ABSTRACT
Objective:To explore the incidence of secondary hemophagocytic lymphohistiocytosis (sHLH) in elderly patients with severe SARS-CoV-2 infection, and to analyze and summarize its clinical features and risk factors for early identification of high-risk groups.Methods:A retrospective cohort study was conducted. From January to May 2020, No. 960 Hospital of People's Liberation Army, the Second Hospital Affiliated to Cheeloo College of Medicine of Shandong Province, the First Rehabilitation Hospital of Shandong Province, the Public Health Clinical Center Affiliated to Shandong University, and Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine received 248 patients over 60 years old who were diagnosed with severe SARS-CoV-2 infection during their assistance to Hubei or support for diagnosis and treatment of SARS-CoV-2 infection in Shandong Province. The clinical data of patients were collected. According to the hemophagocytic lymphohistiocytosis diagnosis scoring (HScore) criteria, the patients were divided into sHLH group (HScore > 169) and non-sHLH group (HScore < 98). The demographic data, clinical features, laboratory results, the proportion of organ failure and 60-day mortality of patients were collected and compared between the two groups. The risk factors of sHLH and 60-day death were evaluated through binary multivariate Logistic regression analysis in elderly patients with severe SARS-CoV-2 infection. The receiver operator characteristic curve (ROC curve) was plotted to analyze the diagnostic value of indicators only or combined for sHLH.Results:Among 248 elderly patients with severe SARS-CoV-2 infection, 82 patients with incomplete data and untraceable clinical outcomes, and 35 patients with HScore of 98-169 were excluded. Finally, 131 patients were enrolled in the final follow-up and statistics, including 25 patients in the sHLH group and 106 patients in the non-sHLH group. Compared with the non-sHLH group, plasma albumin (ALB), hemoglobin (Hb), lymphocyte count (LYM), platelet count (PLT), fibrinogen (Fib) and prealbumin (PAB) in the sHLH group were significantly reduced, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), D-dimer, ferritin (Fer), lactate dehydrogenase (LDH), procalcitonin (PCT), cardiac troponin I (cTnI), triglycerides (TG), interleukin-6 (IL-6), total bilirubin (TBil) were significantly higher. The fever and fatigue in the sHLH group were more severe than those in the non-sHLH group, and the patients in the sHLH group had higher rates of shock, acute kidney injury, liver dysfunction, and cardiac injury than the non-sHLH group. The 60-day mortality of patient in the sHLH group was significantly higher than that in the non-sHLH group [84.0% (21/25) vs. 40.6% (43/106), P < 0.01]. Binary multivariate Logistic regression analysis showed that high Fer [odds ratio ( OR) = 0.997, 95% confidence interval (95% CI) was 0.996-0.998], D-dimer ( OR = 0.960, 95% CI was 0.944-0.977), LDH ( OR = 0.998, 95% CI was 0.997-0.999) and TG ( OR = 0.706, 95% CI was 0.579-0.860) were independent risk factors for sHLH in elderly patients with severe SARS-CoV-2 infection (all P < 0.01), while elevated Fer ( OR = 1.001, 95% CI was 1.001-1.002), LDH ( OR = 1.004, 95% CI was 1.002-1.005) and D-dimer ( OR = 1.036, 95% CI was 1.018-1.055) were independent risk factors for 60-day death of patients (all P < 0.01). The death risk of the sHLH patients was 7.692 times higher than that of the non-sHLH patients ( OR = 7.692, 95% CI was 2.466-23.987, P = 0.000). ROC curve analysis showed that a three-composite-index composed of LDH, D-dimer and TG had good diagnostic value for sHLH in elderly patients with severe SARS-CoV-2 infection [area under the ROC curve (AUC) = 0.920, 95% CI was 0.866-0.973, P = 0.000]. Conclusions:Elderly patients with severe SARS-CoV-2 infection complicated by sHLH tend to be critically ill and have refractory status and worse prognosis. High Fer, LDH, D-dimer and TG are independent risk factors for sHLH, and are highly suggestive of poor outcome. The comprehensive index composed of LDH, D-dimer and TG has good diagnostic value, and can be used as an early screening tool for sHLH in elderly patients with severe SARS-CoV-2 infection.
