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Marked erythrocyte anisopoikilocytosis was noted in a 52-year-old man with relapsed IgD multiple myeloma. Complete blood count showed a white cell count of 14,100/mm3 with 40% circulating plasma cells. Most of the red blood cells (RBCs) were either target cells or microspherocytes, with occasional acanthocytes, stomatocytes, and knizocytes ( Images 1 and 2a). The direct antiglobulin test was negative. He had no history of a hemoglobinopathy or an RBC membrane disorder and had normal erythrocyte morphology during remission. He had renal impairment and grossly deranged liver function with elevated alanine aminotransferase of 128 u/l (normal <40 u/l), gamma glutamyltransferase of 591 u/l (normal <50 u/l) and bilirubin of 174 umol/l (normal <17 umol/l). An ultrasound scan (USS) of liver showed hepatomegaly with diffusely abnormal coarse echogenicity, consistent with infiltration by myeloma.

He had hypercalcemia and hypophosphatemia at presentation, which resolved with treatment over the next 3 weeks.

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Figure 1. Severe anisopoikilocytosis with microspherocytes (solid arrows), acanthocytes (dotted arrows), and a knizocyte (dashed arrow) on the initial blood film at plasma cell leukemic relapse phase of myeloma. Two abnormal plasma cells, one binucleate and the other bilobed, are seen (×100 oil; MGG).

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Figure 2. (a) Initial blood film at relapse showing a bilobed plasma cell and widespread red cell changes including numerous target cells, microspherocytes (solid arrows), occasional acanthocytes and stomatocytes. A single knizocyte (dashed arrow) is also seen. Plasma cells constituted 40% of circulating white cells at this stage (×40; MGG). (b) Less marked red cells changes a week after initiation of treatment. Plasma cells have reduced in number, but circulating forms are still present. Most of the target cells have disappeared but microspherocytosis (solid arrows) remains conspicuous. A single nucleated RBC is seen at the bottom, most likely due to marrow infiltration by myeloma (×40; MGG). (c) Complete clearance of plasma cells from circulation during the 3rd week of treatment. Most of the red cells are now normal, though a few microspherocytes (solid arrows) persist (×40; MGG). (d) Normal blood film at 4th week of treatment (×40; MGG).

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He was treated with a combination of bortezomib, doxorubicin, and dexamethasone, to which he responded rapidly with clearance of plasma cells, normalization of liver function, improvement in renal function and reduction of paraprotein level. All the red cell changes disappeared serially over a period of 4 weeks ( Image 2b–d). USS of liver was repeated at this stage and showed normal size and echo pattern of liver.

In retrospect, this patient had hepatic infiltration by plasma cell leukemia, which reversed completely with chemotherapy. The RBC changes were secondary to this and all abnormalities resolved with return of normal liver function. Target cells and acanthocytes are well described changes with hepatic dysfunction and are believed to be the result of net membrane accumulation of cholesterol, alteration in phospholipids and decreased lecithin cholesterol acyltransferase (LCAT) activity [1, 2]. Knizocytes are triconcave red cells with a band of hemoglobin in the center with an area of pallor on either side and are known to occur in hemolytic states or liver dysfunction. The prominent acquired microspherocytosis noted in this patient is more difficult to explain. In the absence of autoimmune hemolysis, the most likely reason for spherocytosis was the hypophosphatemia which persisted until the 3rd week of treatment. Depletion of phosphate can cause low erythrocyte adenosine triphosphate levels, which in turn can result in spherocytosis [3].

Reversible erythrocyte anisopoikilocytosis of such severity has not been reported so far in conjunction with hepatic infiltration by plasma cell leukemia.

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