A Case of Autoimmune Metaplastic Atrophic Gastritis with Concurrent Pernicious Anemia and Coombs-Negative Hemolysis

Case Report

Ann Hematol Onco. 2023; 10(3): 1424.

A Case of Autoimmune Metaplastic Atrophic Gastritis with Concurrent Pernicious Anemia and Coombs-Negative Hemolysis

Joseph P Marshalek*

Department of Internal Medicine, Harbor-UCLA Medical Center, USA

*Corresponding author: Joseph P Marshalek Department of Internal Medicine, Harbor-UCLA Medical Center, 1000 W Carson Street Torrance, CA, 90502, USA. Email: [email protected]

Received: April 17, 2023 Accepted: May 13, 2023 Published: May 20, 2023


Pernicious anemia is an autoimmune disease characterized by atrophic gastritis and vitamin B12 deficiency. Concurrent hemolytic anemia has been described, however its prevalence and mechanism are not well understood. Herein, we present the case of a 40-year-old female who presented with abdominal pain, fatigue, and a 50-lb weight loss over four months. She was found to have macrocytic anemia, leukopenia, moderate neutropenia, and severe vitamin B12 deficiency. Further laboratory testing (indirect hyperbilirubinemia, low haptoglobin, increased lactate dehydrogenase, low reticulocyte index) implied the presence of intravascular hemolysis with a poor bone marrow response. Peripheral blood smear showed hypersegmented neutrophils consistent with megaloblastic anemia and schistocytes suggestive of hemolysis. Notably, the direct Coombs test was negative.The patient’s serum was positive for anti-intrinsic factor and anti-parietal cell antibodies. Esophagogastroduodenoscopy revealed H. Pylori-negative, metaplastic atrophic gastritis with no evidence of malignancy. Thus, a diagnosis of pernicious anemia was confirmed in addition to hemolytic anemia. She was treated with intramuscular cyanocobalamin, resulting in improvement of symptoms, cytopenias, and hemolytic markers. Hemolysis is a rare complication of vitamin B12 deficiency, and multifactorial anemia must always be considered.

Keywords: Hemolytic anemia; Hemolysis; Autoimmune metaplastic atrophic gastritis; Pernicious anemia; Vitamin B12 deficiency

Abbreviations: G6PD: Glucose-6-Phosphate Dehydrogenase; LDH: Lactate Dehydrogenase


Acquired hemolytic anemia is associated with a wide variety of clinical conditions and is mediated by immune and non-immune mechanisms. Immune-mediated mechanisms of hemolysis include warm and cold autoimmune hemolytic anemia, paroxysmal nocturnal hemoglobinuria, and most cases of drug-induced hemolytic anemia [1-4]. There is a vast array of non-immune causes of hemolytic anemia including thalassemia, sickle cell disease, G6PD deficiency, hereditary spherocytosis, infections, thrombotic microangiopathies, mechanical hemolysis from indwelling devices, hypersplenism, and various pregnancy syndromes [5-12].

Megaloblastic anemia due to vitamin B12-deficient autoimmune gastritis is referred to as pernicious anemia. Anti-intrinsic factor antibodies prevent the formation of the vitamin B12 – intrinsic factor complex which is required for vitamin B12 absorption. As a consequence, there is impaired hematopoiesis as vitamin B12 is a necessary co-factor in the folate-mediated synthesis of nucleic acids. The prevalence of autoimmune gastritis and pernicious anemia are roughly 2% and 0.4%, respectively [13,14].

While vitamin B12 deficiency and iron deficiency anemia are well-established sequelae of autoimmune metaplastic atrophic gastritis due to malabsorption, hemolytic anemia is a notably rare and not well understood complication [15,16]. In a cohort reported by Andres et al [16], the prevalence of hemolytic anemia in patients with vitamin B12 deficiency was 1.5%. However, there is a paucity of research regarding the prevalence and mechanism of concurrent pernicious anemia and hemolytic anemia. It is the aim of this case report to describe a case of severe autoimmune metaplastic atrophic gastritis with concomitant pernicious anemia and Coombs-negative hemolytic anemia.

Case Presentation

A 40-year-old female with Dandy-Walker malformation presented to the emergency room with epigastric pain, fatigue, and a 50-lb weight loss over the past four months. The epigastric pain was burning, non-radiating, and postprandial. On physical examination, the patient had conjunctival pallor and epigastric tenderness without rebound or guarding. No scleral icterus or jaundice was observed. She reported no glossitis, paresthesias, balance problems, or weakness. Sensory examination was normal including proprioception and vibration. Mental status examination was normal, and the patient denied any mood changes.

Complete blood count with differential showed macrocytic anemia (hemoglobin 7.3g/dL, mean corpuscular volume 110.1fL), leukopenia (white blood cell count 2400 per mm3) and moderate neutropenia (absolute neutrophil count 800 per mm³). Folic acid was elevated at 31.6ng/mL, and vitamin B12 was very low (<60pg/mL). Indirect hyperbilirubinemia (4.9mg/dL), low haptoglobin (<8mg/dL), and increased lactate dehydrodenase (LDH=1,204U/L) supported the presence of hemolysis. The reticulocyte index was 0.21, indicating a poor bone marrow response to hemolysis. Peripheral blood smear revealed hypersegmented neutrophils consistent with megaloblastic anemia and schistocytes compatible with hemolysis (Figure 1). Thus, it appeared the patient’s severe vitamin B12 deficiency was leading to both decreased erythrocyte production and increased erythrocyte destruction. Of note, the patient’s direct Coombs test was negative. The patient was started on intramuscular cyanocobalamin 1000mcg daily for vitamin B12 deficiency and given pantoprazole for gastrointestinal symptoms.

Citation: Marshalek JP. A Case of Autoimmune Metaplastic Atrophic Gastritis with Concurrent Pernicious Anemia and Coombs-Negative Hemolysis. Ann Hematol Onco. 2023; 10(3): 1424.