Peripheral blood smear Information and Courses from MediaLab, Inc.

The first group is composed of erythrocytes or red blood cells (RBC's). The main function of the erythrocytes is the transport of oxygen from the lungs to the body tissues. Most of the cells in this Wright's stained peripheral blood smear are red cells. On is shown at the arrowhead.

Two photographs of a peripheral blood smear are submitted for review . The smears are from a 9-month-old baby with a heart valve replacement. In the upper photograph is a nucleated RBC and platelets are decreased. Nucleated red cells and occasional giant platelets indicate an active marrow response. In the process of forcing blood cells through the heart valve, erythrocytes are damaged, schistocytes are formed, and platelets are destroyed leading to thrombocytopenia. In the lower field are schistocytes, acanthocytes, echinocytes (burr cells), spherocytes, and the absence of platelets. The presence of burr cells could represent an artifact of smear preparation, but with the history of valve replacement, the red cell changes are likely the result of red cell damage as the cells circulate through the new valve. This situation is described as Waring Blender Effect because of damage to blood cells passing through the new valve, looking as if they had suffered the onslaught of a blender. Target cells and mild hypochromia may reflect iron deficiency through the loss of iron from destruction of RBC's. Iron loss through red cell destruction may be reflected in some hypochromia.

A 49-year-old male with pneumonia was treated with penicillin. He became jaundiced with yellow sclera. Observe the photograph of his peripheral blood smear. Anisocytosis was observed with pale-centered microcytes and polychromatophilic macrocytes. Since penicillin is a classic offender for autoimmune hemolytic disease, the clinician asked for an antihuman globulin (AHG) test, also known as the Coombs test. A positive AHG reaction occurs when the antibody stimulated by penicillin becomes attached to red blood cells. Hemolysis follows, leaving the patient with jaundice and a peripheral blood smear, as demonstrated in the photograph.

This photograph of a peripheral blood smear from an 18-year-old North African woman with anemia reveals sickle cells. Target cells are not conspicuous. This shifts the diagnostic evidence away from HbSC disease. Cells tagged by arrows are variants of sickle cells. These may appear when multiple abnormal hemoglobin combinations are responsible for the clinical problem. The cell marked by the single arrow is an envelope formed not only in HbS disease but in HbC disease as well. Two arrows tag a blister cell, which, when seen in several fields, should prompt a hemoglobin electrophoresis to determine the presence of an undiagnosed hemoglobinopathy. Blister cells with fuzzy edged pseudo-vacuoles (see photo) are to be distinguished from the pseudo-vacuoles (blister)with razor sharp edges suggesting a microangiopathic state.

The peripheral blood smear of HbH disease presented before is reviewed in the upper photograph.As mentioned, these leptocytes are pale-staining with hemoglobin confined to a thin, flat, cell membrane.Illustrated in the lower photograph are target cells or codocytes (a term derived from a Greek word for hat)Membrane accumulations of phospholipids and cholesterol (particularly in obstructive jaundice) promote target cell formation.When these cells are spread out on a glass slide, a central bump of hemoglobin appears to produce the target, a manifestation of excess cellular membrane compared to the amount of hemoglobin inside.The early descriptions of thalassemias, then called hereditary leptocytosis (Mediterranean anemia, Cooley's anemia), include description of leptocyes, which may have represented HbH disease.

Ovalocytes are rod shaped erythrocytes with nearly parallel lateral walls. If the long axis of an erythrocyte is no more than twice as long as the short axis, the cell is an ovalocyte. If the long axis is more than twice as long as the short axis, the cell is an elliptocyte. Hemoglobin tends to collect at each end of these cells. The ends of the cells are rounded and never pointed, to be differentated from sickle cells. Ovalocytes present in greater than 25% of red cells on the blood smear are characteristic of hereditary ovalocytosis. The oval shape is attributed to a defect in horizontal red cell membrane protein interactions. Lesser numbers of circulating ovalocytes may be present in various anemias including megaloblastic, sideroblastic, iron deficiency, and in thalassemias. A rare ovalocyte (less than 1%) may be found on almost any peripheral blood smear. Resistance to malarial infection may be a beneficial attribute of hereditary ovalocytosis.

What clear courses of action might the clinician take if the technologist reports out from this smear 3+ acanthocytes, 1+ target cells and occasional helmet cells? Gleaning information from the review of peripheral blood smears is important for the technologist, physician, and surely for the patient. Extreme pressures of time constraints and shifting dynamics in communication, from face-to-face encounters to dependency on technology, make innovative solutions to physician-patient information dilemmas imperative. Reporting systems often are geared more toward retrievability, suiting the needs of administrators and record keepers rather than being clearly directed toward improving patient care outcomes. A prime solution to this communication dilemma is to provide technologists with written descriptions and images of specific abnormal findings from peripheral blood smears. With a high degree of probability, these may link directly with underlying information connected to diseases. Mutually understood terms must be established to convert subjective qualitative peripheral blood smear findings into mutually understandable information. For example, regarding the smear shown, it was learned that the patient had recently undergone splenectomy. Creating an integrated communication system for information sharing (providing essential patient information by telephone follow-up or use of a system for e-mail feedback) can help ensure a favorable clinical outcome.

