A 59 y.o. woman presents with fatigue. She has pancytopenia and hemolytic anemia.

Her peripheral smear resembles the one below.

What do you see?

The slide demonstrates ovalocytes, teardrop cells( not schistocytes) and most importantly  hypersegmented PMNs.  Our patient had severe megaloblastic anemia from B12 deficiency which can result in hemolytic anemia in 1.5% of cases.  The term ‘pernicious” was first used by Michael Biermer a German physician to describe an untreatable anemia with an insidious course in 1872.  Whipple,Murphy and Minot discovered a cure  in 1926 when a diet of 120-240grams of raw liver and 120 grams of muscle meat was found to increase the hemoglobin level in affected patients.  B12 cannot be synthesized in humans and its presence in meat and eggs is due to its synthesis by microorganisms in the intestines of animals.

A useful way to think of anemia is to look at whether the RBCs are microcytic, normocytic or macrovytic

B12 deficiency is a common cause of macrocytic anemia and is often seen following bariatric surgery which is why supplementation is recommended.  0.13% of the body’s  total vitamin B12 store is lost per day with B12 which is why it takes two years to become deficient if the diet lacks B12. . In addition to poor diet as in the case of alcoholics,  another cause of B12 deficiency is pernicious anemia.

If diet is the determining factor, it takes a long time to become vit B12 deficient.

Our patient had antigastric parietal cell antibodies at 48 units with normal being < 20  Antiparietal cell antibodies are associated with autoimmune gastritis and pernicious anemia.  The parietal cells of the stomach secrete intrinsic factor, which is necessary for the absorption of vitamin B12. Antiparietal cell antibodies serve as a screening test for autoimmune atrophic gastritis and pernicious anemia. Antiparietal cell antibodies are found in 85% of people with pernicious anemia .  People with autoimmune diseases specifically  autoimmune thyroid disease, vitiligo, and celiac disease may also have these antibodies and should be screened for pernicious anemia.

While hemolysis is common in severe B12 deficiency it occurs before the red cells are fully mature and released from the marrow.  Typically the LDH is very high but the reticulocyte count is not because the hemolysis is “intramedullary”.

Our patient presented with : a B12 level was <150 with normal  being 230-1,250. Haptoglobin was <10, bilirubin was 4 , LDH was 4,6809ml up to 250), Hgb was 4.6 and platelets 44,000. The patient received 1,000 mcg B12 daily for one week followed by weekly injections with follow up with Dr Blinder in 4-6 weeks. She is being monitored for Fe deficiency as Fe levels can drop with hematopoiesis.

Bluish nails are sometimes seen in dark skinned individuals with B12 deficiency. . Decreased glutathione levels results in disinhibition of tyrosinase, an enzyme of melanogenesis leading to increased melanin synthesis.

Andres E, Affenberger S, Zimmer J, et al. Current hematological findings in cobalamin deficiency. A study of 201 consecutive patients with documented cobalamin deficiency. Int J Lab Hematol. 200600755.x.https://pubmed.ncbi.nlm.nih.gov/16430460

Sadagopan N. Severe hemolytic anemia due to vitamin B12 deficiency in six months.   Hematol Rep 2022 Sept 14 (3):210-212.

Ayed Al Qahtani S. Drug-induced megaloblastic, aplastgic and hemolytic anemias: current concepts of pathophysiology and treatment. Int J Clin exp Med 2018;11(6):5501-5512.

Gulati, Gene. Blood Cells.2nd edition.  American Society of Clinical Pathology Press.Hong Kong. 2014. 141.

Carmel R. Hair and fingernail changes in acquired and congenital pernicious anemia.. Arch Intern Med. 1985;145(3):484-485.