Sex Differences in Clinical Presentation of Lower Extremity Deep Vein Thrombosis.

Background: Differences between men and women in the clinical features and extent of lower limb deep vein thrombosis (DVT) may influence DVT diagnostic algorithms involving pretest clinical probability (PTP) assessment, D-dimer, and compression ultrasonography (CUS). Aims: To assess differences in DVT clinical presentation between men and women and their effect on PTP and D-dimer. Methods: We conducted a retrospective study in outpatients referred for suspected DVT of the lower limbs to our vascular emergency department from January 2005 to December 2019. Patients underwent PTP assessment with the Wells score, D-dimer testing, and CUS. Results: More women were referred for suspected DVT than men (M/F: 1,785/2,821; F: 61.4%; p < 0.0001). Women were older than men (median age: 71 vs. 67 years; p = 0.0001), DVT was diagnosed in 436 patients (9.4%) but in more men than women (M: 210 [11.8%] vs. F: 226 [8%]; p = 0.0002), with more proximal DVT in men than women (M: 131 7.3% vs. F: 124 [4.4%]; p = 0.00021). PTP was more likely in men (355 [19.9%]) than women (455 [16.2%]) (p = 0.0011); more men had swelling in the entire limb, increased calf circumference by >3 cm compared with the contralateral limb, and pitting edema, than women. D-dimer levels (available in 65% of patients) were more frequently positive in women with DVT than in men (94.6% vs. 85.7%; p = 0.016). However, a positive D-dimer and/or likely PTP was similarly frequent in men (92%) and women (96%) with DVT. Conclusions: More women than men are referred for suspected DVT, and men have a higher prevalence of proximal DVT. However, current algorithms for DVT diagnosis perform similarly in men and in women.

Six-week low-molecular-weight heparin versus 12-week warfarin for calf deep vein thrombosis: A randomized, prospective, open-label study.

Current guidelines suggest a 3-month anticoagulant treatment course for isolated distal deep vein thrombosis (IDDVT), but shorter durations of treatment are frequently prescribed in clinical practice. We investigated whether a 6-week treatment with low-molecular-weight heparin (LMWH) at intermediate dosage can be an effective and safe alternative to vitamin K antagonists (VKA) in patients with IDDVT (non-inferiority trial). In a multicenter, open-label, randomized trial, 260 outpatients with symptomatic IDDVT were randomly assigned to receive either LMWH followed by VKA for 12 weeks or LMWH 1 mg/kg subcutaneously twice a day for 2 weeks followed by 1 mg/kg subcutaneously once a day for 4 weeks. The follow-up was 6 months and the primary endpoint was the composite measure of recurrent venous thromboembolism (VTE) defined as: recurrence or extension of IDDVT, proximal DVT, and pulmonary embolism (PE). The study was stopped prematurely due to slow recruiting rates. The primary efficacy outcome occurred in 14 patients receiving LMWH (10.8%) and in five patients receiving VKA (3.8%); risk difference was 0.069 (95% CI: 0.006-0.132), hazard ratio 2.8 (95% CI: 1.04-7.55). There was one PE in the VKA group and one proximal DVT in the LMWH group. IDDVT recurrence was 10.0% in the LMWH group versus 3.1% in the VKA group (p = .024). Two patients had clinically relevant bleedings (1.6%) in the LMWH group versus one (0.8%) in VKA group (p = .56). In conclusion, VKA for 12 weeks seems superior to LMWH for 6 weeks in reducing the risk of VTE recurrences in our cohort of outpatients with IDDVT.

Incidence and clinical outcomes of heparin-induced thrombocytopenia: 11 year experience in a tertiary care university hospital.

