Baylor University Medical Center Proceedings July 2017 - 347

Figure 1. Peripheral smear showing a hypersegmented neutrophil and multiple
schistocytes (arrows).

were hyperplastic. No increase in the blast population and no
evidence of an immunophenotypically aberrant cell population
was noted. Serum anti-intrinsic factor antibodies were present. Esophagogastroduodenoscopy was performed and gastric
biopsies were taken. Gastric biopsy showed evidence of reactive gastropathy, though features of atrophic gastritis were not
conﬁrmed. A diagnosis of severe vitamin B12 deﬁciency due
to pernicious anemia with resultant pseudothrombotic microangiopathy was made. Hemoglobin levels remained stable, and
the patient was discharged to home with subcutaneous cyanocobalamin injections.
DISCUSSION
The patient in this case report exhibited an uncommon manifestation of vitamin B12 deﬁciency: pseudothrombotic microangiopathy. The cause of this pseudothrombotic microangiopathy
appeared to be intramedullary destruction of erythrocytes (ineﬀective erythropoiesis) (1). In one case series of 201 patients
with vitamin B12 deﬁciency, 2.5% of patients exhibited pseudothrombotic microangiopathy (2). The infrequent occurrence
of pseudothrombotic microangiopathy makes its accurate identiﬁcation and diagnosis more diﬃcult. Diﬀerentiating between

July 2017

pseudothrombotic microangiopathy and a true microangiopathic
hemolytic anemia, such as TTP, is important, since an inappropriate diagnosis of TTP may lead to numerous unnecessary and
expensive treatments, such as intensive care unit admission and
plasmapheresis (3).
When treating a patient with suspected pseudothrombotic
microangiopathy, laboratory studies are indispensable. The
lactate dehydrogenase (LDH) and bilirubin levels should be
evaluated. A more elevated LDH as well as a relatively normal unconjugated bilirubin is suggestive of pseudothrombotic
microangiopathy. The purported mechanism is that the nucleated erythrocytes in the bone marrow elevate the LDH much
more when they are lysed than unnucleated erythrocytes in
the peripheral blood. In addition, the immature erythrocytes
in the bone marrow contain very little hemoglobin, leading
to only minor elevations in the unconjugated bilirubin when
lysed. Another important laboratory study found to suggest
pseudothrombotic microangiopathy in one case series was a
low reticulocyte count (3). This is expected, as a deﬁciency of
vitamin B12 leads to defective DNA synthesis and production
of megaloblastic cells. Eighty to ninety percent of these cells are
destroyed in the bone marrow through the action of marrow
macrophages. This intramedullary hemolysis is the cause of
the low reticulocyte count (ineﬀective erythropoiesis) (1). The
platelet count should also be examined. The thrombocytopenia
associated with TTP is generally severe, an average of 12,500
platelets/μL (3). The average platelet count of patients with
pseudothrombotic microangiopathy is higher, approximately
70,000 platelets/μL (2, 3). The platelet count in this case report
was atypical for pseudothrombotic microangiopathy in that it
was low normal, 157,000 platelets/μL.
1.

Antony AC. Megaloblastic anemias. In Hoﬀman R, Benz EJ Jr, Shattil
SJ, Furie B, Cohen HJ, Silberstein LE, McGlave P, eds. Hematology, Basic
Principles and Practice, 4th ed. Philadelphia, PA: Elsevier, 2005:519-556.
Andrès E, Aﬀenberger S, Zimmer J, Vinzio S, Grosu D, Pistol G, Maloisel
F, Weitten T, Kaltenbach G, Blickle JF. Current hematological ﬁndings
in cobalamin deﬁciency: a study of 201 consecutive patients with documented cobalamin deﬁciency. Clin Lab Haematol 2006;28(1):50-56.
Noël N, Maigné G, Tertian G, Anguel N, Monnet X, Michot JM, Goujard
C, Lambotte O. Hemolysis and schistocytosis in the emergency department: consider pseudothrombotic microangiopathy related to vitamin
B12 deﬁciency. QJM 2013;106(11):1017-1022.

Pseudothrombotic microangiopathy and vitamin B12 deficiency in pernicious anemia

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Table of Contents for the Digital Edition of Baylor University Medical Center Proceedings July 2017