Reperfusion strategies in stroke with medium-to-distal vessel occlusion: a prospective observational study.

INTRODUCTION: Medium vessel occlusion (MeVO) accounts for 30% of acute ischemic stroke cases. The risk/benefit profile of endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) or the combination of the two (bridging therapy (BT)) is still unclear in MeVO. Here, we compare reperfusion strategies in MeVO for clinical and radiological outcomes. METHODS: This prospective single center study enrolled consecutive patients with AIS due to primary MeVO undergoing IVT, EVT, or BT at a comprehensive stroke center. Primary outcome was good functional status, defined as modified Rankin Scale (mRS) 0-2 at 3-month follow-up. Additional outcomes included mortality, successful recanalization, defined as mTICI ≥ 2b, stroke severity at discharge, and symptomatic intracerebral hemorrhage (sICH) according to SITS-MOST criteria. Logistic regression was modeled to define independent predictors of the primary outcome. RESULTS: Overall, 180 consecutive people were enrolled (IVT = 59, EVT = 38, BT = 83), mean age 75. BT emerged as independent predictor of primary outcome (OR = 2.76, 95% CI = 1.08-7.07) together with age (OR = 0.94, 95% CI = 0.9-0.97) and baseline NIHSS (OR = 0.88, 95% CI = 0.81-0.95). BT associated with a 20% relative increase in successful recanalization compared to EVT (74.4 vs 56.4%, p = 0.049). Rates of sICH (1.1%) and procedural complications (vasospasm 4.1%, SAH in 1.7%) were very low, with no difference across groups. DISCUSSION: BT may carry a higher chance of good functional outcome compared to EVT/IVT only in people with AIS due to MeVO, with marginally higher rates of successful recanalization. Randomized trials are needed to define optimal treatment tailoring for MeVO.

IV Thrombolysis With or Without Endovascular Treatment for Suspected Ischemic Stroke in Patients With Intracranial Tumors.

BACKGROUND AND OBJECTIVES: IV thrombolysis (IVT) for suspected ischemic stroke in patients with intracranial neoplasms is off-label. However, data on risks of intracranial hemorrhage (ICH) are scarce. METHODS: In a multicenter registry-based analysis within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration, we assessed frequencies of symptomatic and fatal ICH after IVT for suspected ischemic stroke in patients with intracranial tumors by descriptive statistics and analyzed associations with clinical and imaging characteristics by binary logistic regression. Definition of symptomatic ICH was based on the clinical criteria of the European Cooperative Acute Stroke-II trial including hemorrhage at any site in cranial imaging and concurrent clinical deterioration. RESULTS: Screening data of 21,289 patients from 14 centers, we identified 105 patients receiving IVT; among them were 29 patients (28%) with additional endovascular treatment, with suspected, that is, imaging-based, or histologically confirmed diagnosis of intracranial tumors. Among 104 patients with CT or MRI after IVT available, symptomatic and fatal ICH were observed in 9 and 4 patients (9% and 4%, respectively). Among 82 patients with suspected or confirmed meningioma, symptomatic and fatal ICH occurred in 6 and 3 patients (7% and 4%), respectively. In 18 patients with intra-axial suspected or confirmed primary or secondary brain tumors, there was 1 symptomatic nonfatal ICH (6%). Of 4 patients with tumors of the pituitary region, 2 patients (50%) had symptomatic ICH including 1 fatal ICH (25%). Tumor size was not associated with the occurrence of symptomatic ICH (odds ratio 2.8, 95% CI 0.3-24.8, p = 0.34). DISCUSSION: In our dataset from routine clinical care, we provide insights on the safety of IVT for suspected ischemic stroke in patients with intracranial tumors, a population that is commonly withheld thrombolysis in clinical practice and prospective trials. Except for a potential high risk of symptomatic ICH after IVT in patients with tumors of the pituitary region, frequencies of symptomatic ICH in patients with intracranial tumors in our cohort seem to be in the upper range of rates observed in previous studies within the TRISP cooperation. These results may guide individual treatment decisions in patients with acute stroke and intracranial tumors with potential benefit of IVT.

Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis.

Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16). Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

Prevalence of pulmonary embolism among patients with recent onset of dyspnea on exertion. A cross-sectional study.

BACKGROUND: Exertional dyspnea is a frequently encountered complaint in clinical practice. However, the prevalence of pulmonary embolism (PE) among patients with dyspnea on exertion has not been reported. OBJECTIVE: The objective of this study was to assess the prevalence of objectively confirmed PE among consecutive patients visiting an emergency department because of recent onset of exertional dyspnea. METHODS: Patients aged ≤75 years with recent (<1 month) marked exertional dyspnea had a systematic workup for PE, irrespective of concomitant signs or symptoms of venous thromboembolism and alternative explanations for dyspnea. PE was excluded on the basis of a low pretest clinical probability and normal age-adjusted D-dimer. All other patients had computed tomography pulmonary angiography. An interim analysis after inclusion of 400 patients would stop recruitment if the 95% confidence interval (CI) of the PE prevalence had a lower limit exceeding 20%. RESULTS: The study was prematurely terminated after the inclusion of 417 patients. In 134 patients (32.1%), PE was excluded based on low clinical probability and normal D-dimer. PE was found in 134 (47.3%) of the remaining 283 patients, for an overall prevalence of 32.1% (95% CI, 27.8-36.8). PE was present in 40 of 204 (19.6%) patients without other findings suspicious for PE and in 94 of 213 patients (44.1%) with such findings. PE involved a main pulmonary artery in 37% and multiple lobes in 87% of the patients. CONCLUSION: The angiographic demonstration of PE is common in patients presenting with recent onset of marked exertional dyspnea, including 20% without other findings suggesting pulmonary embolism.

Fibrinogen Depletion Coagulopathy Predicts Major Bleeding After Thrombolysis for Ischemic Stroke: A Multicenter Study.

BACKGROUND: Symptomatic intracerebral hemorrhage (sICH) and major bleeding can be fatal complications of intravenous thrombolysis (IVT) for acute ischemic stroke. We investigated the impact of early fibrinogen depletion after IVT on major bleeding events. METHODS: This multicenter observational prospective cohort study enrolled 1678 consecutive patients receiving IVT for acute ischemic stroke at 6 Italian centers, undergoing fibrinogen concentration assessment at baseline, 2 hours and 6 hours after IVT. Fibrinogen depletion was defined as a reduction below 200 mg/dL after 2 hours from IVT, or as a reduction below 50% of baseline fibrinogen levels after 2 hours from IVT. Main outcomes were (1) sICH (National Institute of Neurological Disorders and Stroke criteria) and (2) major bleeding defined as fatal bleeding, decrease in the hemoglobin level>2 g/dL/>1 unit transfusion, or bleeding at critical site. Additional outcomes were (1) any ICH, (2) any bleeding, (3) fatal ICH, and (4) sICH according to ECASSII definition. Good functional recovery was defined as modified Rankin Scale score 0 to 2 at 3 months. RESULTS: Overall, 1678 patients were included (mean age 72 years, 46% female). sICH (n=116) and major bleeding (n=297) were associated with lower rate of good functional recovery (P<0.001). Despite similar fibrinogen levels at admission, fibrinogen depletion after 2 hours from IVT was more common in people with sICH, major bleeding and all additional bleeding outcomes. In the backward stepwise multivariable logistic regression model, fibrinogen depletion remained a significant predictor of sICH (OR, 1.55 [95% CI, 1.04-2.32]) and major bleeding (OR, 1.36 [95% CI, 1.03-1.8]). Thirty-one percent of sICH could be attributable to fibrinogen depletion. The association between fibrinogen depletion and worse clinical outcome at 3 months after stroke (P=0.012) was attributable to the higher risk of major bleeding/sICH. CONCLUSIONS: Fibrinogen depletion significantly increases the risk of sICH and major bleeding after IVT for acute ischemic stroke. Fibrinogen depletion represents an independent risk factor for bleeding, and routine assessment could be considered to stratify the risk of ICH. Trials on early fibrinogen repletion are needed to investigate mitigation of bleeding risk.

