Thrombocytopenia in severe iron deficiency anaemia: A report of two cases

Case 1

A 12-month-old boy was referred with severe pallor. Born at term, he was exclusively breast fed for six months and subsequently given cow milk predominantly. Examination was otherwise unremarkable. The full blood count showed microcytic, hypochromic anaemia with elliptocytes and tear drop cells suggestive of iron deficiency and severe thrombocytopenia (Table 1). Stool examination was normal. He received a packed red cell transfusion and one dose of intravenous iron-sucrose followed by oral iron. The haemoglobin and platelet count improved to normal by day 13.

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Table 1.

Haematological parameters and response to treatment.

Patient	1			2
Age	12 months			21 months
Day of hospital stay	1	3	13	1	2
Haemoglobin (g/L)	44	49	93	49	51
Platelets (×109/L)	36	200	650	57	290
White blood cells (cells/mm3)	17.7	14.9	10.6	11.4	19
RDW (%)	25.9	28.2	37.1	22.2	24.2
MCV(fL)	54.8	58.9	73	40	50.4
MCH (fmol/cell)	0.8	0.86	1.25	0.88	0.77
MCHC (mmol/L)	14.5	14.7	17.2	21.8	15.2
Reticulocyte count (%)	0.5	–	–	0.8	–
Serum ferritin (µg/L)	1.13	–	–	2.60	–
Vit B12 (pmol/L)	976.3	–	–	690.9	–
Folic acid (nmol/L)	45.45	–	–	–	–

Case 2

A 21-month-old boy was referred with poor appetite and fever of one week’s duration. Born at term, he was fed breast milk and formula milk till six months of age and was subsequently on a predominant cow milk-based diet (150–170 mL cow milk/day). Examination, except for sever pallor, was unremarkable. The full blood count showed microcytic, hypochromic anaemia suggestive of iron deficiency but again, thrombocytopenia was present (Table 1). Other investigations and management were similar to Case 1. The platelet count was normal by day 3 and haemoglobin by day 10 of treatment.

Neither children described above had high grade fever, bleeding, lymphadenopathy or hepatosplenomegaly. Hence, bone marrow aspiration and biopsy were deferred.

Discussion

Diagnosis of iron deficiency anaemia (IDA) is made by clinical evaluation and assessment of the haemoglobin and serum ferritin level. ¹ Platelet count in IDA is usually normal or high.^2,3 Thrombocytopenia is rare.^4–7 In such a scenario, diseases involving two cell lines such as vitamin B12 deficiency, folic acid deficiency, haematological malignancy, aplastic anaemia and Evan’s syndrome need to be considered.

Thrombocytopenia with IDA was initially described in the 1960s but severe thrombocytopenia was rare and associated with severe IDA.^4,5 Bone marrow aspirates show erythroid hyperplasia and decreased number of megakaryocytes which normalised in 7–10 days after iron therapy. ⁵ Increase in the platelet count following iron therapy is brisk, occasionally as dramatic as tripling of the initial value within 24 h treatment, as seen in both our children (Table 1).^5–7

An interesting study in adults showed that patients with thrombocytopenia with IDA, compared to those with immune thrombocytopenia, had relatively higher platelet counts and lower mean platelet volume. ⁸ The cause of thrombocytopenia in IDA is unclear. One mechanism proposed is increased red cell production at the cost of reduced platelet production due to stem cells common to both lineages competing for the available iron. The other mechanism proposed is a dysfunctional iron-dependent cellular process in the later phase of thrombopoiesis. ⁶

Despite IDA being widespread in low-resource countries, severe thrombocytopenia with IDA has surprisingly not, to our knowledge, been reported before.

In children with severe IDA, a comprehensive clinical evaluation and careful analysis of the basic laboratory tests are essential to look for red flags. A trial of iron therapy may avoid extensive investigations such as bone marrow evaluation and potentially harmful therapy including platelet transfusion or steroids, thereby reducing discomfort and cost. Rising platelet count seems to be an early and reliable marker of response to iron therapy. Underlying mechanisms responsible need further study.