Heparin-induced thrombocytopenia (HIT) is a rare immuno-mediated adverse reaction with high thrombotic and mortality risk. To evaluate incidence and outcomes of HIT cases diagnosed at a tertiary care hospital from 2007 to 2018. A retrospective study was conducted. Patients with suspected HIT underwent 4Ts score assessment and anti-heparin PF4 IgG antibodies ELISA screening test. If the latter was positive, platelet aggregation test (PAT) was performed. If the latter was positive, any form of heparin was stopped, alternative anticoagulants were started and then overlapped with warfarin. HIT incidence was calculated by dividing HIT cases by the mean yearly number of admitted patients over 11 years. Follow-up was 90 days. Among 2125 screening tests, 96 (4.5%) were positive with confirmatory PAT in 82/90 (3.8% for missing data in 6). Median age was 75; 39 patients were surgical and 51 medical. The median 4Ts score was 5. Unfractionated heparin was employed in 34 (37%). HIT incidence was 0.16/1000/patient/years (95% CI: 0.12-0.23) in surgical and 0.15/1000/patient/years (95%: 0.12-0.20) in medical patients. HIT with thrombosis (HIT-T) was observed in 31 patients (0.05/1000/patient/years 95% CI: 0.04-0.1), with venous thromboses in 25 (80%). HIT without thrombosis was observed in 59 patients (0.1/1000 patient/years; 95% CI: 0.08-0.13, twofold vs HIT-T). All cause mortality was 25.5% (95% CI: 17.6-35.4), major bleeding 7.7% (95% CI:3.2-15.3), and thromboembolic complications 3.3% (95% CI:1.1-9.3). HIT is a rare event with high mortality, despite the use of non heparin anticoagulants.

Age-adjusted D-dimer, clinical pre-test probability-adjusted D-dimer, and whole leg ultrasound in ruling out suspected proximal and calf deep venous thrombosis.

D-dimer (DD) and ultrasonography (US) are part of the diagnostic workup for lower-extremity deep vein thrombosis (DVT). Recent studies have shown that adjusting DD level cut-offs by age or clinical pre-test probability (PTP) decreases the use of US. We compared diagnostic accuracy of PTP-adjusted DD and age-adjusted DD in 3883 patients (F: 61.1%; age: 65.3 ± 16.8 y) referred to our unit for clinically suspected DVT. All patients underwent clinical evaluation, DD, and US. Proximal DVT was detected in 477 (12.4%) patients, and distal DVT was isolated in 342 (8.9%) patients. In the remaining 3064 patients there were 23 venous thromboembolic events (0.75%, 95% CI: 0.50-1.12) during the 3-month follow-up. The specificities of DD, age-adjusted DD, and PTP-adjusted DD in patients without high PTP levels were 47% (95% CI: 45-49), 61% (95% CI: 59-62), and 67% (95% CI: 65-68), respectively. The negative predictive value (NPV) was 96% (95% CI: 95-97) for all diagnostic strategies. When only proximal DVTs were considered, the NPV increased to 99% (95% CI: 98-99). US was avoided in 37% (95% CI: 36-38) of patients with a fixed cut-off DD, 48% (95% CI: 47-50) with age-adjusted DD, and 52% (95% CI: 51-54) with PTP-adjusted DD. The failure rate for all DVTs of DD, age-adjusted DD, and PTP-adjusted DD was 2.0% (95% CI: 1.6-2.5), 2.7% (95% CI: 2.2-3.2), and 2.5% (95% CI: 2.1-3.0), respectively. Compared with the standard DD cut-off, both age-adjusted and PTP-adjusted DD reduced the proportion of patients who required US at the cost of a small increase in failure rate.

Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial.

