Search

Background and aims: Fast-track care have been proved to reduce the shortterm 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. Methods: Prospective 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. Results: We 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 followup. 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. Conclusion: Our 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Preventing venous thromboembolic complications in patient with gynecological cancers is a relevant issue and an unmet clinical need. Using a thorough literature search, we found that this problem is underestimated and preventative antithrombotic measures are underused. In addition, there are no specific validated risk assessment tools in this setting to help in clinical practice the identification of patients who are at highest thrombotic risk, who may most benefit from pharmacological anticoagulant prophylaxis, and avoid the anticoagulation-associated bleeding risk in those who are at low risk. We suggest that more research be done in this field to improve these patiens' care. 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. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients' demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2–2.0), major bleedings (RR 1.8; 95% CI 1.3–1.7), and mortality (RR 2.8; 95% CI 1.9–4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight <60 kg, and renal failure were significantly associated with inappropriate LD DOAC prescription. Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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); 6,029 (54.3%) were men; 5,135 (46.4%) were on VKAs, and 5,943 (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, 4,022 (67.7%) patients were naive to anticoagulation, and 2,562 (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 nonmajor 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. [ABSTRACT FROM AUTHOR]

Introduction: Features and prognosis of capsular warning syndrome (CWS) have been poorly investigated prospectively. Aims: The study aimed to characterize CWS clinical features, risk profile, short- and long-term prognosis, among a large TIA cohort. Methods: Prospective cohort study of consecutive TIAs was conducted from August 1, 2010, to December 31, 2017. Demographic and clinical characteristics, risk profile, primary (stroke and composite outcome) and secondary (TIA recurrence, cerebral hemorrhage, new onset atrial fibrillation) outcomes were compared between CWS, lacunar (L), and nonlacunar (NL) TIAs. Results: 1,035 patients (33 CWS, 189 L-TIAs, 813 NL-TIAs) were enrolled. Newly diagnosed (ND) hypertension, hypercholesterolemia, cigarette smoking, and leukoaraiosis were independent risk factors of CWS (p < 0.05). CWS showed the highest stroke (30.3% vs. 0.5% and 1.5% for L-TIAs and NL-TIAs, respectively) and composite outcome risk at follow-up (p < 0.001), but better 3-month post-stroke prognosis (mRS 0–2 90.0% vs. 36.8%; p = 0.002). CWS-related stroke mostly occurred <48 h (80.0%) and had a small vessel occlusion etiology (100%), affecting more often the internal capsule (60.0%). Dual antiplatelet therapy (DAPT) versus single antiplatelet therapy was associated with lower 3-month cumulative stroke incidence (12.5% vs. 57.1%; p = 0.010). Intravenous thrombolysis (IVT) showed similar 3-month efficacy and safety in strokes after TIAs groups (median mRS 0, IQR 0–1; p = 0.323). Conclusions: CWS is associated with higher stroke risk and better functional prognosis than L- and NL-TIAs. CWS risk profile is consistent with severe small vessel disease, and ND hypertension could represent a major risk factor. DAPT and IVT seem effective and safe in preventing and treating stroke following CWS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The impact of the COVID-19 pandemic has been dramatic worldwide, with China, Italy, and now US at its epicenter. Researchers and clinicians are studying and testing different approaches in the attempt to prevent the infection and minimize its severity. Major efforts are focused on optimizing mechanical ventilation, antiviral, and supportive treatment; however, the role of heparin and low molecular weight (LMW) heparin in this setting has been largely overlooked. This review summarizes the available evidence about the role of heparan sulfate as a key entry mechanism for SARS-CoV-2; the efficacy of heparin and LMW heparin in counteracting its entry into the cell, the recent experimental findings obtained in in vitro studies using the LMW heparin enoxaparin Inhixa®, the role of heparin and LMW heparin in modulating the cytokine storm, and the evidence for the use of LMW heparin in the prevention and treatment of the thromboembolic complications of COVID-19. The available evidence suggests that LMW heparin appears as a promising tool in the treatment of COVID-19. Whether its systematic use is associated with a reduction in complications and ultimately mortality of these patients is being tested in several studies starting worldwide. [ABSTRACT FROM AUTHOR]

