Proof in the Peripheral Smear: Severe Vitamin B12 Deficiency Mimicking Thrombotic Thrombocytopenic Purpura
Authors: Moh Frederick Van , Das Debapria , Houjeij Hourhan , Fritz Adam J 
Published: November 2020

Introduction:

Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency where timely plasmapheresis reduces mortality. There are a few cases where benign etiologies mimic TTP and patients may receive unnecessary plasma exchange. Interdisciplinary decision-making is invaluable to avoid expenses and complications of more invasive treatments.

Case Presentation:

A 38-year-old male with self-reported history of asthma presented with generalized weakness and syncope. He endorses 2-week of bilateral leg pain with numbness, loss of taste, and nausea. Vital signs were remarkable for tachycardia in 110s and hypotension at 101/52. Labs showed hemoglobin 3.3, WBC 3.6, platelet 83, MCV 93.9, reticulocyte 1.1%, total bilirubin 1.4, haptoglobin &lt;8, LDH 2652, negative Coombs test, and creatinine 1.2. Vitamin B12 level was &gt;2000, however value was drawn near the time of administration of intramuscular vitamin B12. There was concern for TTP due to an intermediate PLASMIC score of 5. However, given that presentation was more consistent with vitamin B12 deficiency, plasmapheresis was deferred after a discussion with pathology.

Peripheral blood smear showed anisocytosis, macrocytes, schistocytes, and hypersegmented neutrophils. ADAMTS13 activity returned 62%. Pernicious anemia was diagnosed with labs revealed homocysteine &gt;50, methylmalonic acid 41.97, positive anti-parietal cell antibody, and positive intrinsic factor antibody. Hemoglobin stabilized at around 8 after transfusions. Lab showed haptoglobin 13 and LDH 1211 on discharged after daily vitamin B12 injections. Patient was discharged with weekly injections and last gastric biopsy reveal atrophic gastritis.

Discussion:

The decision to closely monitor our patient versus initiation of plasmapheresis was based on clinical symptoms of neuropathy and reduced taste consistent with vitamin B12 deficiency. Our patient's lab values and peripheral smear were also more reassuring of a nutritional deficiency. Severe vitamin B12 deficiency is thought to cause both intramedullary and extramedullary hemolysis. Intramedullary hemolysis caused by destruction of erythrocytes leading to ineffective erythropoiesis is more common. Conversely, the mechanism of extramedullary hemolysis is not well established. It is thought that the pro-oxidative qualities of homocysteine can promote thrombosis and endothelial dysfunction and subsequent microangiopathy. This phenomenon, commonly called pseudothrombotic microangiopathy, mimics TTP.

Few laboratory values can help distinguish between TTP and an intramedullary process. First, reduced reticulocyte count suggests defective DNA synthesis and destruction of megaloblastic cells by bone marrow macrophages. A high MCV in the setting of low reticulocyte count is suggestive of vitamin B12 deficiency. Blood smear may also show multiple hypersegmented polymorphonuclear cells and macrocytosis in addition to schistocytes. Additionally, LDH tends to be more substantially elevated in intramedullary hemolytic processes like vitamin B12 deficiency. This is attributed to high LDH content of nucleated erythrocytes when compared to mature red blood cells. Immature erythrocytes contain less hemoglobin than mature red blood cells and bilirubin is relatively less elevated in vitamin B12 deficiency. Lastly, platelet counts tend to be higher in vitamin B12 deficiency than in TTP.

Disclosures

No relevant conflicts of interest to declare.