Anticoagulant therapy is a cornerstone treatment for coronavirus disease 2019 (COVID-19) due to the high rates of thromboembolic complications associated with this disease. We hypothesized that chronic antithrombotic therapy could play a protective role in patients hospitalized for COVID-19. Retrospective, observational study of all patients admitted to our hospital for ≥ 24 h from March 1 to May 31, 2020 with SARS-CoV-2. The objective was to evaluate clinical outcomes and mortality in COVID-19 patients receiving chronic anticoagulation (AC) or antiplatelet therapy (AP) prior to hospital admission. A total of 1612 patients were evaluated. The mean (standard deviation; SD) age was 66.5 (17.1) years. Patients were divided into three groups according to the use of antithrombotic therapy prior to admission (AP, AC, or no-antithrombotic treatment). At admission, 9.6% of the patients were taking anticoagulants and 19.1% antiplatelet therapy. The overall mortality rate was 19.3%. On the multivariate analysis there were no significant differences in mortality between the antithrombotic groups (AC or AP) and the no-antithrombotic group (control group). Patients on AC had lower ICU admission rates than the control group (OR: 0.41, 95% CI, 0.18–0.93). Anticoagulation therapy prior to hospitalization for COVID-19 was associated with lower ICU admission rates. However, there were no significant differences in mortality between the patients receiving chronic antithrombotic therapy and patients not taking antithrombotic medications. These findings suggest that chronic anticoagulation therapy at the time of COVID-19 infection may reduce disease severity and thus the need for ICU admission.

Background: Patient self-management (PSM) of vitamin K antagonists (VKA) seems a very promising model of care for oral anticoagulation in terms of efficacy and safety. In comparison with other management models of VKA therapy, the number of scientific publications supporting the advantages of PSM is more limited. Currently, most of the scarce information comes from randomized clinical trials. Moreover, a small number of studies have assessed PSM of VKA therapy in real life conditions. Methods: We analyzed clinical outcomes of 927 patients in a single center (6018.6 patient-years of follow-up). Recruitment took place between 2002 and 2017. All patients followed a structured training program, conducted by specialized nurses. Results: Fifty percent of individuals had a mechanical heart valve (MHV), 23% suffered from recurrent venous thromboembolism (VTE) or high-risk thrombophilia, and 13% received VKA therapy because of atrial fibrillation (AF). Median follow-up was 6.5 years (range 0.1-15.97 years), median age was 58.1 years (IQR 48-65.9) and 46.5% were women. The incidence of major complications (either hemorrhagic or thromboembolic) was 1.87% patient-years (pt-ys) with a 95% CI of 1.54-2.27. The incidence of major thromboembolic events was 0.86% pt-ys (95% CI 0.64-1.13) and that of major hemorrhagic events was 1.01% pt-ys (95% CI 0.77-1.31). The incidence of intracranial bleeding was 0.22% pt-ys (95% CI 0.12-0.38). In terms of clinical indication for VKA therapy, the incidence of total major complications was 2.4% pt-ys, 2.0% pt-ys, 0.9% pt-ys and 1.34% pt-ys for MHV, AF, VTE and other (including valvulopathies and myocardiopathies), respectively. Clinical outcomes were worse in patients with multiple comorbidities, previous major complications during conventional VKA therapy, and in older individuals. The percentage of time in therapeutic range (TTR) was available in 861 (93%) patients. Overall, the mean (SD) of TTR was 63.6 ± 13.4%, being higher in men (66.2 ± 13.1%) than women (60.6 ± 13.2%), p < 0.05.

Aims Direct oral anticoagulants (DOAC) are progressively replacing vitamin K antagonists in the prevention of thromboembolism in patients with atrial fibrillation. However, their real-world clinical outcomes appear to be contradictory, with some studies reporting fewer and others reporting higher complications than the pivotal randomized controlled trials. We present the results of a clinical model for the management of DOACs in real clinical practice and provide a review of the literature. Methods The MACACOD project is an ongoing, observational, prospective, single-center study with unselected patients that focuses on rigorous DOAC selection, an educational visit, laboratory measurements, and strict follow-up. Results A total of 1,259 patients were included. The composite incidence of major complications was 4.93% py in the whole cohort vs 4.49% py in the edoxaban cohort. The rate of all-cause mortality was 6.11% py for all DOACs vs 5.12% py for edoxaban. There weren’t differences across sex or between Edoxaban reduced or standard doses. However, there were differences across ages, with a higher incidence of major bleeding complications in patients >85 years (5.13% py vs 1.69% py in <75 years). Conclusions We observed an incidence of serious complications of 4.93% py, in which severe bleeding predominated (3.65% py). Considering our results, more specialized attention seems necessary to reduce the incidence of severe complications and also a more critical view of the literature. Considering our results, and our indirect comparison with many real-world studies, more specialized attention seems necessary to reduce the incidence of severe complications in AF patients receiving DOACs.