Background: Heparin administration in COVID-19 patients is recommended by expert consensus, although evidence about dosage, duration and efficacy are limited. We aim to investigate the association between different dosages of low molecular weight heparin (LMWH) and mortality among COVID-19 hospitalized patients. Methods and Results: Retrospective study of 450 laboratory-confirmed COVID-19 patients admitted to Sant'Orsola Bologna Hospital from March 01 to April 10, 2020. Clinical, laboratory and treatment data were collected and analyzed. The in-hospital mortality between COVID-19 patients treated with standard prophylactic LMWH dosage vs. intermediate LMWH dosage was compared. Out of 450 patients, 361 received standard deep vein thrombosis (DVT) prophylaxis enoxaparin treatment (40-60mg daily) and 89 patients received intermediate enoxaparin dosage (40–60 mg twice daily) for 7 days. No significant differences in the main demographic characteristics and laboratory testings at admission were observed in the two heparin regimen subgroups, except for older age and prevalence of hypertension in the group treated with "standard" prophylaxis LMWH dosage. The intermediate LMWH administration was associated with a lower in-hospital all-cause mortality compared to the "standard" prophylactic LMWH dosage (18.8% vs. 5.8%, p = 0.02). This difference remained significant after adjustment with the propensity score for variables that differed significantly between the dosage groups (OR= 0.260, 95% CI 0.089–0.758, p=0.014). Conclusions: Intermediate LMWH dosage seems to be associated with lower incidence of mortality compared to standard DVT prophylaxys in hospitalized COVID-19 patients. Our study paves the way to further pathophysiological investigations and controlled studies of anticoagulation therapy in Covid-19 disease. [ABSTRACT FROM AUTHOR]

Introduction: To measure direct factor Xa inhibitor (apixaban, edoxaban, rivaroxaban) concentrations, dedicated chromogenic anti‐Xa assays are recommended as suitable methods to provide rapid drug quantification. Moreover, the high‐performance liquid chromatography with ultraviolet detection (HPLC‐UV) is reported as a reliable quantitative technique. We investigated seven anti‐Xa assays and an HPLC‐UV method for measurement of apixaban and rivaroxaban levels in patients enrolled in the START‐Register. Methods: A total of 127 apixaban and 124 rivaroxaban samples were tested by HPLC‐UV and the following anti‐Xa assays: Biophen DiXaI and Heparin LRT (Hyphen BioMed), Berichrom and Innovance Heparin (Siemens), STA‐Liquid Anti‐Xa (Stago Diagnostics), Technochrom anti‐Xa (Technoclone), and HemosIL Liquid Anti‐Xa (Werfen). Each method was performed in one of the participating laboratories: Bologna, Cremona, Florence, and Padua. Results: Our data confirmed the overestimation of apixaban and rivaroxaban levels by the antithrombin‐supplemented anti‐Xa method (Berichrom). Performances and reproducibility of the six anti‐Xa assays not supplemented with antithrombin and the HPLC‐UV method were good, with limits of quantification from 8‐39 ng/mL (apixaban) and 15‐33 ng/mL (rivaroxaban). The six chromogenic methods showed good concordances with the quantitative HPLC‐UV [bias: −26.9‐22.3 ng/mL (apixaban), −11.3‐18.7 ng/mL (rivaroxaban)]. Higher bias and wider range between limits of agreement were observed at higher concentrations [<100 ng/mL: bias −21.3‐4.1 ng/mL (apixaban) and −6.2‐3.8 ng/mL (rivaroxaban); >200 ng/mL: bias −42.2‐36.8 ng/mL (apixaban) and −20.1‐68.9 ng/mL (rivaroxaban)]. Conclusion: Overall, the anti‐Xa assays not supplemented with antithrombin and the HPLC‐UV method proved to be suitable for apixaban and rivaroxaban quantification. [ABSTRACT FROM AUTHOR]

