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Vitamin B12 Deficient Megaloblastic Anemia Mimicking Thrombotic Thrombocytopenic Purpura

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Megaloblastic anemia is a benign disorder characterized by ineffective hematopoiesis due to lack of vitamin B12 or folate. Megaloblastic anemia could be easily treated with either vitamin B12 or folate. However, a megaloblastic anemia patient may show schizocyte and hemolytic anemia with thrombocytopenia, necessitating to exclude urgent diseases like thrombotic thrombocytopenic purpura. We have experienced the vitamin B12–deficient megaloblastic anemia patient mimicking thrombotic thrombocytopenic purpura. We should know the rare coexistence of hemolytic anemia with megaloblastic anemia in severe cases.


Megaloblastic anemia (MA) is a disorder characterized by ineffective hematopoiesis due to lack of vitamin B12 or folate and caused by chronic atrophic type A gastritis or total gastrectomy [1, 2]. MA could be easily diagnosed by the deficiency of vitamin B12 or folate and could be easily treated with either vitamin B12 or folate [1, 2]. However, if the MA patient showed schizocyte and hemolytic anemia with drastic thrombocytopenia, we might face with the dilemma of distinguishing other important and urgent diseases like thrombotic thrombocytopenic purpura (TTP). We have experienced the vitamin B12–deficient MA patient mimicking thrombotic thrombocytopenic purpura.

Case Presentation

A 69-year-old Japanese woman was admitted to our clinic with epigastric pain. She had undergone a total gastrectomy with combined resection of the transverse colon, pancreas, and spleen for gastric cancer at the age of 62. She visited our hospital 3 years after gastrectomy. At that time, she did not present any anemia or thrombocytopenia. Blood tests on admission showed megaloblastic anemia: red blood cell (RBC) count 1.01 × 1012/L, hemoglobin 4.1 g/dL, mean corpuscular volume (MCV) 123.8 L, white blood cell (WBC) count 4.6 × 109/L, and platelet count 155 × 109/L. Other laboratory tests revealed lactate dehydrogenase 4053 IU/L (normal range 106–211), aspartate aminotransferase 221 U/L (normal range 5–40), alanine aminotransferase 60 U/L (normal range 5–35), total bilirubin 4.3 mg/dL (normal range 0.3–1.0), direct bilirubin 1.2 mg/dL, serum B12 less than 50 pg/mL (normal range 180–914), and folic acid 9.6 ng/mL (normal range 3.1–12.9). Schizocyte was detected in peripheral blood and haptoglobin was undetectable (Fig. 1a). Bone marrow examination revealed hyperplasia of erythroid lineage with megaloblastic changes (Fig. 1b). She was diagnosed as having MA, absorption deficiency of vitamin B12 due to gastrectomy. She was repeatedly treated with intramuscular vitamin B12. Because her platelet suddenly dropped to 39 × 109/L count in a week, we determined the activity of ADAMTS13 in the serum to rule out the possibility of thrombotic thrombocytopenic purpura (TTP) for the cause of schizocyte, hemolytic anemia, and thrombocytopenia. We also performed the direct Coombs test and two-colored flow cytometric analysis for CD59 and CD55 in red blood cell to define the cause of hemolytic anemia. However, the activity of ADAMTS13 was normal, the Coombs test was negative, and CD59 and CD55 were both positive. As she did not have any bleeding problems, she was treated with vitamin B12 and she did not receive any transfusion. Her platelet count fully recovered with additional week, and anemia also recovered gradually.

Fig. 1

Smear of peripheral blood (a) and bone marrow (b) (magnification × 400). The panels show May-Grunwald-Giemsa staining (a, b)


Coexistence of hemolytic anemia mimicking TTP is quite rare, and only few publications have been reported with severe MA case, like our case [3, 4]. In our case, as it took several days for the blood cells to recover by replacing vitamin B12, we had to face with the drastic thrombocytopenia mimicking TTP. But our patient did not show any consciousness disturbance or renal impairment, which could be frequently observed in TTP cases. We think it is possible to distinguish true complications of TTP and pseudo-TTP by following the patient’s symptom carefully in most cases. However, in cases of vitamin B12–deficient megaloblastic anemia presented with renal manifestations and neurological abnormalities, it would be really challenging. In those cases, it is necessary to determine the activity of ADAMTS13 in the serum.

In conclusion, it is important to recognize that hemolytic anemia with thrombocytopenia mimicking TTP could be seen in severe MA case.


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Correspondence to Yutaka Shimazu.

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Shimazu, Y., Edagawa, T. & Nohgawa, M. Vitamin B12 Deficient Megaloblastic Anemia Mimicking Thrombotic Thrombocytopenic Purpura. SN Compr. Clin. Med. 2, 235–236 (2020). https://doi.org/10.1007/s42399-019-00210-1

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  • Megaloblastic anemia
  • Thrombotic thrombocytopenic purpura
  • Vitamin B12 deficiency
  • Hemolytic anemia
  • Thrombocytopenia