Patrick C. J. Ward

Iron Deficiency Anemia, β-Thalassemia Minor, and Anemia of Chronic Disease A Morphologic Reappraisal

We observed increased numbers of an infrequently referenced poikilocyte, the prekeratocyte, in iron deficiency anemia (IDA) compared with beta-thalassemia minor and anemia of chronic disease (ACD) and, therefore, chose to quantify these cells and other morphologic features in these anemias. Prekeratocytes were observed in 31 (78%) of 40 IDAs vs 11 (37%) of 30 beta-thalassemias (P = .001) and 5 (13%) of 40 ACDs (P < .001) and averaged 0.78 per 1,000 RBCs in IDA vs 0.21 in beta-thalassemia (P < .001) and 0.075 in ACD (P < .001). Pencil cells also were more commonly seen and more numerous in IDAs than in beta-thalassemia or ACD. Target cells were present in most IDAs and thalassemia and in similar numbers. Basophilic stippling was seen in only 5 (17%) of the beta-thalassemias. Our results lend quantitative support to prekeratocytes and pencil cells as morphologic features favoring the diagnosis of IDA but fail to support the diagnostic usefulness of target cells and basophilic stippling in discriminating IDA and beta-thalassemia minor.

Interpretation of ascitic fluid data.

Except in the case of chylous or hemorrhagic effusion, the gross appearance of ascitic fluid is not especially helpful in the investigation of ascites of unknown origin. The differential diagnosis of ascites rests on more objective data obtained from chemical and cytologic analyses. Both routine and special ascitic fluid tests are listed here, and test results are interpreted as they apply to four major disease states.

Investigation of macrocytic anemia.

The three most common causes of macrocytosis--vitamin B12 or folate deficiency, liver disease, and reticulocytosis--usually can be differentiated on the basis of red cell indexes and morphologic findings. Bone marrow studies are not indicated. In reticulocytosis, the mean corpuscular volume (MCV) rarely exceeds ll0 cu mu and a reticulocyte count quickly establishes the diagnosis. In liver disease, macrocytosis is also mild and uniform. The RBCs are round. In megaloblastic anemia, the MCV may exceed 150 cu mu. The RBCs vary considerably in size and shape. The macrocytes tend to be oval. Serum vitamin B12 determination remains the best test for unmasking vitamin B12 deficiency. It should be ordered in conjunction with serum and red cell folate determinations in the course of investigating a macrocytic anemia. When vitamin B12 deficiency has been established, a Schilling test or plasma uptake test is indicated to pinpoint the cause.

Interpretation of synovial fluid data

The routine battery of tests for synovial fluid analysis includes culture and Gram staining, polarizing microscopy, and total WBC and differential counts. If the volume of fluid collected is low, culture and polarizing microscopy have highest priority. Synovial fluid data are diagnostic in only two diseases: septic arthritis and crystal-induced arthritis. In traumatic arthritis, degenerative joint disease, rheumatoid arthritis, and systemic lupus erythematosus, synovial fluid data may provide evidence supporting the diagnosis.

Cytoplasmic inclusions in leukocytes : An unusual manifestation of cryoglobulinemia

Cryoglobulins are circulating immunoglobulins characterized by reversible, cold-induced precipitation. A variety of laboratory abnormalities, including hypocomplementemia, elevated erythrocyte sedimentation rate, rheumatoid factor activity, pseudoleukocytosis, and pseudothrombocytosis, are associated with cryoglobulinemia. Extracellular, faintly basophilic, amorphous deposits of cryoglobulins occasionally have been described in blood smears. In the present study, smears prepared from blood collected at room temperature from 6 patients with cryoglobulinemia exhibited neutrophil and, occasionally, monocyte inclusions containing clear, light pink, or faintly basophilic amorphous material. The inclusions were absent in smears from blood collected and maintained at 37 degrees C. Ultrastructural examination revealed that the material within the leukocyte inclusions was consistent with phagocytosed immunoglobulins. The identification of characteristic cytoplasmic inclusions in leukocytes may be an important clue in the early recognition of cryoglobulinemia.

Cerebrospinal fluid data. 1. Interpretation in intracranial hemorrhage and meningitis.