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.

Predictive value of Tmax perfusion maps on final core in acute ischemic stroke: an observational single-center study.

PURPOSE: To assess utility of computed tomography perfusion (CTP) protocols for selection of patients with acute ischemic stroke (AIS) for reperfusive treatments and compare the diagnostic accuracy (ACC) in predicting follow-up infarction, using time-to-maximum (Tmax) maps. METHODS: We retrospectively reviewed consecutive AIS patients evaluated for reperfusive treatments at comprehensive stroke center, employing a multimodal computed tomography. To assess prognostic accuracy of CTP summary maps in predicting final infarct area (FIA) in AIS patients, we assumed the best correlation between non-viable tissue (NVT) and FIA in early and fully recanalized patients and/or in patients with favorable clinical response (FCR). On the other hand, the tissue at risk (TAR) should better correlate with FIA in untreated patients and in treatment failure. RESULTS: We enrolled 158 patients, for which CTP maps with Tmax thresholds of 9.5 s and 16 s, presented sensitivity of 82.5%, specificity of 74.6%, and ACC of 75.9%. In patients selected for perfusion deficit in anterior circulation territory, CTP-Tmax > 16 s has proven relatively reliable to identify NVT in FCR patients, with a tendency to overestimate NVT. Similarly, CTP-Tmax > 9.5 s was reliable for TAR, but it was overestimated comparing to FIA, in patients with unfavorable outcomes. CONCLUSIONS: In our experience, Tmax thresholds have proven sufficiently reliable to identify global hypoperfusion, with tendency to overestimate both NVT and TAR, not yielding satisfactory differentiation between true penumbra and benign oligoemia. In particular, the overestimation of NVT could have serious consequences in not selecting potential candidates for a reperfusion treatment.

Imaging features and ultraearly hematoma growth in intracerebral hemorrhage associated with COVID-19.

PURPOSE: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. METHODS: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19 +) versus controls without COVID-19 (COV19 -). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. RESULTS: A total of 33 COV19 + patients and 321 COV19 - controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19 + population. uHG was significantly higher among COV19 + patients (median 6.2 mL/h vs 3.1 mL/h, p = 0.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE) = 0.31 (0.11), p = 0.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE) = 0.29 (0.13), p = 0.026). CONCLUSIONS: ICH in COV19 + patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms.

Treatment Decision-Making of Secondary Prevention After Venous Thromboembolism: Data From the Real-Life START2-POST-VTE Register.

Patients with venous thromboembolism (VTE) should receive a decision on the duration of anticoagulant treatment (AT) that is often not easy to make. Sixteen Italian clinical centers included patients with recent VTE in the START2-POST-VTE register and reported the decisions taken on duration of AT in each patient and the reasons for them. At the moment of this report, 472 (66.9%) of the 705 patients included in the registry were told to stop AT in 59.3% and to extend it in 40.7% of patients. Anticoagulant treatment lasted ≥3 months in >90% of patients and was extended in patients with proximal deep vein thrombosis because considered at high risk of recurrence or had thrombophilic abnormalities. d-dimer testing, assessment of residual thrombus, and patient preference were also indicated among the criteria influencing the decision. In conclusion, Italian doctors stuck to the minimum 3 months AT after VTE, while the secondary or unprovoked nature of the event was not seen as the prevalent factor influencing AT duration which instead was the result of a complex and multifactorial evaluation of each patient.

The stroke mothership model survived during COVID-19 era: an observational single-center study in Emilia-Romagna, Italy.