Male patients, especially the young, are at a higher risk of recurrent venous thromboembolism (RVTE) than females. Recent scientific reports show the use of D-dimer does not help predict RVTE risk in males. In the present report, we reviewed the data obtained in the DULCIS study (main report published in Blood 2014), focusing on D-dimer results recorded in non-elderly patients of both genders included in the study, and their relationship with RVTE events occurring during follow-up. Using specifically designed cutoff values for positive/negative interpretation, serial D-dimer measurements (performed during warfarin treatment and up to 3 months after discontinuation of anticoagulation) in 475 patients (males 57.3%) aged ≤ 65 years were obtained. D-dimer resulted positive in 46.3% and 30.5% of males and females, respectively (p = 0.001). Following management procedure, anticoagulation was stopped in 53.7% of males and 69.5% of females, who had persistently negative D-dimer results. The rate of subsequent recurrent events was 1.7% (95% CI 0.5-4.5%) and 0.4% (95% CI 0-2.5%) patient-years in males and females, respectively, with upper limits of confidence intervals always below the level of risk considered acceptable by international scientific societies for stopping anticoagulation (< 5%). In conclusion, using sensitive quantitative assays with specifically designed cutoff values and serial measurements during and after discontinuation of anticoagulation, D-dimer testing is useful to predict the risk of RVTE and is of help in deciding the duration of anticoagulation in both male and female adult patients aged up to 65 years. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background D-dimer levels measured during and after vitamin K antagonist withdrawal may be used in clinical practice to assess the individual risk of recurrent venous thromboembolism. Currently, direct oral anticoagulants (DOACs) are frequently used in venous thromboembolism treatment; however, their pharmacokinetics and pharmacodynamics characteristics are completely different than vitamin K antagonists. The present study aimed at comparing the results of D-dimer levels during and after anticoagulation withdrawal in patients with venous thromboembolism treated with DOACs or warfarin. Material and methods D-dimer levels were measured in 527 patients (“cases”) during DOACs treatment (T0) and after 15 (T15), 30 (T30), 60 (T60) and 90 (T90) days after their discontinuation and in 527 patients (“controls”) enrolled in the DULCIS study (all treated with warfarin), matched for sex, age (+/-3 y), type of D-dimer assay and site of venous thromboembolism. Both cases and controls received anticoagulant treatment after a first venous thromboembolism event that was unprovoked or associated with weak risk factors. Results The rate of positive D-dimer results was significantly higher in cases than in controls at T0 (10.8% vs 5.1%, p = 0.002) and at T30 (18.8% vs 11.8%, p = 0.019), as well as at the other time-points, though not statistically significant. Conclusion D-dimer levels during and after stopping an anticoagulant treatment for a venous thromboembolism episode differ between patients treated with a DOAC than in those treated with warfarin. Specifically designed prospective studies are warranted to reassess the use of Ddimer as predictor of the risk of recurrent venous thromboembolism in patients treated with DOACs. [ABSTRACT FROM AUTHOR]