OBJECTIVE: To compare two different treatment durations of rivaroxaban in patients with symptomatic isolated distal deep vein thrombosis (DVT). DESIGN: Randomised, double blind, placebo controlled clinical trial. SETTING: 28 outpatient clinics specialising in venous thromboembolism. PARTICIPANTS: 402 adults (≥18 years) with symptomatic isolated distal DVT. INTERVENTIONS: After receiving standard dose rivaroxaban for six weeks, participants were randomly assigned to receive rivaroxaban 20 mg or placebo once daily for an additional six weeks. Follow-up was for 24 months from study inclusion. MAIN OUTCOMES MEASURES: The primary efficacy outcome was recurrent venous thromboembolism during follow-up after randomisation, defined as the composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism. The primary safety outcome was major bleeding after randomisation until two days from the last dose of rivaroxaban or placebo. An independent committee adjudicated the outcomes. RESULTS: 200 adults were randomised to receive additional rivaroxaban treatment and 202 to receive placebo. Isolated distal DVT was unprovoked in 81 (40%) and 86 (43%) patients, respectively. The primary efficacy outcome occurred in 23 (11%) patients in the rivaroxaban arm and 39 (19%) in the placebo arm (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03, number needed to treat 13, 95% confidence interval 7 to 126). Recurrent isolated distal DVT occurred in 16 (8%) patients in the rivaroxaban arm and 31 (15%) in the placebo arm (P=0.02). Proximal DVT or pulmonary embolism occurred in seven (3%) patients in the rivaroxaban arm and eight (4%) in the placebo arm (P=0.80). No major bleeding events occurred. CONCLUSIONS: Rivaroxaban administered for six additional weeks in patients with isolated distal DVT who had an uneventful six week treatment course reduces the risk of recurrent venous thromboembolism, mainly recurrent isolated distal DVT, over a two year follow-up without increasing the risk of haemorrhage. TRIAL REGISTRATION: EudraCT 2016-000958-36; ClinicalTrials.gov NCT02722447.

Guidelines on the management of abdominal aortic aneurysms: updates from the Italian Society of Vascular and Endovascular Surgery (SICVE).

The objective of these Guidelines was to revise and update the previous 2016 Italian Guidelines on Abdominal Aortic Aneurysm Disease, in accordance with the National Guidelines System (SNLG), to guide every practitioner toward the most correct management pathway for this pathology. The methodology applied in this update was the GRADE-SIGN version methodology, following the instructions of the AGREE quality of reporting checklist as well. The first methodological step was the formulation of clinical questions structured according to the PICO (Population, Intervention, Comparison, Outcome) model according to which the Recommendations were issued. Then, systematic reviews of the Literature were carried out for each PICO question or for homogeneous groups of questions, followed by the selection of the articles and the assessment of the methodological quality for each of them using qualitative checklists. Finally, a Considered Judgment form was filled in for each clinical question, in which the features of the evidence as a whole are assessed to establish the transition from the level of evidence to the direction and strength of the recommendations. These guidelines outline the correct management of patients with abdominal aortic aneurysm in terms of screening and surveillance. Medical management and indication for surgery are discussed, as well as preoperative assessment regarding patients' background and surgical risk evaluation. Once the indication for surgery has been established, the options for traditional open and endovascular surgery are described and compared, focusing specifically on patients with ruptured abdominal aortic aneurysms as well. Finally, indications for early and late postoperative follow-up are explained. The most recent evidence in the Literature has been able to confirm and possibly modify the previous recommendations updating them, likewise to propose new recommendations on prospectively relevant topics.

Thrombotic burden, D-dimer levels and complete compression ultrasound for diagnosis of acute symptomatic deep vein thrombosis of the lower limbs.