Background and purpose Renal excretion of direct oral anticoagulants (DOACs) varies depending on the drug. Hypothetically, an increased glomerular filtration rate (GFR) may lead to suboptimal dosing and a higher thromboembolic events incidence. However, real-world patient data do not support the theoretical risk. The aim is to analyse DOAC outcomes in patients with normal and high (≥90 mL/min) GFR, focusing on biological parameters and thrombotic/haemorrhagic events. Methods Observational prospective single-centre study and registry of patients on DOACs. Follow-up was 1,343 patient-years. A bivariate analysis was performed of baseline variables according to GFR (<90 mL/min vs ≥90 mL/min). Anti-Xa activity before and after drug intake (HemosIL, Liquid Anti-Xa, Werfen) was measured for edoxaban, apixaban, and rivaroxaban; diluted thrombin time for dabigatran (HEMOCLOT); and additionally, plasma concentrations in edoxaban (HemosIl, Liquid Anti-Xa suitably calibrated). Results 1,135 patients anticoagulated with DOACs were included and 152 patients with GFR ≥90 mL/min. Of 18 serious thrombotic complications during follow-up, 17 occurred in patients with GFR <90 mL/min, and 1 in a patient with GFR ≥90 mL/min. A higher incidence of complications was observed in patients with normal GFR, but the difference was not statistically significant (p>0.05). No statistically significant differences with clinical relevance were observed between the normal or supranormal groups in anti-Xa activity or in edoxaban plasma concentrations. Conclusions There was no increased incidence of thrombotic/haemorrhagic complications in our patients treated with DOACs, including 66% treated with edoxaban, and patients with GFR ≥90 mL/min. Likewise, drug anti-Xa activity and edoxaban plasma concentration did not seem to be influenced by GFR.

The familial platelet disorder with associated myeloid malignancy (FPDMM) is an autosomal dominant platelet disorder, caused by germline RUNX1 mutations, with predisposition to develop hematologic malignancies, especially acute myeloid leukemia. In many of the FPDMM families reported, the platelet defect was a delta-storage-pool disease (d-SPD) which can also be found without leukemia propensity. However, it has not been studied whether the two types of d-SPD have a common nature. Platelet ultrastructure, previously very little studied, may be one of the aspects to be analyzed to solve this question. We analyzed the ultrastructural characteristics of platelets in 5 members of a family with FPDMM. The family included three generations and all affected members had a RUNX1 deletion: chr21:36349450-36572837 (Rio-Machin et al. Nat Commun 2020;11:1044). None of the patients studied had developed leukemia at the time of the platelet study. We compared the results with those of 24 patients with d-SPD non-associated with leukemia and with those of 15 healthy individuals. Platelets were processed by transmission electron microscopy by standard methods. On the electron micrographs, morphometric analysis of the following structures was performed: 1) Platelets: size and shape, 2) Intraplatelet corpuscular structures (dense granules, alpha granules, mitochondria, lipid droplets): size and number (per platelet and per square micrometer of platelet area), 3) Surface-connected canalicular system (SCS): mean area of individual channel sections and mean percentage of the total SCS area with respect to the platelet area, 4) Glycogen masses: total area with respect to the platelet area. The morphological traits of the platelets and organelles measured above were also evaluated and the dense granules were classified into 4 different types depending on the appearance of their solid core (Weiss et al. Br J Haematol 1993;83:282). The dense tubular system and other ultrastructural characteristics were evaluated by morphology only. The main features of the platelet ultrastructure in patients with FPDMM were (Fig 1, Table 1): 1) slight increase in platelet size while preserving the discoidal shape, 2) moderate reduction in the number of dense granules, which showed a reduced proportion of type 1 granules (with the solid core occupying more than 50 % of the granule) and an increased proportion of type 2 and type 3 granules, with a solid core reduced or fragmented respectively, 3) marked increase and dilatation of SCS with some elements filled by a substance of unknown origin, 4) moderate increase in dense tubular system with occasional complex formation. The platelet ultrastructure was similar to that described in the non-associated d-SPD group (Pujol-Moix et al. Haematologica 2000;85:619) although there were some differences (Table 1): in FPDMM platelets the dense granules were less reduced but more dysmorphic, and the SCS, equally dilated, contained a substance that was not observed in the d-SPD platelets. Given that all the findings described belong to the same family, it would be necessary to evaluate the platelet ultrastructure in additional families and extend the study to other characteristics of d-SPD. Only in this way, it would be possible to know to what extent the platelet defect of FPDMM and that of non-associated d-SPD shared a pathogenic mechanism. Disclosures No relevant conflicts of interest to declare.