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.

Resumo Introdução A importância da mutação C677T no gene da metilenotetrahidrofolato redutase (MTHFR) em mulheres com infertilidade permanece controversa. Objetivo Avaliar se a mutação MTHFR C677Témais frequente em mulheres inférteis, e se pode ser associada com a ocorrência de infertilidade na população brasileira. Métodos Estudo de caso-controle, com avaliação de 130 mulheres com infertilidade atendidas em clínica privada no período de março de 2003 a março de 2005 (dados previamente publicados) e 260 mulheres férteis atendidas no ambulatório de planejamento familiar de nossa instituição no período de abril de 2012 a março de 2013. Análise dos dados Foram utilizados os testes de Qui-quadrado e Exato de Fisher para o estudo da associação entre a presença damutação MTHFR C677T e o antecedente de infertilidade. Resultados A frequência da mutação foi de 58,5% nos casos (n = 76) e de 49,2% nos controles (n = 128). Dentre os casos, 13 apresentavam esta mutação em homozigose (10%). Nos controles, a homozigose foi encontrada em 23 mulheres férteis (8,8%). Estas diferenças não foram estatisticamente significativas. Conclusões Este estudo sugere que a presença da mutação MTHFR C677T não constitui fator de risco para infertilidade, mesmo em casos de homozigose. Estudos complementares são necessários para ratificar se a investigação desta mutação deve ser considerada desnecessária em mulheres com infertilidade.

Abstract Introduction The importance of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in infertile women remains controversial. Objective To evaluate if the MTHFR C677T mutations are more frequent in infertile women, and if they can be associated with the occurrence of infertility in the Brazilian population. Methods This case-control study included 130 infertile women consulting at a private clinic betweenMarch 2003 andMarch 2005 (data previously published), and 260 fertile women attending the family planning outpatient clinic of our institution between April 2012 and March 2013. Data analysis The Chi-squared and Fisher Exact tests were used to evaluate the association between the presence of the MTHFR C677T mutation and a history of infertility. Results The frequency of the mutation was of 58.5% for the case group (n = 76) and of 49.2% for the fertile controls (n = 128). The mutation was homozygous in 13 women in the case group (10%) and in 23 of the fertile women in the control group (8.8%). These differences were not statistically significant. Conclusions These results suggest that the presence of the MTHFR C677T mutation does not constitute a risk factor for infertility, even when themutation is homozygous. Further studies are needed to confirm whether research on this mutation should be considered unnecessary in women with infertility.

Studies evaluating circulating endothelial cells by flow cytometry are faced by a lack of con- sensus about the best combination of monoclonal antibodies to be used. The rarity of these cells in peripheral blood, which represent 0.01% of mononuclear cells, drastically increases this challenge. Objective: The aim of this study is to suggest some combinations of markers that would safely and properly identify these cells. Methods: Flow cytometry analysis of circulating endothelial cells was performed applying three different panels composed of different combinations of the CD144, CD146, CD31, CD133, CD45 and anti-Vascular endothelial growth factor receptor-2 antibodies. Results: In spite of the rarity of the events, they were detectable and presented similar interperson numbers of circulating endothelial cells. Conclusion: The combination of markers successfully identified the circulating endothelial cells in healthy individuals, with the use of three different panels confirming the obtained data as reliable.

CONTEXTO: A presença de níveis plasmáticos elevados da homocisteína tem sido associada à ocorrência de trombose arterial e venosa. Uma das causas da elevação da homocisteína plasmática é a presença da mutação C677T no gene da enzima metilenotetrahidrofolato redutase (MTHFR). O anticorpo anticardiolipina (ACA) é associado à ocorrência de trombose e faz parte da síndrome antifosfolípide, juntamente com outras complicações clínicas, como aborto recorrente e óbito fetal. TIPO DE ESTUDO: Relato de caso. RELATO DE CASO: Secundigesta, 19 anos, com antecedente de trombose venosa profunda no puerpério anterior. A investigação de fatores trombofílicos revelou a presença do ACA-IgM e da mutação homozigota C677Tno gene da MTHFR. Foram administradas 55.000 UI/dia de heparina subcutânea, entre a 15ª e a 36ª semanas de gestação, quando evoluiu espontaneamente para parto vaginal. O puerpério transcorreu sem intercorrências e a paciente recebeu alta hospitalar no terceiro dia pós-parto, mas sob tratamento com anticoagulante oral.

CONTEXT: High plasmatic homocysteine levels have been associated with arterial and venous thrombosis. The C677T methylene tetrahydrofolate reductase (MTHFR) gene mutation is one of the known causes for high homocysteine levels in plasma. Anticardiolipin antibody (ACA) is also associated with thrombosis and, along with other clinical complications such as recurrent abortion and stillbirth, is part of the antiphospholipid syndrome. DESIGN: Case report. CASE REPORT: A 19-year-old woman with two gestations and one parity (G2P1) had exhibited deep venous thrombosis in her previous puerperal period. Investigation of thrombophilic factors revealed ACA-IgM and heterozygous C677T mutation in the MTHFR gene. Lupus anticoagulant, protein C, protein S and antithrombin III deficiencies, and Leiden factor V and the G20210A mutation in the prothrombin gene, were not detected. The patient received 55,000 IU of subcutaneous heparin daily, from the 15th to the 36th week of pregnancy, when vaginal delivery took place. There were no clinical complications during the puerperal period and she was discharged three days after delivery, while still using oral anticoagulants.