BACKGROUND: Diagnostic algorithms for deep vein thrombosis (DVT) include D-dimer for its high negative predictive value, thus reducing the need for imaging. Small thrombi may be associated with low D-dimer levels, increasing false negatives. AIM: To assess the sensitivity and thus the false negative rates of standard and age-adjusted D-dimer cut offs for isolated distal DVT (IDDVT) in outpatients. MATERIALS AND METHODS: We enrolled consecutive outpatients with suspected DVT of the lower limbs referring to our vascular emergency department from 2009 to 2018. Patients underwent D-dimer testing (STA, Stago, cut-off: 500 µg/L), pretest clinical probability (PTP) evaluation and complete compression ultrasonography. Follow-up was 3 months. RESULTS: Among 3948 patients (M:1554-39%, median age 69), 486 proximal DVTs (12.3%) and 348 IDDVTs (8.8%) were diagnosed. Median D-dimer was higher in proximal than IDDVT (3960 vs 1400 µgr/L; p = 0.001). The false negative rate of the standard D-dimer cut-off was 2% (95%CI: 0.8-3.2%) for proximal DVT and 14.7% (95% CI: 11-81%) for IDDVT. The false negative rate of the age-adjusted cut-off was 4.9% (3-7%) for proximal DVT and 19.5% (95% CI: 15.4-24.7%) for IDDVT. CONCLUSIONS: Small calf thrombi are associated with low D-dimer levels, and age-adjusted D-dimer may be below the cut-off more frequently in subjects with IDDVT than standard cut-off D-dimer, although such D-dimer levels might exclude IDDVT that require treatment.

Relevance of immobility as a risk factor for symptomatic proximal and isolated distal deep vein thrombosis in acutely ill medical inpatients.

Immobility is a well-recognized risk factor for deep vein thrombosis (DVT) in surgical patients, whereas the level of DVT risk conferred by immobility is less defined in patients on medical wards. The aim of this study was to establish whether immobility and its duration are associated with the risk of DVT in acutely ill medical inpatients. We conducted a cohort study in acutely ill medical inpatients. Patients underwent whole leg ultrasound for suspected lower extremity DVT and were divided into two groups according to presence or absence of immobility, defined as total bed rest or sedentary without bathroom privileges. The endpoint was the detection of proximal DVT or isolated distal DVT (IDDVT). Among the 252 acutely ill medical inpatients with immobility (age 82.6 ± 10.3 years, female 63.9%), ultrasound showed 36 (14.3%) proximal DVTs and 39 (15.5%) IDDVTs, while there were 11 (4.4%) proximal DVTs and 26 (10.5%) IDDVTs among the 248 inpatients without immobility (age 73.6 ± 14.2 years, female 54.8%). The risk of proximal DVT was higher in immobile than in mobile patients (OR 3.59, 95% CI: 1.78-7.23, p = 0.0001), whereas the risk of IDDVT was similar between the two groups (OR 1.56, 95% CI: 0.92-2.66, p = 0.111). During the first 3 days of hospitalization, the frequency of all DVTs was similar in patients with and without immobility, but it was 0.26 ± 0.03 vs 0.18 ± 0.03, respectively, after 4 days. In conclusion, immobility for more than 3 days is a risk factor for proximal DVT in acutely ill medical inpatients.

Heparin-induced thrombocytopenia and COVID-19.

Heparin-induced thrombocytopenia (HIT) has not been included as a possible cause of thrombocytopenia in Coronavirus Disease 2019 (COVID-19) patients. We report a case of HIT in a patient with COVID-19 treated with heparin. A 78-yearold man was admitted to our hospital for acute respiratory failure and acute renal failure due to SARS-CoV-2 infection; in intensive care unit, one 5000IU heparin dose (day 0, platelet count 305000/µL). On day 2, haemoglobin started to decrease and heparin was stopped. On day 10, platelet count was 153000/µL and 5000IU calcium heparin subcutaneously twice daily was started. The platelet further decreased, reaching 49000/µL on day 17, and the patient was investigated for suspected HIT: an IgG specific chemiluminescence test for heparin- PF4 antibodies was positive and a femoral DVT was found at ultrasound. Argatroban was started, platelet count increased without any bleeding and thrombosis complication. Our experience shows that HIT may develop in heparin treated COVID-19 patients and should be included among the possible cause of thrombocytopenia in such patients.

Failure of Fondaparinux in Autoimmune Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin that is associated with life-threatening thrombotic complications. More rarely, HIT may begin after stopping of heparin or after flushes of heparin (autoimmune HIT). Fondaparinux has been proposed as a candidate treatment for HIT, but there are few data on its use in autoimmune HIT. An 86-year-old man with a history of diabetes mellitus, arterial hypertension, and hypercholesterolemia was admitted to our hospital for carotid endarterectomy. During surgery, only one heparin dose of 5,000 U was used. Platelet count started to decrease on the 11th day after surgery. Since the patient was not receiving heparin treatment/prophylaxis, HIT was not suspected. On day 19, platelet count was 61 × 10 3 /µL, and the patient was investigated for a diagnosis of HIT. Immunoglobulin (Ig)-G-specific enzyme-linked immunosorbent assay (ELISA) was positive and HIT was confirmed by a platelet aggregation test; fondaparinux 5 mg once a day was started. During fondaparinux treatment, platelet count did not increase and a lower leg deep vein thrombosis occurred. Fondaparinux was stopped and rivaroxaban 15 mg twice a day was started. Platelet count returned to base line after 10 days from fondaparinux withdrawal. There was no thrombotic event or bleeding complication during rivaroxaban treatment. Anecdotal evidence suggests risk of failure of fondaparinux treatment for autoimmune HIT and supports the use of rivaroxaban for treatment of HIT, justifying larger studies.

Upper extremity deep vein thrombosis treated with direct oral anticoagulants: a multi-center real world experience.

Upper-extremity deep vein thrombosis (UEDVT) accounts for about 5-10% of all cases of deep vein thrombosis (DVT). It is often associated with cancer and/or presence of a central venous catheter (CVC), but it may also occur in the absence of these favoring conditions. The safety and efficacy of using direct oral anticoagulants (DOACs) in subjects with UEDVT has not been systematically evaluated and the only data available in the literature derive from anecdotal evidence, analysis of registries, and small single-centre studies. In addition, a specific analysis of UEDVT not associated with cancer and/or CVC has never been made. In this study, we specifically focused on patients with no cancer and without a CVC who were diagnosed with a first episode of UEDVT and were treated with a DOAC. We studied 61 patients, treated in six Italian centres between January 2014 and December 2018. Treatment lasted at least 3 months in all patients. In terms of efficacy, no recurrence of thrombosis or pulmonary embolism were recorded, while Doppler ultrasonography, performed after at least three months of treatment, documented in all cases either partial or complete recanalization of obstructed veins. In terms of safety, no cases of major bleedings were recorded. This is the only series available in the literature of patients treated with DOACs for UEDVT not associated with cancer and/or CVC. This small multicenter real world experience supports the concept that DOACs might be safe and effective for treating UEDTV. Further studies are required to better understand the role of DOACs in these patients.

Coronary artery disease and restenosis after peripheral endovascular intervention are predictors of poor outcome in peripheral arterial disease.

Background: Few data are available on long-term atherothrombotic events after percutaneous transluminal angioplasty (PTA) for peripheral arterial disease (PAD). Restenosis after PTA may be a marker of a more aggressive atherothrombosis.Aim: To ascertain whether restenosis detected by duplex sonography (DUS) after PTA for iliac and femoro-popliteal disease is associated with a higher risk of cardiovascular events.Methods: We conducted a prospective cohort study of patients undergoing iliac or femoro-popliteal PTA for PAD. Patients were seen at one month, six months, one year and every year thereafter after PTA. At each visit, DUS was performed and accordingly restenosis was stratified into two categories (absent/present). The outcome was the composite of major adverse cardiovascular events (MACE).Results: Two hundred and fifty patients (aged 69 ± 11 years, male 59.2%) were enrolled. During a mean follow-up of 1207 ± 904 days, 102 (40.8%) patients developed restenosis. Restenosis was more frequent in patients with diabetes and critical limb ischaemia. MACEs (n = 76) were more frequent in the patients that developed restenosis vs. those that did not (40.2 vs. 23.6%, p = .005). Predictors of MACEs were diabetes (HR 2.02, 95%CI: 1.19-3.41, p = .009), presence of coronary heart disease at enrolment (HR 2.84, 95%CI: 1.78-4.53, p = .001) and restenosis (HR 1.87, 95%CI: 1.16-3.00, p = .010).Conclusion: Restenosis at DUS, diabetes, and coronary heart disease in patients who underwent iliac or femoro-popliteal PTA for PAD are associated with increased risk of arterial thrombotic event. Intervention trials are required to show the benefit of different therapeutic approaches in such patients at high risk of clinical deterioration.

