort study.

Isolated distal deep vein thrombosis (IDDVT) is a common clinical manifestation of venous thromboembolism (VTE). However, there are only scant and heterogeneous data available on the long-term risk of recurrent VTE after IDDVT, and the optimal therapeutic management remains uncertain. We carried out a retrospective cohort study of consecutive patients diagnosed with symptomatic IDDVT between 2004 and 2011, according to a predefined short-term treatment protocol (low molecular weight heparin (LMWH) for 4-6 weeks). The primary outcome was the occurrence of recurrent VTE. A total of 321 patients were enrolled. IDDVT was associated with a transient risk factor or cancer in 165 (51.4%) and 56 (17.4%) patients, respectively. LMWH was administered for 4-6 weeks to 280 patients (87.2%), who were included in the primary analysis. Overall, during a mean follow-up of 42.3 months, 42 patients (15%) developed recurrent VTE, which occurred as proximal DVT or PE in 21 cases. The recurrence rate of VTE per 100 patient-years was 3.5 in patients with transient risk factors, 7.2 in patients with unprovoked IDDVT, and 5.9 in patients with cancer ( p=0.018). At multivariable analysis, unprovoked IDDVT and previous VTE were significantly associated with recurrent VTE (HR 2.16, 95% CI 1.12-4.16 and HR 1.97, 95% CI 1.01-3.86, respectively). In conclusion, the long-term risk of recurrent VTE after IDDVT treated for 4-6 weeks is not negligible, in particular in patients with unprovoked IDDVT or cancer. Further studies are needed to clarify whether a longer, but definite treatment duration effectively prevents these recurrences.

Relationship between ABO blood group and hemorrhage: a systematic literature review and meta-analysis.

Several studies have suggested that patients with non-O blood group have an increased risk of both venous and arterial thromboembolic events. On the contrary, the role of ABO blood group on the risk of bleeding complications remains unclear. Thus, we performed a meta-analysis of the literature with the aim of assessing this potential association. MEDLINE and Embase databases were searched from 1946 to March 2012. Studies comparing the prevalence of different ABO blood groups in bleeding patients as well as in controls without bleeding complications were potentially includible. Two reviewers independently selected studies and extracted study characteristics, quality, and outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial and pooled using a random-effects model. Twenty-two studies totalling 9,468 bleeding patients and more than 450,000 controls were included. The prevalence of O blood group was significantly higher in bleeding patients than in controls, with a resulting pooled OR of 1.33 (95% CI = 1.25 to 1.42; p < 0.001). The result of this meta-analysis of a very large sample of bleeding patients and controls suggests that O blood group is a potentially important genetic risk factor for bleeding. High-quality prospective studies are warranted to confirm these preliminary findings.

New direct thrombin inhibitors.

Direct thrombin inhibitors (DTIs) are a class of anticoagulants that bind selectively to thrombin and block its interaction with its substrates. Dabigatran etexilate and AZD0837, the new generation of DTIs, are now under intense development, and are potentially of great interest for internists. Dabigatran etexilate is a potent, non-peptidic small molecule that specifically and reversibly inhibits both free and clot-bound thrombin by binding to the active site of thrombin molecule. It has been already licensed in the European Union and in Canada for the prevention of VTE in patients undergoing hip- and knee-replacement surgery. Ongoing trials are evaluating its efficacy and safety for the treatment of deep venous thrombosis and pulmonary embolism, primary and secondary prevention of VTE, prevention of systemic embolism in patients with non-valvular atrial fibrillation, and prevention of cardiac events in patients with acute coronary syndromes. AZD0837 is the prodrug of ARH06737, a potent, competitive, reversible inhibitor of free and fibrin-bound thrombin. At present, only limited, preclinical, phase I and phase II clinical data have been presented. The drug has now entered a phase III clinical program in the population of patients with atrial fibrillation. Their properties and the oral administration render these compounds, theoretically, more convenient than both vitamin K antagonist and low molecular weight heparins. However, only reports from clinical practice patterns over the next months and years will tell us how and when to use the new DTIs.

The embolic storm: dramatic peripheral complications of left ventricular thrombosis after myocardial infarction.