Introduction: Co‐administration of enoxaparin and a direct oral factor Xa inhibitor (xabans: apixaban, edoxaban, rivaroxaban) could give rise to the problem of overlapping the anti‐Xa activity when measuring direct oral anticoagulant (DOAC) levels. We aimed to evaluate in vitro the degree of the interference of increasing enoxaparin concentrations on xaban plasma levels measured by different chromogenic anti‐Xa assays with drug‐specific calibrators and controls. Methods: Seven plasma samples were spiked with apixaban, edoxaban, or rivaroxaban at fixed concentration, and enoxaparin at increasing concentrations (0, 0.125, 0.250, 0.50, 1.0, 1.50, and 2.0 IU/mL). The evaluated chromogenic assays were as follows: Biophen DiXaI and Biophen Heparin LRT (Hyphen BioMed), Berichrom Heparin and Innovance Heparin (Siemens), STA‐Liquid Anti‐Xa (Stago Diagnostics), Technochrom anti‐Xa (Technoclone), and HemosIL Liquid Anti‐Xa (Werfen). Results: The presence of enoxaparin caused increased DOAC levels, with over‐estimation depending on the anti‐Xa assay and on the heparin concentration in the sample. The smallest over‐estimation was in the sample with enoxaparin 0.125 IU/mL and the greatest in the sample with enoxaparin 2.0 IU/mL (0%, 3.1%, and 7.4% vs 583.8%, 526.1%, and 415.2% for apixaban, edoxaban, and rivaroxaban, respectively). Biophen DiXaI showed lower interference compared to other methods (maximum over‐estimation in the presence of enoxaparin 2.0 IU/mL: 56.4% dosing rivaroxaban by Biophen DIXaI vs 583.8% dosing apixaban by Berichrom Heparin). Conclusion: The presence of enoxaparin interferes with xabans measurement by chromogenic anti‐Xa assays causing falsely elevated DOAC levels, the over‐estimation being dependent on the anti‐Xa assay and on the heparin concentration in the sample. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The recent position paper of the European Society of Cardiology (ESC) on cardiovascular toxicity of cancer treatments has attracted considerable interest by healthcare professionals, since it is the first concrete help in the difficult task of monitoring and approaching cardiovascular side effects of anticancer treatments. The ESC expert opinion was not intended as a clinical practice guideline; however, it reports major cardiovascular complications grouped into nine categories, addressing current clinical strategies for prevention and mitigation. In this point of view, we discuss key challenges emerging from critical appraisal of the ESC position paper: (1) the wide spectrum of cardiovascular toxicities associated with oncological drugs, focusing on targeted agents, (2) managing strategies in patients with cardiac implantable devices, (3) the underappreciated (but emerging) immune-related cardiovascular toxicities of checkpoint inhibitors, which may also result in severe heart failure and fulminant myocarditis, (4) the evolving role of anticoagulation in oncology, and the evidence supporting (or not) the use of direct-acting oral anticoagulants in cancer-associated thrombosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic or unprovoked venous thromboembolism is an event occurring in the absence of any apparent provoking or triggering environmental risk factors, such as surgery, trauma, and immobilization. Areas covered: Unprovoked VTE can be associated with occult cancer, but only limited, and not extensive cancer screening, may be warranted, as the rate of occult cancer is low in such patients. Routine thrombophilia testing is not currently recommended as it does not influence the management of the disease. The duration of anticoagulation for unprovoked VTE after the first three months is still debated as the disease tends to recur regardless of treatment duration. Expert commentary: Prognostic scores incorporating patient related risk factors, such as age and sex, and global markers of hypercoagulability, such as D-dimer, have been proposed for identifying high risk patients who are candidates for extended anticoagulation beyond three months. Direct oral anticoagulants, aspirin and sulodexide could be alternative to vitamin K antagonists (VKA) for long term treatment in such patients. The most up to date guidelines suggest DOACs over VKA for non-cancer VTE in the first three months and also long-term in subjects at low or moderate risk of bleeding, albeit with grade 2B strength of recommendation. [ABSTRACT FROM AUTHOR]

Background: Laboratory investigation with specific factor XIII (FXIII) assays plays a crucial role in diagnosis of FXIII deficiency. According to the International Society on Thrombosis and Hemostasis (ISTH), it is necessary a blank sample with iodoacetamide, provided by the kit or locally prepared, when the ammonia release assays are used, to avoid FXIII activity overestimation. Methods: In this study we set up a modification of the Berichrom FXIII chromogenic assay, in which iodoacetamide was added by the BCS analyzer in the reaction mixture of the blank sample, without modifications of the original reagents. We analyzed 100 plasma samples of outpatients with clinical symptoms suggestive of a bleeding diathesis (20 samples had FXIII activity <20%). Results: In all samples blank subtraction significantly reduced FXIII activity, mostly in the low activity range group (from 10.1% to 2.4%, p<0.0001). In this group correction with iodoacetamide also increased the agreement with the immunoassay and allowed FXIII activity measure up to 0%. Conclusions: Despite the low number of samples included in the study, the described automatic procedure seemed to decrease FXIII activity overestimation and, especially for low activity range samples (<20%), to improve the agreement between FXIII activity and concentration. Our data suggested that iodoacetamide correction could allow the detection of severe FXIII deficiencies (activity <5%) otherwise undiagnosed using the original method. [ABSTRACT FROM AUTHOR]