OBJETIVO: Avaliar a eficácia de um selante biológico, a cola de fibrina autóloga, na cirurgia dermatológica. TIPO DE ESTUDO: Estudo prospectivo, randomizado. PARTICIPANTES: 14 doentes com dois tumores cutâneos epiteliais malignos, principalmente faciais e simétricos, para avaliação comparativa no mesmo indivíduo. LOCAL: Serviço de Dermatologia do Hospital de Clínicas da UNICAMP. PROCEDIMENTOS: A cola foi preparada, previamente, com amostra de 50 ml de sangue autólogo. Após a exérese do tumor, seguiu-se a colocação de enxertos ou cicatrização por segunda intensão. VARIÁVEIS: Hemostasia, adesão, tempo cirúrgico e evolução do tecido de granulação, clínica e histologicamente. RESULTADOS: Os resultados com a cola mostraram hemostasia e adesão imediata dos enxertos, com redução significativa do tempo cirúrgico e nas feridas abertas houve hemostasia imediata e maior tecido de granulação clinicamente mas sem diferenças histológicas, no 7º dia, entre os grupos. CONCLUSÃO: Concluiu-se que é recurso adjuvante na cirurgia do câncer de pele.

OBJECTIVE: To evaluate the efficiency of biological sealant, an autologous fibrin glue, in dermatological surgery. DESIGN: Randomized clinical trial. SETTING: The Dermatology Service of Hospital das Clínicas, Universidade de Campinas (UNICAMP), referral center. PATIENTS: 14 patients with malign epithelial cutaneoos tumors participated in the evaluation, each having two tumors, generally facial and symmetrical, in order to perform a comparative evaluation on the same individual. PROCEDURES: The glue was prepared beforehand with a sample of autologous blood. Surgical extirpation of the tumor was followed by grafts or second intention healing. OUTCOMES: The efficiency of the sealant was then evaluated in relation to hemostasis, adhesion, surgical time and evolution of the granulation tissue, clinically and histologically. RESULTS: Immediate hemostasis and graft adhesion, with a significant reduction of surgical time, and in the open wounds there was immediate hemostasis and a clinical increase in granulation tissue, but with no histological differences among the groups on the 7th day. CONCLUSION: It is an adjuvant resource in skin cancer surgery.

OBJETIVO: Este estudo teve por objetivo avaliar alguns componentes do sistema calicreína-cininas em pacientes com leucemia aguda não linfoblástica (LANL) e compará-los a um grupo controle normal. DESENHO E LOCAL: Um estudo prospectivo foi realizado no Hemocentro de Campinas, São Paulo, uma Instituição de atendimento em hematologia, de nível terciário. PARTICIPANTES: Inicialmente 35 pacientes diagnosticados como LANL, entre 1988 1991 , foram considerados para participar do estudo. Onze pacientes foram excluídos de acordo com os critérios de exclusão: presença de infecção/septicemia, transfusão sanguínea ou quimioterapia prévia. Ao final foram analisados 24 pacientes portadores de LANL, e comparados a um grupo controle normal. MÉTODOS: Os parâmetros analisados foram a procalicreina plasmática, o C1 -inibidor, a alfa 2-macroglobulina, o tempo de tromboplastina parcial ativado, o tempo de protrombina, o fator XII, o fator XI, o fator V e a pré-albumina. MENSURAÇÃO: A análise estatística foi realizada através do teste de Wilcoxon. Também verificou-se a presença de correlação entre vários parâmetros analisados. RESULTADOS: Os níveis de procalicreína plasmática (p=0.02) e de pré-albumina (p=0.03) estavam significativamente diminuídos e o tempo de protrombina significativamente prolongado (p=0.003) no grupo de pacientes, quando comparados ao grupo controle. No grupo de pacientes observou-se uma correlação positiva entre a procalicreína e a pré-albumina plasmática (r=0.49, valor crítico=0.43, p<0.05), e entre o tempo de protrombina e o fatorV (r=0.54, valopr crítico=0.44, p<0.05). Não houve correlação entre os parâmetros avaliados e o número de células blásticas circulantes ou o subtipo de leucemia. CONCLUSÕES: Esses resultados sugerem uma ativação da fase de contato e/ou comprometimento da função de síntese proteica hepática em pacientes portadores de LANL, podendo contribuir para as complicações dessa patologia.

The objective of the present study was to evaluate factors of the plasma kallikrein system in patients with acute nonlymphoblastic leukemia (ANLL), and compare the results to a normal control group. A prospective study was performed in the Tertiary Health Care Institution, Hemocentro, Campinas State University, Campinas, São Paulo, Brazil. Thirty-five patients, diagnosed as ANLL between 1988 and 1991, were considered for participation. Eleven patients were not elegible, according to the exclusion criteria: infection/ septicemia, previous treatment or blood transfusion. The study was performed with 24 ANLL patients, average age 34 years (16-69 years), 14 men and 10 women. Nineteen healthy volunteers, workers from the Hematology Center, average age 32 years (21-59 years), 11 men and 8 women, were the control group. Plasmatic prekallikrein, C1-inhibitor, alpha 2-macroglobulin, activated partial thromboplastin time, prothrombin time, factor XII, factor XI, factor V and prealbumin were measured. Plasmatic prekallikrein (p=0.02) and prealbumin (p=0.03) were significantly decreased, and prothrombin time increased (p=0.003) in the patient group when compared to the control. Significant correlation (r=0.49, critical value=0.43, p<0.05) between prekallikrein and prealbumin, and between prothrombin time and factor V (r=0.54, critical value=0.44, p<0.05) was demonstrated in the patient group. No correlation was found between parameters analysed and circulant blast count or leukemia subgroups. Statistical analysis was performed by theWilcoxon test. Correlation between the parameters was also verified. These results suggest activation of the contact system or impaired liver synthesis in patients with ANLL, and could contribute to disease complications.