Left ventricular thrombus is a common complication after acute myocardial infarction. Although anticoagulant treatment has an established role in reducing the rate of thrombus formation and embolic phenomena during acute myocardial infarction, prior studies showed that left ventricular thrombus and systemic embolization may develop irrespective of adequate anticoagulant therapy. We present a descriptive case of a patient with left ventricular thrombus who experienced dramatic peripheral embolic events soon after the onset of anterior myocardial infarction despite full anticoagulation, and we discuss possible pathogenesis.

Traditional and non traditional risk factors in accelerated atherosclerosis in systemic lupus erythematosus: role of vascular endothelial growth factor (VEGATS Study).

OBJECTIVE: To evaluate the role of vascular endothelial growth factor (VEGF) in accelerated atherosclerosis in patients with Systemic Lupus Erythematosus (SLE). METHODS: We have enrolled 80 SLE female patients and 80 age-matched healthy control females who underwent a structured interview, physical examination, routine laboratory tests, VEGF plasma level determination and B-mode ultrasonography of carotid arteries to determine carotid intima media thickness (IMT). Framingham risk factors for cardiovascular events were also calculated and VEGF plasma levels were correlated with traditional and nontraditional cardiovascular risk factors. RESULTS: SLE was significantly associated with higher mean IMT values (0.74+/-0.15 mm versus 0.59+/-0.12 mm in controls, p<0.001) and higher mean plasma VEGF levels (307.9+/-292.2 pg/mL versus 120.7+/-118.4 pg/mL in controls, p<0.001) independently from age, smoking habits, and Framingham risk factors. A significant correlation was also found between IMT and VEGF values (r=0.25; p<0.001). CONCLUSION: We show that SLE patients have increased mean IMT and VEGF values as compared with healthy age-matched controls and that IMT and VEGF values are independently and directly associated with SLE disease.

Residual venous obstruction in patients with a single episode of deep vein thrombosis and in patients with recurrent deep vein thrombosis.

Residual venous obstruction (RVO) in patients with previous deep vein thrombosis (DVT) of the lower limbs has been suggested as an independent risk factor for recurrent venous thromboembolism (VTE). RVO could be a marker of a persistent prothrombotic state. We have compared the rate of RVO in patients with DVT and a personal history of at least one previous episode of VTE to the rate of RVO among patients with a first episode of DVT. All patients underwent compression ultrasonography (CUS) of the lower limbs 1 year after index DVT. RVO was arbitrarily defined as a thrombus occupying, at maximal compressibility, more than 20% of the vein area in the absence of compression. 50 consecutive patients with recurrent DVT and 50 age and sex-matched patients with a single episode of DVT were enrolled. The index event was idiopathic in 62% of patients with recurrent DVT and in 60% of patients with a single episode. In 74% of patients with recurrent DVT the index event occurred in either the contralateral leg or in a different segment of the ipsilateral leg. RVO was detected in 50% of patients with a single episode of DVT and in 88% of patients with recurrent DVT (p<0.00001). The prevalence of RVO is significantly higher in patients with recurrent DVT than in patients with a single episode. This finding supports the importance of RVO as a potential marker of a persistent prothrombotic state.

Home-treatment of deep vein thrombosis in patients with cancer.

BACKGROUND AND OBJECTIVES: Outpatient treatment of deep vein thrombosis (DVT) has become a common practice. However, in some centers cancer patients with DVT are excluded from home treatment because they have a higher risk of both bleeding and recurrent DVT. We performed a retrospective review of clinical practice patterns to assess the rate of cancer patients who were deemed eligible for outpatient treatment of their DVT. DESIGN AND METHODS: The charts of patients from the Thrombosis Units at two tertiary care institutions were reviewed. All patients with objectively documented DVT at our institutions are treated through the Thrombosis Units. Patients are treated as outpatients unless they require admission for other medical problems, are actively bleeding or have pain that requires parenteral narcotics. Outpatient treatment was with low molecular weight heparin (LMWH) followed by warfarin or with LMWH alone. RESULTS: Over a period of almost four years there were 321 patients with cancer, 167 (52.5%) of whom had metastatic disease. The most frequent sites of cancer were genitourinary tract (21.2%), breast (20.5%), and gastrointestinal system (18.4%). Treatment with LMWH and warfarin was prescribed to 67% and LMWH alone to 33%. One hundred and ninety-seven patients (61.4%) were entirely treated at home. There were no differences between patients treated at home and hospitalized patients with regard to gender, mean age, site of cancer, presence of metastases, and treatment. After 3 months, recurrent thromboembolism occurred in 6.1% of patients treated at home and in 4.8% of hospitalized patients (p=0.64), and major bleeding in 1.0% and 4.8%, respectively (p=0.03). One hundred and sixty patients died (49.8%), 100 (50.7%) in the home treatment group and 60 (48.4%) of the hospitalized patients. INTERPRETATION AND CONCLUSIONS: Home treatment of DVT in cancer patients is safe and feasible in almost two-thirds of cases. Outpatient management of antithrombotic treatment did not increase the rate of adverse events, even if the stage of the disease was advanced.