Initial analysis of the peripheral blood picture is made in most clinical laboratories with an automated instrument. Samples are selected for further analysis when quantitative or qualitative abnormalities beyond a defined standard are found. The following are examples of quantitative RBC abnormalities that may prompt a blood smear review. Each laboratory, however, should develop its own guidelines: Hgb: < 8 or >18 g/dL (<10 or > 21g/dL in a newborn)Hct: <20% or > 60% in adults (<40% or >65% in a newborn)MCHC: <29 g/dLMCV: <69 femtoliters (fl) or >110flFlags generated by the hematology analyzer that indicate possible red cell abnormalities or spurious resultsAny of these findings should be followed up with a peripheral blood smear review.

A reproducible blood smear review requires every peripheral smear be prepared for consistent openness and clarity. Consistency is maintained by uniform handling of every blood smear. Good results may be expected when the preparation is begun with only a small drop of blood at one end of a clean glass slide. The drop is smeared lightly and quickly so as to leave a thin (feathery) edge where all cells may be examined individually, particularly red blood cells. The site of examination then is chosen away from clumping, piling, or bumping of cells against each other, perhaps a site five or six oil fields from the end of the feathery portion. Such an area for examination is illustrated in the photograph.

A smudge cell is centered in the photograph. In some laboratories, a semi-quantitative estimate of the number of smudge cells may be made; in others, a report of "smudge cells present" may suffice. The point is that a language for reporting semi-quantitative estimates must be established for any atypical cells appearing in the peripheral blood smear. This reporting scheme must be understood by the physician in order to maximize patient care outcomes through his/her decision making process. For example, in the context of this exercise, does it make any difference to the physician if you report few or many smudge cells; or, is a report of smudge cells present sufficient? The answer to this question applies not only to smudge cells, but to the reporting of any other atypical white cells as well. An agreement must be reached between the hematology laboratory and clinical services as to how semi-quantitative estimates will impact the need for further testing in view of patient care outcomes.

The following pages in this presentation includes a series of white blood cell abnormalities that may be identified in a peripheral blood smear. Many of the cases will simulate the practice of a peripheral smear review by a hematology morphologist. He/she must asses what responses in patient care may be triggered by the clinician attempting to interpret the reported findings on a peripheral smearObservations of white blood cell abnormalities in the peripheral blood smear should be reported so as to direct the physician to an immediate specific diagnosis, such as: (1) atypical lymphocytes suggesting infectious mononucleosis rather than leukemia, (2) toxic granules in neutrophils as in acute infections, or atypical granules suggesting a genetic disorder, (3) an unusual mix of cells, such as too many or too few neutrophils, monocytes, or other myeloid cells, and (4) the presence of giant platelets, myelocytes, or other cells suggesting a myelodysplastic syndrome.In summary, laboratory data should be presented to clinicians in a user friendly way to promote effective decision making. The design of the data base of information must be directed toward providing clinically helpful information clearly and quickly in order to facilitate appropriate action in terms of optimizing patient care outcomes.d

The presence of atypical inclusions within the cytoplasm of neutrophils and other leukocytes should lead to a clinical investigation of the setting for these findings.Atypical neutrophil inclusions may be seen in the following disorders: Chediak-Higashi syndrome, May-Hegglin anomaly, Alder-Reilly anomaly, Fechtner , Sebastian, Epstein and Alport-like syndromes and in infectious and toxic conditions (in the form of Doehle bodies).Although a specific entity may not be evident from examination of the peripheral blood alone, it is important that hematology technologists include a comment reporting on the presence of these inclusions or granules. A clinical investigation with further hematologic and genetic studies may then appropriately be considered.Many of the disorders with atypical neutrophil cytoplasmic granules are also associated with platelet abnormalities, particularly giant platelets (lower photograph).Therefore, when atypical granules are recognized, scanning of the peripheral blood smear for atypical platelets may be revealing. These observations serve as readily identifiable markers for acquired and genetic human maladies, and as a guide for unraveling the reasons for a patient's suffering and impaired health.

As mentioned on the previous page, high percentages of eosinophils may be present in the peripheral blood smears of patients with a variety of conditions--asthma, urticaria, Loeffler's syndrome, larval parasitic infections and in chronic eosinophilic leukemia. One exception to the association of eosinophilia with parasitic infections is a fatal case of disseminated strongyloidiasis reported many years ago by Miale (Hematology--5th Edition, Mosby, pg. 776, 1977) in which the peripheral blood eosinophilia was masked by the administration of corticosteroids.