Advances in diagnosis and treatment of the haemolytic anaemias

Research at UCL on human haemolytic anaemias, known as the 'hereditary stomatocytoses', has improved diagnosis of these conditions, and has raised awareness of the potential impact on donated blood.

The hereditary stomatocytoses are a class of human haemolytic anaemias in which the membrane of the red blood cell 'leaks' the salt atoms sodium and potassium. These 'leaky' cells have a tendency to swell and burst in the circulation. Research over the last 20 years by Professor Gordon Stewart (UCL Medicine) has furthered the molecular understanding of these diseases, resulting in advances in diagnosis and clinical management.

Prior to work by Professor Stewart, patients with stomatocytosis were commonly diagnosed with a related condition, hereditary spherocytosis. He identified characteristics of the two diseases which allowed them to be clearly differentiated. Patients with spherocytosis benefit from having their spleens removed, but in stomatocytosis this is potentially fatal - accurate diagnosis means that patients avoid this harmful treatment.

According to one patient with the condition, many members of her family experienced severe problems after splenectomy. Those who did not have the procedure are well, however, with few complications. "We have anaemia, and we need occasional transfusions," she reports. "But none of the breathing problems or other complications which other family members have experienced."

The research also demonstrated that many of these patients were also being misdiagnosed with hyperkalaemia (high plasma potassium). True hyperkalaemia is a medical emergency. In patients with stomatocytosis the plasma potassium is in fact normal, but the unique characteristics of their blood mean that when it a blood sample is taken, the blood begins to separate as the sample cools towards room temperature, giving it the appearance of hyperkalaemia.

Patients would often be unnecessarily treated as a result. "High plasma potassium levels were a bother to us all," reports one patient. "After any blood test we would be recalled to hospital as an emergency." Professor Stewart's research means that this anomaly is now understood correctly, saving countless hospital visits and repeated tests for these patients.

Professor Stewart has also collaborated with Dr Lesley Bruce at NHS Blood and Transplant. Their work identified a rare mutation which causes a mild form of the condition, but one which could have a serious effect on blood donations by these patients. Red cells from affected donors show a major salt leak at refrigerator temperatures only, and the cells are unsuitable for storage in blood transfusion, as the blood is likely to cause true hyperkalaemia when administered to a recipient. The National Blood Transfusion Service is now implementing a screening strategy on all donated blood in order to avoid this complication.

Stewart and colleagues have also shown that the very rare inherited metabolic condition phytosterolaemia (sitosterolaemia), in which patients can develop very high blood cholesterol levels due to a defect in the regulation of absorption of dietary cholesterol, can be diagnosed cheaply and simply from the blood count and blood film. This enables effective treatment of the condition, as patients do not respond to statins, the mainstay of raised cholesterol treatment.