Diagnostic Biomarkers for Adult Hemophagocytic Lymphohistiocytosis in Critically Ill Patients (HEMICU)

Study Overview
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Brief Summary
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Hemophagocytic lymphohistiocytosis in adults (HLH) is at 68% mortality whereas 78% of all cases remain undiagnosed though therapies are available which clearly reduce mortality. The investigators aim to systematically investigate this life-threatening hyperinflammatory syndrome in intensive care units (ICU) in order to detect biomarkers that are highly sensitive and highly specific for HLH in ICU compared to patients with sepsis.

Detailed Description
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The investigators will draw blood samples of 100 patients at the time of diagnosis (each 50 with suspected or diagnosed HLH/sepsis) to determine a cytokine panel (c reactive protein (CRP), procalcitonin (PCT), interleukin (IL) 1β, IL-6, IL-8, IL-10, IL-18, IL-33, tumor necrosis factor (TNF) α, interferon (IFN) ɣ, soluble IL-2 receptor (sIL-2R), the EBV and CMV viral loads, human immunodeficiency virus (HIV) antibodies and -antigen, perforin, fibrinogen, triglycerides, bilirubin, lactate dehydrogenase, liver transaminases, sodium, serum albumin, electrophoresis, glycosylated ferritin, the microRNAs miR-205-5p, miR-194-5p and miR-30c-5p, perforin, CD107a and high immune status (differential blood count, T cells, B cells, NK cells, T helper cells, cytotoxic T cells, CD4 / CD8 ratio, HLA-DR of CD8 +, CD11a of CD8, CD57 of CD8, CD28 of CD8 +, HLA-DR of monocytes, CD56bright and CD69 of NK cells). The results of this study serve the development of new clinical concepts in order to safely diagnose HLH at an early stage, to distinguish from sepsis and to reduce the fatal consequences.

Official Title
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Diagnostic Biomarkers for Adult Hemophagocytic Lymphohistiocytosis in Critically Ill Patients (HEMICU)

Conditions
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Hemophagocytic Lymphohistiocytosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female critically ill patients At least 18 years old Suspected or diagnosed HLH Exclusion Criteria: Female patients: Pregnancy Female patients: Breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients<br>50 patients with sepsis versus 50 patients with HLH [anticipated] | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of HLH in intensive care units based on HLH-2004 criteria | HLH patients are followed up until the end of hospital stay or death. | Up to 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensive care unit stay |  | Participants will be followed up for the duration of hospital length of stay, an expected average of 4 weeks | 
| Hospital stay |  | Participants will be followed up for the duration of hospital length of stay, an expected average of 8 weeks | 
| Mortality | Mortality after 30 and 180 days | Up to 180 days | 
| Cytokine panel | 1 blood sample of Cytokine panel (CRP, PCT, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-33, TNF-α, IFN-ɣ, sIL-2R, ferritin) collection at time of diagnosed HLH | Up to 180 days | 
| Epstein Barr Virus (EBV) and Cytomegalovirus (CMV) viral loads | 1 blood sample collection at time of diagnosed HLH | Up to 180 days | 
| Glycosylated ferritin | 1 blood sample collection at time of diagnosed HLH | Up to 180 days | 
| microRNAs miR-205-5p, miR-194-5p and miR-30c-5p | 1 blood sample collection at time of diagnosed HLH | Up to 180 days | 
| Perforin and CD107a | 1 blood sample collection at time of diagnosed HLH | Up to 180 days | 
| Human immunodeficiency virus antibodies and -antigen | 1 blood sample collection at time of diagnosed HLH | Up to 180 days | 
| Fibrinogen |  | Up to 180 days | 
| Triglycerides |  | Up to 180 days | 
| Bilirubin |  | Up to 180 days | 
| Lactate dehydrogenase | Lactate dehydrogenase is measured in U/l | Up to 180 days | 
| Liver transaminase (ASAT) | ASAT [U/l] | Up to 180 days | 
| Liver transaminases (ALAT) | ALAT [U/l] | Up to 180 days | 
| Sodium |  | Up to 180 days | 
| Serum albumin |  | Up to 180 days | 
| Serum protein electrophoresis | Serum protein Electrophoresis (%) is used to separate and quantify the serum protein components into serum albumin, alpha-1 globulins, alpha-2 globulins, beta 1 and 2 globulins, and gamma Globulins. | Up to 180 days | 
| Detailed immune status | The immune status is analyzed by differential blood count [/nl], T cells [/nl], B cells [/nl], NK cells [/nl], T helper cells [/nl], cytotoxic T cells [/nl], CD4 / CD8 ratio, HLA-DR of CD8+ [%], CD11a of CD8 [%], CD57 of CD8 [%], CD28 of CD8+ [%], HLA-DR of monocytes [antigen/cell], CD56bright [%] and CD69 [%] of NK cells. | Up to 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophagocytic Lymphohistiocytosis (HLH), Hemophagocytic syndrome (HPS), critically ill, Intensive care unit (ICU)