Hemophagocytic Lymphohistiocytosis
Conditions
Keywords
Hemophagocytic Lymphohistiocytosis (HLH), Hemophagocytic syndrome (HPS), critically ill, Intensive care unit (ICU)
Brief summary
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
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.
Interventions
None listed
Sponsors
Charite University, Berlin, Germany
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of HLH in intensive care units based on HLH-2004 criteria | Up to 180 days | HLH patients are followed up until the end of hospital stay or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to 180 days | Mortality after 30 and 180 days |
| Cytokine panel | Up to 180 days | 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 |
| Epstein Barr Virus (EBV) and Cytomegalovirus (CMV) viral loads | Up to 180 days | 1 blood sample collection at time of diagnosed HLH |
| Glycosylated ferritin | Up to 180 days | 1 blood sample collection at time of diagnosed HLH |
| microRNAs miR-205-5p, miR-194-5p and miR-30c-5p | Up to 180 days | 1 blood sample collection at time of diagnosed HLH |
| Perforin and CD107a | Up to 180 days | 1 blood sample collection at time of diagnosed HLH |
| Human immunodeficiency virus antibodies and -antigen | Up to 180 days | 1 blood sample collection at time of diagnosed HLH |
| Triglycerides | Up to 180 days | — |
| Bilirubin | Up to 180 days | — |
| Lactate dehydrogenase | Up to 180 days | Lactate dehydrogenase is measured in U/l |
| Liver transaminase (ASAT) | Up to 180 days | ASAT \[U/l\] |
| Liver transaminases (ALAT) | Up to 180 days | ALAT \[U/l\] |
| Sodium | Up to 180 days | — |
| Serum albumin | Up to 180 days | — |
| Serum protein electrophoresis | Up to 180 days | 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. |
| Detailed immune status | Up to 180 days | 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. |
| Fibrinogen | Up to 180 days | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| HLA Typing | At the beginning of the investigation | HLA testing identifies the major HLA genes a person has inherited and their corresponding antigens that are present on the surface of their cells. |
Countries
Germany
Outcome results
None listed