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Biomedical subjects

J D Bessman

Publications and source records attributed to J D Bessman.

At least 37 records · Page 2Linked to original sources

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.

Adolescent↗

Use of mean platelet volume improves detection of platelet disorders.

Classification of platelet disorders has been based on the platelet count. Addition of a second variable, mean platelet volume (MPV), to the routine blood count allows classification of patients into 9 categories: high, low, or normal MPV, and high, low or normal platelet count. We studied 1,244 adult inpatients. 1,134 had both platelet values normal. 11 patients had high MPV and low platelet count: all had hyperdestructive causes. 15 patients had high MPV and normal platelet count: 12 had heterozygous thalassemia, and three had iron deficiency. Seven patients had high MPV and high platelet count: causes included myeloproliferative disorders, inflammation, iron deficiency, and splenectomy, 25 patients had high platelet counts and normal MPV: the causes were inflammation, infection, sickle cell anemia, iron deficiency, or chronic myelogenous leukemia. 52 patients had an MPV that was inappropriately low for the platelet count (high, normal, or low). All had sepsis, splenomegaly, aplastic anemia, chronic renal failure, or a disease being treated with myelosuppressive drugs. High MPV thus appears correlated with myeloproliferative disease or thalassemia; and low MPV, with cytotoxic drugs or marrow hypoplasia. Addition of MPV to the platelet count allows subtler disorders to be detected (when the platelet count is normal), and allows distinction of the cause of thrombocytopenia.

Blood Cell Count↗

The relation of megakaryocyte ploidy to platelet volume.

To determine how alterations of megakaryocyte proliferation will affect platelet production, we measured mean platelet volume (MPV), platelet volume heterogeneity, platelet count, and mean megakaryocyte ploidy in 42 patients. In normal subjects, mean platelet volume and megakaryocyte ploidy were related inversely but nonlinearly to platelet count, whereas mean platelet volume and platelet volume heterogeneity were related directly. In patients with immune thrombocytopenic purpura (low platelet count, MPV above normal, and increased megakaryocyte ploidy), and in those with reactive thrombocytosis (high platelet count, low MPV and megakaryocyte ploidy), the relation of MPV to megakaryocyte ploidy, platelet volume heterogeneity, and platelet count resembled or extended the relations found in normal subjects. By contrast, in patients with aplastic anemia or megaloblastic anemia, or in patients who were undergoing chemotherapy for leukemia, heterogeneity was increased abnormally at any MPV, and both MPV and megakaryocyte ploidy were substantially lower, at any platelet volume, than in normals or the above other groups. The most common ploidy class was 8N in all patients, and the mean megakaryocyte ploidy correlated directly and linearly with mean platelet volume. The data show that bone marrow with megakaryocytes of higher ploidy produces platelets that are both larger and more heterogeneous.

Blood Platelets↗

Spurious automated red cell values in warm autoimmune hemolytic anemia.

Two patients with warm autoantibodies to their red cells had a mean cell volume artifactually elevated by red cell agglutination. Red cell size distribution histograms directly showed doublets and triplets of normal-size red cells. This phenomenon is similar to the spurious macrocytosis previously reported due to cold agglutinins, but was not reversible by warming.

Adult↗

Nondiscrete heterogeneity of human erythrocytes: comparison of Coulter-principle flow cytometry and Soret-hemoglobinometry image analysis.

In the blood of normal subjects, the volumes of single erythrocytes are distributed with a coefficient of variation (CV) of 10.8 +/- 1.8%; while in hemoglobinopathies, CV increases proportionately to the degree of anemia produced. Using single cell Soret-band hemoglobinometry and focused-aperture impedance counting, we compared the distribution of red cell volume, area, hemoglobin content, and hemoglobin concentration in normals and subjects with anemic disorders. The CV, nondiscrete heterogeneity, is first, a general characteristic of biologic measurement, second, a sensitive indicator of abnormality of erythropoiesis, and third, consistently less for hemoglobin concentration than for volume, area, or hemoglobin content of the same cells.

