Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy

ABSTRACT Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy.

Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

Abdominal obesity and the risk of venous thromboembolism among women: a potential role of interleukin-6.

BACKGROUND: Abdominal obesity increases the risk of venous thromboembolism (VTE). It remains unclear to what extent inflammation contributes to the risk of VTE from abdominal obesity. Our objectives were to investigate the association between abdominal obesity and VTE and the effect of inflammation on this association in a case-control study comprised of women. METHODS: We included 84 patients with VTE (18-60 years of age) and 100 controls. Waist circumference (WC), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) levels were determined at least 7 months after the thrombotic event. RESULTS: A total of 51 patients (61%) and 43 (43%) controls had abdominal obesity (WC ≥88 cm). The odds ratios (OR) adjusted for age were 2.40 [95% confidence interval (CI) 1.06-5.41; P=0.035] for a WC ≥88 cm compared to a WC <80 cm; the association was attenuated after adjusting for IL-6 (OR 1.86, 95% CI 0.80-4.33; P=0.149). For every 10-cm increment in WC, the risk of VTE adjusted for age increased by 1.38 (95% CI 1.08-1.77; P=0.010). The effect of an increased WC on the risk of VTE was again attenuated when IL-6 was entered in the regression model (OR 1.24, 95% CI 0.95-1.61; P=0.109). Risk estimates did not substantially change with adjustment for hsCRP. CONCLUSION: Our data indicate that the association between VTE and an increased WC was attenuated after adjustment for IL-6, suggesting a potential role of this interleukin in mediating the link between abdominal obesity and VTE.

Performance of Platelin LS and dilute Russell's viper venom for the screening of lupus anticoagulant in patients with venous thromboembolism.

Lupus anticoagulant is associated with thrombosis and pregnancy morbidity, and its detection is of major clinical importance. The nature and concentration of phospholipids strongly influence the sensitivity of activated partial thromboplastin time (aPTT) reagents to lupus anticoagulant. We investigated the ability of Platelin LS, an aPTT reagent, to screen lupus anticoagulant among 94 patients with venous thromboembolism by comparing its performance with the dilute Russell viper venom time (dRVVT). Twenty-four patients had an abnormal aPTT and dRVVT, whereas 37 only had a prolonged dRVVT. In users of oral anticoagulants (n = 56), the dRVVT prolonged more frequently than the aPTT (98.2 vs 39.3%, P < 0.0001). After the mixing study, seven patients maintained abnormal aPTT and dRVVT ratios, five of whom had prolonged mixture with both tests. The agreement in the mixing study between aPTT and dRVVT was substantial (kappa = 0.78, 95% confidence interval = 0.48-1.00). Except for one patient, the aPTT screened all cases that demonstrated phospholipid dependency of their inhibitor during the confirmatory procedure with the dRVVT. In conclusion, the aPTT using Platelin LS was highly associated with the presence of lupus anticoagulant detected by the dRVVT among patients with venous thromboembolism, and could be reliably employed as a screening assay for lupus anticoagulant.

Cerebral venous thrombosis and hepatitis: case report / Trombose venosa cerebral e hepatite: relato de caso

Among the many infective causes of cerebral venous thrombosis (CVT), viral hepatitis is been regarded as a rare associated condition. We report on a 56-years-old man presenting CVT associated with hepatitis B and C coinfections outlining probable pathogenic mechanisms. We suggest that virus B and C serology should be performed in the cases of cerebral venous thrombosis with unknown etiology.

Dentre as várias causas infecciosas de trombose venosa cerebral (TVC), a hepatite viral tem sido reconhecida como causa rara de TVC. Relatamos sobre um homem de 56 anos com TVC associada a coinfecção pelos vírus B e C da hepatite, ressaltando possíveis mecanismos patogênicos. Sugerimos que sorologia para vírus da hepatite B e C deveria ser solicitado em todos os casos de TVC de origem indeterminada.

Cerebral venous thrombosis and hepatitis: case report.

Among the many infective causes of cerebral venous thrombosis (CVT), viral hepatitis is been regarded as a rare associated condition. We report on a 56-years-old man presenting CVT associated with hepatitis B and C coinfections outlining probable pathogenic mechanisms. We suggest that virus B and C serology should be performed in the cases of cerebral venous thrombosis with unknown etiology.

Tuberculosis: an uncommon cause of cerebral venous thrombosis?

Several infectious etiologies are related to cerebral venous thrombosis (CVT), but a review of literature showed only few cases related to tuberculosis (TB), and only one with neurological manifestations. We report an unusual case of CVT related to TB and mutation in prothrombin gene. A 38-man black presented abrupt right hemiparestesis, and hemiparesis. Investigations revealed CVT. Cerebral spinal fluid (CSF) examination evidenced an infection by Mycobacterium. He was heterozygous for G20210A prothrombin mutation. Probably, hypercoagulability mechanisms of TB, added to mutation of prothrombin gene increase the risk of CVT.

[Effects of two trypanosomicide drugs, gention violet and WR6026, on platelet concentrates preservation]. / Efeito de dois agentes tripanosomicidas, violeta de genciana e WR6026, na preservação de concentrado de plaquetas.

In order to verify the viability of platelet concentrate during its preservation period when added with two trypanosomicidal chemical substances, gentian violet and quinoline WR6026, we tested these concentrates and verified the following parameters: number of platelets, pH and platelet aggregation test with a pair of agonists. Significant alterations were observed in the platelet concentrate treated with gentian violet suggesting important damage to the platelet viability. With WR6026 similar values to the controls were observed, opening new perspectives for the utilization of this salt for the chemoprophylaxis of transfusional Chagas' disease in highly endemic regions.