[Current issues in the initial phase of warfarin therapy]. / Attuali problemi nella fase iniziale dei trattamenti con warfarin.

Warfarin is the most commonly used vitamin K antagonist (VKA), based on its demonstrated efficacy in the prevention and treatment of venous and arterial thromboembolism. Optimal management of warfarin therapy is a daily challenge, mainly because of its complex pharmacokinetics and pharmacodynamics. In particular, the induction phase of warfarin treatment is unpredictable, thus placing patients to an increased risk of excessive anticoagulation, which predisposes to bleeding, or to prolonged subtherapeutic anticoagulation, which predisposes to thrombosis and often mandates extended therapy with parenteral anticoagulants. A number of algorithms has been developed to initiate warfarin therapy. Unfortunately, most have failed to gain widespread acceptance. In this review we briefly discuss the results of published clinical trials that assessed different initial approaches to warfarin therapy, their main findings and limitations. In summary, we can conclude that there is sufficient evidence to support the use of different starting doses of warfarin based on both individual and disease-specific factors. In particular, younger outpatients require higher starting doses of warfarin (7.5-10 mg) than older and hospitalized patients (2.5-5 mg), and than patients following cardiopulmonary by-pass surgery. However, further clinical studies are necessary to identify the best strategy to individualize warfarin initiation therapy.

Weight gain after acute deep venous thrombosis: a prospective observational study.

INTRODUCTION: The onset of acute disorders often results in a significant reduction in physical exercise, thus predisposing to further increase in body weight. Weight gain is strongly associated with an increase in metabolic and cardiovascular risk factors. The aim of this study was to assess weight changes occurring after an episode of acute deep venous thrombosis (DVT). MATERIALS AND METHODS: To compare the prevalence of overweight and obesity at baseline and 6 months after acute DVT, and to compare weight changes between patients with DVT treated in hospital or at home over a similar time frame, we evaluated 72 patients (mean age 59.8+/-15.3 years, 34 men and 38 females) with objectively diagnosed DVT. Body mass index (BMI) was recorded at baseline and at 6 months; waist circumference was recorded at 6 months to assess individual patterns of body fat distribution. RESULTS: At baseline, BMI was 27.6+/-4.6 kg/m(2). Overweight and obesity were observed in 33 (45.8%) and 19 (26.4%) patients, respectively. After 6 months, BMI was 28.7+/-5.0 kg/m(2). The prevalence of overweight and obesity was 44.4% and 32%, respectively; visceral pattern of body fat distribution was found in 64.8% of overweight or obese patients. Mean weight gain was 7.12%; inpatients (n=42) showed a higher weight gain than outpatients (n=30) (8.6% and 4.9%, respectively, p=0.046). CONCLUSIONS: We observed a significant weight gain after acute DVT. This weight gain was more marked in hospitalised patients than in outpatients. Our findings suggest that weight control should be considered in all patients with acute DVT.