INTRODUCTION: A reduction of the hospitalization and reperfusion treatments was reported during COVID-19 pandemic. However, high variability in results emerged, potentially due to logistic paradigms adopted. Here, we analyze stroke code admissions, hospitalizations, and stroke belt performance for ischemic stroke patients in the metropolitan Bologna region, comparing temporal trends between 2019 and 2020 to define the impact of COVID-19 on the stroke network. METHODS: This retrospective observational study included all people admitted at the Bologna Metropolitan Stroke Center in timeframes 1 March 2019-30 April 2019 (cohort-2019) and 1 March 2020-30 April 2020 (cohort-2020). Diagnosis, treatment strategy, and timing were compared between the two cohorts to define temporal trends. RESULTS: Overall, 283 patients were admitted to the Stroke Center, with no differences in demographic factors between cohort-2019 and cohort-2020. In cohort-2020, transient ischemic attack (TIA) was significantly less prevalent than 2019 (6.9% vs 14.4%, p = .04). Among 216 ischemic stroke patients, moderate-to-severe stroke was more represented in cohort-2020 (17.8% vs 6.2%, p = .027). Similar proportions of patients underwent reperfusion (45.9% in 2019 vs 53.4% in 2020), although a slight increase in combined treatment was detected (14.4% vs 25.4%, p = .05). Door-to-scan timing was significantly prolonged in 2020 compared with 2019 (28.4 ± 12.6 vs 36.7 ± 14.6, p = .03), although overall timing from stroke to treatment was preserved. CONCLUSION: During COVID-19 pandemic, TIA and minor stroke consistently reduced compared to the same timeframe in 2019. Longer stroke-to-call and door-to-scan times, attributable to change in citizen behavior and screening at hospital arrival, did not impact on stroke-to-treatment time. Mothership model might have minimized the effects of the pandemic on the stroke care organization.

Anticoagulation in Italian patients with venous thromboembolism and thrombophilic alterations: findings from START2 register study.

BACKGROUND: Randomised control trials have assessed the efficacy and safety of direct oral anticoagulants in the prophylaxis and treatment of venous thromboembolism (VTE). Positive but limited results have been reported in patients with inherited thrombophilia. Using an Italian, multicentre, prospective registry of consecutive patients presenting with symptomatic, acute VTE, we aimed to assess which factors are involved in making the choice of the drug that best fits the patient's risk profile in a large real-world setting of VTE patients. MATERIALS AND METHODS: We investigated 4,866 VTE patients who took oral anticoagulants in the period between 2012 and April 2018 to prevent a new thromboembolic episode. RESULTS: The large majority of patients who underwent thrombophilic screening, regardless of the results obtained, were prescribed direct oral anticoagulants rather than conventional anticoagulant therapy (p<0.001). During anticoagulation, bleeding events occurred more frequently in patients on conventional anticoagulant therapy (4.2%) than in those receiving direct oral anticoagulants (1.8%) and an increase in bleeding events was observed in patients who tested positive at the thrombophilic screening. Overall, a higher number of recurrent VTE was observed in patients not screened for thrombophilia (n=36; 1.7%) than in those screened (n=20; 0.7%; adjusted odds ratio: 2.2; 95% confidence interval: 1.2-4.1). DISCUSSION: The present data confirm previous findings from other post-marketing registries and suggest that the choice of oral anticoagulation is strongly driven by patients' characteristics and VTE manifestations. Factors leading to the prescription of thrombophilic screening may identify a patient with a lower risk of VTE recurrence during anticoagulation.

Oral anticoagulation in very elderly patients with atrial fibrillation: Results from the prospective multicenter START2-REGISTER study.

