Combined hereditary spherocytosis and β-thalassaemia trait: A rare co-existence

INTRODUCTION

β-thalassaemia trait (βTT) is the most common inherited haemolytic anaemia in India and its presence is mostly undetected due to its asymptomatic clinical course.¹ However, βTT should be diagnosed for premarital and genetic counselling and to prevent the number of births of affected children, in turn reducing the financial burden on the affected family. Detection of combined haemolytic anaemia is on a rise due to better screening modalities in haemoglobinopathies. We report a patient with co-existing hereditary spherocytosis (HS) (which has an overall low prevalence in India) and βTT and the clinical outcome.

THE CASE

A 16-year-old male presented with generalized weakness for 6 months. On physical examination, he had pallor, icterus and hepatosplenomegaly. Ultrasound of the abdomen revealed hepatosplenomegaly with cholelithiasis. Liver function tests showed raised total bilirubin of 3.4 mg/dl (indirect bilirubin: 2.8 mg/dl and direct bilirubin: 0.6 mg/dl).

Complete blood counts revealed haemoglobin (Hb) of 8.4 g/dl with high red cell count (5.3×10⁶/μL) and increased red cell distribution width (RDW) of 20.4%. Peripheral smear showed predominantly normocytic normochromic red cells along with few microcytic hypochromic red cells, spherocytes and polychromatophils (Fig 1a and b). Reticulocyte count was 4.2%. A work up for haemolytic anaemia was advised. Direct Coomb test was negative. Serum lactate dehydrogenase was raised (455 IU/L). Hb electrophoresis revealed an increased Hb A2 (4.1%) and Hb F (1.5%) (Fig 1c).

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FIG 1.

(a) Microphotograph showing presence of uniformly distributed spherocytes (Leishman stain; ×100). (b) Peripheral blood smear showing uniform spherocytes (arrowheads) and polychromatophils (arrow). (Leishman stain; ×400). (c) Haemoglobin capillary zone electrophoresis showing raised haemoglobin A2 indicative of beta-thalassaemia trait. (d) Osmotic fragility test showing right shift reflecting increased fragility of patient’s red blood cells as compared to normal control.

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Osmotic fragility test (OFT) showed normal fragility of red blood cells (RBCs). Since normal OFT did not correlate with presence of spherocytes, incubated OFT was done and after 24 hours it was positive. The patient underwent therapeutic splenectomy and cholecystectomy, which on histopathological examination showed features of congestive splenomegaly and chronic calculous (pigmented) cholecystitis, respectively. Following surgery, the patient showed relief of symptoms and is asymptomatic till date (Fig 1d).

His father and elder sister had also been diagnosed with HS. Family screening for βTT showed his mother to be positive for βTT.

DISCUSSION

HS in an inherited haemolytic anemia with low prevalence in India. On the other hand, βTT is a more common inherited haemolytic anaemia with an overall prevalence of 1.4%–17% with an average of 3.3%.^2,3 Co-existence of HS with βTT is extremely rare and few cases have been reported in the literature.⁴ Haemolytic anaemia, that manifests secondary to this combination, has a variable clinical severity.

The major problem in HS is that the circulating spherocytes lack certain surface proteins leading to decreased surface to volume ratio. Hence, the RBCs lose their normal biconcave structure and become spheroidal and rigid, resulting in reduced flexibility. When these rigid RBCs pass through the splenic vasculature, their reduced deformability results in trapping of cells leading to further loss of membrane by the action of splenic macrophages, ultimately leading to haemolysis. This property of spherocytes forms the basis for the increased red cell osmotic fragility in HS.

In thalassaemia, the RBCs have a reduced cell volume secondary to loss of globin chains and almost a near-normal surface area, thus resulting in an increased surface to volume ratio.^3,5 Compared to HS RBCs, thalassaemic RBCs have increased resistance to osmotic fragility. When HS and βTT co-exist, the combination of reduced surface area in HS and reduced cell volume in BTT results in a near-normal surface to volume ratio.⁶ This results in a wide range of clinical and laboratory findings in patients with HS and βTT simultaneously. This could also explain the cause of mild haemolysis as seen in our patient, reflected by intermittent jaundice and a mildly elevated reticulocyte count of 4.2%.

In our patient, the presence of uniform spherocytes in the peripheral smear and reticulocytosis in a background of intermittent jaundice and splenomegaly, supported by increased incubated osmotic fragility of RBCs, resulted in a diagnosis of HS. However, the presence of target cells was not seen on the smear. The RDW was also raised due to co-existence of spherocytes, polychromatophils and a few microcytic hypochromic RBCs. The microcytic hypochromic red cells of βTT and spherocytes of HS had opposite properties with regards to their fragility and this probably leads to reduced severity of haemolysis.^7–9 Hence, if both HS and βTT coexist, the latter silences the HS and ameliorates and masks the degree of haemolysis.