Background: Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT).Objective: To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT.Design: Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16 hospitals in Europe and the United States.Patients: 406 inpatients and outpatients with suspected UEDVT.Measurements: The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up.Results: The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%).Limitations: This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally.Conclusion: The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Background: Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, D-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT). Objective: To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. Design: Diagnostic management study. (ClinicalTrials.gov: NCT01324037) Setting: 16 hospitals in Europe and the United States. Patients: 406 inpatients and outpatients with suspected UEDVT. Measurements: The algorithm consisted of the sequential application of a clinical decision score, Ddimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal Ddimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up. Results: The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal Ddimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%). Limitations: This study was not powered to show the safety of the substrategies. DDimer testing was done locally. Conclusion: The combination of a clinical decision score, Ddimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT. [ABSTRACT FROM AUTHOR]

The Prolong study shows that continuing vitamin K antagonists (VKA) in patients with abnormal d-dimer (evaluated by a qualitative assay, Clearview Simplify d-dimer) results in a significant reduction of venous thromboembolism (VTE) recurrence. The present study retrospectively analyzes a subgroup of patients enrolled in the Prolong study with a view to calculate cut-off values for six quantitative d-dimer methods to predict the risk of VTE recurrence. We measured d-dimer levels by VIDAS d-dimer Exclusion (bioMerieux), STA Liatest d-dimer (DiagnosticaStago), HemosIL d-dimer and HemosIL d-dimer HS (Instrumentation Laboratory), Innovance d-dimer (Siemens) and AutoDimer (Trinity Biotech) in frozen plasma aliquots sampled 30 ± 10 days after VKA cessation in 390 patients enrolled in the Prolong study. During follow-up (562.7 years), 28 patients had recurrent VTE (7.2%, 5.0% person-years). Since d-dimer levels are positively correlated with age and significantly lower in men, we calculated method-specific cut-off values according to age and gender. The HRs for VTE recurrence calculated using method-specific cut-off values based on age and gender are higher than those using cut-off values indicated by the manufacturers for VTE exclusion in symptomatic outpatients. These data suggest that method-specific cut-off values calculated according to patient age and gender can be more accurate in identifying patients at a higher risk for VTE recurrence. These method-specific cut-off values are being evaluated in the ongoing prospective management multicenter DULCIS study. [ABSTRACT FROM AUTHOR]

Purpose: Warfarin dosing is affected by clinical and genetic variants, but the contribution of the genotype associated with warfarin resistance in pharmacogenetic algorithms has not been well assessed yet. We developed a new dosing algorithm including polymorphisms associated both with warfarin sensitivity and resistance in the Italian population, and its performance was compared with those of eight previously published algorithms. Methods: Clinical and genetic data ( CYP2C9*2, CYP2C9*3, VKORC1 -1639 G > A, and VKORC1 3730 G > A) were used to elaborate the new algorithm. Derivation and validation groups comprised 55 (58.2% men, mean age 69 years) and 40 (57.5% men, mean age 70 years) patients, respectively, who were on stable anticoagulation therapy for at least 3 months with different oral anticoagulation therapy (OAT) indications. Results: Performance of the new algorithm, evaluated with mean absolute error (MAE) defined as the absolute value of the difference between observed daily maintenance dose and predicted daily dose, correlation with the observed dose and R value, was comparable with or slightly lower than that obtained using the other algorithms. The new algorithm could correctly assign 53.3%, 50.0%, and 57.1% of patients to the low (≤25 mg/week), intermediate (26-44 mg/week) and high (≥ 45 mg/week) dosing range, respectively. Our data showed a significant increase in predictive accuracy among patients requiring high warfarin dose compared with the other algorithms (ranging from 0% to 28.6%). Conclusions: The algorithm including VKORC1 3730 G > A, associated with warfarin resistance, allowed a more accurate identification of resistant patients who require higher warfarin dosage. [ABSTRACT FROM AUTHOR]