Direct oral anticoagulants (DOACs) have shown similar efficacy and safety with respect to warfarin in patients with atrial fibrillation (AF). However, the proportion of patients aged ≥85 years enrolled in clinical trials was low and the applicability of their results to very elderly patients is still uncertain. We have carried out a prospective cohort study on AF patients aged ≥85 years enrolled in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) and treated with either VKAs or DOACs, with the aim to evaluate mortality, bleeding and thrombotic rates during a long-term follow-up. We enrolled 1124 patients who started anticoagulation at ≥85 years with VKA (58.7%) or DOACs (41.3%), Clinical characteristics of patients were similar, except for a higher prevalence of coronary artery disease and renal failure in VKAs patients and of a history of previous bleeding and previous stroke/TIA in patients on DOACs. Median CHA2DS2VASc and HAS-BLED scores were similar between the two groups. During follow-up, 47 major bleedings (rate 2.3 x100 pt-yrs) and 19 stroke/TIA (0.9 x100 pt-yrs) were recorded. The incidence of bleeding was similar between patients on VKAs and DOACs. Patients on DOACs showed a higher rate of thrombotic events during treatment (rate 1.84 and 0.50,respectively). Mortality rate was higher in patients on VKAs than in patients on DOACs (HR 0.64 (95% CI 0.46-0.91). In conclusion, we confirm the overall safety and effectiveness of anticoagulant treatment in very elderly AF patients, with lower mortality rates in DOACs patients, similar bleeding risk, and a higher risk for cerebral thrombotic events in DOACs patients.

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.

Mechanical prosthetic heart valves: Quality of anticoagulation and thromboembolic risk. The observational multicenter PLECTRUM study.

BACKGROUND: Patients with a mechanical prosthetic heart valve implantation need to be treated with a vitamin K antagonist (VKA) due to a substantially high risk of thromboembolism. In this study we report data on patients with mechanical heart valves (MV), with the aim of evaluating the thromboembolic risk in relation to the type and site of implantation, quality of anticoagulation and risk factors associated with thromboembolism. METHODS: Observational retrospective multicenter study among Centers affiliated to the Italian Federation of Anticoagulation Clinics (FCSA) on patients with MV implanted after 1990 and followed for the management of anticoagulation. RESULTS: We analyzed 2357 patients with mechanical heart valves (55.2% males), followed for 24,081 years. During the follow-up, 164 thromboembolic events (0.67/100 pt-yrs) and 243 major bleedings (1.0/100 pt-yrs) occurred. The median Time in Therapeutic Range (TTR), calculated in all intended INR classes, was 60% (IQR 47-74%). The rates of thrombotic events were significantly higher in patients intended to stay at therapeutic ranges >INR 2.0-3.0. The presence of atrial fibrillation, history of thromboembolism and of mitral prosthesis were independently associated with thromboembolism. However, a bad quality of anticoagulation (TTR <47%, 25°percentile of our population) was not correlated with thromboembolism. CONCLUSIONS: A low rate of bleeding and thromboembolic events in patients with mechanical heart valves were found, despite the sub-optimal anticoagulation control. The thromboembolic risk was not associated with the low TTR.

Vitamin K antagonist therapy: changes in the treated populations and in management results in Italian anticoagulation clinics compared with those recorded 20 years ago.

Vitamin K antagonists (VKA) are the most widely used anticoagulants in the world. An appropriate management of treated patients is crucial for their efficacy and safety. The prospective, observational, multicenter, inception-cohort FCSA-START Register, a branch of START Register (NCT02219984) included VKA-treated patients managed by centers of Italian Federation of anticoagulation clinics (AC). Baseline patient characteristics and data during treatment were analyzed and compared with those of ISCOAT study, performed by the Federation and published in 1996/7. 5707 naïve patients [53% males, mean age 73.0 years (28.1% >80 years)], 61.6% treated for atrial fibrillation (AF), and 28.0% for venous thromboembolism were included. During the 8906 patient-years (pt-yrs) of observation, 123 patients had major bleeding (MB) (1.38% pt-yrs; fatal: 0.11% pt-yrs), while non-major clinically relevant bleeds were 144 (1.62% pt-yrs). Bleeding was more frequent in elderly (≥70 years; p = 0.04), and during initial 3-month therapy (p = 0.02). Bleeding rate was 2.5% pt-yrs for temporally related INR results <3.0, increasing to 12.5% for INR ≥ 4.5. Thrombotic events were 47 (0.53% pt-yrs; 4 fatal 0.04% pt-yrs). Compared with ISCOAT-1996/7 results, patients older than 80 y are increased from 8 to 28% (p < 0.01), and those treated for AF are increased from 17 to 61%. The quality of anticoagulation control and incidence of MB are not different. However, thrombotic complications fell drastically from 3.5 to 0.53% pt-yrs (p < 0.01), with lower mortality (p = 0.01). VKA-treated patients monitored in Italian AC have good clinical results, with low bleeding and thrombotic complications rates. Important changes in the treated population and improvement in thrombotic complications are detected compared with the ISCOAT-1996/7 study.

