FIT screening

The FIT-based screening test is easy and therefore manages to attract high participation rates – the main driver behind the success of any national or regional screening programme. Generally, national or regional administrations assume responsibility for managing the logistics, financials and efficiency of the programme in close cooperation with their selected laboratory partners.

For further information, you can check our FIT for screening microsite.




Pathogen:Bacteria →Gram-positive cocci →Streptococcus pyogenes
Transmission:Airborne or via contact of mucous membranes with contaminated surfaces
Geographical range:Worldwide
Incidence:1.5 million sepsis cases per year in Europe and North America (no data available from other continents)

Case history

A 65-year-old man arrives at the intensive care unit a few days after undergoing a surgical hip replacement. Following mild postoperative recovery on a normal hospital ward, the man’s health condition suddenly worsens and his vital signs are immediately measured: heart rate = 98/min, respiratory rate = 24/min, temperature = 38.2° C, systolic blood pressure = 110. Considering these signs, the doctor immediately orders a complete blood and lactate count and blood culture test in order to investigate a suspected incipient sepsis.

Sepsis pathophysiology and diagnosis

Sepsis is a life-threatening illness caused by the body’s response to an infection. Sepsis is caused by the body’s immune response triggered by an infection – mostly by bacteria, but also fungi, viruses or parasites can cause sepsis. The most common organs for primary infection are the lungs, brain, urinary tract and abdominal organs. Risk factors for sepsis are very young and old age, a weakened immune system caused by a variety of different conditions including cancer, diabetes, major trauma or burns (1). In the case of severe sepsis, organ dysfunction, hypotension, an elevated heart rate, rapid breathing and high lactate levels are typical.

Sepsis is always caused by a combination of factors related to the particular invading microorganism and to the status of the patient's immune system. The early phase of sepsis – characterised by excessive inflammation – can be followed by a prolonged period of decreased function of the immune system (immune paralysis). There are various microbial factors which can cause the septic inflammatory response. An invading pathogen is recognised by its pathogen-associated molecular patterns (e.g. lipopolysaccharides and flagellin in gram-negative bacteria; lipoteichoic acid and muramyl dipeptide in gram-positive bacteria). These molecular patterns are recognised by the innate immune system’s pattern recognition receptors (e.g. toll-like receptors, NOD-like receptors) and the receptors trigger will cause an intracellular signalling cascade, consequentially leading to the expression of pro-inflammatory cytokines (e.g. interleukin 6, tumour necrosis factor). The cytokines can activate coagulation factors leading to blood vessel endothelial damage and can subsequently lead to intravascular formation of blood clots in small vessels which can cause organ failure (2).

Early diagnosis is important in order to manage sepsis properly. The initiation of directed antibiotic therapy early on is an important factor to reduce mortality. Generally, diagnosis of sepsis is confirmed when at least two systemic inflammatory response syndrome (SIRS) criteria are fulfilled and the patient has a confirmed or suspected infection (3). Importantly, a new sepsis identification “The Third International Consensus Definitions for Sepsis and Septic Shock” based on the quick sepsis-related organ failure assessment (qSOFA) score for a patient with suspected sepsis was recently released. It only uses three symptoms (two of the conditions have to be fulfilled) to assess the septic state of the patient: altered mental status, increased respiratory rate and low blood pressure (4). Other definitions and terminologies currently in use for sepsis, severe sepsis, septic shock and organ dysfunction have also been revised (4).

Untreated septic state can promptly lead to severe sepsis – typically, with the sign of sepsis-induced end organ damage and persistent severe sepsis, it can lead to septic shock (5).
The differential diagnosis for sepsis is complex and has to exclude the non-infectious conditions that may cause the signs of SIRS, such as acute pancreatitis, burns, anaphylaxis, heart failure etc. Over the past years, a variety of individual biochemical markers have been identified and published in scientific literature. However, due to the complex pathophysiology of sepsis, no fully accepted biomarker with proven clinical utility is widely used currently for the diagnosis of sepsis. Generally, the patient clinical signs are still the most important factors for clinicians to diagnose sepsis.

