Acanthocytosis—Biochemical and Physiological Considerations

ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 10, No. 3 Copyright © 1980, Institute for Clinical Science, Inc. Acanthocytosis—Biochemical and Physiological Considerations JAMES J. BIEMER, M.D. Pathology Department, St. Joseph’s Hospital, and University of South Florida, College of Medicine Tampa, FL 33677 ABSTRACT Acanthocytosis represents an unusually pathological variant of red cell morphology which is encountered in a diverse group of inherited and ac quired disease states. While the morphological features are similar in all instances, the biochemical lesions frequently differ. Most demonstrable abnormalities involve lipids although those acanthocytes associated with the McLeod phenotype are probably due to an alteration in a membrane protein. Acanthocytes, regardless of their etiology, usually have a decreased survival in the circulation owing to splenic sequestration and destruction. Introduction Young red cells, known as reticulocytes, with a frequently folded excess mem A great deal of interest has been gener brane, persist approximately two days in ated by observation of the wide array of the peripheral blood while their cyto pathological and physiological forms that plasmic organelles are discharged, and can be assumed by the normally bicon each undergoes remodeling with sym cave human red blood cell, the discocyte. metrical membrane loss to assume its To survive its normal 100 to 120 days’ life normal discocyte configuration. As the span, the red cell must undertake a con cell ages, a series of changes occur includ tinuous circulatory journey, approximat ing additional membrane loss, increased ing 175 miles, frequently requiring corpuscular hemoglobin concentration negotiation of capillaries and slit-like because of water and cation loss, de spaces as small as 1/20 its diameter. Its creased enzyme activity, increased biconcave configuration with optimal methemoglobin content and decreased surface-to-volume ratio enhances its deformability. It is probably largely be ready deformability to negotiate those cause of the latter that these senescent tight spaces without damage, and also best primarily now spherical cells are detected serves its gas exchange function with its and destroyed by the spleen as they at freely movable molecular hemoglobin tempt to pass its narrow passages. The vast content (figure 1). majority of normal circulating cells are, 238 0091-7370/80/0500-0238 $01.80 © Institute for Clinical Science, Inc. ACANTHOCYTOSIS 2 3 9 F ig u r e 1. T h e m a rk e d alteration of shape is por trayed as a normally deformable erythrocyte negotiates a tight interen- dothelial cell space of the spleen (10,000 x). however, discocytes which, when ob The report of Brecher and Bessis9 has served while flowing in vivo, assume a well illustrated the stages of discocyte- vast variety of dynamic transitions in form eehinocyte transformation and elluci- largely related to flow rates and vessel dated many of the factors associated with size.31 echinocyte formation. Extrinsic factors The following discussion pertains to de causing crenation include plasma incu formed red cells which are spiculated and bated at 37°C for 24 hours, lysolecithin, specifically known as acanthocytes. high levels of fatty acid and many others. These must be differentiated from a vari Intrinsic factors include aging of red cells ety of red cells known to have one or more which is probably related to depressed spiny projections. Many of these cells are adenosine triphosphate, (ATP) and wash of well defined pathogenesis, e.g., sickle ing cells in saline and the “glass effect” of cells associated with sickle cell hemoglo observing cells between slide and cover bin; schizocytes (helmet, fragmented or slip. Brecher and Bessis feel that echino- triangular cells), associated with micro cytes probably occur in various diseases angiopathic hemolytic anemia where the but that previous reports of such must be cells are injured by intravascular fibrin carefully reevaluated by examination of strands, diseased vessel walls, or by car fresh cells between plastic cover slips to diac valve prostheses; and tear drop cells exclude artifactual crenation. (dacrocytes), typically associated with Acanthocytes (spur or aeanthoid cells), myelofibrosis or abnormal hematopoiesis. on the other hand, are distinctly different Lastly, there is the echinocyte, (burr, cre- cells having 5 to 10 spicules of varying nated or berry cell), which is an ovoid or length irregularly distributed over the red spherical cell with 10 to 30 spicules cell surface (figure 2). The individual evenly distributed over its surface. spicules have knobby ends. Under the 2 4 0 BIEMER echinocytes which will then stand out in sharp contrast to acanthocytes which