Sysmex Sverige

Do you know which disease fits this month’s case? Then test your knowledge in the quiz below!

What caused this woman’s very poor condition? Chronic myelogenous leukaemia (CML)
Severe sepsis and acute respiratory distress syndrome from Legionella pneumophila
Atypical chronic myelogenous leukaemia (aCML), BCR-ABL1 negative
Acute exacerbation of chronic obstructive pulmonary disease (COPD)

Online version of this month´s case:


The pathogen name for answer "b" printed on the calendar is not correct. The correct name is Legionella pneumophila. Sorry for the confusion.

The correct answer to August´s quiz is:

Severe sepsis and acute respiratory distress syndrome from Legionella pneumophila

Scattergrams and microscopy:

Patient history: a complete blood count with full profile was ordered for a 73-year old woman on the intensive care ward.



Interpretation and differential diagnosis:

The answer can be inferred from…



  • Leukocytosis: High WBC
  • Neutrophilia: High NEUT#
  • High reactivity of neutrophils: High NEUT-RI
  • Presence of immature granulocytes: High IG# and IG%; “IG Present” flag
  • Absence of basophils
  • Absence of the “Blasts?” flag



Case history

A 73-year old female patient was admitted to an ICU ward with respiratory distress syndrome and high fever. A complete blood count with full profile was ordered.


Case results

Blood analysis showed a mild anaemia with a normal reticulocyte count. The RET-He and Delta-He values were low, indicating problems with haemoglobinisation of newly formed reticulocytes. Anaemia is an unspecific symptom which is common to many conditions such as iron deficiency, chronic infections and malignancies that affect the bone marrow. In addition, a moderate leukocytosis with a high neutrophil to lymphocyte ratio was observed. Mild anaemia and leukocytosis can be observed in multiple conditions of a neoplastic or reactive origin. In this case, fluorescence of neutrophils was strongly increased (NEUT-RI 60.4 channels, compared to the normal value of around 45 channels), indicating a reactive condition. The moderate leukocytosis made a leukaemia unlikely because in leukaemia the leukocyte count is usually higher. In addition, high numbers of immature granulocytes (IG), traces of erythroblasts and the absence of blasts support the diagnosis of a bacterial sepsis. The observed blood analysis results – neutrophilia, high fluorescence of neutrophils, poor haemoglobinisation of reticulocytes (functional iron deficiency), presence of erythroblasts – are typical for a bacterial sepsis.


The following answers are incorrect for the described reasons


Chronic myelogenous leukaemia (CML)

A severe leukocytosis with WBC counts above 100,000/μL and less than 20% blasts (usually less than 2% blasts) are typical findings in CML. Furthermore, most patients have high absolute basophil and monocyte counts, which were not observed in this case. Thrombocytopenia is not typical for CML and most patients have a normochromic, normocytic anaemia (1). CML is not associated with a reactive leukocytosis so CML neutrophils usually have a normal NEUT-RI, which was prominently increased here. In addition, the observed left shift is typical for an infection but not for CML. The neutrophil count would also be higher in CML than what was observed in this case.


Atypical chronic myelogenous leukaemia (aCML), BCR-ABL1 negative

Atypical CML (aCML) is a leukaemic disorder with myelodysplastic as well as myeloproliferative features at the time of diagnosis (1). A high monocyte count and a leukocytosis due to high numbers of neutrophils and myeloid precursors, as observed in this case, are typical findings in aCML. However, aCML neutrophils are dysplastic and therefore may have a decreased intracellular complexity (NEUT-GI), and they are not reactive and therefore have a normal fluorescence (NEUT-RI). The normal NEUT-GI, increased NEUT-RI and normal monocyte count in this case serve to exclude aCML as a cause of the leukocytosis in this patient.


Acute exacerbation of chronic obstructive pulmonary disease (COPD)

COPD is a common respiratory condition involving the airways and characterized by airflow limitation. It is associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. Due to the damage to the lungs and limited oxygen uptake, the body is subjected to chronic hypoxia and reacts by producing more red blood cells to compensate for it. In the presented case, IRF is high, but RET# and RET% are normal so these findings do not support the diagnosis or COPD. Chronic inflammation, which is often observed in COPD, is associated with moderate neutrophilia, but the high number of immature granulocytes (IG) and the high neutrophil fluorescence (NEUT-RI) observed in this case are not typical for an inflammatory reaction in COPD.

Underlying disease:

Legionella pneumophila

Legionella pneumophila is an aerobic Gram-negative bacillus that causes legionellosis or Legionnaires’ disease (2). The microorganism is found in aquatic systems. Legionnaires' disease is transmitted by inhalation of aerosolized water and/or soil contaminated with the bacteria. It is not airborne and it is not transmitted from person to person. Sources where temperatures allow the bacteria to thrive include hot-water tanks, cooling towers, and evaporative condensers of large air-conditioning systems, such as those commonly found in hotels and large office buildings. The incidence of Legionnaires’ disease depends on the degree of contamination of the water reservoir, the intensity of exposure to the contaminated water, and the susceptibility of the host. During infection the bacteria internalize and proliferate within the phagosomes of alveolar macrophages and blood monocytes.

Legionella is a common cause of community-acquired pneumonia in immunocompromised patients and of hospital-acquired pneumonia in all groups of patients. Legionellosis is associated with a high mortality rate of up to 25%.

Clinical symptoms of Legionnaires’ disease are not specific and include fever, gastrointestinal symptoms and pneumonia. Initial respiratory signs and symptoms are not prominent. Gastrointestinal signs and symptoms are usually common, with diarrhoea, nausea, vomiting, and abdominal pain. Patients are usually lethargic, with headache and occasional stupor.

