Role of Genetic and Acquired Prothrombotic Risk Factors in Genesis of Sudden Sensorineural Hearing Loss.

The methylenetetrahydrofolate reductase C677T mutation, factor V G1691A (factor V Leiden) mutation, prothrombin G20210A mutation and 8 other laboratory values associated with increased thrombotic risk were analyzed in 40 patients with sudden sensorineural hearing loss (SSHL). The results were compared with those obtained from 120 controls not affected by SSHL. We found a statistically significant higher frequency of hyperhomocysteinemia in the SSHL group compared with controls, and that this was also associated with the presence of homozygosity for the MTHFR C677T mutation. The study results suggest that SSHL might be caused, among other factors, by a combination of these 2 variables. We suggest that this analysis of the MTHFR C677T mutation should be further investigated to establish the etiology of SSHL, and that the same analysis should be taken into account in those patients with high levels of homocysteine

Development of systemic autoimmune diseases in healthy subjects persistently positive for antiphospholipid antibodies. long-term follow-up study

We longitudinally followed a single-center cohort of anti-phospholipid (aPL) positive healthy subjects to evaluate the evolution to systemic autoimmune diseases (sAD) and to describe clinical and serological associated features. Since 2010, we have consecutively screened healthy subjects who were positive, in at least two consecutive determinations, for one or more aPL [anti-Cardiolipin (aCL) IgM/IgG, anti-Beta2Glycoprotein I (aB2GPI) IgM/IgG, Lupus Anticoagulant (LA)]. All subjects were evaluated every six months, or in accordance with the patient's clinical course, in order to record the development of clinical and laboratory features suggestive for sAD. Ninety-five subjects [M/F 20/75, median age at first determination 46 years, Interquartile Range (IQR) 19] were enrolled. Thirty-three subjects (34.7%) were positive for only one aPL [15 (15.8%) for aCL, 15 (15.8%) for LA, and 5 (5.3%) for aB2GPI]; 37 (38.9%) had double positivity [32 (33.6%) for aCL and aB2GPI; 5 (5.3%) for aCL and LA], 23 (24.2%) had triple positivity. We prospectively followed up our cohort for a median period of 72 months (IQR 84). During a total follow-up of 7692 person-months, we found an absolute risk for sAD development equal to 1.8%. Specifically, 14 (14.7%) patients developed a sAD: in four patients (4.2%), after developing a thrombotic event, an antiphospholipid syndrome was diagnosed, 7 (7.4%) patients developed an Undifferentiated Connective Tissue Disease after a median period of 76 months (IQR 75.5), and lastly, three (3.1%) patients could be classified as affected by Systemic Lupus Erythematosus according to the ACR/EULAR 2019 criteria. The presence of triple positivity status resulted in being significantly associated with the progression to sAD (p-value = 0.03). In conclusion, we observed the development of sAD in almost 15% of aPL positive subjects. Triple positivity was significantly associated with this progression, suggesting a possible role as biomarker for this condition. Thus, our results could suggest the need for periodic follow-up for such patients to assess early diagnosis and treatment

SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke

Background and purpose: Acute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). Aims of this study were to compare clinical/radiological characteristics, endothelial and coagulation dysfunction between acute ischemic stroke (AIS) patients with and without COVID-19 and to investigate if and how the SARS-CoV-2 spike protein (SP) was implicated in triggering platelet activation. Methods: We enrolled AIS patients with COVID-19 within 12 h from onset and compared them with an age- and sex-matched cohort of AIS controls without COVID-19. Neuroimaging studies were performed within 24 h. Blood samples were collected in a subset of 10 patients. Results: Of 39 AIS patients, 22 had COVID-19 and 17 did not. Admission levels of Factor VIII and von Willebrand factor antigen were significantly higher in COVID-19 patients and positively correlated with the infarct volume. In multivariate linear regression analyses, COVID-19 was an independent predictor of infarct volume (B 20.318, Beta 0.576, 95%CI 6.077-34.559; p = 0.011). SP was found in serum of 2 of the 10 examined COVID-19 patients. Platelets from healthy donors showed a similar degree of procoagulant activation induced by COVID-19 and non-COVID-19 patients' sera. The anti-SP and anti-FcγRIIA blocking antibodies had no effect in modulating platelet activity in both groups. Conclusions: SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS

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

D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study.

D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study, we aimed to assess the value of an algorithm incorporating serial D-dimer testing and administration of reduced-dose apixaban (2.5 mg twice daily) only to patients with a positive test. A total of 732 outpatients aged 18 to 74 years, anticoagulated for ≥12 months after a first unprovoked VTE, were included. Patients underwent D-dimer testing with commercial assays and preestablished cutoffs. If the baseline D-dimer during anticoagulation was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286 [39.1%]) were left without anticoagulation. At the first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval [CI], 4.5-11.2), including symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding occurring in patients off anticoagulation vs that in those receiving apixaban (1.1%; 95% CI, 0.4-2.6; adjusted hazard ratio [HR], 8.2; 95% CI, 3.2-25.3). In conclusion, in patients anticoagulated for ≥1 year after a first unprovoked VTE, the decision to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced-dose apixaban against recurrences. This trial was registered at www.clinicaltrials.gov as #NCT03678506

Low in‑hospital mortality rate in patients with COVID‑19 receiving thromboprophylaxis: data from the multicentre observational START‑COVID Register

Abstract COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease,and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years

Immune thrombocytopenia during covid-19 pandemic: An italian monocentric experience

Over the last 2 years, different cases of immune thrombocytopenia (ITP) in patients affected by SARS-CoV2 have been reported. The management of SARS-CoV2 in subjects with simultaneous or previous ITP can be challenging because of the great involvement of the haemostatic system in this viral infection. In this report, we describe the management and outcome of patients with newly diagnosed (ND), chronic and previous ITP, infected by COVID-19, referred to the Haematology Institute of University Hospital Policlinico Umberto I in Rome. Steroids + immunoglobulins for ND or relapsed ITP and continuation of home therapy for chronic ITP are advised, although further knowledge is required

The treatment of upper extremities deep vein thrombosis related to thoracic outlet syndrome with direct oral anticoagulants

Venous thoracic outlet syndrome (VTOS) is a manifestation of venous symptoms that occurs when the subclavian vein is compressed and it may present clinically with acute venous thrombosis of the axillo-subclavian vein. Evidence for the optimal approach to the management of this condition is sparse and actually anticoagulation alone is not considered an option. Herein we reported our experience with direct oral anticoagulants in patients with upper extremities deep vein thrombosis, due to VTOS, who refused endovascular approach or surgery