The rate of resolution of a first episode of pulmonary embolism (PE) is uncertain. A baseline test indicating any residual PE is pivotal in aiding a more accurate diagnosis of recurrent PE. This study aimed to assess the rate and risk factors of residual PE with either multidetector computed tomography imaging (MDCT) or lung perfusion scan (LPS) using a cross-sectional study in which consecutive patients were enrolled with a first objectively documented episode of symptomatic PE, and who were considered for possible treatment withdrawal after at least 3 months of anticoagulation. A first cohort of patients ( n = 80) underwent MDCT, while the subsequent cohort ( n = 93) underwent LPS. The two cohorts had similar characteristics, and 98.3% of patients had non high-risk index PE. MDCT detected residual PE in 15% of subjects (12/80, 95% CI 8-25%) after a mean of 9 months of anticoagulation. No clinical characteristics were significantly associated with residual PE at MDCT. LPS detected residual PE in 28% (26/93, 95% CI 19-38%) of patients after a period of a mean of 9 months of anticoagulation with a significant association with increasing age and known pulmonary disease. Resolution of PE was high after a first episode of non high-risk PE treated with heparin followed by at least 3 months of anticoagulation. Age and coexistent pulmonary disease influence the presence of residual PE detected by LPS, but not by MDCT. Further studies are warranted in which the presence of residual embolism is detected by repetition of the same test that had been initially carried out. [ABSTRACT FROM AUTHOR]

Evaluation of the risk of recurrent venous thromboembolism (VTE) is required to determine the optimal duration of secondary prophylaxis. Application of global assays reflecting the pro- versus anti-coagulant balance in vivo would be desirable. We aimed at investigating the relationship between recurrent VTE and the Protac-induced coagulation inhibition (PICI) assay, which is based on tissue factor-induced thrombin generation measured by a chromogenic substrate. One-hundred-ninety patients were followed-up after a first episode of unprovoked, objectively documented VTE for 2.7 years after stopping treatment with vitamin K antagonists (VKA). PICI was measured 1 month after stopping treatment as the percentage of the OD values recorded without or with Protac. The lower the PICI%, the greater the pro- versus anti-coagulant imbalance. The study outcome was objectively-documented symptomatic recurrent VTE. Patients with PICI% ≤ 74% had crude hazard-ratios (HR) (95% CI) for recurrent VTE of 2.86 (1.01–8.12) as compared to those with PICI% > 87%. After adjustment for age, gender, type of index event, VKA duration and normal/abnormal D-Dimer, HR (95% CI) were substantially unchanged [2.91 (1.01–8.38)]. The corresponding values after further adjustment for the above variables plus the absence/presence of the most frequent thrombophilic alterations were 3.38 (1.16–9.84). These HR values compare favorably with those obtained in a previous study investigating the thrombin generation test performed in the presence of thrombomodulin. In conclusion, the measurement of PICI helps to identify patients at higher risk of VTE recurrence. Advantages of PICI over thrombin generation tests are easy performance in general clinical laboratories, easy standardization and no special equipment. [ABSTRACT FROM AUTHOR]