Laboratory results


Case interpretation

The XN results of the 65-year-old man admitted to the intensive care unit revealed a normal WBC count, but, with a high relative increase in neutrophils to lymphocytes ratio (NEUT/LYMPH = 17). The high ratio is a sign of the activation of the innate immune response. The cause of the immune activation in this case could be due to bacterial infection, or result from a non-infectious immune response thanks to e.g. implant immune hypersensitivity. Except for the normal WBC count, the three criteria for SIRS were found positive (body temperature, heart and respiratory rate), and although the infectious cause was quite likely due to the operation he underwent a few days before, the septic cause of the systemic inflammatory response reaction needs to be confirmed or considered highly likely before broad-spectrum antibiotic treatment is indicated.

To assess the infectious innate immune response, several indicative parameters from the XN results have been considered in the diagnosis. In the WDF channel, the neutrophils showed very high activation – NEUT-RI = 64.8 FI (fluorescence intensity; the normal level is in the range of 42-50 FI) and combined with highly increased activation of monocytes – MONO-SFL = 151.4 FI (fluorescence intensity) and a slightly increased parameter AS-LYMPH = 0.5% (antibody synthesizing lymphocytes; T-independent plasma cells ), the results could indicate early onset of severe bacterial infection as the increase of these parameters is typical for initial innate immune defence against bacterial pathogens. The normal WBC level and only slightly increased IG = 0.6% (immature granulocyte) level indicate that the blood count was measured at a time point before the actual high neutrophil turnover (high number of immature granulocytes from the bone marrow and high number of mature cells from the marginated peripheral blood vessel pool) would be detected in the peripheral blood typical for the next phase of onset of the infection. Also, the absence of eosinophils supports the suspicion of a bacterial infection compared to a non-infectious inflammatory immune response.

The PLT-F channel revealed the severe thrombocytopenia and an increased immature platelet fraction (IPF = 10.3%). This observation could support the differential diagnosis of septic state, as severe infections can cause thrombocytopenia due to increased platelet destruction from the disseminated intravascular coagulation process, endothelial damage or platelet aggregation caused by bacterial endotoxins adhering to platelet membranes.

The RET channel revealed a pathology in erythropoiesis represented by a negative Delta-He value (-1.1 pg). Under normal physiological conditions Delta-He is a positive value. The negative Delta-He value is a sign of an acute infection. Iron sequestration by ferritin in macrophages restricts iron availability for extracellularly occurring pathogens. The mechanism suppresses iron availability to the erythropoietic progenitor cells by retaining iron in the macrophages. The low plasma iron rapidly induces hypoferremia and a decrease in functional iron availability in bone marrow leads to a decrease in the RET-He value and subsequently to the negative Delta-He value.

The lactate level measured at the time of admission was 4.2 mmol/L.

The XN blood count results – with a high likelihood – exclude a non-infectious cause of systemic inflammatory response syndrome (SIRS) on the patient due to the observed pattern of early onset pathogen-related immune defence response. The diagnosis of sepsis caused by bacteria was confirmed by a blood culture positive for Streptococcus pyogenes (two days after the ICU admission). However, the antibiotic treatment was started 2 hours after the admission due to the doctor’s strong suspicion of sepsis and the worsening of men conditions after the administration of intravenous fluid and other medical interventions.


  1. Sepsis Questions and Answers. Centers for Disease Control and Prevention (CDC). May 22, 2014.
  2. Nimah M & Brilli RJ (2003): Coagulation dysfunction in sepsis and multiple organ system failure. Crit Care Clin. Jul;19(3):441-58.
  3. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. (1992): Crit Care Med. Jun;20(6):864-74.
  4. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. (2016): The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. Feb 23;315(8):801-10.
  5. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R (2013): Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. Feb;41(2):580-637.

Sysmex parameters

Our Glossary

An alphabetical listing of scientific terms

Explore our Glossary

Wallpaper 2016

Enjoy our Media Centre
  • All
  • Documents
  • Podcast
  • Images
  • Videos
See the Podcast