An exotic cause of haemolytic anaemia
Dr.Edmond S.K.Ma
Division of Haematology, Department of Pathology,
The University of Hong Kong, Queen Mary Hospital, Hong Kong
Case presentation:
The patient, who was now aged 31 and worked as an artist for an advertisement firm, presented at the age of 2 years with jaundice and splenomegaly. Investigations were considered compatible with haemolytic anaemia but the underlying cause was not established. He was given blood transfusions once every few months whenever the haemoglobin (Hb) dropped to 4-5 g/dL.
Subsequently, careful review of the blood film showed many stomatocytes. At the age of 4 years, a splenectomy was performed because of its size. He received oral penicillin for 2 years after splenectomy but was stopped by himself. He was given pneumovax at the age of 19. His Hb had remained at around 10 g/dL ever since splenectomy and remained transfusion independent.
He had normal growth and sexual development. He was married and had a 3-year old daughter. He attended yearly follow up, and was on folate supplementation only. His last attended on January 2001 and he was well apart from being jaundiced, although he had a palpable liver of 6 cm below right costal margin.
He was a native of Guangdong province and was 4th child among 5 siblings. His parents were not consanguineous. His parents and siblings had been investigated for presence of stomatocytes and haemolytic anaemia, but results were normal.
Laboratory investigations:
Latest blood counts: haemoglobin 10 g/dL, white cell count 5.8 X 109/L, platelet count 432 X 109/L, reticulocytes 13%
Red cell indices: MCV 141 fL, MCH 37.6 pg, MCHC 26.5 g/dL, RDW 13.5%
G6PD screen: normal
Direct Coombs' test: negative
Cold antibody screen: negative
Methaemalbumin: < 0.1 mg/dL (normal)
Urine haemosiderin: negative
Haptoglobin: 0.32 g/L (normal range: 0.16-1.97 g/L)
Hb pattern: HbF 0.6%, HbA2 3%, HbH bodies negative, Hb variant not detected by HPLC analysis
Total bilirubin: 102 µmol/L (normal range: 7-19 µmol/L)
Direct bilirubin: 12 µmol/L (normal range: 0-6 µmol/L)
Lactate dehydrogenase: 304 IU/L (normal range: 197-401 IU/L)
Na+ = 138 mmol/L
K+ = 5.1 mmol/L and 6 mmol/L on separate occasions, re-checked on fresh and warmed sample = 4 mmol/L
Liver enzymes and thyroid function normal
Iron status normal
HBsAg and HbsAb: both negative
Review of blood film showed numerous stomatocytes (Figures 1 & 3) with associated red cell polychromasia (Figure 2). Circulating normoblasts (arrowhead) and stippled red cells (arrow) were also present (Figure 2). Howell-Jolly bodies (arrow) were found that correlated with prior splenectomy (Figure 4).
Diagnosis
Hereditary stomatocytosis, overhydrated form
Discussion
Hereditary stomatocytosis (HS) and allied disorders are genetic defects of the red cell membrane that result in altered permeability to univalent cations, Na+ and K+. They show increased membrane permeability to these cations and stomatocytic morphology to a variable degree. In frankly haemolytic patients, the intracellular Na+ and K+ are always abnormal. If the concentration of these ions is normal in a haemolytic patient, the diagnosis of HS can be excluded.
The commoner form is dehydrated HS (also known as hereditary xerocytosis) and includes kindreds showing pseudohyperkalaemia or perinatal oedema or both. The pseudohyperkalaemia in these cases is temperature dependent, and occurs due to a net loss of K+ from red cell when they are cooled to room temperature. There is a compensatory increase in Na+ and K+ pump rates. However, the rates of pump and cation leakage became disparate at around 20oC, so that the steady state intracellular K+ cannot be maintained at room temperature, producing net K+ loss and pseudohyperkalaemia. Interestingly our patient with overhydrated HS also showed pseudohyperkalaemia, indicating that this association may not be restricted to the dehydrated form of disease.
Splenectomy in dehydrated HS patients may be complicated in adult life by a tendency to develop venous thromboembolism, which may result in pulmonary hypertension and death. It has been shown in in vitro studies that a high percentage of HS erythrocytes adhere to endothelial monolayers. This thromboembolic risk mandates that the diagnosis of stomatocytosis be excluded before splenectomy is contemplated for suspected spherocytosis.
More recently, the gene responsible for both dehydrated HS and the related disorder, familial pseudohyperkalaemia, has been mapped to 16q23-qter.
The very high MCV and low MCHC in our patient is characteristic of overhydrated HS. Conversely in dehydrated HS, the MCHC should be increased. The pathophysiological basis for overhydrated HS remains elusive but is most probably related to stomatin deficiency in the erythrocyte membrane. The function of stomatin is currently unknown and it may act as an anchor for cytoskeletal proteins.