Proximal and isolated distal deep vein thrombosis and Wells score accuracy in hospitalized patients.

Deep vein thrombosis (DVT) is an important cause of morbidity and mortality in hospitalized patients. The Wells score for DVT pretest probability (PTP) was validated in outpatients, but its utility for inpatients is unclear. The aim of this study was to establish the prevalence of inpatient proximal and distal DVT and the Wells score performance in inpatients. A single-center cross-sectional study was conducted in a university hospital. During 183 days, all inpatients with suspected lower-extremity DVT were evaluated with the Wells score and whole-leg ultrasound. Among 634 inpatients (age 77.5 ± 13.8 years, males 39.3%), 507 (80.0%) were from medical wards and 127 (20.0%) from surgical wards. During the study period, there were 11,662 hospital admissions in the surgical/medical services. Whole-leg ultrasound detected 128 DVTs (20.2%); 51 (39.8%) were proximal and 77 (60.1%) were isolated distal DVTs. Estimated DVT prevalence in hospital setting was 1.09% (95% CI 0.93-1.31), and isolated distal DVT prevalence was 0.66% (95% CI 0.53-0.82). DVT frequency in low-, moderate-, and high-PTP groups was 9.8%, 24.3%, and 41.5%, respectively (p = 0.001). The area under the receiver operating characteristic curve for the Wells score was 0.67 ± 0.03 for all DVTs and 0.75 ± 0.04 for only proximal DVTs. A high PTP had a sensitivity of 24% (95% CI 14-37%) and a specificity of 93% (95% CI 91-95%) for proximal DVT diagnosis. In hospitalized patients, isolated distal DVT has a higher incidence than expected, and the Wells score accuracy for proximal DVT is similar to that found in outpatients.

Validation of the STA-Liatest DDi assay for exclusion of proximal deep vein thrombosis according to the latest Clinical and Laboratory Standards Institute/Food and Drug Administration guideline: results of a multicenter management study.

: Recommended strategy for venous thromboembolism (VTE) diagnosis includes the use of sensitive D-dimer (DDi) assays along with pretest probability (PTP) assessment. The Clinical and Laboratory Standards Institute (CLSI) recently issued a guideline (US FDA endorsed) on DDi in VTE exclusion. Such guideline specifies the ideal D-dimer assay characteristics and target population. Demonstrate STA-LiatestD-Di performance combined with a PTP score for proximal deep vein thrombosis (pDVT) exclusion in a CLSI compliant study. International, multicenter, prospective nonrandomized, noninterventional clinical outcome management study conducted in a standard-of-care setting. DDi was measured in DVT-suspected consecutive low/moderate PTP outpatients, without conditions possibly impacting DDi values independently of thrombosis presence (age >80, pregnancy, postoperative, cancer) using a 0.5 µg/ml (FEU) threshold for DVT exclusion. Results were used to determine test performance. One thousand two hundred and thirty-four patients (17 centers) signed informed consent. Nine hundred and eighty (mean age: 55) with valid results (494 negative DDi) completed the study (DVT prevalence: 8.7%). STA-LiatestD-Di performance exceeded CLSI/FDA requirements: sensitivity: 100% (95% CI 95.8-100%), NPV: 100% (95% CI 99.3-100%). STA-LiatestD-Di associated with PTP score showed excellent performance for pDVT exclusion, as recently demonstrated for pulmonary embolism. The assay allows safe VTE exclusion, avoiding unnecessary imaging tests.