Efeito de dois agentes tripanosomicidas, violeta de genciana e WR6026, na preservação de concentrado de plaquetas / Effects of two trypanosomicide drugs, gention violet and WR6026, on platelet concentrates preservation

Visando verificar a viabilidade do concentrado de plaquetas, após sua preservação com substâncias, que adicionadas ao sangue sejam capazes de destruir o Trypanosoma cruzi, testamos concentrado de plaquetas estocado com a violeta de genciana e a quinolina WR6026. A viabilidade foi avaliada através da contagem do número de plaquetas, da medida do pH e agregação plaquetária com par de agonistas durante seu período de estocagem. Alterações significativas foram observadas nos concentrados plaquetários tratados com violeta de genciana sugerindo comprometimento da viabilidade plaquetária. Com o WR6026 foram observados valores similares aos controles, abrindo perspectivas para o emprego deste sal na quimioprofilaxia da doença de Chagas transfusional, em regiões altamente endêmicas.

Ativação plaquetária na esclerose sistêmica a alternativas metodológicas para sua avaliação / Platelet activation in systemic sclerosis and methodological options to its assessment

A esclerose sistêmica (ES) é uma doença sistêmica caracterizada por microangiopatia, exuberante atividade do fibroblasto e anormalidades imunológicas. A faceta microangiopática é responsável pela maioria das complicações com potencial mortalidade. A interação entre o endotélio e as plaquetas desempenha um papel importante na fisiopatologia da ES. Evidências de ativação plaquetária na ES incluem níveis séricos elevados de substâncias derivadas das plaquetas (fator 4 plaquetário, fator de Von Willenbrand, tromboxane A2 e Beta-tromboglobulina), agregados plaquetários circulantes, anormalidades ultraestruturais nas plaquetas e a presença de plaquetas aderidas ao endotélio. A presente revisão aborda de forma crítica os princípios e problemas potenciais dos principais métodos de avaliação da função e ativação plaquetárias. A avaliação da capacidade de agregação das plaquetas é feita com e sem a adição de agonistas (adenosina difosfato, colágeno e adrenalina). A ativação plaquetária pode ser avaliada de duas formas: pela dosagem da concentração plasmática de substâncias que são liberadas pela ativação plaquetária (ex., tromboxone, fator 4 plaquetário) e pela mensuração da expressão em membrana plaquetária de moléculas que são transportadas para a membrana plaquetária durante o processo de ativação das plaquetas (ex., GMP-140 e glicoproteína IIb/IIIa). Uma contribuição recente para este campo foi dada pela demonstração de que a enolase específica de neurônios (NSE) é liberada das plaquets para o plasma em pacientes com ES em atividade. Assim, a dosagem da NSE, que é um exame disponível nos principais laboratórios com ênfase na dosagem de marcadores tumorais, pode se tornar um marcador de atividade plaquetária de grande utilidade em diversas condições clínicas.

Hemorrhagic and thrombotic complications in patients with myeloproliferative diseases

Objective: To correlate the incidence of hemorrhage and thrombosis to bleeding time (BT) and platelet aggregation in 27 consecutive patients with myeloproliferative diseases (MPD). Design: Retrospective study. Setting: Public tertiary referral center. Patients: Eighteen patients with chronic myelogenous leukemia (CML), 5 with polycytemia vera (PV), 2 with essential thrombocytemia (ET) and 2 with idiopathic myelofibrosis (MF). Duke's BT and epinephrine-induced platelet aggregation were performed on the patients and on 10 healthy individuals. Results: Eleven patients presented symptoms (41 percent): 9 with hemorrhage (33 percent) and 5 with thrombosis (19 percent). There were less symptomatic patients in the CML group (28 percent) than in the other MPD (67 percent), without statistical significance (Fisher, p=0.06). Duke's BT was longer in symptomatic patients (Mann-Whitney, p<0.05). Platelet aggregation was abnormal in 7 patients (26 percent) and 71 percent of them were symptomatic (Fisher, p=0.07) Conclusions: The high incidence of bleeding and thrombosis in patients with MPD was related to prolonged BT, but not to platelet aggregation abnormalities.

Comparaçäo entre os métodos de cromatografia de troca iônica e cromatografia de afinidade para a dosagem de hemoglobina glicolisada (HbA1) / Comparison between ion exchange chromatography and affinity chromatography methods for the measurement of the glycosylated hemoglobin (bA1)

O método de cromatografia de afinidade para a dosagem de hemoglobina foi comparado com o método de cromatografia de troca iônica em minicolunas. Os resultados obtidos em indivíduos normais e pacientes diabéticos pelos dois procedimentos tiveram uma alta correlaçäo (r = 0,91), mas os valores obtidos foram mais baixos pelo ensaio de afinidade. As concentraçöes aparentes de HbA1 pelo método de troca iônica estiveram acima do normal nos pacientes urêmicos e nos homozigotos para anemia falciforme. Todavia, nestes estados com baixa sobrevida dos eritrócitos as concentraçöes de HbA1 pela cromatografia de afinidade estiveram normais ou abaixo do normal. O método de cromatografia de afinidade parece ser mais específico do que o método de troca iônica na medida da hemoglobina glicosilada