Background The PROLONG study showed that D-dimer (D-d) testing could help tailor the duration of anticoagulation after idiopathic venous thromboembolism (VTE). In this report the initial 18 month study follow-up was extended for 1 year. Materials and Methods D-d was measured 1 month after anticoagulation withdrawal for a first episode of idiopathic VTE. Patients with a normal D-d did not resume anticoagulation, while patients with an abnormal D-d were randomized to either resume or not resume treatment. The primary outcome was the composite of recurrent VTE and major bleeding. Secondary end-points were cardiovascular events, newly diagnosed cancers and deaths. Results D-d was abnormal in 222/608 (36.5%) patients. Average follow-up was 2.55 years. Twenty-eight events occurred in the 121 patients who stopped anticoagulation (23.1%, 9.6% person-years) and five in the 101 patients who resumed anticoagulation (5.0%, 2.0% person-years, adjusted hazard ratio-HR = 3.76; P = 0.008). Recurrence rate was higher in patients with abnormal D-d who stopped anticoagulation than in patients with normal D-d (51 events in 386 patients −13.2%; 5% person-years; adjusted HR 1.70; P = 0.045). The adjusted HR ratio associated with normal D-d versus abnormal D-d in patients who resumed anticoagulation was 2.7 ( P = 0.042). An abnormal D-d was associated with a non significant higher risk of cardiovascular events and newly diagnosed cancers vs normal D-d. Conclusions Patients with an abnormal D-d at 1 month after withdrawal of VKA have a significant risk of recurrence over a 2.55 year follow-up and they benefit from resuming anticoagulation. [ABSTRACT FROM AUTHOR]

This study prospectively evaluated the relationship between activated partial thromboplastin time (aPTT) and risk of venous thromboembolism (VTE) recurrence after oral anticoagulant (OA) withdrawal in patients with a previous unprovoked VTE event. Six hundred twenty-eight patients (331 males; median age: 67 years) were followed after OA interruption (mean follow-up = 22 months). Three to four weeks from OA discontinuation patients were given a complete thrombophilic work-out, including aPTT (automated aPTT). Recurrent symptomatic VTE events (objectively documented) occurred in 71/628 (11·3%, 6·8/100 person-years) patients. The VTE recurrence rate was 17·5% and 7·5% in patients with aPTT in the lower (ratio ≤0·90) and in the upper (ratio >1·05) quartiles. The recurrence risk was more than twofold higher in patients with ratio ≤0·90 versus those of the reference category [Relative risk (RR): 2·38 (95% confidence interval (CI): 1·18–4·78)]. As expected, the increase in recurrence risk disappeared after adjustment for factor VIII, IX and XI levels [RR: 1·74 (95%CI: 0·43–2·76)]. In contrast, the risk was persistently increased in patients with a ratio ≤0·90 [RR: 2·07 (95%CI: 1·02–4·18)] after adjustment for age, gender andd-dimer level. The aPTT predictive value was independent of the presence of inherited thrombophilic alterations. In conclusion, abnormally short aPTT values are associated with a significantly increased risk of VTE recurrence. [ABSTRACT FROM AUTHOR]