will be converted to acantho-echinocytes, rec ognizable by bifurcation of the spicules. Lastly, scanning electron microscopy fol lowing immediate fixation of fresh blood has provided the reference standard by which the subtle diferences in spiculated cells have been defined.4 While originally described as one of the diagnostic hallmarks of abetalipopro teinemia (ABL),3 acanthocytes have been described in a number of seemingly re lated and unrelated conditions, which F ig u r e 2. Artistic composite illustrating a cen will be discussed (see table I). Regardless trally placed discocyte with acanthocytes at the 12,2, of their etiology, they almost invariably and 7 o’clock positions and echinocytes at 4 and 9 have a decreased life span although this o ’clock. may range from a severe hemolytic anemia requiring transfusions to a mild, light microscope on an air dried smear, barely detectable compensated hemolytic state. For a thorough discussion of the im acanthocytes and echinocytes may occa sionally be difficult to differentiate. How plications of altered red cell shape, their membranes, deformability, and hemolytic ever, typical echinocytes have a serrated outline with small projections more or less anemia, the reader is referred to the fol evenly spaced over the circumference of lowing comprehensive reviews; Weed,54 the red cells while acanthocytes have a Shohet and Ness,48 Lessin et al31 and few spicules of varying length and thick Mohandas et al.39 ness projecting irregularly from the cell surface. Red Cell Membranes—General Wet preparations have the advantage of Background allowing more of a three dimensional ap pearance, which is often helpful. Brecher The basic lesion in the acanthocyte ap and Bessis9 also suggest adding an pears to be limited to its membrane since, echinocytogenic substance, such as to date, there has been no abnormality plasma with lysolecithin, in doubtful demonstrated in hemoglobin, cation cases. This will convert the discocytes to transport, red cell antibodies or gluta thione and ATP levels.26 The more com monly encountered forms of acan T A BLE I thocytosis exhibit rather marked altera Diseases Associated with Acanthocytosis tions of the red cell membrane lipids al though there is increasing evidence that Majority of red cells are acanthocytes proteins play a major role in membrane 1. Spur cell anemia with severe liver disease 2. Abetalipoproteinemia properties. 3. Homozygous hypobetalipoproteinemia To date, methods for isolation and 4. McLeod phenotype characterization of membrane proteins Minority of red cells are acanthocytes 1. Certain neurological disorders without lipid are less well developed than those for abnormalities lipids, so our information regarding pro 2. Infantile pyknocytosis - vitamin E deficiency 3. Miscellaneous conditions teins is less complete.45 Hence, while most of the following discussion will ACANTHOCYTOSIS 241 dwell upon lipid alterations, it should be the various theories of membrane struc borne in mind that proteins may also be ture and lipid exchange, the reader is re changed either primarily or secondarily. ferred to several excellent recent reviews To illustrate this point, one instance of of the subject.11,35,45,54 acanthocytosis is cited, namely the McLeod phenotype, where a protein alt Spur Cell Anemia eration is the probable principle or pri mary lesion. Abnormalities in serum lipoproteins are The red cell membrane is composed of known to induce secondary changes in lipid and protein in approximately equal red cells by modifying the equilibrium of amounts by weight. Phospholipids and the passive exchange of lipids between free cholesterol constitute nearly 95 per plasma and erythrocytes.45 In liver disease cent of the total lipid and, on a molar basis, of both the obstructive or hepatocellular phospholipids and cholesterol are present type, the red cells may becom e laden w ith in nearly equal amounts.45 The molecular cholesterol and, to a lesser extent, phos arrangement of the membranes is un pholipid. Thus, the membranes exhibit a known although the various studies have marked increase in the cholesterol-phos- generally evolved into two basic con pholipid (C/P), ratio. When examined on cepts, namely; the membrane is vis air-dried blood smears, they are fre ualized as a sea of lipid containing islands quently “targeted,” reflecting the acquisi of protein47 or as a protein membranous tion of membrane surface area caused by skeleton containing lakes of lipid.35 Both the added cholesterol. concepts suggest that the zones of fluid Using osmotic fragility as an indirect lipid within the membrane form the envi measure of membrane surface, it has been ronment for membrane proteins. Much of found that these cells exhibit increased this

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