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This practical guidance, endorsed by the Brazilian Society of Thrombosis and Hemostasis and The Brazilian Society of Angiology and Vascular Surgery, the International Union of Angiology and the European Venous Forum, aims to provide physicians with clear guidance, based on current best evidence-based data, on clinical strategies to manage antithrombotic strategies in patients with coronavirus disease 2019.

In adults with immune thrombocytopenic purpura (ITP), steroids are usually proposed as first-line therapy, but long-term complete responses are obtained in no more than 20% of patients. For the remaining patients, splenectomy is considered the treatment of choice, with reported "cure" rates from 60-70%. However, the inherent risks of surgery and sepsis after splenectomy without a guarantee of success justify the search for strategies aimed to avoid splenectomy. Here we retrospectively evaluated the results of dapsone treatment in ITP patients that failed first-line therapy with steroids. These patients received dapsone 100 mg/day for a minimum of 30 days before splenectomy was considered. Efficacy was defined as a sustained rise in platelet counts (>50 x 10(9)/l) clearly attributed to dapsone treatment. Among 52 steroid-dependent or refractory patients, dapsone resulted in sustained increases in platelet counts in 44.2% of patients, after a median follow-up of 21.10 months after treatment initiation. The long-term efficacy of dapsone in this setting is further corroborated by the observation that none of the "responding" patients required splenectomy in the follow-up, compared to 69.0% of the "non-responding" patients. Dapsone-related adverse events were mild and promptly reversed by treatment withdrawal. The results of our retrospective analysis suggest that dapsone is a safe and effective second-line agent for steroid-dependent or refractory ITP patients. Because of its well-known safety profile and low cost compared to other potential second-line treatments for ITP, a trial course of dapsone should be viewed as an attractive option before splenectomy in steroid-dependent of refractory adult ITP patients.

The differential diagnosis of immune (ITP) and hereditary macrothrombocytopenia (HM) is key to patient management. The immature platelet fraction (IPF) represents the subset of circulating platelets with higher RNA content, and has been shown to distinguish hypo- from hyperproliferative thrombocytopenias. Here we evaluated the diagnostic accuracy of IPF in the differential diagnosis between HM and other thrombocytopenias in a population of patients with post-chemotherapy thrombocytopenia (n = 56), bone marrow failure (n = 22), ITP (n = 105) and HM (n = 27). TPO levels were also measured in HM and ITP matched for platelet counts. Platelet counts were similar in all patient groups. Higher IPF values were observed in both ITP (12.3%; 2.4–65.6%) and HM (29.8%; 4.6–65.9%) compared to hypoproliferative thrombocytopenias. IPF values were also higher in HM compared to ITP, yielding a diagnostic accuracy of 0.80 (95%CI 0.70–0.90; P < 0.0001) to distinguish these two conditions. Intra- and inter-assays reproducibility of IPF in HM patients revealed that this is a stable parameter. In conclusion, IPF is increased in HM compared to both ITP and other thrombocytopenias and contributes to the differentiation between ITP and HM. Further studies are warranted to understand the biological rationale of these findings and to its incorporation in diagnostic algorithms of HM.

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The aim of this study was to assess the incidence and risk factors for recurrent venous thromboembolism (VTE) in a Hispanic population. We prospectively followed 343 patients after a first episode of objectively proven VTE. We excluded all patients with VTE at unusual sites, older than 70 years old, with neoplasia, liver or renal chronic disease and antiphospholipid syndrome. Predictors for recurrence were evaluated by Cox model. The probability of recurrent VTE was estimated by the method of Kaplan-Meier. The cumulative probability of recurrent VTE was 19.1% in 5 years and 30.0% in 10 years. Male sex [relative risk (RR) 1.7, 95% confidence interval (CI) 1.0-2.8], spontaneous first VTE (RR 2.9, 95% CI 1.7-5.0) and FII G20210A mutation (RR 4.2, 95% CI 1.9-9.4) were independent risk factors for recurrent VTE. The fibrinogen, coagulation factors VIII, IX, X and XI were measured in 200 patients and were not associated to thrombotic recurrence risk. This study indicates that the incidence of recurrent VTE is high in Hispanics and depends on clinical and laboratory findings. In this population, FII G20210A mutation may represent a specific risk factor for recurrence. The inclusion of different ethnic populations in epidemiological studies of VTE as well as new approaches to the management of anticoagulation therapy in Hispanics is warranted.

Coagulation activation is a prominent feature of SARS-CoV-2 infection (COVID-19). Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We thus sought to assess activation of the contact system and intrinsic pathway in subjects with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by ELISA, while extrinsic pathway activation was assessed by microvesicle tissue factor-mediated factor Xa generation (MVTF). Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and thirty age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 were demonstrated by increased plasma levels of factor XIIa:C1 esterase inhibitor (FXIIa:C1), kallikrein:C1, FXIa:C1, FXIa:1antitrypsin, and FIXa:antithrombin (FIXa:AT). MVTF levels were also increased in COVID-19 subjects. Since FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both the contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically the total length of hospitalization, length of ICU stay, and extent of lung CT changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.

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