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The bone marrow, the body's largest organ in blood cell production, plays a crucial role in the formation and release of red blood cells, platelets, and granulocytes. Any disorders affecting the bone marrow can lead to pancytopenia, a condition characterized by reduced levels of all three types of blood cells in the bloodstream (Anuj S et al., 2023).
Pancytopenia manifests through symptoms of bone marrow failure such as pale skin, shortness of breath, bleeding, easy bruising, and an increased risk of infections (Anuj S et al., 2023). These symptoms, when severe, can be life-threatening, underscoring the critical nature of this condition. It is not a specific disease but a clinical condition resulting from various underlying causes, including autoimmune disorders, genetic conditions, infections, malignancies and nutritional deficiencies. It is defined by specific thresholds: hemoglobin levels below 12 g/dL in women and 13 g/dL in men; platelet counts under 150,000 per microliter, and white blood cells below 4,000 per microliter (or an absolute neutrophil count of less than 1,800 per microliter). However, these parameters can vary depending on age, sex, ethnicity, and specific clinical circumstances (Vargas-Carretero et al., 2019).
Pancytopenia can have multiple contributing factors, highlighting the complex nature of this condition. Sometimes, symptoms may be mild enough to go unnoticed until routine blood tests reveal low counts. In other cases, it can be severe and life-threatening, requiring urgent medical attention. The underlying mechanisms behind pancytopenia depend on its cause. It can occur due to decreased production or increased destruction of blood cells.
When caused by reduced cell production, pancytopenia is often due to nutritional deficiencies or bone marrow failure, a condition known as aplastic anemia. Aplastic anemia may occur without a known cause (idiopathic) or be triggered by an autoimmune response, infections (such as hepatitis, parvovirus B19, HIV, cytomegalovirus, or Epstein-Barr virus), or exposure to toxic drugs and chemotherapy agents like carbamazepine, carbimazole, chloramphenicol, dapsone, and methotrexate. It can also result from poor nutritional intake, as seen in those with eating disorders or chronic alcoholism, or from malabsorption conditions (Takeshima M et al., 2018).
Increased peripheral destruction of blood cells is another cause of pancytopenia. It is associated with various autoimmune disorders (such as systemic lupus erythematosus and rheumatoid arthritis) and conditions causing splenic sequestration, such as alcoholic liver cirrhosis, HIV, tuberculosis, and malaria. These conditions often affect platelets and red blood cells more than white blood cells. Sepsis can also cause pancytopenia through multiple mechanisms, including bone marrow suppression, splenic sequestration (hypersplenism), and consumptive coagulopathy. These mechanisms usually operate together. Viruses can also induce pancytopenia through several pathways that affect hematopoietic stem cells (King KY et al., 2011). In the case of SARS-CoV-2, a massive cytokine storm has been suggested as a mechanism (Zhao Y, 2021; Mehta P et al., 2020).
Genetic conditions like paroxysmal nocturnal hemoglobinuria (PNH) can also lead to pancytopenia. Paroxysmal nocturnal hemoglobinuria is caused by the absence of specific proteins, such as CD55 and CD59, which usually protect cells from destruction by the complement system. This condition involves a mutation in the phosphatidylinositol glycan class A gene, resulting in cell destruction vulnerability (Anuj S et al., 2023).
References
Anuj S, Vijeta T, Namrata A, Sudhakar S. Pathophysiology of pancytopenia: Understanding blood cell production and regulation in the bone marrow. International Journal of Current Pharmaceutical Research. ISSN-0975-7066 Vol 15 Issue 4, 2023.
Vargas-Carretero CJ, Fernandez-Vargas OE, Ron-Magaña AL, Padilla-Ortega JA, Ron-Guerrero CS, Barrera-Chairez E. Etiology and clinico-hematological profile of pancytopenia: experience of a Mexican Tertiary Care Center and review of the literature. Hematology. 2019 Dec;24(1):399-404.
Takeshima M, Ishikawa H, Kitadate A, Sasaki R, Kobayashi T, Nanjyo H, Kanbayashi T, Shimizu T. Anorexia nervosa-associated pancytopenia mimicking idiopathic aplastic anemia: a case report. BMC Psychiatry. 2018 May 25;18(1):150.
King KY, Goodell MA. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nat Rev Immunol. 2011 Sep 09;11(10):685-92.
Zhao Y, He J, Wang J, Li WM, Xu M, Yu X, Wu W, Sun C, Xu Z, Zhang W, Hu Y, Huang H. Development of pancytopenia in a patient with COVID-19. J Med Virol. 2021 Mar;93(3):1219-1220.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ., HLH Across Specialty Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. Assessed and Endorsed by the MedReport Medical Review Board
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