Advances of the past decade in automated hematology.

During the decade of the 1980s, a wealth of information accumulated concerning automation in hematology. Recent technological advances led the way to the development of blood cell analyzers capable of performing a ten-parameter (or greater) complete blood count and five-parameter (or greater) differential leukocyte count on a small amount of whole blood and in an accurate, efficient, and economical way. The authors summarize the available information concerning the data generated by these analyzers, the mechanisms involved in the data generation, and the clinical applications and usefulness or limitations of the so-called new complete blood count parameters and of the automated differential as it compares with the manual differential.

Differential leukocyte count: manual or automated, what should it be?

Today's automated hematology analyzers capable of performing a full CBC and a differential leukocyte count (DLC) on whole blood, particularly in a closed tube system, using cytochemistry or impedance-based flow cytometry technology coupled with laser light scattering, conductivity and/or differential cell lysis, are here to stay. Their need and popularity among at least the large, cost and quality-conscious clinical laboratories have been growing for the past few years and will continue to do so in the years ahead. The efficiency and reliability of several of these analyzers in performing complete CBCD (CBC and DLC) and in flagging significant abnormalities have been tested and found acceptable with the need to review a stained blood smear or perform a manual DLC to confirm or obtain additional information on selected cases.

Myeloproliferative disorders. Classification and diagnostic features with special emphasis on chronic myelogenous leukemia and agnogenic myeloid metaplasia.

Leukocytosis, mild anemia, thrombocytosis, and panhyperplasia in the marrow characterize the early stages of most of the CMPD, whereas extramedullary hematopoiesis (such as in the spleen or liver), peripheral cytopenias (anemia, leukopenia, or thrombocytopenia), and myelofibrosis, with or without osteosclerosis, reflect the changes seen in the later stages. Transitions among the different CMPD and termination in acute leukemia or marrow failure also are common. CML often is characterized by leukocytosis and the presence of the entire spectrum of granulocytes (mature and immature) in the blood and marrow, reduced LAP, hypercellularity with prominent granulocytic hyperplasia in the marrow, Ph chromosome, and bcr-abl gene rearrangement. Typical features of AMM include leukoerythroblastosis, teardrop poikilocytosis, anemia, increased or normal LAP, prominent megakaryocytic hyperplasia in the marrow, dyshematopoiesis, and hyperplastic or fibrotic/sclerotic marrow.

Structure and function of the bone marrow and hematopoiesis.

Bone marrow, a well-organized tissue located within the bone cavities, is richly innervated and highly vascularized but devoid of lymphatics. Structurally, it consists of two major cellular elements, the stromal cells (reticular cells--fibroblasts, endothelial cells, adipocytes, and so on) and the parenchymal cells (hematopoietic cells). Functionally, it serves as the primary site for hematopoiesis and as a major reticuloendothelial organ involved in immune responses (cellular and humoral) and removal of senescent and abnormal cells and particulate material. An uncommitted pluripotential hematopoietic stem cell, itself a product of the differentiation of mesenchymal cells of the yolk sac and capable of self-replication, undergoes proliferation and differentiation in an orderly manner, generating immature committed progenitors with uni-, bi-, or trilineage specificity. These committed progenitors also multiply and differentiate in a sequential fashion, ultimately producing mature cells that are released into the circulation. Under steady state conditions, the cell death/loss is balanced by cell production by virtue of regulatory mechanisms that apparently involve (1) cell-cell interaction between marrow cells and (2) production of humoral growth and/or inhibitory factors by stromal and parenchymal cells individually or in concert. Some of these regulators of hematopoiesis have been isolated, purified, molecularly cloned, and characterized. The availability of recombinant growth factors has stimulated clinical trials of these factors as therapeutic agents.

Bone marrow examination: techniques and interpretation.

Proper evaluation of the bone marrow requires adequate sampling, appropriate specimen processing, sufficient clinical history, and review of representative blood smears and pertinent laboratory data. Aspiration and needle biopsy should be performed at the same time routinely. Aspirate smears, touch preparations from the biopsy, and sections from the aspirate and biopsy should be processed appropriately and examined in a systematic fashion to perform a comprehensive evaluation considered essential to arrive at or rule out a diagnosis, or as an adjunct in the management of patients, particularly those undergoing chemotherapy and/or radiotherapy.