Analysis of Variance↗

Improved classification of anemias by MCV and RDW.

New automated blood cell analyzers provide an index of red cell volume distribution width (RDW) or heterogeneity and a histogram display of red cell volume distribution. We have developed a classification of red cell disorders, based on mean corpuscular volume (MCV) or red cell size, heterogeneity, and histograms, to guide diagnosis from the peripheral blood analysis. The distinction of iron deficiency anemia from heterozygous thalassemia or the anemia of chronic disease and the detection of early iron and folate deficiency is improved. Red cell volume distribution histograms identify red cell fragmentation or agglutination, dimorphic populations, and artifactual counting of lymphocytes as red cells. We recommend the use of these new variables in the initial classification of anemia by the practicing physician.

Anemia↗

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.

Anemia, Aplastic↗

Platelet size in thrombocytopenia due to sepsis.

In normal persons, the mean platelet volume varies inversely but nonlinearly with the platelet count. Those with immune platelet destruction have a mean platelet volume that conforms to normal values. Nine patients with thrombocytopenia due to post-trauma sepsis without disseminated intravascular coagulation had a lower than normal mean platelet volume as the platelet count fell. In six patients who recovered, the mean platelet volume increased to the normal value before the platelet count began to rise. In contrast, three patients who did not recover from sepsis had no change from the low mean platelet volume and thrombocytopenia. Since mean platelet volume can now be part of the routine blood count, it is a useful variable to assay the degree of bone marrow suppression in the patient with thrombocytopenia and can be used as a predictor of recovery from thrombocytopenia.

Abdominal Injuries↗

The inverse relation between platelet volume and platelet number. Abnormalities in hematologic disease and evidence that platelet size does not correlate with platelet age.

We determined the platelet count and MPV in 100 normal subjects, in 147 subjects with thrombocytopenia or thrombocytosis due to other than primary hematologic disorders, and in smaller groups with immune or septic thrombocytopenia or iron deficiency. In these groups, the inverse, nonlinear relation between MPV and platelet count was the same as in a previous study of normal subjects. The same relation between platelet volume and count was found in individual patients as platelet counts rose during recovery from immune or septic thrombocytopenia. The concomitant progressive fall in MPV during recovery from thrombocytopenia, at which times rapidly rising platelets counts were necessarily associated with a population of young platelets, suggests that magnitude of stimulation of thrombopoiesis, not platelet age, is the major determinant of platelet volume. In contrast, as compared to normal persons with similar platelet counts, MPV was increased in subjects with heterozygous thalassemia but decreased in patients receiving chemotherapy for malignancy or renal transplantation. The undefined mechanism of regulation of platelet formation from megakaryocytes, reflected by the inverse relation of platelet size and count, thus seems altered in these disorders. Platelet volume is an easily obtained variable that appears to be useful in the evaluation of abnormal platelet production.

Anemia, Hypochromic↗

Platelet size in health and hematologic disease.

In normal subjects, mean platelet volume (MPV) has an inverse, nonlinear relation with platelet count, while platelet volume heterogeneity has a direct, nonlinear relation with MPV. Compared with the reference range established for normal subjects, patients with chronic lymphocytic leukemia, atherosclerotic heart disease, diabetes mellitus, and chronic undifferentiated schizophrenia had normal platelet volume mean and heterogeneity. Patients treated with cytotoxic chemotherapy for acute nonlymphocytic leukemia, patients with megaloblastic anemia, and patients with aplastic anemia had abnormally small platelets with increased heterogeneity. Patients with chronic myelogenous leukemia had abnormally large platelets with increased heterogeneity.

Anemia, Megaloblastic↗

Growth of human malignant micromegakaryocytes in vitro.

