22nd July 2024

Bone marrow failure

Overview of bone marrow failure

Production of RBCs, WBCs and platelets occurs in the bone marrow, but in certain conditions where demand is increased there can be haematopoiesis in the liver and spleen. Different cells arise from different lineages, and issues can arise in any or all parts of cell production and differentiation.

Pancytopenia

Pancytopenia is a reduction in all peripheral blood cell lineages and usually diagnosed when the three main cell lines – haemoglobin, platelets and neutrophils – are below the normal ranges. Patients may present with symptoms associated with cytopenias (infections, fatigue, dyspnoea, bruising or bleeding) or the underlying disease process.

Blood tests including FBC, reticulocytes, urea and electrolytes (U&E), clotting screen and blood film should be sent, and the patient may subsequently undergo a bone marrow biopsy.

There are many different causes of pancytopenia, which can be broadly grouped into: bone marrow infiltration, bone marrow aplasia and blood cell destruction or sequestration.

Aplastic anaemia

This is a disorder whereby the bone marrow ceases to produce stem cells, leading to pancytopenia. It can present with symptoms related to reduction in any of the cell lineages, for example anaemia, infection or bleeding.

An FBC shows evidence of cytopenia (at least 2 cytopenias needed for diagnosis: Hb <100 g/L, platelet <50 10⁹/L, neutrophils <1.5 10⁹/L). Reticulocytes are low as the bone marrow is hypo-productive. Bone marrow biopsy confirms the diagnosis with a hypocellular marrow but no abnormal cell populations or fibrosis (suggestive of leukaemia and myelofibrosis respectively).

Acquired aplastic anaemia is commonly idiopathic, but causes include drugs (chloramphenicol, NSAIDs – indomethacin, gold), viral illness, PNH and SLE.

Treatment varies depending on the severity. Asymptomatic patients may only need observation or supportive transfusions. Severe disease (reticulocytes <50 x10⁹/L, platelets <20 x 10⁹/L and neutrophils <0.5 x10⁹/L) can be cured with a stem cell transplant, however this is reserved for those under the age of 40 who are medically fit, as otherwise prognosis is poor. For those who are likely not able to tolerate stem cell transplantation or those with more moderate disease, treatment with triple therapy (eltrombopag, horse antithymocyte globulin and cyclosporine) is another option. Supportive care is considered for frailer patients (performance status >2).

Agranulocytosis

This is a reduction in granulocytes (includes neutrophils, basophils and eosinophils), which increases the risk of infection. Patients will often present with recurrent infections or oral ulcerations, although it can be asymptomatic.

It is often secondary to drugs (carbimazole, propylthiouracil, clozapine, sulfonamides, gold or dapsone), and patients on these medications need to be monitored and safety netted to present for medical attention if any signs of a fever.

Treatment includes stopping the offending medication and consideration of granulocyte colony-stimulating factor (GCSF). Bone marrow biopsy may not be needed if the presentation is likely secondary to a high-risk drug.

References

• Berliner N. Approach to the adult with pancytopenia [Internet]. Newburger P, Rosmarin A, editors. UpToDate. 2021 [cited 2022 Jan 22]. Available from: https://www.uptodate.com/contents/approach-to-the-adult-with-pancytopenia
• Coates T. Drug-induced neutropenia and agranulocytosis [Internet]. Newburger P, Rosmarin A, editors. UpToDate. 2022 [cited 2022 May 31]. Available from: https://www.uptodate.com/contents/drug-induced-neutropenia-and-agranulocytosis
• Lipton J. Assessment of pancytopenia [Internet]. BMJ Best Practice. 2021 [cited 2022 Jan 17]. Available from: https://bestpractice.bmj.com/topics/en-gb/1024
• Marsh J, Kulasekararaj A. Aplastic anaemia in adults [Internet]. BMJ Best Practice. 2018 [cited 2022 Jan 15]. Available from: https://bestpractice.bmj.com/topics/en-gb/96
• Olson T. Aplastic anemia: Pathogenesis, clinical manifestations, and diagnosis [Internet]. Mentzer W, Rosmarin A, editors. UpToDate. 2021 [cited 2022 Jan 22]. Available from: https://www.uptodate.com/contents/aplastic-anemia-pathogenesis-clinical-manifestations-and-diagnosis
• Provan D, Baglin T, Dokal I, De Vos J. Oxford Handbook of Clinical Haematology [Internet]. 4th ed. Oxford: Oxford University Press; 2015 [cited 2021 Dec 17]. Available from: https://oxfordmedicine.com/view/10.1093/med/9780199683307.001.0001/med-9780199683307
• Olson T, Dunbar C. Treatment of aplastic anemia in adults [Internet]. Larson R, Rosmarin A, editors. UpToDate. 2022 [cited 2022 May 31]. Available from: https://www.uptodate.com/contents/treatment-of-aplastic-anemia-in-adults
• Wilkinson I, Raine T, Wiles K, Goodhart A, Hall C, O’Neill H. Haematology. In: Oxford Handbook of Clinical Medicine (10 ed) [Internet]. Oxford University Press; 2017 [cited 2021 Dec 11]. Available from: https://oxfordmedicine.com/view/10.1093/med/9780199689903.001.0001/med-9780199689903-chapter-8