Preoperative localization of intermittently bleeding small intestinal tumors using Tc-99m labeled red blood cell scanning. Report of two cases.

Frequent tagged red blood cell scans offer an important diagnostic adjunct to help define a site of intermittent bleeding. Success is based upon scanning at two-to-four-hour intervals. Two patients are presented who experienced intermittent episodes of melena and hematochezia over prolonged periods of time. In each case an extensive diagnostic work-up had been performed on multiple occasions and failed to demonstrate the source. Utilizing a Technetium-99 macroaggregated albumin (Tc-99m) tagged red blood cell scan, an intermittently bleeding lesion within the small bowel was identified in each instance. In order to detect an intermittently bleeding lesion within the small bowel, more frequent scanning intervals are recommended. Due to rapid clearing of tagged red blood cells into the colon from the small-bowel bleeding point, the source may be obscured by longer, routine scanning intervals.

Epithelioid granulomas of the bone marrow in non-Hodgkin's lymphoproliferative malignancies.

Ten cases of epithelioid granulomas in the bone marrow of patients with various non-Hodgkin's lymphoproliferative malignancies have been encountered. These included six with non-Hodgkin's lymphoma (three histiocytic and three poorly differentiated lymphocytic types), three with multiple myeloma, and one with acute lymphoblastic leukemia. The bone marrow was not involved by the primary disease in two of the six patients with lymphoma, whereas three with lymphoma showed both granulomatous and lymphomatous lesions in the same marrow specimens, and in one, these lesions were seen in the marrow at different times. The three myeloma patients showed evidence of both myeloma and granulomas in their marrow. In the case of acute lymphoblastic leukemia, the bone marrow showed only granulomas, the leukemic process being in complete remission. Although small numbers of similar cases have been reported before, the authors were unable to find a previous report of acute lymphoblastic leukemia associated with bone marrow granulomas. Although the pathogenesis and the clinical significance of the granulomatous lesion of the bone marrow in non-Hodgkin's lymphoproliferative malignancies are unknown, this lesion should be differentiated from infectious or lipid granulomas as well as from involvement by the primary disease.

Rapid processing of urine specimens by urine screening and the AutoMicrobic system.

A total of 1,500 clean-voided urine specimens were analyzed for the presence of bacteria by urine screening with the Autobac 1 system. The specimens found positive by this method were further processed on the same day for identification and for antimicrobial susceptibility testing on the AutoMicrobic system with the Enterobacteriaceae-plus Card and the General Susceptibility Card, respectively. The inocula for these tests were prepared from the centrifuged and washed growth in the eugonic broth aspirated from the Autobac cuvette chambers. Of 1,500 specimens that were analyzed, 183 contained single isolates of gram-negative bacilli. The results of these rapid procedures were compared with results for the same organisms isolated from urine specimens cultured by the conventional method. The data showed 92.3% agreement for identification and a correlation of 93.6% for antibiotic susceptibility between the two procedures. It is concluded that gram-negative bacilli can be rapidly identified and tested for antimicrobial susceptibility with a high degree of accuracy from the centrifuged eugonic broth after urine screening. These findings also suggest that the AutoMicrobic system provides a rapid and convenient method for same-day processing of positive urine cultures when combined with the urine screening procedure.

Apparent colistin-related false sensitivity with the Autobac I system.

False sensitivities were occasionally encountered in antibiotic-free chambers of the Autobac I system. This unusual phenomenon occurred randomly among gram-negative bacilli and appears to be colistin-related.

Reactive plasmacytic lesions of the bone marrow.

A consecutive series of 1,000 bone marrow aspirates was analyzed for percentage of plasma cells, incidence of plasmacytic satellitosis, associated clinical disease states, lymphoid follicles, lipid granulomas, hemosiderin content, and various combinations thereof. Plasmacytosis was a common finding, and tended to parallel the presence of lymphoid follicles, lipid granulomas and plasmacytic satellitosis. The latter is emphasized as a normal phenomenon, may reflect morphologically a physiologic response of the B cell system to antigenic stimulation, and is conspicuously absent in plasmacytic neoplasia. Various secretory forms of plasma cells are illustrated.