Manifestation of Pancytopenia Associated with COVID-19 as Paroxysmal Nocturnal Hemoglobinuria (PNH) and Aplastic Anemia (AA)

Abstract

We report two cases of pancytopenia in patients after recovering from a mild COVID-19, now presenting as paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. These cases illustrate a common pathway whereby a viral trigger causes the clonal expansion of a hematological disorder. Although the association of both cases with COVID-19 is temporal and COVID-19 may be an incidental diagnosis, the growing evidence related to the hematological effects of SARS-CoV-2 infection highlights the need for further investigation into the hematological consequences of COVID-19, particularly in the post-pandemic era.

Keywords: SARS-CoV-2; aplastic anemia; paroxysmal nocturnal hemoglobinuria.

Figure 1

Mechanisms of SARS-CoV-2 on hematopoietic cells. The SARS-CoV-2 virus has two primary mechanisms: direct viral entry (above, inset) and through inciting an immune response (below). Direct viral entry, via ACE2 receptors, may upregulate Nlrp3 inflammasome expression, leading to pyroptosis, viral replication within HSCs, and apoptosis. Immune response causes the activation of T cells that respond to HSCs and subsequent immune attack, leading to the proliferation of inflammatory signals and a cytokine storm. HSC: hematopoietic stem cell; ACE2: angiotensin-converting enzyme 2; and Nlrp3: NOD-like receptor family pyrin domain containing 3. Different color circles represent cells and the corresponding labels of each cell are given in the figure.

Figure 2

Implications of SARS-CoV-2 virus: immunologic attack and PNH clonal expansion. Normal bone marrow (black circle), with or without PIGA mutation, encounters SARS-CoV-2 virus, leading to immunologic attack and hypoplastic bone marrow (red circle). Direct or indirect mechanisms may cause HSC death, resulting in variable PNH clonal expansion and bone marrow hypoplasia. RBC: red blood cell; WBC: white blood cell; PNH: paroxysmal nocturnal hemoglobinuria; GPI: glucose phosphate isomerase; and PIGA: phosphatidylinositol N-acetylglucosaminyltransferase subunit A. Different color circles represent cells and the corresponding labels of each cell are given in the figure.