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.

D-dimer for the diagnosis of upper extremity deep and superficial venous thrombosis.

BACKGROUND: D-dimer role is well established in the diagnostic work-up for lower limb deep vein thrombosis (DVT), however it has not been formally tested for clinically suspected upper extremity DVT and/or superficial vein thrombosis (SVT). AIM: To ascertain D-dimer diagnostic accuracy for upper extremity DVT and/or SVT. STUDY DESIGN: We performed a single centre management study in outpatients referred by emergency or primary care physicians for clinically suspected upper extremity DVT. All patients underwent D-dimer testing (cut-off value: ≤500 ng/mL), and a B-mode and color Doppler ultrasonography examination. In case of either technical problems or anatomical barriers, ultrasonography was repeated after 5-7 days. All patients were followed up for three months for the occurrence of symptomatic DVT and/or SVT and/or pulmonary embolism. RESULTS: We enrolled 239 patients (F: 63.6%; mean±SD age: 58.3±16.8). At the initial diagnostic work-up, DVT was detected in 24 (10%) patients while SVT in 35 (14.6%) patients. During follow-up, one upper extremity DVT was found. D-dimer levels were higher in patients with DVT than in those without. Sensitivity and specificity of D-dimer for DVT were 92% (95%CI: 73-99%) and 60% (95%CI: 52-67%) respectively, with a negative predictive value of 98% (95%CI: 93-100%), whereas for SVT they were 77% (95%CI: 59-89%) and 60% (95%CI: 52-67%) respectively, with a negative predictive value of 93% (95%CI: 86-97%). CONCLUSIONS: D-dimer has a negative predictive value ≥93% for excluding DVT in symptomatic outpatients and it can be a useful test in the diagnostic work-up of suspected upper extremity DVT.

Two years outcome of isolated distal deep vein thrombosis.

BACKGROUND: Isolated distal deep vein thrombosis (IDDVT) is frequently found in symptomatic outpatients, but its long term outcome is still uncertain. AIMS: To assess IDDVT long term outcome and the impact of IDDVT characteristics on outcome. METHODS: In a prospective, single center study we enrolled symptomatic outpatients in whom IDDVT was detected by whole-leg compression ultrasonography. Patients with provoked IDDVT were treated with low molecular weight heparins (LMWH) for 30 days while those with unprovoked IDDVT received with vitamin K antagonists (VKA) for three months. The primary end-point was the rate of the composite of pulmonary embolism (PE), proximal deep vein thrombosis (DVT), and IDDVT recurrence/extension during 24 month follow-up. RESULTS: 90 patients (age 61 ± 18, male 48.9%) were enrolled. Risk factors for thrombosis were reduced mobility (34.4%), obesity (25.3%), surgery (15.6%), and previous DVT (15.6%) and cancer in 8 patients (8.9%). Eighty-eight patients were treated (56 with LMWH and 32 with VKA). During follow-up (median 24 ± 2 months), 17 events were recorded, which included 3 PE (two in cancer patients), 4 proximal DVTs (one in cancer patient) and 10 IDDVT. Male sex (HR 4.73 CI95%: 1.55-14.5; p=0.006) and cancer (HR 5.47 CI95%: 1.76-17.6; p=0.003) were associated with a higher risk of complications, whereas IDDVT anatomical characteristics, anticoagulant therapy type, and provoked IDDVT were not. CONCLUSIONS: The risk of recurrent venous thromboembolism after IDDVT may be relevant in male patients or in patients with active cancer. Larger studies are needed to address this issue.