Red Cell Disorders Laboratory

The Red Cell Disorders Laboratory performs clinical testing, research and teaching related to the workup, diagnosis and treatment of hemoglobinopathies and thalassemia, as well as Hemoglobin A1c testing for diabetic control.

The hemoglobinopathies and thalassemias are a heterogeneous group of hereditary disorders prevalent worldwide. In the United States at least 8 million people have some form of hemoglobinopathy or thalassemia. Hemoglobinopathies are defined as conditions in which structurally abnormal hemoglobins are synthesized. In contrast, thalassemias are defined as those conditions in which mutation leads to a quantitative reduction in normal globin synthesis. Some hemoglobinopathies can result in decreased globin synthesis or stability and therefore also have features of thalassemia.

Diagnostic screening studies are useful for:

• The identification of disorders for which treatment may be beneficial.
• Guidance in providing genetic counseling.
• The identification of the cause for incidentally detected microcytosis.

Clinical Features

Hemoglobinopathies and thalassemias often have no clinical manifestations. However, patients with sickling disorders and β thalassemia major have severe disease resulting in transfusion dependence, iron overload and other adverse manifestations. Other disorders such as Hb H disease, β thalassemia intermedia or combinations of hemoglobinopathies and thalassemias can cause mild to moderate anemia that are generally not transfusion-dependent, but can result in iron overload.

Laboratory Features

A common laboratory feature of all thalassemias is microcytosis, which is smaller than normal red blood cells. This differentiates thalassemias from hemoglobinopathies, which usually have normal red cell indices. An exception is hemoglobin E, which is found in Southeast Asian populations. This is an abnormal hemoglobin that is expressed at low levels, manifests clinically as a mild form of β thalassemia and thus exhibits microcytosis. Iron deficiency should be excluded as a cause of microcytosis prior to screening for thalassemia, since false-negative results for thalassemia testing can occur in the setting of iron deficiency.

Patients with α and β thalassemia trait may be mildly anemic - data from our series of patients indicates that hematocrit levels may be as low as 31% in children and non-pregnant women and 35-37% in men with thalassemia trait. Patients with hematocrits below these cutoffs require additional evaluation.

Laboratory Directors

Daniel E. Sabath, MD, PhD, Division Head, Director, Hematology Division, Coagulation, and Red Cell Disorders

Maryam Asif, MD, MBBS, Associate Director, Hematology Division, Coagulation, and Red Cell Disorders

Diagnostic Testing

In most populations, iron deficiency is the most common cause of microcytosis and should be ruled out prior to screening for thalassemia. The altered hemoglobin fractions required for the diagnosis of thalassemia may be absent in the presence of iron deficiency. A thalassemia work-up includes testing that will aid in the diagnosis of thalassemia, the identification of variant hemoglobins, and the assessment of iron status. Initial testing includes determination of red blood cell indices (CBC, preferably provided by the ordering location via the Thalassemia Clinical Data Sheet), hemoglobin electrophoresis (isoelectric focusing) and cation exchange high-performance liquid chromatography (HPLC) for confirmation and quantification of Hb A2, Hb F, and variant hemoglobins. If all are found to be normal for the age of the patient, no additional testing is indicated. Additional testing will be reflexively performed if any abnormalities are found. The clinical and laboratory data are collated and an interpretive report is issued. Workups can be ordered as follows:

• Hb Disorder Thalassemia Reflex Pnl w/CBC [HBTHLI]
• Hb Disorder Thalassemia Reflexive Panel [HBTHAL] (provide CBC data from within past 30 days)

See also: Thalassemia Clinical Data Sheet

Research

Lab Medicine welcomes collaboration with researchers. Please contact laboratory for more information.

Teaching

The Red Cell Disorders laboratory participates in training programs for undergraduate medical laboratory science students, medical students, clinical pathology residents, hematopathology fellows, hematology-oncology fellows and transfusion medicine fellows. In addition, a Master of Science degree is offered in Laboratory Medicine with concentration in Hematology area. Please see the Department of Laboratory Medicine and Pathology Education page for more information.

Contacts

Red Cell Disorders Lab
325 9th Ave
Room GWH 47, Box 359743
Seattle, WA 98104
Tel: 206.744.3549