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

Can you explain the mild thrombocytopenia in this patient? Idiopathic thrombocytopenic purpura (ITP)
Malaria caused by Plasmodium vivax infection
Rheumatoid arthritis

Online version of this month´s case:


It has been brought to our attention that the schizont, visible on the peripheral blood smear, is too large and contains too many merozoites for a Plasmodium malariae infection. Follow up confirmed that this was a Plasmodium vivax infection. We apologize for the confusion.


The correct answer to January´s quiz is:

Malaria caused by Plasmodium vivax infection

Scattergrams and microscopy:


Interpretation and differential diagnosis:

The answer can be inferred from…

  • Presence of the action message ‘Difference between WNR and WDF. Check the results’, caused by differences in WBC counts from the WDF channel (9.53 x 109/L) and WNR channel (5.64 x 109/L)
  • Presence of an abnormal neutrophil population in the WDF scattergrams: increased neutrophil granularity (NEUT-GI) and two neutrophil populations in the SSC-FSC scattergram
  • Unreliable results for all WBC differential parameters, caused by the presence of the abnormal neutrophil population
  • Combination of relative neutrophilia and normal neutrophil reactivity (NEUT-RI)

Case history

A 34-year old man who frequently travels to Papua New Guinea visited his physician with a fever, nausea, headache and painful joints. Considering the man’s travel history, a complete blood count with WBC differential and reticulocyte analysis was performed to investigate a possible malaria infection.

Case results

Absolute neutrophil counts were normal but close to 95% of all WBC in the peripheral blood were classified as neutrophils indicating a relative neutrophilia. Furthermore, the Neutrophil-Granularity-Intensity (NEUT-GI) was increased while the Neutrophil-Reactivity-Intensity (NEUT-RI) was normal. Interestingly, the SSC-FSC scattergram of the WDF channel showed two neutrophil populations and the WBC count from the WDF channel was much higher than the count from the WNR channel (9.53 x 109/L compared to 5.64 x 109/L). This is indicative of nucleic acid-containing cellular inclusions in RBC, which don’t interfere with the WBC count in the WNR channel due to the strong lysis reagent. Since RBC are not completely lysed in the WDF channel, they are visible as an additional neutrophil population. The presence of this abnormal neutrophil population in the scattergram without signs of neutrophil activation (normal NEUT-RI) pointed to a P. vivax infection. The negative Delta-He and low RET-He are inflammatory signs, while a mild thrombocytopenia is common in malaria (1) but also in the alternative diagnoses. Malaria was confirmed in the peripheral blood smear, which showed the presence of parasites in the early Schizont stage.

(*Please note that Sysmex offers for XN-Class analysers a new software that triggers a flag ‘iRBC?’ (inclusions in RBC) flag in such situations. An automated correction of the WBC count and the differential is part of the algorithm.)

The following answers are incorrect for the described reasons


Idiopathic thrombocytopenic purpura (ITP)

ITP is an autoimmune haematological disorder in which autoantibodies against platelet antigens induce accelerated platelet destruction, leading to a reduction in peripheral blood platelets. ITP causes a characteristic purpuric rash and a tendency to bleed, for example from the nose or periodontal gums. It is difficult to distinguish ITP from other causes of thrombocytopenia so its diagnosis is a process of exclusion. Megakaryopoietic activity of the bone marrow is typically enhanced in ITP patients but it was probably normal or decreased in the presented patient (normal MPV and P-LCR values) suggesting a production problem rather than accelerated platelet destruction. In addition, ITP patients don’t have a (pseudo)neutrophilia or ineffective erythropoiesis so an ITP was highly unlikely.

Rheumatoid arthritis

A rheumatoid arthritis (RA) diagnosis was also explored because the patient had painful joints. Like ITP, RA is also an autoimmune disease; RA-associated autoantibodies affect the lining of the joint cavities (synovium) in synovial joints. Over time this causes deformation of the joints leading to serious disability when left untreated. RA affects 1.1% of women and 0.4% of men. RA is associated with an inflammatory response, which was not seen here: WBC counts were normal and lymphocyte counts were decreased here.

Acute Legionella pneumonia infection

Acute bacterial infections, like a Legionella pneumonia infection, are characterised by increased granulation and activation of neutrophil granulocytes. NEUT-GI was increased here, which could point to hypergranulation associated with an infection. However, NEUT-RI is also increased in patients with bacterial infections because DNA transcription is increased during neutrophil activation, resulting in elevated cellular nucleic acids in the form of messenger RNA (mRNA). Consequently, staining of activated neutrophils with Fluorocell-WDF leads to an increased side fluorescence and high NEUT-RI. The WDF scattergram of this patient revealed a relative neutrophilia and an increased NEUT-GI but NEUT-RI was normal and therefore a Legionella pneumonia infection was unlikely.

Underlying disease:

Laboratory findings

Normocytic, normochromic anaemia with leucocytopenia and thrombocytopenia may be present on initial screening. High-grade P. falciparum infection causes severe anaemia and an increase in the reticulocyte count. Traces of protein, urobilinogen and conjugated bilirubin may be found on urinalysis. In severe P. falciparum infections, massive haemolysis plus circulating immune complexes produce acute renal insufficiency or failure (‘blackwater fever’) with haemoglobinuria, proteinuria, elevated blood urea nitrogen (BUN) and elevated serum creatinine. If serum creatinine rises disproportionately higher than BUN (ratio >10-12:1), renal failure must be considered. While hyperbilirubinaemia usually results from haemolysis, impairment of liver function may also be indicated by increased liver enzymes (ALT, AST), prolonged prothrombin time and decreased serum albumin. This may cause diagnostic confusion with viral hepatitis. The hypoglycaemia, often present in P. falciparum infections results from increased consumption of glucose by parasitised RBC.

Malaria control and treatment

Between 2000 and 2012, mortality from malaria infections decreased by 42% while the number of infections dropped by 25% worldwide (2). Control has traditionally relied on:

  1. Control of the Anopheles mosquito vector by removal of breeding sites, use of insecticides and the use of insecticide-impregnated screens and bed nets;
  2. Diagnostic testing;
  3. Treatment with artemisinin-based combination therapy (ACT).

Although several candidate malaria vaccines are currently in clinical trials, a long hoped-for effective vaccine has not yet materialised and resistance to existing therapies and insecticides remains a concern. Treatment largely relies on antimalarial drugs, such as ACT for P. falciparum or chloroquine for P. vivax in areas where this drug is still effective (P. falciparum is resistant to chloroquine in most malaria-affected areas). In addition, sulfadoxine-pyrimethamine is recommended as a preventative therapy in pregnant women and children in endemic countries where parasite resistance to this drug is of little consequence. Artemisinin (4), extracted from sweet wormwood (Artemisia annua), has long been the most potent antimalarial drug available and it has been widely used to treat multidrug-resistant malaria. However, parasite resistance to artemisinin has been detected in Cambodia, Myanmar, Thailand and Vietnam so the World Health Organization (WHO) recommends gradually replacing artemisinin mono-therapy with ACT (2).


  1. Lampah DA et al. (2014): Severe Malarial Thrombocytopenia: A Risk Factor for Mortality in Papua, Indonesia. J Infect Dis: early online.
  2. World Health Organization (2013): World Malaria Report.
  3. Muentener P et al (1999): Imported malaria (1985–95): trends and perspectives. Bulletin of the World Health Organization 77: 560–565.
  4. Eckstein-Ludwig U et al (2003): Artemisinins target the SERCA of Plasmodium falciparum. Nature 424(6951): 957-961.

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