Finding knizocytes in a peripheral blood smearJean Francois Lesesve,1* Loıc Garcon,2 and Thomas Lecompte1

A 61-year-old female with unremarkable medical historyand no evidence of chronic alcohol abuse presented withacute liver failure secondary to massive paracetamol over-dose. Laboratory tests indicated: Hb 11.5 g/dL (referencevalue, RV � 12), WBC 13.8 3 109/L (RV � 10), platelets45 3 109/L (RV � 150), bilirubin 238 lmol/L (RV � 25),GOT/ASAT 210 UI/L (VR < 30), GPT/ALAT 103 UI/L(RV< 40), alcaline phosphatase 212 UI/L, RV < 120), choles-terol 3.2 mmol/L (RV � 3.9), and triglycerids 6.5 mmol/L(RV �1.7). The plasma did not show visible hemolysis.Blood smear (Image 1, May Grunwald Giemsa, 31000)demonstrated numerous knizocytes in a background ofmoderate poıkilocytosis.Knizocytes are triconcave RBCs with a ‘‘ridge,’’ a ‘‘bridge’’

separating the three concavities (in scanning electronmicrograph), or a strip of hemoglobin crossing the clearcentral area (in standard staining). They are very rarelyobserved in routine practice even if their percentage wasestimated once 0.6% ± 0.5 in healthy controls (min-maxvalues: 0–2.5%) [1]. By contrast, they are regularly seen in

newborns where they are considered as relatively youngRBCs with impaired membrane deformability usually amongstomatocytes, spherocytes, and erythrocytes with spiculesand protrusions (echinocytes/acanthocytes) [2]. In adults,they are mainly observed in the context of anomalies of thecholesterol metabolism related to any acute liver dys-function. As the RBCs morphology is influenced by the

Image 1. Mosaic image of knizocytes (May-Grunwald-Giemsa 10003).

1Service d’Hematologie biologique, Centre Hospitalier Universitaire, Nancy,France; 2Service d’Hematologie biologique, Hopital Hotel Dieu, Paris, France

Conflict of interest: No

*Correspondence to: J.F. Lesesve, Service d’Hematologie Biologique, CHUNancy, 54511 Vandoeuvre, France. E-mail: jf.lesesve@chu-nancy.fr

Received for publication 3 January 2011; Revised 26 January 2011; Accepted31 January 2011

Am. J. Hematol. 87:105–106, 2012.

Published online 11 February 2011 in Wiley Online Library (wileyonlinelibrary.com).DOI: 10.1002/ajh.22007

AJH Educational Material Images in Hematology

VVC 2011 Wiley Periodicals, Inc.

American Journal of Hematology 105 http://wileyonlinelibrary.com/cgi-bin/jhome/35105

membrane lipid content and as RBCs exchange continu-ously lipids with plasma [3], change in circulating lipids lev-els associated with acute liver disease can alter the RBCsshape, in a delay shorter than their lifetime, as recentlyreported in this journal [4] or by others [5]. More chronically,knizocytes and/or target cells are observed in patients withfamilial lecithin/cholesterol acyltransferase deficiency, whichinduce a decrease in the membrane deformability and as aconsequence a higher RBCs fragility [4,6]. Knizocytes arealso frequently observed in chronic liver diseases aschronic hepatitis or cirrhosis (alcoholic or postviral causes)where they can account for up to 15% of the red cells [7].Alcohol abuse induce a variety of changes in the RBC mor-phology, including typically round macrocytes, stomatocytesbut also knizocytes related to the presence of acetalde-hyde-derived epitopes both on the cell membrane andinside the RBCs [8].Although nonspecific, observation of knizocytes on a

blood smear should prompt an assessment of liver functionand lipid parameters.

References1. Wilhelm Z, Sedlackova M, Kleinova J. Morphology of erythrocytes of patients

with ovarian cancer. Wien Klin Wochenschr 2004;116:676–678.2. Ruef P, Linderkamp O. Deformability and geometry of neonatal erythrocytes

with irregular shapes. Pediatr Res 1999;45:114–119.3. Rees DC, Iolascon A, Carella M, O’marcaigh AS, Kendra JR, Jowitt SN,

Wales JK, Vora A, Makris M, Manning N, Nicolaou A, Fisher J, Mann A,Machin SJ, Clayton PT, Gasparini P, Stewart GW. Stomatocytic haemolysisand macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocy-topenia) is the haematological presentation of phytosterolaemia. Br J Haema-tol 2005;130:297–309.

4. Islam MS, Anoop P. Transient erythrocyte changes caused by infiltration ofliver by plasma cell leukemia. Am J Hematol 2011;86:67–68.

5. Lesesve JF, Garcon L, Lecompte T. Transient red-blood-cell morphologicalanomalies after acute liver dysfunction. Eur J Haematol 2010;84:92–93.

6. Suda T, Akamatsu A, Nakaya Y, et al. Alterations in erythrocyte membranelipid and its fragility in a patient with familial lecithin:cholesterol acyltrasferase(LCAT) deficiency. J Med Invest 2002;49:147–155.

7. Turchetti V, Bellini MA, Leoncini F, et al. Blood viscosity and red cell morphol-ogy in subjects suffering from cirrhosis before and after treatment with S-adenosyl-L-methionine (SAM). Clin Hemorheol Microcirc 2000;22:215–221.

8. Latvala J, Parkkila S, Melkko J, et al. Acetaldehyde adducts in blood andbone marrow of patients with ethanol-induced erythrocyte abnormalities. MolMed 2001;7:401–405.

106 American Journal of Hematology

images in hematology