Thalassemia diagnosis in a blood donor from a unique trimorphic red blood cell population observed in the recipient.

Abstract

Red cell distribution curves are an integral part of red blood cell (RBC) automated hematology analysis and are available on virtually all automated analyzers. Visual scanning of the histogram gives a good initial sense of the range, size, shape and other prominent features of the RBC morphology [1]. The study of the histogram in combination with other parameters such as the amount of variation (anisocytosis) in cell size present in a patient sample (RBC distribution width or RDW) and the mean corpuscular volume (MCV), has been shown to be useful in the diagnosis and management of a number of RBC disorders. These include macro and microcytoses, hemolytic anemias, thalassemia, delayed transfusion reactions or homozygous hemoglobinopathies, amongst others [2, 3]. In addition, the study of the RBC histogram may be helpful in the identification of laboratory artifacts. For instance, we have recently reported a study describing how the observation of the histogram in a patient was the key to revealing an anticoagulant-dependent pseudomacrocytosis that went unnoticed in the peripheral blood smear [4]. In this work, we present a case in which the unique RBC histogram observed in a transfused patient played a pivotal role for the indirect diagnosis of thalassemia in the blood donor. A 79-year-old woman was admitted to our hospital because of fatigue and dyspnea. Blood tests revealed a low hemoglobin concentration of 69 g/L and a MCV of 131 fl, when normal values are between 80 and 100 fl. The peripheral blood smear showed macro-ovalocytosis and hypersegmentation of neutrophils. Amongst biochemical parameters, only lactate dehydrogenase (LDH) was altered, showing an activity of 1364 IU/L (reference values should generally be lower than 300 IU/L). All these findings were suggestive of megaloblastic anemia, which was confirmed by the presence of a low vitamin B12 concentration (121.8 pmol/L). Replacement therapy with parenteral vitamin B12 was initiated and two units of RBC concentrate were transfused because of the patient’s history of atrial fibrillation. One day after the transfusion a blood sample was collected and evaluated by a Beckman Coulter LH 750 hematology analyzer (Beckman Coulter, Brea, CA, USA). The anemia and macrocytosis were partially corrected (hemoglobin rose to 81 g/L and MCV decreased to 103.7 fl), but a marked anisocytosis was observed (RDW was 47.1% when normal range is 11%–14.5%). Most interestingly, the RBC histogram showed an exceptional trimorphic RBC distribution (Figure 1A). In the histograms from automated blood analyzers, the number of events counted (y-axis) is plotted versus the cell size or volume (x-axis). The mean value of the histogram distribution is the MCV of the sample. The coefficient of variation is equivalent to the RDW. Microcytic RBC, large platelets and debris fall to the left portion of the curve, and macrocytic RBC and small leukocytes fall to the right [5]. With these premises, we can clearly discern three different peaks from right to left: 1) a macrocytic population (peak 1), which was similar to that initially detected in the patient (Figure 1B); 2) a normocytic population corresponding to transfused RBC and the few new RBC generated after the treatment (peak 2); *Corresponding author: Dr. Jose Manuel Vagace, Service of Haematology, Infanta Cristina Hospital, Av. Elvas s/n, Badajoz 06071, Spain, E-mail jvagacev@gmail.com Maria Dolores de la Maya: Service of Haematology, Infanta Cristina Hospital, Badajoz, Spain Guillermo Gervasini: Department of Medical and Surgical Therapeutics, Medical School, University of Extremadura, Badajoz, Spain