Abnormalities in laboratory values are likewise nonspecific and can include indications of hepatic and renal dysfunction, thrombocytopenia, leukocytosis, and hypophosphatemia.

Prompt diagnosis of Legionnaires’ disease and initiation of appropriate therapy can decrease the mortality rate. Microbiological diagnosis requires specialized media (i.e., buffered charcoal yeast extract media) and can take several days. A rapid urine test for legionella antigen can substantially decrease the time to diagnosis.

As the bacillus replicates intracellularly, antibiotics such as penicillin and cephalosporin that cannot penetrate the host’s cell membrane are relatively ineffective against legionellae. Antibiotics with good intracellular penetration such as macrolides, quinolones, tetracycline, and rifampin can provide effective treatment. Patients who receive appropriate and timely treatment early usually experience symptomatic relief in three to five days.



Sepsis is among the most common causes of death in hospitalized patients (3).

Sepsis is a clinical syndrome that complicates severe infection. It arises from the host response to infection, which is directed to kill the invading pathogens. For this reason, patient outcomes from sepsis are determined not only by the viability of the invading pathogen, which can be directly toxic and destructive to tissue, but even more so by the host response, which may be excessive and result in collateral organ and tissue damage. The septic response is characterized by the cardinal signs of inflammation (vasodilation, leukocyte accumulation, increased microvascular permeability) occurring in tissues that are remote from the infection site.

The following terms help to understand the definition of sepsis:


Systemic Inflammatory Response Syndrome (SIRS): SIRS is a clinical syndrome that is a form of dysregulated inflammation. The term SIRS has routinely been associated with both infectious processes (sepsis) and non-infectious insults, such as an autoimmune disorder, pancreatitis, vasculitis, thromboembolism, burns or surgery. SIRS is defined as two or more abnormalities in temperature, heart rate, respiration, or white blood cell count

Infection: Infection is the invasion of normally sterile tissue by organisms.

Bacteraemia: Bacteraemia is the presence of viable bacteria in the blood.

Sepsis: Sepsis is the clinical syndrome that results from a dysregulated inflammatory response to an infection that is non-resolving and deleterious, often leading to organ dysfunction. Sepsis is defined as the presence (probable or documented) of infection together with systemic manifestations of inflammation (signs of SIRS). 

Severe sepsis: Severe sepsis refers to sepsis-induced tissue hypoperfusion or organ dysfunction.

Septic shock: Septic shock is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation.

Multiple organ dysfunction syndrome: Multiple organ dysfunction syndrome (MODS) refers to progressive organ dysfunction in an acutely ill patient, such that homeostasis cannot be maintained without intervention. It is at the severe end of the severity of illness spectrum of both SIRS and sepsis.


The outcomes and the success of treatment of sepsis depend on timely-applied therapy. Therefore, early recognition of sepsis is essential for improved mortality rates.

The following haematological parameters reported by the XN-Series analysers can sensitively detect developing infections and sepsis and can be used to support the diagnosis, especially efficiently in combination with each other and with other common infection biomarkers, such as procalcitonin and C-reactive protein.

NEUT-RI – reactivity of neutrophils, expressed by their fluorescence (4). Activation of neutrophils is one of the earliest anti-infection mechanisms, and increased NEUT-RI can be observed already during the earliest phase of infection.

NEUT# – as a response to infection, the neutrophil count increases due to the release of the bone marrow granulocyte pool into the blood. Like the NEUT-RI, it is a very early sign of infection.

IG# – the absolute count of immature granulocytes. When the pool of mature neutrophils in the bone marrow is exhausted, the immature granulocytes are released into the blood stream from the bone marrow. Besides, haematopoiesis is stimulated, therefore large amounts of immature granulocytes are produced in the bone marrow. An increase of the IG# count is a sign of an acute and advanced stage of an infection (5).

AS-LYMP – antibody-synthesizing lymphocytes. During an acute infection, neutrophils and macrophages phagocyte the invading organisms and present the antigens to B-lymphocytes, which in turn differntiate into plasma cells and synthesize antibodies against the pathogens. These antibody-synthesizing lymphocytes have a very high fluorescence in the WDF channel and can be easily detected by the analyser. An elevated AS-LYMP count is a sign of a mature ongoing infection.

Delta-He – the difference in haemoglobin content between mature red blood cells and reticulocytes. As one of the mechanisms against a bacterial infection, macrophages lock away iron, to impair the metabolism of the pathogens. This leads to a functional iron deficiency condition, and as a result to deficient haemoglobinisation of reticulocytes. Normally the Delta-He value is positive, but as the infection progresses, it decreases and can become negative. Out of the listed parameters, this is a later indication of an ongoing infection.

Another parameter, NRBC – the count of erythroblasts in peripheral blood, is a sign of a poor prognosis and high mortality risk in sepsis.



  1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, A. PS, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed2008.
  2. DeMello D, Kierol-Andwes L and Scalise P. (2007) Severe sepsis and acute respiratory distress syndrome from community-acquired legionella pneumonia: case report. Am J Crit Care; 16(3):320-317
  3. Reinhart K, Bauer M, Riedemann N et al. (2012) New approaches to sepsis: Molecular diagnostics and biomarkers. Clin Microbiol Rev 25:4
  4. Cornet E, Boubaya M and Troussard X. (2015) Contribution of the new XN-1000 parameters NEUT-RI and NEUT-WY for managing patients with immature granulocytes. Int J Lab Hem; epub ahead of print
  5. Nierhaus A, Klatte S, Linssen J et al. (2013) Revisiting the white blood cell count: immature granulocytes count as a diagnostic marker to discriminate between SIRS and sepsis – a prospective, observational study. BMC Immunology, 14:8

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