Impact of severe hematological abnormalities in the outcome of hospitalized patients with influenza virus infection

Abstract

Although hematological abnormalities have been described among patients with influenza virus infection, little is known about their impact on the outcome of the patients. The aim of this study was to assess the frequency and clinical impact of severe hematological abnormalities in patients with confirmed influenza virus infection. This was an observational retrospective study including all adult patients with diagnosis of influenza virus infection hospitalized from January to May 2016 in our institution. Influenza virus infection was diagnosed by means of rRT-PCR assay performed on respiratory samples. Poor outcome was defined as a composite endpoint in which at least one of the following criteria had to be fulfilled: (a) respiratory failure, (b) SOFA ≥2, or (c) death. Two hundred thirty-nine patients were included. Applying the HLH-04 criteria for the diagnosis of hemophagocytic syndrome, cytopenias (hemoglobin ≤9 g/dl, platelets <100,000/μl or neutrophils <1,000/μl) were present in 51 patients (21%). Patients with hematological abnormalities showed higher SOFA scores, respiratory failure, septic shock and in-hospital mortality than the remaining patients. The composite endpoint was present in 33.3% in the cytopenias group vs. 13.3% in the group without cytopenias (p=0.001). In a multivariate analysis, variables associated with the composite endpoint were: use of steroids prior to present admission (OR: 0.12; 95% CI: 0.015-0.96, p=0.046), presence of any hematological abnormality (OR: 3.54; 95% CI:1.66-7.51, p= 0.001), and LDH>225 U/l (OR:4.45; CI:1-19.71, p=0.049). Hematological abnormalities are not uncommon among hospitalized patients with influenza virus infection, and they are associated with a poorer outcome.

Influence of viral load in the outcome of hospitalized patients with influenza virus infection

“…On the contrary, other authors have found that high influenza viral load is associated with a longer duration of hospital stay in adults with viral acute respiratory illness [5]. On this basis, we decided to analyze the role of influenza viral load in the outcome of the patients included in the same cohort of our previous paper [1].…”

“…We recently reported the potential role of severe hematological abnormalities as prognostic markers in hospitalized patients with influenza virus infection [1]. However, the role of viral load in the clinical outcome and/or in the appearance of some severe hematological abnormalities was not evaluated.…”

Prognostic value of hematological parameters

“…Hemophagocytic lymphohistiocytosis in influenza is caused by an increase in proinflammatory cytokines, which increases hemophagocytic macrophage proliferation and activation in the reticuloendothelial system. As a result, the number of leukocytes and platelets decreases rapidly [20,21]. Lalueza et al [21] studied the effects of severe hematological abnormalities in patients admitted to hospital for influenza virus infection; they pointed out that these hematological abnormalities are especially common at the onset of the disease and cause hospitalization and poor prognosis.…”

“…As a result, the number of leukocytes and platelets decreases rapidly [20,21]. Lalueza et al [21] studied the effects of severe hematological abnormalities in patients admitted to hospital for influenza virus infection; they pointed out that these hematological abnormalities are especially common at the onset of the disease and cause hospitalization and poor prognosis. In a study of hematological findings of influenza, when H1N1 infection was diagnosed, 8 (25.8%) patients had leukopenia and 6 patients (19.4%) had thrombocytopenia, It has been reported that H1N1 infection can lead to various hematological findings including cytopenia and hemophagocytosis [22].…”

“…In influenza, hemophagocytic lymphohistiocytosis occurs because of an increase in proinflammatory cytokines, which increase hemophagocytic macrophage proliferation and activation in the reticuloendothelial system. As a result, the numbers of leucocytes and platelets decrease rapidly [20,21,22]. In routine diagnostic laboratory examinations, there are significantly more leukopenia, neutropenia, and lymphopenia in cases of influenza when compared with control or other upper respiratory tract infections.…”