Thromboelastometry analysis of thrombocytopenic dengue patients: a cross-sectional study

Research article Open Access Open Peer Review Thromboelastometry analysis of thrombocytopenic dengue patients: a cross-sectional study Felipe Maia de Toledo Piza1Email author, Thiago Domingos Corrêa1, Alexandre Rodrigues Marra1, João Carlos Campos Guerra1, Roseny dos Reis Rodrigues1, 2, Andrea Aparecida Rocco Villarinho1, Valdir Fernandes de Aranda1, Sandra Christina Pereira Lima Shiramizo1, Maria Roza de Jesus de Lima1, Esper Georges Kallas2 and Alexandre Biasi Cavalcanti2 BMC Infectious DiseasesBMC series – open, inclusive and trusted201717:89 https://doi.org/10.1186/s12879-017-2204-4 ©  The Author(s). 2017 Received: 15 July 2016Accepted: 14 January 2017Published: 19 January 2017 Open Peer Review reports Abstract Background Dengue virus infection (DVI) is a prevalent and potentially fatal viral disease associated with coagulopathy. So far, the coagulation profile of DVI patients with thrombocytopenia has not been assessed through a viscoelastic test such as rotational thromboelastometry. We aimed to describe the prevalence and characteristics of coagulation abnormalities in dengue fever outpatients with thrombocytopenia, addressed by both rotational thromboelastometry and conventional coagulation tests. Methods This was a cross-sectional study conducted between April 6th and May 5th 2015 in São Paulo, Brazil during a dengue outbreak. Thromboelastometry (ROTEM®) and the conventional coagulation tests prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT), platelet count and fibrinogen levels were performed in 53 patients with DVI and thrombocytopenia. Results Despite a median interquartile range (IQR) platelet count of 77 (63–88) x 109/L in DVI patients, conventional coagulation tests and plasma fibrinogen levels were within the normal range. Subjects demonstrated hypocoagulability in 71.7% (38/53) in INTEM and 54.7% (29/53) in EXTEM DVI patients. FIBTEM analyses detected only 5.7% (3/53) with hypocoagulability among this population. The median (IQR) clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF) on INTEM were, respectively, 177 (160–207) sec, 144 (108–178) sec and 48 (42–52) mm. On EXTEM, median (IQR) CT, CFT and MCF were, respectively, 69 (65–78) sec, 148 (126–198) sec and 49 (44–55) mm. Median (IQR) MCF on FIBTEM was 15 (13–18) mm. Conclusion Thromboelastometry impairment is highly prevalent in DVI patients with thrombocytopenia, particularly in INTEM and EXTEM analyses, while standard coagulation tests are normal in this setting. Clinical implications remain to be established. Keywords International Normalize RatioDisseminate Intravascular CoagulationDengue Hemorrhagic FeverAlpha AnglePlasma Fibrinogen Level Background Dengue is by far the most incident human arbovirus disease [1], with over 2.5 billion people living in high-risk transmission areas [2]. The World Health Organization (WHO) estimates 50–100 million of dengue virus infections (DVI) per year, resulting in 500,000 hospitalizations and 20,000 deaths worldwide [1, 2]. Dengue hemorrhagic fever (DHF) represents a severe clinical presentation of DVI and is characterized by the presence of varying degrees of hemostatic disorders [3, 4]. Intense and amplified cytokine release, along with the complement activation, result in endothelial dysfunction, platelet destruction and consumption of coagulation factors, which may lead to a life threatening disseminate intravascular coagulation (DIC) [5, 6]. Indeed, blood coagulation disorders are commonly observed in patients with DHF and dengue shock syndrome [6, 7]. Many studies have assessed the coagulation system in DVI through conventional coagulation tests such as the prothrombin time (PT), international normalized ratio (INR), thrombin time (TT), and activated partial thromboplastin time (aPTT) [3, 6, 8, 9]. Nevertheless, conventional coagulation tests were validated to monitor vitamin K antagonists and heparin therapy [10, 11]. Although conventional coagulation tests have not been validated to predict and/or to guide therapy in acute (acquired) hemorrhage, they have been widely used for this purpose [10]. Conventional coagulation tests results may take a few hours to be completed and reported, they track the complexity of hemostatic impairment poorly, and most frequently, they reflect late coagulopathy disorders [10–13]. Rotational thromboelastometry (ROTEM®) is a point of care test that promptly provides (5–30 min) information about the dynamics of clot formation, stabilization and dissolution, reflecting the in vivo hemostasis at the bedside [12]. ROTEM provides more clinically useful and reliable information than the conventional coagulation tests in critically ill patients [13, 14], yielding a graphical presentation of fibrin polymerization process, involving fibrinogen and platelet function, and fibrinolysis [13]. To our knowledge, no study has evaluated the coagulation profile of patients with DVI with rotational thromboelastometry. Therefore, we aimed at describing the prevalence of coagulation abnormalities addressed by both thromboelastometry and conventional coagulation tests in cases of dengue fever outpatients with thrombocytopenia. Additionally, we evaluated the correlation between conventional coagulation tests and thromboelastometry in this population of patients. Methods Study design and setting This was a cross-sectional study conducted during a DVI outbreak in São Paulo, Brazil between April 6th and May 5th 2015. This study was approved by the University of São Paulo Institutional Review Board [Comissão de Ética para Análise de Projetos e Pesquisas (CAPPesq), approval number: 0652/09]. All patients provided informed consent prior inclusion in this study. Participants Patients were screened at an outpatient clinic established in a neighborhood in the city of São Paulo with high incidence of DVI. Patients with at least 24 h of fever (axillary temperature >37.8 °C), in addition to a positive dengue virus (DV) specific immunoglobulin IgM/IgG or non-structural protein-1 (NS1) antigen rapid test (DENGUE DUO Bioeasy®, Kyonggi-Do, South Korea) and platelet count <100 x 109/L were consecutively included in this study (Fig. 1). Fig. 1 Patients’ flow diagram Exclusion criteria included pregnancy, presence of oncologic or hematologic disorders, solid or bone marrow transplantation, secondary thrombocytopenia, previous known coagulopathy, chronic hepatitis B or C, chronic renal failure and use of anti-platelet therapy or vitamin K antagonists. Dengue virus infections triage, support and blood sampling All patients who visited the outpatient clinic had their clinical history taken to obtain information on length of time, type and severity of symptoms and vital signs analysis (arterial blood pressure, axillary temperature and heart rate) (Fig. 2). Demographic data, comorbidities, clin (...truncated)