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 ageadjusted 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

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

Padua Prediction Score and Hospital-Acquired Proximal and Isolated Distal Deep Vein Thrombosis in Symptomatic Patients

Background: Hospital-acquired deep vein thrombosis (DVT) is an important cause of morbidity and mortality. Objectives: The purpose of this study was to evaluate the prevalence of proximal lower limb DVT and isolated distal DVT (IDDVT) and their relationship to the Padua Prediction Score (PPS) in acutely ill, hospitalized patients. Methods: In a single-center cross-sectional study, all inpatients from medical departments with suspected lower-extremity DVT were evaluated with whole-leg ultrasonography during 183 days from 2016 to 2017. Results: Among the 505 inpatients (age 78.0 ± 13.3, females 59.2%) from medical departments, 204 (40.2%) had PPS ≥ 4, but only 54.4% of them underwent pharmacological thrombo-prophylaxis. Whole-leg ultrasonography detected 47 proximal DVTs (9.3%) and 65 IDDVTs (12.8%). Proximal DVT prevalence was higher in patients with high PPS vs. those with low PPS (12.7% vs. 7.0% p = 0.029, respectively), whereas IDDVT prevalence was similar in patients with high and low PPS (14.7% vs. 11.6% p = 0.311, respectively). The area under the receiver operating curve (AUC) for the PPS was 0.62 ± 0.03 for all DVTs, 0.64 ± 0.04 for proximal DVTs, and 0.58 ± 0.04 for IDDVTs. Conclusions: In hospitalized patients, IDDVT had similar prevalence regardless of PPS risk stratification. Adherence to thrombo-prophylaxis in patients was still far from optimal. Keywords: Padua prediction score; calf deep vein thrombosis; deep vein thrombosis; diagnosis; inpatients; isolated distal deep vein thrombosis

Gynecological Cancer and Venous Thromboembolism: A Narrative Review to Increase Awareness and Improve Risk Assessment and Prevention

The prevention and appropriate management of venous thromboembolism in cancer patients is of paramount importance. However, the literature data report an underestimation of this major problem in patients with gynecological cancers, with an inconsistent venous thromboembolism risk assessment and prophylaxis in this patient setting. This narrative review provides a comprehensive overview of the available evidence regarding the management of venous thromboembolism in cancer patients, focusing on the specific context of gynecological tumors, exploring the literature discussing risk factors, risk assessment, and pharmacological prophylaxis. We found that the current understanding and management of venous thromboembolism in gynecological malignancy is largely based on studies on solid cancers in general. Hence, further, larger, and well-designed research in this area is needed

Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis

Objective To determine the effect of sex on the risk of recurrent venous thromboembolism in all patients and in patients with venous thromboembolism that was unprovoked or provoked (by non-hormonal factors)

Management of anticoagulation in atrial fibrillation patients in Italy: insight from the <i>Atrial Fibrillation-Survey on Anticoagulated Patients Register</i> (AF-START)

The survey on anticoagulated patients register (START-Register) is an independent, prospective, inception-cohort observational study aimed at providing information on patients on vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) in Italy. In this study, we describe the cohort of atrial fibrillation (AF) patients in the START-Register and report outcomes and changes in anticoagulant prescription from 2011 to 2021. The study included 11,078 AF patients, enrolled in 47 Italian centers distributed all over the Country; the median age was 77 years (range 18-99 years); 6029 (54.3%) were men; 5135 (46.4%) were on VKAs, and 5943 (53.6%) were on DOACs. Warfarin was the most prescribed VKA (98.4%), and apixaban was the most prescribed DOAC (31.6%). Among DOAC users, 4022 (67.7%) patients were naive to anticoagulation, and 2562 (43.1%) patients were treated with a reduced dose. DOAC patients were significantly older than VKA patients (median age 79 years vs 76 years respectively, P<0.001), but no gender difference was detected. The mean CHA2DS2VASc score was higher in DOAC users than in VKA users (3.7 vs 3.6; P=0.03). The mean HAS-BLED score was not different between the two groups. During follow-up, 542 bleeding events were recorded [2.44 per 100 patient-years (pt-yrs)]; 240 were major (1.08 per 100 pt-yrs), and 301 were clinically relevant non-major bleedings (1.34 per 100 pt-yrs). 146 thrombotic events were recorded during follow-up (0.66 per 100 pt-yrs). The total mortality rate was 3.5 per 100 pt-yrs; the mortality rate was 4.54 per 100 pt-yrs among patients on VKAs and 2.31 per 100 pt-yrs among patients on DOACs. During the last 10 years, in Italy, AF patient management has changed with the large spread of DOACs all over the Country. DOAC patients are frequently treated with reduced doses and show a lower mortality rate in comparison to patients on VKAs

Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19: A Consensus Statement Based on Available Clinical Trials.

Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients

Enhancing stroke risk prediction in patients with transient ischemic attack: insights from a prospective cohort study implementing fast-track care

Background and aimsFast-track care have been proved to reduce the short-term risk of stroke after transient ischemic attack (TIA). We aimed to investigate stroke risk and to characterize short- and long-term stroke predictors in a large cohort of TIA patients undergoing fast-track management.MethodsProspective study, enrolling consecutive TIA patients admitted to a Northern Italy emergency department from August 2010 to December 2017. All patients underwent fast-track care within 24 h of admission. The primary outcome was defined as the first stroke recurrence at 90 days, 12 and 60 months after TIA. Stroke incidence with 95% confidence interval (CI) at each timepoint was calculated using Poisson regression. Predictors of stroke recurrence were evaluated with Cox regression analysis. The number needed to treat (NNT) of fast-track care in preventing 90-day stroke recurrence in respect to the estimates based on baseline ABCD2 score was also calculated.ResultsWe enrolled 1,035 patients (54.2% males). Stroke incidence was low throughout the follow-up with rates of 2.2% [95% CI 1.4–3.3%] at 90 days, 2.9% [95% CI 1.9–4.2%] at 12 months and 7.1% [95% CI 5.4–9.0%] at 60 months. Multiple TIA, speech disturbances and presence of ischemic lesion at neuroimaging predicted stroke recurrence at each timepoint. Male sex and increasing age predicted 90-day and 60-month stroke risk, respectively. Hypertension was associated with higher 12-month and 60-month stroke risk. No specific TIA etiology predicted higher stroke risk throughout the follow-up. The NNT for fast-track care in preventing 90-day stroke was 14.5 [95% CI 11.3–20.4] in the overall cohort and 6.8 [95% CI 4.6–13.5] in patients with baseline ABCD2 of 6 to 7.ConclusionOur findings support the effectiveness of fast-track care in preventing both short- and long-term stroke recurrence after TIA. Particular effort should be made to identify and monitor patients with baseline predictors of higher stroke risk, which may vary according to follow-up duration

Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations–State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist