Intended for healthcare professionals

Endgames Case Review

A link between asthenia, pallor, and jaundice

BMJ 2016; 353 doi: (Published 07 June 2016) Cite this as: BMJ 2016;353:i2937
  1. João Tavares, physician in general internal medicine1,
  2. Gisela Eugénio, resident in rheumatology2,
  3. Suzana Calretas, consultant physician in general internal medicine3,
  4. Rui Silva, pathologist4,
  5. Rui Santos, consultant physician in general internal medicine and clinical professor of medicine3,
  6. Armando Carvalho, consultant physician in general internal medicine and clinical professor of medicine3
  1. 1Hospitais da Universidade de Coimbra, Coimbra 3000-075, Portugal
  2. 2Department of Rheumatology, Hospitais da Universidade de Coimbra
  3. 3Department of Internal Medicine, Hospitais da Universidade de Coimbra
  4. 4Department of Pathology, Hospitais da Universidade de Coimbra
  1. Correspondence to: J Tavares joaoptavares{at}

A 45 year old white man presented to the emergency department with progressively worsening weakness and chest discomfort on moderate intensity physical activity over the past two months. He also reported paleness and “yellowish eyes” in the past month. He had a history of anxiety, treated with alprazolam as needed.

At presentation, his vital signs were normal. On physical examination he had mild generalised pallor, scleral icterus, and tender non-painful hepatomegaly.

He was admitted to the internal medicine ward for further evaluation.

Laboratory studies showed haemoglobin 70 g/L (reference range 13-17), mean corpuscular volume 111.5 fL (83-101), haematocrit 19.4% (40-50%), leucocyte count 3.3×109/L (4-10), platelet count 151×109/L (150-450), reticulocyte production index 0.52 (>2), lactate dehydrogenase 1460 U/L (125-220), total bilirubin 35.92 μmol/L (5.13-20.52), direct bilirubin 11.97 μmol/L (1.71-8.55), haptoglobin <0.07 g/L (0.30-2), vitamin B12 57.55 pmol/L (156-672), ferritin 177 ng/mL (50-250), and folic acid 26.74 nmol/L (>12.24). The peripheral blood smear showed macrocytosis and hypersegmented neutrophils.

Antibodies against parietal cells were positive; Coombs test and anti-intrinsic factor antibodies were negative.

Upper gastrointestinal endoscopy showed atrophic gastritis of the body and fundus. Staining for Helicobacter pylori was negative (fig 1). Biopsy confirmed the presence of type A atrophic gastritis with moderate intestinal metaplasia.

Fig 1 Gastric body fragments showing glandular atrophy plus moderate intestinal metaplasia and a moderate mononuclear infiltrate of the lamina propria (haematoxylin and eosin stain, original magnification ×100)


  1. What is the most likely diagnosis?

  2. What strategy can primary care practitioners take to reach the diagnosis?

  3. What are the differential diagnoses?

  4. How is this condition managed?

  5. How is this condition followed up?


1. What is the most likely diagnosis?

Short answer

Pernicious anaemia with intramedullary haemolysis as a result of ineffective erythropoiesis.


Pernicious anaemia is a macrocytic anaemia caused by vitamin B12 (cobalamin) deficiency, as a consequence of an intrinsic factor …

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