The “Blue Marrow”: when inappropriateness in laboratory medicine leads to unnecessary invasive procedures—a case report

Introduction

In vitamin B12 deficiency, bone marrow suppression is common and can potentially affect all cell lines, but megaloblastic anemia is the most frequent (1,2). The clinical manifestations of vitamin B12 deficiency are different and comprise cutaneous involvement (hyperpigmentation, jaundice, vitiligo), gastrointestinal (glossitis), neuropsychiatric (areflexia, cognitive impairment, gait abnormalities, irritability, olfactory impairment, peripheral neuropathy) and hematologic involvement (anemia macrocytic, leukopenia, thrombocytopenia, thrombocytosis (3). The causes of vitamin B12 deficiency are numerous, such as decreased ileal absorption (ileal resection, Chron disease, tapeworm infection), decreased intrinsic factor that is necessary for a correct absorption of this vitamin (atrophic gastritis, pernicious anemia, post-gastrectomy syndrome), inadequate intake (alcohol abuse, older patients, vegan or strict vegetarians) and prolonged medication use (histamine H2 blockers, proton pump inhibitors, metformin) (3). In this case report we emphasize the importance of an accurate anamnesis to guide the choice of the most appropriate laboratory tests to arrive at the correct diagnosis, avoiding unnecessary clinical procedures. We present this case in accordance with the CARE reporting checklist (available at https://jlpm.amegroups.com/article/view/10.21037/jlpm-24-40/rc).

Case presentation

A young adult male presented to the emergency department of our hospital for marked asthenia for about a week, with a weight loss of approximately six kilograms in the last month and repeated episodes of nausea and vomiting. Negative family history of gastrointestinal diseases. The patient was not taking any medications and denies melena and hematemesis and no relevant past interventions. His admission laboratory investigations showed severe anemia, with a hemoglobin of 39 g/L (3.9 g/dL) [reference interval (RI) 13.0–17.5 g/dL], red blood cells 1.13×10⁶/µL (RI 4.50–5.90×10⁶/µL) mean corpuscular volume (MCV) 98.2 fL (RI 80–96 fL) platelets 26×10³/µL [RI (150–410)×10³/µL] and white blood cells 1.88×10³/µL [RI (3.6–10.5)×10³/µL]. The complete blood cell count (CBC) was performed on a Sysmex XN analyzer (Sysmex, Kobe, Japan). Serum creatinine, cardiac troponin, potassium, sodium, alanine aminotransferase, lipase, were in the respective RI. The other laboratory investigations performed at admission showed an increased total bilirubin of 2.36 mg/dL (RI <1.4 mg/dL), an increased procalcitonin of 0.22 ng/mL (RI <0.05 ng/mL) and a heavy increase of lactate dehydrogenase with a value of >1,800 U/L (RI 120–230 U/L). All these determinations were performed on Cobas instrumentation (Roche Diagnostics GmbH, Mannheim, Germany) according to the manufacturer’s instructions. Due to the results reported on the CBC, a blood film was prepared, and the suspicion of a possible acute hematological disease has raised. Probably due to the considerable dysplasia of cells in the myeloid series and prolonged international normalized ratio (INR) 1.38 (RI 0.85–1.20) acute promyelocytic leukemia has been suspected and trans-retinoic acid administration is started immediately. The next day a bone marrow aspirate is performed, and the microscopic evaluation showed a hypercellular bone marrow with erythropoietic hyperplasia, with megaloblasts instead of normoblasts; alterations also of the granulopoiesis with typical giant band neutrophils and immature giant cells (giant metamyelocytes) without evidence of acute hematological neoplasms (Figures 1,2). This picture is typical in case of severe deficit of vitamin B12, and trans-retinoic acid therapy is immediately stopped in the light of the characteristics of the bone marrow examination, a vitamin B12 determination was performed, and the result shows a severe vitamin deficiency (<100 pg/mL, RI 197–771 pg/mL). In the normal range, the level of folates and the detection of transglutaminase antibodies was negative. The following day, gastric parietal cell and anti-intrinsic factor autoantibodies were determined, both of which evaluated positive at high titers. Subsequently, an endoscopic stomach examination with biopsies of the gastric mucosa was performed with a typical finding of autoimmune gastritis. The final diagnosis was made of pernicious anemia and vitamin B12 supplementation was started. Note that in the following days, the patient has also claimed to be a strict vegetarian. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Figure 1 Bone marrow blood, May Grünwald Giemsa staining, magnification ×10, numerous basophilic erythroblasts are observed.

Figure 2 Bone marrow blood, May Grünwald Giemsa staining, magnification ×63, megaloblastosis of erythroblasts is observed.

Discussion

This case report is a particularly good example of inappropriateness in laboratory medicine for the failure to request the appropriate test for the right patient at the right time, specifically the measurement of vitamin B12, which leads to a delay in proper diagnosis and the execution of invasive and potentially dangerous procedures that could have been avoided. Laboratory medicine has become a fundamental discipline in the diagnostic process and in medical care (4). The issue of appropriateness plays an increasing role in medicine, and at this regard the concept of appropriateness in laboratory medicine has evolved over years. A pragmatic definition of inappropriateness may be that the procedures for which the risks of harm to the patient clearly outweigh the potential benefits are inappropriate (5). There are different diagnostic errors that can result from inappropriate requests, i.e., requesting an inappropriate test, not requesting an appropriate test, misinterpreting a test, delays, and errors in providing laboratory results (6). A less conspicuous aspect is the inappropriate request for failure to demand a laboratory test necessary for a better management of the diagnostic process.

Conclusions

Vitamin B12 deficiency can manifest itself with multiple signs and symptoms reflecting the involvement of different body functions. An accurate anamnesis is always necessary to best direct the diagnostic pathway with the request for the most appropriate laboratory tests. The inappropriate request for laboratory tests can lead to unnecessary and sometimes even potentially dangerous invasive maneuvers on the patient. With the spread of strict vegan or vegetarian diets some nutritional deficits could increase significantly.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jlpm.amegroups.com/article/view/10.21037/jlpm-24-40/rc

Peer Review File: Available at https://jlpm.amegroups.com/article/view/10.21037/jlpm-24-40/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jlpm.amegroups.com/article/view/10.21037/jlpm-24-40/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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