In substantiating a diagnosis of intracranial hemorrhage, the most important laboratory findings are RBCs, free hemoglobin, or hemoglobin breakdown products in the CSF. When the Gram stain is negative and results of bacterial, viral, and fungal cultures are pending. CSF WBC and differential counts and glucose and lactic acid levels may provide clues to the cause of meningitis. In addition, counterimmuno-electrophoresis and other immunologic techniques that facilitate the diagnosis of meningitis are now becoming more widely available.

The lymphoid leukocytoses

The experienced morphologist can be extremely helpful to the clinician by virtue of his or her ability to distinguish among the various subtypes of reactive lymphocytoses. An awareness on the part of the clinician as to the nuances of subclassification may lead to earlier diagnosis of a disease process. Broadly, proliferations of normal lymphocytes point to infectious lymphocytosis or Bordetella pertussis infection. Proliferations of atypical lymphocytes, especially when minimum diagnostic criteria are present or there are four or more Downey III forms per 100 WBCs, suggest infectious mononucleosis. Proliferations of immunoblasts reflect hypersensitivity reactions to drugs or autoimmune disease. Proliferations of proplasmacytes or plasma cells favor viral hepatitis, drug reactions (notably to sulfa drugs), or rubella. Quantitative data may help refine the morphologic implications. Cumulatively, qualitative and quantitative data should lead the clinician to a judicious selection of confirmatory serologic tests and hence to earlier diagnosis.

White blood cell changes in hyperthermia

A 58-year-old homeless man was found unconscious in a street shelter in Dallas at 19.33 h. At 19.43 h, the following data were recorded: blood pressure 126/64 mm Hg, pulse 130/min, respirations 20/min. At 20.12 h his temperature was 41.9 C. The ambient temperature in the city at the time of initial examination was 33 C and humidity 53%. Physical examination was unremarkable. Laboratory studies showed: haemoglobin concentration 177 g/l, mean cell volume 90.5 fl, white cell count 6.7 · 10/l and platelet count 221 · 10/l. The differential count was normal. Of the neutrophils examined in films, 20% had ‘botryoid’ or grape-like nuclei, each with six or more lobes, often in wheel-spoke array (left panels). Of the lymphocytes, 44% exhibited nuclear budding or lobation (central panels). Rare monocytes appeared binucleate or hyperlobed (right panels), a feature not previously reported. A serum cocaine level was reported as high. The above findings in a blood film are typical of the hyperthermia of heat stroke, generally defined as a temperature of 41.1 C (106 F) or more, in the absence of sepsis. The numbers of ‘botryoid’ neutrophils in films is very variable, from 4% to 80% having been reported. Nuclear changes in lymphocytes are usually less common than those observed in neutrophils. In experiments performed by one of us (RMcK), botryoid neutrophils and hyperlobated lymphocytes could be observed in control normal blood heated to 108 F (42.2 C) for 10 min. Among the many causes of hyperthermia, heat stroke remains the most common. Other causes of hyperthermia include the malignant hyperthermia of anaesthesia (use of volatile halogenated anaesthetics in conjunction with depolarizing muscle relaxants) and the neuroleptic malignant syndrome (triggered by drugs such as haloperidol). Hyperthermia is also a known consequence of the therapeutic use of monamine oxidase inhibitors and the recreational use of drugs such as amphetamines and cocaine. The combination of cocaine abuse and concomitant high ambient temperature is known to be associated with a substantial increase in mortality, each factor contributing to stress on the cardiovascular system. Both factors were probably operative in the present case. To date, botryoid neutrophils have been reported in heat stroke and in haemorrhagic shock and encephalopathy syndrome, a rare disease of infants considered to be a variant of heat stroke.

Investigation of microcytic anemia.

This article on microcytic anemia is the first of several on laboratory investigation of anemia. Microcytic anemia, characterized by a mean corpuscular volume of less than 80 cu mu, is usually due to iron deficiency or chronic disease but may signify thalassemia minor. Exact identification of the cause is important, since inappropriate iron therapy may be useless or even dangerous.

A Mysterious Malady: the Malachowski-Wright-Giemsa Stain to the Rescue

Abstract A patient entered hospital with a puzzling absolute monocytosis. Admitting blood smears had been stained with Diff-Quik, a Romanowsky stain. When additional smears were stained using a standard Malachowski-Wright-Giemsa method, the reason for the monocytosis became abundantly clear.