ABSTRACT
Objective:To assess the implications of hormone therapy on confirmation of clinical diagnosis and prognosis of adult hemophagocytic syndrome (HPS) in the emergency department setting.Methods:The eligible 34 patients admitted with suspected HPS in the Emergency Department of Peking University People's Hospital from September 2019 to August 2021 were respectively collected. The patients were divided into the death group and survival group according to the prognosis and divided into early hormone therapy group and standard hormone therapy group according to the timing of hormone application. Patients in the early hormone therapy group were divided into the routine 4 criteria group and non-routine 4 criteria group according to the conditions of meeting the four HLH-2004 diagnostic criteria. Medical records of the following were collected and statistically analyzed: complete blood count, blood biochemical index, coagulation function, serum ferritin, NK cell activity, sCD25 level, peripheral blood smear, bone marrow biopsy, abdominal ultrasound scan, and abdominal CT on admission, and recheck the clinical indicators such as blood count, blood biochemical index and blood coagulation dunction 5-7 days later.Results:①Patients from the death group were older, with higher APACHEⅡ scores and SOFA scores, higher total bilirubin, and lower serum albumin. ② Univariate Logistic analysis showed age ( OR=1.098, CI: 1.019-1.183, P=0.014), APACHE Ⅱ score ( OR=1.144, CI: 1.017-1.285, P=0.024), SOFA score ( OR=1.441, CI: 1.079-1.925, P=0.013) were associated with the risk of death. Multivariate Logistic analysis showed that age ( OR=1.099, CI: 1.014-1.190, P=0.021) was associated with the risk of death. There was no significant correlation between early hormone therapy and clinical prognosis. Kaplan-Meier survival curves showed that there was no difference in the 60-day survival rate between the early hormone therapy group and the standard hormone therapy group. ③ The level of triglyceride still increased after early hormone therapy, and the number of indexes meeting the diagnostic criteria of HLH-2004 increased significantly. All patients met the criteria of Hscore>169, and 3 patients did not meet at least 5 diagnostic criteria of HLH-2004, accounting for 16.7% of the total cases of early hormone therapy. ④ Starting hormone therapy when the four HLH-2004 diagnostic criteria were met could reduce the length of hospital stay. Prothrombin time and activited partial thomboplastin time were closer to normal levels in patients 5-7 days after treatment. Early hormone therapy had no significant effect on treatment response and in-hospital death risk. There were no significant differences in APACHE Ⅱ score, SOFA score, confirmation of diagnosis, treatment response, clinical prognosis, and related clinical indicators after hormone therapy between the routine 4 criteria and non-routine 4 criteria groups. Conclusions:Initiation of early hormone therapy has no significant effect on the confirmation of clinical diagnosis, treatment response, in-hospital mortality, and 60-day survival rate of patients with HPS, and can quickly correct coagulation dysfunction and effectively reduce the length of hospital stay. An earlier start of hormonal therapy (meeting the four HLH-2004 diagnostic criteria) may be considered by the emergency physician when a patient is highly suspected of HPS diagnosis
ABSTRACT
Haemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disorder resulting from uncontrolled hyperinflammatory response. There had been increase in cases of one of the secondary form of HLH, i.e., infectionassociated haemophagocytic syndrome (IAHS) in severe dengue in recent years. However, the condition remains under diagnosed due to lack of awareness compounded by the lack of validated diagnostic criteria. Severe hepatitis with prolonged cytopenias, severe hyperferritinemia, hypofibrinogenemia and persistent fever were evident in all four cases reported. All the subjects survived with supportive care and adjuvant steroid therapy. Prospective controlled studies are needed to develop diagnostic criteria and management protocol for IAHS in severe dengue.