Mononuclear cells from the peripheral blood of a patient with megakaryoblastic transformation of Philadelphia chromosome-positive chronic myelogenous leukemia were cultured. Morphological and cytochemical studies and cell ploidy determinations were done daily for 4 days. PAS staining of the cells increased progressively during culture. Ultrastructural study of circulating and cultured cells revealed demarcation membranes and alpha granules indicating the cells were micromegakaryocytes. Deoxyribonucleic acid synthesis, determined by 3H-thymidine uptake, peaked at 72 hours. The DNA content of cultured cells was diploid at all times. All 15 metaphases analyzed at 72 hours were Ph1-positive. Malignant (Ph1-positive) megakaryoblasts and micromegakaryocytes grown successfully were capable of partial cytoplasmic maturation as demonstrated by glycogen deposition and increase in subcellular organelles, while endoreduplication was impaired. Malignant megakaryoblasts and micromegakaryocytes can be grown successfully in short term liquid culture and have more complete maturation in vitro than observed in vivo.

Cell Division↗

Mean platelet volume. The inverse relation of platelet size and count in normal subjects, and an artifact of other particles.

We measured whole-blood mean platelet volume (MPV) and platelet count, determined by the Coulter Counter model S-Plus, in 683 normal subjects. There was nonlinear, inverse relation between MPV and platelet count throughout the normal range of platelet count: the change in MPV was most pronounced at the lower platelet counts. Because of this non-linear relation, "platelet-crit," the product of platelet count and MPV, was not constant, but varied directly with platelet count. Thus, the definition of "normal" values for MPV requires simultaneous reference to platelet count. In the whole blood of 13 patients, non-platelet cell fragments spuriously increased the automated platelet count. Seven patients with erythrocyte fragmentation had spuriously high MPV also: correct MPV and platelet count could be obtained from platelet rich plasma (PRP). In five patients with leukemic blast fragmentation, MPV remained spuriously low and platelet count spuriously high in PRP: only phase count allowed correct count. A patient with megakaryoblastic leukemia had megakaryoblast fragments confused for platelets.

Adolescent↗

Evaluation of automated whole-blood platelet counts and particle sizing.

The Coulter Counter model S-Plus measures the erythrocyte, leukocyte, and platelet counts, and the mean cell volume of erythrocytes and platelets. Two additional features are novel to the instrument: erythrocyte distribution width (RDW), an index of erythrocyte volume heterogeneity, and mean platelet volume. For 677 subjects, we compared these measurements with complete blood counts obtained by a standard instrument, platelet counts from platelet-rich plasma (PRP), and histograms of erythrocyte and platelet volumes generated by free-standing equipment. The two methods correlated well (r = 0.97) for the complete blood count and the mean platelet volume. The whole-blood platelet count correlated well (r = 0.97) with the PRP platelet count, with whole-blood counts on average 5% higher than PRP counts. The whole-blood index of erythrocyte volume heterogeneity, RDW, correlated less well (r = 0.81) with the erythrocyte coefficient of variation measured by histogram. RDW was abnormal for three of 100 normal subjects with normal histograms. RDW was less sensitive (78% vs. 97%) and less specific (94% vs. 97%) than erythrocyte histograms in distinguishing iron deficiency from heterozygous alpha- or beta-thalassemia. We conclude that the Coulter Counter Model S-Plus reliably measures complete blood cell count, platelet count, and mean cell volumes, but analyzes erythrocyte volume distribution less well than does a histogram.

Blood Cell Count↗

Spurious macrocytosis, a common clue to erythrocyte cold agglutinins.

In four patients with cold agglutinins, erythrocyte mean corpuscular volume was increased. Erythrocyte volume histograms showed that in each case macrocytosis was due entirely to doublet erythrocytes counted as single cells. For two of the four patients, macrocytosis was reported intermittently, when the blood had been allowed to cool to room temperature during laboratory processing. For these two patients, macrocytosis due to doublet erythrocytes could be elicited in vitro proportionate to the degree of cooling of the blood and could be abolished to rewarming to 37 C. Two other patients had macrocytosis constantly during the acute illness. Otherwise unexplained macrocytosis may reflect cold agglutinin activity without overt hemolysis, particularly if the macrocytosis is intermittent.

Adult↗