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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2016.tde-05102016-130612
Document
Author
Full name
Felipe Maia de Toledo Piza
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Cavalcanti, Alexandre Biasi (President)
Serpa Neto, Ary
Corrêa, Thiago Domingos
Diament, Decio
Rodrigues, Roseny dos Reis
Title in Portuguese
Papel da tromboelastometria em pacientes com dengue e trombocitopenia
Keywords in Portuguese
Dengue
Estudo observacional
Estudos transversais
Testes de coagulação sanguínea
Transtornos da coagulação sanguínea
Trombocitopenia
Tromboelastografia/métodos
Abstract in Portuguese
INTRODUÇÃO: Dengue é uma doença viral prevalente e potencialmente fatal associada à alteração da permeabilidade capilar e coagulopatia. Entretanto, não há estudos concernentes aos achados tromboelastométricos nesta doença. Realizamos o presente estudo para analisar pacientes com dengue e plaquetopenia por meio de um exame rápido, efetivo e a beira leito comparando com os exames convencionais de coagulação. MÉTODOS: Trata-se de um estudo observacional e transversal conduzido entre os dias 6 de abril a 5 de maio de 2015, em São Paulo, Brasil, durante epidemia de dengue. Foi realizado tromboelastometria ROTEM® em 53 pacientes com dengue e trombocitopenia em associação com exames convencionais de coagulação: tempo de protrombina (TP), international normalized ratio (INR), tempo de tromboplastina parcial ativado (TTPa), tempo de trombina (TT), contagem de plaquetas, fibrinogênio e d-dímero. Um grupo controle de pacientes foi estabelecido para comparação do status tromboelastométrico. RESULTADOS: Um total de 38 pacientes de 53 (71,7%) apresentaram anormalidades no INTEM e 29/53 (57,4%) no EXTEM. Em contrapartida, alterações no FIBTEM foram encontradas apenas em 3/53 (5,7%). Houve significância estatística em pacientes correlacionando alterações tromboelastométricas no EXTEM e INTEM e contagem de plaquetas (p=0,052) e (p=0,005), respectivamente; assim como os valores de fibrinogênio (p=0,006) e (p=0,021), respectivamente. O grupo controle (GC) apresentou status tromboelastométrico normal em 10/10 (100%) na análise do INTEM, EXTEM, FIBTEM. Avaliação do EXTEM demonstrou significância estatística entre o GC e o grupo Dengue: CT (p=0,044); CFT (p<0,001); MCF (p < 0,001) e Alpha (p < 0,001). Foram observados níveis normais de fibrinogênio (mediana: 290) e altos níveis de d-dímero (mediana: 1330) com IQR (800-1840). Todos os pacientes (53/53) apresentavam trombocitopenia abaixo de 100 x 109/L (mediana 77 x 109/L) IQR (63-88). Exames convencionais de coagulação revelaram-se completamente normais: TP (mediana: 100%) IQR (90-100); INR (mediana: 1,0) IQR (1,0-1,1); TTPa (mediana: 28,9 segundos) IQR (26,0-32,5) e TT (mediana: 18,2 segundos) IQR (17,0-19,5). Apenas (7/49) 14,3% pacientes apresentaram sangramento e (3/52) 5,8% necessitou de hospitalização. Não houve associação entre alterações tromboelastométricas com sangramento ou hospitalização. CONCLUSÕES: Dengue representa um processo inflamatório intenso, mantendo níveis normais de fibrinogênio. Portanto, FIBTEM mantém-se normal promovendo boa formação do coágulo sem risco imediato de sangramento. Não houve correlação entre os achados tromboelastométricos com os exames convencionais de coagulação, sugerindo que testes viscoelásticos são exames mais sensíveis para análise de coagulopatia precoce nessa população
Title in English
Thromboelastometry role in patients with dengue and thrombocytopenia
Keywords in English
Blood coagulation tests
Blood coagulation disorders
Cross-sectional studies
Dengue
Observational study
Thrombelastography/methods
Thrombocytopenia
Abstract in English
INTRODUCTION: Dengue is a prevalent and potentially fatal viral disease associated with plasma leakage and coagulopathy, though no information is available on thromboelastometric profile. We performed this study to analyze dengue fever patients with thrombocytopenia clot changes through point-ofcare thromboelastometry tests and standard coagulation tests. METHODS: This was an observational, transversal and cross sectional study conducted between April 6th and May 5th 2015 in São Paulo, Brazil, during a dengue outbreak. Thromboelastometry ROTEM® was performed in 53 patients with dengue and thrombocytopenia, in association with conventional coagulation tests: prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT); platelet count, fibrinogen level, and d-dimer. A control group of 10 patients was established to compare thromboelastometry profiles. RESULTS: A total of 38 patients in 53 (71,7%) had abnormalities in INTEM, 29 in 53 (57,4%) in EXTEM. Conversely, FIBTEM was abnormal in 3/53 (5,7%). Statistical analysis revealed significant relation in those patients with impairment EXTEM and INTEM with lowered platelet (p=0,052) and (p=0,005) respectively and lowered fibrinogen levels (p=0,006) and (p=0,021) respectively. Control group (CG) had normal status in 10/10 (100%) of INTEM, EXTEM, FIBTEM analysis. EXTEM analysis demonstrated statistical differences between CG and dengue group: CT (p=0,044); CFT (p < 0,001); MCF (p < 0,001) and Alpha (p < 0,001). Normal levels of fibrinogen (median: 290) and high levels of ddimer (median: 1330) IQR (800-1840) were found. All patients (53/53) had platelet under 100 x 109/L (median 77 x 109/L) IQR (63-88). Standard coagulation tests were completely normal: PT (median: 100%) IQR (90-100); INR (median: 1,0) IQR (1,0-1,1); aPTT (median: 28,9 seconds) IQR (26.0- 32,5) and TT (median: 18,2 seconds) IQR (17,0-19.5). Only (7/49) 14,3% patients had bleeding manifestations and (3/52) 5,8% needed hospitalization. There was no association between altered thromboelastometry with bleeding manifestations or hospitalization. CONCLUSIONS: Dengue represents an intense inflammatory process, maintaining normal levels of fibrinogen. FIBTEM remains normal providing good clot strength without immediate bleeding risk. There were no correlation between thromboelastometry findings and standard coagulation exams, suggesting that viscoelastic tests are more sensible method to analyze early coagulation impairments in this population
 
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Publishing Date
2016-10-06
 
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