Body mass index is associated with the development of the post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT). Little is known about prognostic factors that might identify patients at high risk for the development of PTS. Body mass index (BMI) has been previously reported to be associated to the development of PTS. The aim of this study was to assess the association between BMI and other anthropometric parameters and PTS in a general population of DVT patients. In a prospective cohort study, 83 consecutive patients with objective diagnosis of DVT underwent physical examination. BMI was recorded at baseline and at 12 months, and waist circumference was recorded at 12 months to assess individual patterns of body fat distribution. The presence of PTS at 12 months was ascertained using a validated clinical scale. Sixty-three patients (75.9%) were overweight or obese at 12 months, 60 (72.3%) had a weight gain over 1 year. Twenty patients developed PTS (24.1%). Mean BMI was significantly higher in patients who developed PTS than in patients who did not (29.6 and 27.2 Kg/m(2), respectively, p = 0.022). A BMI of > 28 Kg/m(2) predicted early onset of PTS (OR 3.54, 95% CI 1.07-12.08, p = 0.017). Neither patterns of fat distribution nor weight gain in 1 year were correlated with PTS (p = 0.918 and p = 0.775, respectively). BMI is significantly correlated with the development of PTS. Patients with DVT should be encouraged to avoid weight gain. Reducing patient weight might be an important strategy to prevent PTS.

The initial phase of oral anticoagulation with warfarin in outpatients with deep venous thrombosis.

Patients with deep venous thrombosis (DVT) treated out of hospital usually start warfarin with the recommended 5 mg loading dose and have their International Normalized Ratio (INR) test performed every 2-3 days. Thus, achievement of the therapeutic range may be more difficult than for inpatients, possibly resulting in extended duration of low molecular weight heparin (LMWH) treatment. We retrospectively examined the charts of 55 DVT outpatients (mean age, 61.4 years; 30 males) to assess the actual duration of LMWH treatment and to identify predictors of a slow achievement of the INR range. Thirty patients (54.4%) reached the therapeutic INR range and stopped LMWH within 7 days, and 25 patients (45.6%) had to continue for an average of 10.5 days. The latter group was significantly younger than the former (57 and 65 years, respectively; P = 0.039). Patients younger than 60 years old had an odds ratio for an extended treatment of 4.92 (P = 0.0057). Algorithms with different loading doses of warfarin according to age should be proposed for outpatient treatment of DVT.

Plasma measurement of D-dimer levels for the early diagnosis of ischemic stroke subtypes.

BACKGROUND: Different coagulation abnormalities according to stroke subtypes have been reported. We have assessed the clinical utility of D-dimer, a product of fibrin degradation, in the early diagnosis of stroke subtypes. METHODS: Patients hospitalized after an acute ischemic cerebrovascular event underwent D-dimer assay (STA Liatest D-Dimer) (reference level, <0.50 micro g/mL) on days 1, 6 +/- 1, and 12 +/- 1 and were studied to identify stroke subtypes. RESULTS: We included 126 patients (mean age, 75.5 years) and 63 age-matched control subjects. Stroke subtypes were cardioembolic in 34 patients (27%), atherothrombotic in 34 (27%), lacunar in 31 (25%), and unknown in 27 (21%). At all 3 measurements, D-dimer levels were significantly higher in the cardioembolic group (mean +/- SEM, 2.96 +/- 0.51, 2.58 +/- 0.40, and 3.79 +/- 0.30 micro g/mL, respectively) than in the atherothrombotic (1.34 +/- 0.21, 1.53 +/- 0.26, and 2.91 +/- 0.23 micro g/mL, respectively) (P<.05) and lacunar (0.67 +/- 0.08, 0.72 +/- 0.15, and 0.64 +/- 0.06 micro g/mL, respectively) groups (P<.01). The difference was also significant between the latter 2 groups (P<.01). We found no difference between the lacunar group and controls (0.53 +/- 0.14 micro g/mL). According to day 1 measurements, the optimal cutoff point for predicting cardioembolic stroke was 2.00 micro g/mL, resulting in a specificity of 93.2% and in a sensitivity of 59.3%. For predicting lacunar stroke, the cutoff point was 0.54 micro g/mL, with a specificity of 96.2% and a sensitivity of 61.3%. CONCLUSION: The increasing use of the D-dimer assay in clinical practice could be extended to patients presenting with acute cerebrovascular ischemic events to help predict stroke subtype.

Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial.

