Finding knizocytes in a peripheral blood smear

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A 61-year-old female with unremarkable medical history and no evidence of chronic alcohol abuse presented with acute liver failure secondary to massive paracetamol overdose. Laboratory tests indicated: Hb 11.5 g/dL (reference value, RV ≥ 12), WBC 13.8 × 109/L (RV ≤ 10), platelets 45 × 109/L (RV ≥ 150), bilirubin 238 μmol/L (RV ≤ 25), GOT/ASAT 210 UI/L (VR < 30), GPT/ALAT 103 UI/L(RV < 40), alcaline phosphatase 212 UI/L, RV < 120), cholesterol 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 Grünwald Giemsa, ×1000) demonstrated numerous knizocytes in a background of moderate poïkilocytosis.

Illustration Image 1.

Mosaic image of knizocytes (May-Grünwald-Giemsa 1000×).

Knizocytes are triconcave RBCs with a “ridge,” a “bridge” separating the three concavities (in scanning electron micrograph), or a strip of hemoglobin crossing the clear central area (in standard staining). They are very rarely observed in routine practice even if their percentage was estimated once 0.6% ± 0.5 in healthy controls (min-max values: 0–2.5%) [1]. By contrast, they are regularly seen in newborns where they are considered as relatively young RBCs with impaired membrane deformability usually among stomatocytes, spherocytes, and erythrocytes with spicules and protrusions (echinocytes/acanthocytes) [2]. In adults, they are mainly observed in the context of anomalies of the cholesterol metabolism related to any acute liver dysfunction. As the RBCs morphology is influenced by the membrane lipid content and as RBCs exchange continuously lipids with plasma [3], change in circulating lipids levels associated with acute liver disease can alter the RBCs shape, in a delay shorter than their lifetime, as recently reported in this journal [4] or by others [5]. More chronically, knizocytes and/or target cells are observed in patients with familial lecithin/cholesterol acyltransferase deficiency, which induce a decrease in the membrane deformability and as a consequence a higher RBCs fragility [4, 6]. Knizocytes are also frequently observed in chronic liver diseases as chronic 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 morphology, including typically round macrocytes, stomatocytes but also knizocytes related to the presence of acetaldehyde-derived epitopes both on the cell membrane and inside the RBCs [8].

Although nonspecific, observation of knizocytes on a blood smear should prompt an assessment of liver function and lipid parameters.

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