An 8-year-old boy presents to the emergency department with shortness of breath, gradually getting worse over the last few days. He has a history of sickle cell disease. On examination, he has conjunctival pallor, normal auscultation of the chest and no hepatosplenomegaly. His blood results are shown below:


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|--------------|:-------:|---------------|
|Haemoglobin|72    g/L|(M) 130 - 170, (F) 115 - 155|
|White Cell Count|1.2x10<sup>9</sup>/L|3.0 - 10.0|
|Platelets|43x10<sup>9</sup>/L|150 - 400|
|Mean Cell Volume (MCV)|88 fL|80 - 96|
|Reticulocytes|1x10<sup>9</sup>/L|25 - 100|


Which of the following is the most likely cause of this patient's blood results?

Options:
explanation: Acute chest syndrome is a severe complication of sickle cell disease. It is caused by infarction of lung tissue as the sickled red blood cells occlude pulmonary vasculature. Typical presenting features include fever, cough, chest pain and shortness of breath. Their physical examination can be normal, or findings such as crepitations and reduced air entry on auscultation can be found. Anaemia and thrombocytopenia are also typical features. However, this would not explain the white cell count. The main differentiating biochemical feature is this patient's reticulocyte count. There will be a high reticulocyte count in acute chest syndrome as the body is trying to produce red blood cells to replace those lost in haemolysis. A low reticulocyte count indicates a failure of bone marrow. This makes aplastic crisis secondary to parvovirus B19 infection the most likely diagnosis
name: Acute chest syndrome
label: d
answer: no
explanation: Autoimmune haemolytic anaemia can present as a normocytic (or macrocytic) anaemia. However, this would not typically cause a low white cell or platelet count. Reticulocyte count is also characteristically high in autoimmune haemolytic anaemia as the body is trying to compensate and produce more red blood cells
name: Autoimmune haemolytic anaemia
label: b
answer: no
explanation: B12 deficiency anaemia presents with a macrocytic anaemia. In this case, this patient presented with a normocytic anaemia. This would also not explain the leukopenia and thrombocytopenia in this patient's blood tests. Of note, a combination of iron deficiency anaemia and megaloblastic anaemia can present as a normocytic anaemia, as the macrocytic and microcytic cells create a normocytic mean cell volume. This could be further investigated with a red cell distribution width. However, this is more common in conditions like coeliac disease. Given this patient's clear history of sickle cell disease and the presence of leukopenia, thrombocytopenia and a low reticulocyte count, aplastic crisis secondary to parvovirus B19 infection is the most likely diagnosis
name: B12 deficiency
label: c
answer: no
explanation: An aplastic crisis is a sickle cell crisis associated with the bone marrow not producing any cells. The most common cause is infection with parvovirus B19. Parvovirus B19 causes fifth's disease (also known as slapped cheek syndrome or erythema infectiosum), usually a benign, self-resolving childhood illness. In children with sickle cell disease, their red blood cells have a much shorter survivability meaning that cessation of new blood cell production, which can be associated with parvovirus B19 infection, can lead to pancytopenia over days. Features that point to this diagnosis include a history of sickle cell disease, acute onset of pallor and breathlessness over a few days, normal auscultation and pancytopenia with normocytic anaemia. Reticulocyte count is another key feature in this question. In haemolytic anaemias, reticulocyte count is high as the body tries to make red blood cells to compensate for the haemolysis. Low reticulocyte count suggests red cell production failure, making aplastic crisis secondary to parvovirus B19 infection the most likely diagnosis. Of note, although chest auscultation is often normal in anaemia, a flow murmur may be heard in severe anaemia
name: Parvovirus B19 infection
label: a
answer: yes
explanation: Acute lymphoblastic leukaemia (ALL) can also present with pancytopenia, although it typically affects children under 6. Lymphadenopathy and hepatosplenomegaly are characteristic features of leukaemia, although their absence does not rule out leukaemia. Although patients with ALL can present with low haemoglobin and low platelets, the white cell count is characteristically high. This is because the bone marrow produces an excessive amount of lymphoblasts (lymphocyte precursors), which reduces the proportion of bone marrow able to produce other cells (leading to thrombocytopenia and anaemia). The low white cell count makes acute lymphoblastic leukaemia unlikely in this patient
name: Acute lymphoblastic leukaemia
label: e
answer: no

Correct answer: a