BACKGROUND: Excessive anticoagulation due to warfarin use is associated with hemorrhage. Subcutaneously administered vitamin K has not been evaluated for the treatment of warfarin-associated coagulopathy, yet it is widely used. OBJECTIVE: To show that oral vitamin K is more effective than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. DESIGN: Randomized, controlled trial. SETTING: Two teaching hospitals. PATIENTS: Patients with an international normalized ratio (INR) between 4.5 and 10.0. INTERVENTION: Warfarin therapy was withheld, and 1 mg of vitamin K was given orally or subcutaneously. MEASUREMENTS: The primary outcome measure was the INR on the day after administration of vitamin K. Secondary outcome measures were hemorrhage and thrombosis during a 1-month follow-up period. RESULTS: 15 of 26 patients receiving oral vitamin K and 6 of 25 patients receiving subcutaneous vitamin K had therapeutic INRs on the day after study drug administration (P = 0.015; odds ratio, 4.32 [95% CI, 1.13 to 17.44]). CONCLUSION: Oral vitamin K lowers INR more rapidly than subcutaneous vitamin K in asymptomatic patients who have supratherapeutic INR values while receiving warfarin.

Thrombosis prophylaxis in medical patients: a retrospective review of clinical practice patterns.

BACKGROUND AND OBJECTIVES: The risk of venous thromboembolism in medical patients is comparable to the risk in general surgical patients. Thromboprophylaxis is recommended for specific medical patients, but its use in clinical practice is unknown. DESIGN AND METHODS: We conducted a retrospective review of the charts of consecutive patients discharged from 2 departments of Internal Medicine, one in the teaching hospital of Varese and one in the non-teaching hospital of Angera, Italy, from October to December 2000. We selected the charts of patients with clinical conditions at increased risk of venous thromboembolism requiring thromboprophylaxis according to consensus statements. The use of antithrombotic drugs and contraindications to prophylaxis were documented. RESULTS: We screened a total of 516 charts, 265 in Varese and 251 in Angera and we identified 165 patients (103 and 62, respectively) at risk of venous thromboembolism because of malignancy (53), heart failure (34), stroke (33), acute infections (23), acute respiratory failure (18), acute rheumatic disorders (3), and inflammatory bowel disease (1). Forty-two patients had contraindications to antithrombotic drugs and 11 were already on long-term oral anticoagulant treatment. Among the 112 remaining patients, prophylaxis was prescribed to 52 patients (46.4%), 35 of 60 in Varese (58.3%) and 17 of 52 in Angera (32.7%, p=0.0067). Patients with stroke and heart failure were significantly more likely to receive thromboprophylaxis than other groups of patients. INTERPRETATION AND CONCLUSIONS: Prophylaxis of venous thromboembolism is underused in medical patients and the proportion of patients receiving antithrombotic drugs varies with the medical condition which precipitated hospital admission. The low rate of usage of prophylaxis suggests that preventable cases of thromboembolism are occurring and that better education of physicians is required to increase the usage of thromboprophylaxis.

Selecting patients for home treatment of deep vein thrombosis: the problem of cancer.

BACKGROUND AND OBJECTIVES: Patients with deep vein thrombosis are selected for home treatment on the basis of their clinical and social condition. Cancer is frequently associated with venous thromboembolism and is often considered an exclusion criterion for outpatient treatment. We investigated the impact of cancer on the outpatient management of venous thrombosis. DESIGN AND METHODS: We performed a prospective, cohort study on consecutive patients with objectively documented deep vein thrombosis. All were assessed for home treatment. Hospital admission was recommended in the presence of common exclusion criteria. All patients were treated with low molecular weight heparin and warfarin. Information on previous, active, or suspected cancer was collected. Recurrent thrombosis, bleeding and mortality were documented at a 3-month follow-up. RESULTS: One hundred patients were included; 72 were entirely treated at home (mean age: 61.2 years). There were 22 patients with known cancer: 12 (55%) were managed as outpatients (16.5% of the outpatient population) and 10 were hospitalized (36% of the inpatient population), 6 because of a poor clinical condition, 4 because further investigation of their malignancy was required. The presence of cancer and the likelihood of poor compliance were the most frequent reasons cited for in-hospital treatment. Overall, event rates at 3 months were comparable to those reported in previous studies in the outpatient population and slightly higher in the inpatient population (recurrent thrombosis 1.5% and 7%; bleeding 5.5% and 10.7%; mortality 4% and 18%, respectively). INTERPRETATION AND CONCLUSIONS: Cancer was the most common reason cited for in-hospital treatment. Nevertheless, more than half of the patients with known cancer were safely and effectively treated at home.