The combination of oral anticoagulation (OAC) and aspirin was the antithrombotic treatment initially adopted after coronary stenting (PCI-S). Although dual antiplatelet therapy with aspirin and a thienopyridine subsequently proved safer and more effective, OAC and aspirin combination is still used in patients with an indication for long-term OAC undergoing PCI-S. The absolute (AR) and relative (RR) risk of cardiac events and hemorrhagic/vascular complications of OAC and aspirin versus antiplatelet therapy were evaluated in a meta-analysis of four historical clinical trials. In 2,436 patients, the RR of a 30-day primary composite endpoint of death, myocardial infarction and the need for revascularization was significantly reduced by antiplatelet therapy (RR 0.41; 95% CI 0.25–0.69), whereas the RR of stent thrombosis (RR 0.26; 95% CI 0.06–1.14) and major bleeding (RR 0.36; 95% CI 0.14–1.02) was not statistically different. The 30-day AR of death, myocardial infarction, need for revascularization, major bleedings and vascular complications with OAC and aspirin were 0.65, 3.8, 4.2, 6.4 and 6.6%, respectively. In conclusion, due to the low AR of adverse events, the combination of OAC and aspirin appears an acceptable treatment after PCI-S in patients in whom long-term OAC is deemed mandatory. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The factors associated with persistent instability of oral anticoagulant treatment (OAT) were investigated in a case-control study. The most unstable patients from 35 Italian anticoagulation clinics were matched with stable controls, for gender, age and OAT indication. Socio-demographic data, medical history, dietary and life habits, cytochrome P450 CYP2C9 variants, blood cell count, liver and renal functions were investigated. An‘Abbreviated Mental Test’ (AMT) and a questionnaire to assess patient compliance to, and comprehension of, OAT indications and mechanisms were administered. An International Normalized Ratio (INR) above 4·5 was more frequently found in cases (n = 77) than controls (n = 80) (12·3% vs. 0·4%;P < 0·0001). The odds ratio for instability was significantly higher for: people who workedversuspensioners, acenocoumarolversuswarfarin, and an insufficient score in the AMT and/or in the questionnaire. Cytochrome P450 CYP2C9 variants*1/*3 or*2/*3 or*3/*3 were more frequent among cases than controls (29·9% vs.15·0%;P = 0·042). No differences were observed as regards the other variables. In conclusion, we found that high intra-individual variability in OAT control was multifactorial, but poor OAT comprehension was prevalent. [ABSTRACT FROM AUTHOR]

Background: Unrecognized thrombophilic defects increase the risk of venous thromboembolism (VTE) in women during oral contraception (OC). We evaluated the sensitivity and specificity of a family history of VTE to identify thrombophilia in women before OC and after venous thrombotic complications during OC. Methods: Thrombophilia screening was performed after obtaining a family history by means of a standardized questionnaire in (1) thrombosis-free women before OC and (2) women after an episode of VTE during OC. Results: We evaluated 479 thrombosis-free women before OC (age range, 15-49 years); family history was positive in 49 (10.2%). Thrombophilic defects were identified in 36 participants (7.5%; 95% confidence interval [CI], 5%-10%), 3 of whom had a positive family history (8.3%). The sensitivity and positive predictive value of family history of thrombophilic defects were 8.3% (95% CI, 2%-22%) and 6.1% (95% CI, 1%-17%), respectively. We also evaluated 189 women after VTE complications during OC (age range, 15-49 years); family history was positive in 48 (25.4%; 95% CI, 19%-32%), 22 of whom had a thrombophilic defect (45.8%; 95% CI, 31%-61%). Thrombophilic defects were identified in 81 women (42.8%; 95% CI, 36%-50%). The sensitivity and positive predictive value of family history of thrombophilic defects were 27.2% (95% CI, 18%-38%) and 45.8% (95% CI, 31%-61%), respectively. Conclusion: Family history of VTE has low sensitivity and positive predictive value for identifying women with thrombophilia who are more susceptible to VTE complications during OC. [ABSTRACT FROM AUTHOR]

Presents letters to the editor concerning medical issues. Lower urinary tract symptoms in middle aged and elderly men and prostatic problems; Family history and risk of venous thromboembolism with oral contraception; Perineal massage in pregnancy; Others.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition and it is associated with increased in vivo thrombin generation that needs to be treated with non-heparin anticoagulants such as direct thrombin inhibitors (DTIs). DTIs require parenteral administration and are associated with a non negligible risk of major bleeding. We describe a case of HIT treated with rivaroxaban, a direct oral factor Xa inhibitor which could be used to inhibit the generation of thrombin, instead of DTIs. A 68 year-old man with a thrombosis confined to the internal gastrocnemius and soleal veins developed HIT during enoxaparin 80 mg twice a day. Enoxaparin was stopped and rivaroxaban 20 mg once a day was started. Platelet count returned to base line after 6 days from enoxaparin withdrawal. After 3 months rivaroxaban was stopped and the patient had an uneventful course. This case report supports the hypothesis that rivaroxaban may be candidate for treatment of HIT, and larger studies are justified. [ABSTRACT FROM AUTHOR]