Andexanet alfa to reverse the anticoagulant activity of factor Xa inhibitors: a review of design, development and potential place in therapy.

Direct oral anticoagulants are associated with rates of major bleeding which are not negligible, albeit lower than those associated with vitamin K antagonists. No specific reversal agent for factor Xa (FXa) direct inhibitors is currently available for clinical use. A modified activated human FXa decoy protein, andexanet alfa, is being developed that binds FXa direct inhibitors in their active site, thus reversing their anticoagulant effect. The purpose of this article is to review the design, development and clinical trials of andexanet alfa. Andexanet alfa was shown to reverse FXa inhibitors anticoagulant activity both in thrombosis animal models, healthy volunteers and patients with acute major bleeding. Andexanet alfa has been studied in double-blind, placebo-controlled phase II and III studies. A preliminary report of the phase III study showed that an effective hemostasis was obtained after andexanet alfa infusion in the majority of the patients with acute major bleeding associated with FXa inhibitors. Additional studies are ongoing and andexanet alfa is expected to be launched in the market in the near future.

Thrombin generation and intracranial atherosclerotic disease in patients with a transient ischaemic attack.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is responsible for at least 10% of transient ischaemic attacks (TIA). Thrombin generation has been shown to be associated with several atherosclerotic conditions and may be relevant in the pathogenesis of TIA from ICAD. OBJECTIVE: To evaluate the association between thrombin generation and ICAD in patients with TIA. MATERIALS AND METHODS: Consecutive patients with confirmed diagnosis of TIA by vascular neurologist were enrolled. Within 24h from diagnosis, all the patients underwent: blood samples including thrombin generation search, electrocardiography, brain CT scan, blood pressure (BP) measurement, supra-aortic echo-Doppler, transcranial Doppler (TCD) and standard echocardiogram. Thrombin generation was measured as endogenous thrombin potential (ETP) in platelet-rich plasma (PRP) and in platelet-poor plasma (PPP), in the presence and in the absence of thrombomodulin (TM). RESULTS: 120 patients (male 52.5%), aged 69±16years were enrolled. Ten patients on warfarin treatment had significantly lower ETP than the others. Among the remaining, ETP in the presence or absence of TM did not differ according to TOAST classification aetiology (large vessel vs. cardioembolic vs. lacunar vs. others). In PRP, ETP was similar in patients with ICAD and in those without (1748±160 vs. 1851±36nM·min, p=0.393), whereas, ETP measured in presence of thrombomodulin was higher in patients with than in those without ICAD (2045±99 vs. 1715±41nM·min, p=0.011). In PPP, ETP was similar in patients with ICAD and in those without, whereas thrombin peak was higher in patients with ICAD than in those without both in the presence (165±17 vs. 130±5nM, p=0.036) and in the absence of TM (178±19 vs. 142±5nM, p=0.037). CONCLUSION: ETP measured in presence of TM is enhanced in patients with ICAD, supporting that thrombomodulin-protein C pathways is relevant in TIA from ICAD. These hypothesis-generating data suggest that thrombin generation may be relevant in cerebral ischaemia from intracranial disease, and justify larger studies.

Diagnostic Accuracy of a New d-Dimer Assay (Sclavo Auto d-Dimer) for Exclusion of Deep Vein Thrombosis in Symptomatic Outpatients.

