Pseudo-Thrombotic Microangiopathy 2/2 B12 Deficiency

Thank you to Dr. Fleming for presenting an interesting case of an older gentleman with confusion, GI symptoms and pancytopenia. On the peripheral smear there were schistocytes and several signs pointing to MAHA so he was started on plasmapheresis. However, as he did not readily improve and remained confused, further investigation into MAHA unveiled profound vitamin B12 deficiency. With B12 supplementation his counts improved. This was similarly described in a 2016 case report in the International Journal of Critical Illness & Injury Science.

  Schistocytes and hypersegmented neutrophil on a peripheral smear in a similar case of B12 deficiency. Veit K. Pseudothrombotic microangiopathy and vitamin B12 deficiency in pernicious anemia.   Proceedings (Baylor University Medical Center)  . 2017;30(3):346-347.

Schistocytes and hypersegmented neutrophil on a peripheral smear in a similar case of B12 deficiency. Veit K. Pseudothrombotic microangiopathy and vitamin B12 deficiency in pernicious anemia. Proceedings (Baylor University Medical Center). 2017;30(3):346-347.

Pseudo-TTP associated with B12 deficiency was first described in children with inherited B12 disorders. Deficiency in B12 leads to increased erythrocyte rigidity and decreased deformability. Hemolysis is mostly intramedullary as opposed to intravascular. Additionally, elevated homocysteine can cause endothelial dysfunction and MAHA. It is rare with a 2006 case series of 201 patients with B12 deficiency documenting 10% with severe anemia or thrombocytopenia and 2.5% of those with smears mistaken for TTP. Thus, it can often lead to a missed diagnosis and unnecessary plasmapheresis. There are a few ways to tell the difference between B12 deficiency and TTP:

  • young RBCs have more LDH and less hemoglobin than mature RBCs thus, intramedullary destruction (as seen in B12 deficiency) leads to comparatively higher LDH (often greater than 3k) and lower unconjugated bilirubin
  • the reticulocyte count will be inappropriate low for the level of anemia as B12 deficiency is a hypoprolifeative anemia
  • review of the peripheral smear will show "bizarre microcyte with preserved central pallor" and hypersegmented neutrophils, macro-ovalocytes and Howell Jolly bodies in B12 deficiency whereas the most classic helmet-shapted schistocytes are seen in TTP (see below)
  Peripheral smears where A and B = true TTP -  à   note helmet-shaped schistocytes with dark staining and  C and D = “pseudo TTP” due to B12   à   note “bizarre microcytes with preserved central pallor”, hypersegmented neutrophil, and macro-ovalocyte w/ Howell-Jolly body in D. Abbott, DW; Friedman KD; Karafin MS. Differentiation of pernicious anemia from thrombotic thrombocytopenic purpura: The clinical value of subtle pathologic findings. Transfusion and Aphresis Science, 2016.

Peripheral smears where A and B = true TTP -à note helmet-shaped schistocytes with dark staining and C and D = “pseudo TTP” due to B12 à note “bizarre microcytes with preserved central pallor”, hypersegmented neutrophil, and macro-ovalocyte w/ Howell-Jolly body in D. Abbott, DW; Friedman KD; Karafin MS. Differentiation of pernicious anemia from thrombotic thrombocytopenic purpura: The clinical value of subtle pathologic findings. Transfusion and Aphresis Science, 2016.

The patient was evaluated for various etiologies of B12 deficiency with no avail. It is presumed that this is secondary to chronic proton pump inhibitor use. For more information, please see this 2013 article in JAMA.