Quantitative anisocytosis as a discriminant between iron deficiency and thalassemia minor

The coefficient of variation (CV) of red cell size, as measured by electronic red cell sizing (erythrography), was less than 14.0% in 20 normal subjects. In 22 of 25 patients with beta-thalassemia minor and microcytosis (mean corpuscular volume [MCV] less than 70 fl), CV was less than 14.0%; in the other 3, CV was 14.0%--14.9%. In 53 patients with iron deficiency anemia and MCV less than 70 fl, CV always was greater than 14.0%. In 7 patients with alpha-thalassemia minor and MCV less than 70 fl, CV was less than 14.0% in all 7. Among patients with microcytosis, erythrography appears to be an excellent technique for rapidly distinguishing between iron deficiency and alpha or beta thalassemia minor.     

Evaluation of BCDE, a microcomputer program to analyze automated blood counts and differentials

A microcomputer program (BCDE) has been developed to analyze automated blood cell counts and differentials' similarity to normal values or to 36 disease categories. In 50 normal subjects, the analytic program listed the correct diagnosis as the first diagnosis in 49 cases (the only diagnosis in 44) and second of two diagnoses in one case. In 182 subjects with known hematologic disorders, the correct diagnosis was listed first in 134 and second or third in an additional 40. Subjects with iron deficiency, heterozygous thalassemia, immune thrombocytopenia, anemia of chronic disease, reactive thrombocytosis, acute infection, and chronic leukemia had the disorder identified as the most likely one by the analytic program with both sensitivity greater than 80% and specificity greater than 98%. Subjects with acute leukemia, folate deficiency, sickle cell anemia, cytotoxic chemotherapy, and chronic liver disease had the disorder identified as most likely by the program with a sensitivity less than 80%. In a different 11 cases with known hematologic status, a panel of 37 physicians identified the disorder(s) or normality only 72% of the time, whereas the analytic program listed the correct diagnosis first in 10 of 11 (91%). The analytic program appears useful for both triage of normal from abnormal data and for the initial differential analysis of abnormal data.     

Microcytic polycythemia. Frequency of nonthalassemic causes

A high RBC count combined with a low mean volume generally is attributed to thalassemia minor, either alpha or beta, or to polycythemia vera with iron deficiency. Among 330 patients with a mean corpuscular volume (MCV) less than 70 cumu, 35 had increased RBC counts. Of these, 26 had thalassemia minor and four had polycythemia vera. Five had secondary polycythemia (four from hypoxia, one from hypernephroma) with incidental iron deficiency. In the four of these patients given iron, the RBC count remained above normal and the MCV rose to normal. The RBC size distribution curves reliably distinguished between thalassemia minor and polycythemia with iron deficiency.     

Thrombocytopenia due to defective platelet production

An increasing number of kindreds with thrombocytopenia have been described in the past decade as platelet counts have been done regularly. These patients are delineated from ITP, recognizing that some patients with hereditary thrombocytopenia may benefit from splenectomy. Until more information on platelet biochemical information is available, these disorders have been categorized by platelet size, now quantifiable as mean platelet volume (MPV). The availability of rapid and quantitative measurement of platelet count and MPV allow a better understanding of megakaryocyte proliferation and platelet production. The evolving changes of MPV during treatment and recovery from chemotherapy will now allow a forecast of marrow hypoplasia, since the platelet count and increase in MPV follow the increase in megakaryocyte ploidy to herald marrow regeneration. It is anticipated that the careful plotting of the MPV relationship to the platelet count will allow the physician to evaluate marrow function indirectly, in many cases replacing repeated bone marrow studies.     

Platelet MAO concentration and molecular activity: II. Comparison of normal and schizophrenic populations

Platelet monoamine oxidase (MAO B) in 59 normal and 57 RDC-diagnosed medicated and unmedicated schizophrenic subjects was analyzed for whole platelet and extracted activities, specific concentration, and molecular activity. A novel radioimmunoassay using a monoclonal antibody elicited to human platelet MAO was used. Female schizophrenics showed no differences from female normals in MAO measures; however, these data could not be clearly evaluated because of confounding effects of age and drugs. Male schizophrenics treated with neuroleptics expressed significantly reduced whole platelet MAO activity, compared to untreated male patients. Compared with normal males, male schizophrenics showed significantly lowered molecular activities, along with elevated specific concentrations, which did not appear to be explained solely by drug usage. Additional mechanisms explaining the diminished molecular activity in male schizophrenics may be the presence of an endogenous irreversible inhibitor or a genetically determined, possibly structural, variant of MAO B.     

Persistence of abnormal RBC and platelet phenotype during recovery from aplastic anemia

Sixteen adults with chronic acquired aplastic anemia had abnormally large RBCs and abnormally small platelets before chemotherapy. During their therapy, transfusion initially obscured these macrocytic RBCs. In the eight who had erythropoietic recovery, endogenous RBCs again were macrocytic, and platelets remained small whether or not the platelet count increased. The percentage of cells containing hemoglobin F changed in only one of the eight subjects. In contrast, the eight who did not have erythropoietic recovery had no reappearance of macrocytes. Of 19 other previously treated patients whose hemoglobin level had recovered to normal for seven to 196 months, 16 had increased mean corpuscular volume (101 to 133 femtoliters) and abnormally small platelets. We conclude that in aplastic anemia the appearance of macrocytes reliably and easily predicts RBC recovery. Furthermore, even in treated, apparently recovered subjects, an abnormality of blood cell size remains.     

Red blood cell fragmentation. Improved detection and identification of causes

The peripheral blood film and the red blood cell size distribution histogram were examined for evidence of red blood cell fragments in 2,350 subjects. To distinguish subjects with greater than or equal to 10 fragments/1,000 red blood cells (abnormal) from normal, examination of the blood film was 0.83 sensitive and 0.30 specific, whereas examination of the histogram was 0.97 sensitive and 0.87 specific. The most common causes of abnormal fragmentation were malignancy with cytotoxic chemotherapy and severe iron deficiency. In two subjects, an abnormal red blood cell fragmentation pattern was the clue to a spectrin mutant in subjects with an automated blood count previously evaluated as normal. The data suggest two conclusions: the red blood cell volume histogram appears more accurate than the peripheral blood film for routine identification of red blood cell fragments; and asymptomatic spectrin abnormality identifiable by abnormal histogram may be a relatively common disorder.