In patients presenting non-high clinical pretest probability (PTP), a negative d-dimer can exclude venous thromboembolism without imaging tests. However, each d-dimer assay should be validated in prospective studies. We evaluated an automated d-dimer immunoassay using the Sclavo Auto d-dimer (Sclavo Diagnostics Int, Sovicille, Italy) provided by Dasit Diagnostica (Cornaredo, Milan, Italy). Three hundred two consecutive outpatients suspected of leg deep vein thrombosis (DVT) with non-high PTP were included. The Sclavo Auto d-dimer assay was evaluated on 2 analyzers (Sysmex CA-7000 and Sysmex CS-2100; Sysmex Corporation, Kobe, Japan, provided by Dasit). The cutoff value (200 ng/mL) was established a priori. Prevalence of DVT was 11.9%. Since no false-negative patients were detected, the sensitivity and negative predictive values (NPVs) were 100% (sensitivity = CA-7000: 100% [95% confidence interval, CI: 93.3-100], CS-2100: 100% [95% CI: 93.3-100]; NPV = CA-7000: 100% [95% CI: 97.9-100], CS-2100: 100% [95% CI: 98.0-100]). Specificity was 65.4% (95% CI: 59.4-71.1) and 69.2% (95% CI: 63.3-74.7) for CA-7000 and CS-2100, respectively. Specificity increased when a higher cutoff value (234 ng/mL) was used for patients aged ≥60 years without compromising the safety. Assay reproducibility was satisfactory at concentrations near the cutoff value (total coefficient of variations <10%). In conclusion, the Sclavo Auto d-dimer assay was accurate when used for DVT diagnostic workup in outpatients with non-high PTP. Based on its high sensitivity and NPV, it can be used as a stand-alone test in outpatients with non-high PTP. Given its high specificity, the number of patients in whom further imaging techniques can be avoided increased, improving the yield of the test.

Treatment of Isolated Below the Knee Deep Vein Thrombosis.

The natural history of isolated distal deep-vein thrombosis (IDDVT) is still uncertain, as well as the real clinical risks associated with the disease and the need for its diagnosis and treatment. While more and more IDDVTs are diagnosed in everyday clinical practice, their appropriate therapeutic management is, unfortunately, far from straightforward, and different recommendations on how patients with diagnosed IDDVT should be treated are present between expert professionals and even among international guidelines. The present article aims at briefly reviewing the issue of IDDVT therapy in general, particularly focusing on the different approaches to the treatment of the disease that have been suggested by recent guidelines, those that are currently adopted in clinical practice, and necessary future directions.

The incidence of heparin-induced thrombocytopenia in patients treated with low molecular weight heparin for superficial vein thrombosis.

BACKGROUND: The risk of heparin induced thrombocytopenia (HIT) associated with low molecular weight heparin (LMWH) for treatment of superficial vein thrombosis (SVT) is uncertain. As a result the necessity of platelet count monitoring is unclear in this setting. AIMS: To assess the risk of HIT in outpatients treated with LMWH for SVT. METHODS: In a prospective single centre study we included all symptomatic outpatients in whom a real-time B-mode and color Doppler ultrasonography examination revealed SVT without DVT. Patients treated with vitamin K antagonists or fondaparinux were excluded. Patients received full dose enoxaparin for 1week followed by half therapeutic dose for 3weeks or parnaparin 8500UI aXa for 10days followed by 6400UI aXa once daily for 20days. Platelet count was performed on the day of diagnosis (D0) and 7 (D7), and 14 (D14) days afterward. Primary outcomes were the rate of thromboembolic events and of HIT during a 3-month follow-up. RESULTS: 678 outpatients (age: 64.7±16.2years, male: 42.0%) were evaluated. During follow-up, 7 venous thrombo-embolic events were recorded (1.03% CI 95%: 0.50-2.11%), while no major bleeding was observed (0.0% CI 95%: 0.0-0.56%). Platelet count was 255±93×10(9)/L at D0, 245±93×10(9)/L at D7 (p=0.204 vs. D0) and 261±116×10(9)/L at D14 (p=0.405 vs. D0). No fall in platelet count>50% and no case of HIT were recorded (HR 0.0% CI 95%: 0-0.56%). CONCLUSIONS: A 4-week LMWH treatment for SVT is associated with an incidence of HIT lower than 0.6% and platelet count monitoring may be omitted in this setting.